Osteoporosis

Key clinical point: Roux-en-Y gastric bypass (RYGB) correlated with greater reduction in areal bone mineral density (aBMD) and greater increase in bone turnover markers vs. sleeve gastrectomy (SG).

Major finding: From baseline to 1 year, aBMD in femoral neck, total hip, and lumbar spine decreased significantly more after RYGB than after SG (mean [95% confidence interval] between group differences: −2.8% [−0.8% to −4.7%], −3.0% [−0.9% to −5.0%], and −4.2% [−2.1% to −6.4%], respectively). The increase in procollagen type 1 N-terminal propeptide and C telopeptide of type I collagen was significantly higher after RYGB vs. SG (P less than .001).

Study details: This randomized, triple-blind, single-center trial included 109 patients with severe obesity and type 2 diabetes randomly assigned (1:1) to RYGB (n = 54) or SG (n = 55).

Disclosures: The study was funded by the Morbid Obesity Center, Vestfold Hospital Trust. F Fatima received an educational grant (PhD) from South-Eastern Norway Regional Health Authority. Other authors had nothing to disclose.

Source: Hofsø D et al. J Clin Endocrinol Metab. 2020 Nov 5. doi: 10.1210/clinem/dgaa808.

Key clinical point: Roux-en-Y gastric bypass (RYGB) correlated with greater reduction in areal bone mineral density (aBMD) and greater increase in bone turnover markers vs. sleeve gastrectomy (SG).

Major finding: From baseline to 1 year, aBMD in femoral neck, total hip, and lumbar spine decreased significantly more after RYGB than after SG (mean [95% confidence interval] between group differences: −2.8% [−0.8% to −4.7%], −3.0% [−0.9% to −5.0%], and −4.2% [−2.1% to −6.4%], respectively). The increase in procollagen type 1 N-terminal propeptide and C telopeptide of type I collagen was significantly higher after RYGB vs. SG (P less than .001).

Study details: This randomized, triple-blind, single-center trial included 109 patients with severe obesity and type 2 diabetes randomly assigned (1:1) to RYGB (n = 54) or SG (n = 55).

Disclosures: The study was funded by the Morbid Obesity Center, Vestfold Hospital Trust. F Fatima received an educational grant (PhD) from South-Eastern Norway Regional Health Authority. Other authors had nothing to disclose.

Source: Hofsø D et al. J Clin Endocrinol Metab. 2020 Nov 5. doi: 10.1210/clinem/dgaa808.

Key clinical point: Roux-en-Y gastric bypass (RYGB) correlated with greater reduction in areal bone mineral density (aBMD) and greater increase in bone turnover markers vs. sleeve gastrectomy (SG).

Major finding: From baseline to 1 year, aBMD in femoral neck, total hip, and lumbar spine decreased significantly more after RYGB than after SG (mean [95% confidence interval] between group differences: −2.8% [−0.8% to −4.7%], −3.0% [−0.9% to −5.0%], and −4.2% [−2.1% to −6.4%], respectively). The increase in procollagen type 1 N-terminal propeptide and C telopeptide of type I collagen was significantly higher after RYGB vs. SG (P less than .001).

Study details: This randomized, triple-blind, single-center trial included 109 patients with severe obesity and type 2 diabetes randomly assigned (1:1) to RYGB (n = 54) or SG (n = 55).

Disclosures: The study was funded by the Morbid Obesity Center, Vestfold Hospital Trust. F Fatima received an educational grant (PhD) from South-Eastern Norway Regional Health Authority. Other authors had nothing to disclose.

Source: Hofsø D et al. J Clin Endocrinol Metab. 2020 Nov 5. doi: 10.1210/clinem/dgaa808.

Key clinical point: Compared with denosumab, zoledronic acid (ZA) therapy for osteoporosis and possibly for malignancy-related bone disease is associated with modestly increased risk for incident atrial fibrillation (AFib) in the first year of treatment.

Major finding: In the osteoporosis cohort, the risk for AFib was higher with ZA vs. denosumab over 1 year (incidence rate [IR], 18.6 vs. 14.9 per 1,000 person-years; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.04-1.50). In the malignancy cohort, a nonsignificant trend toward an increased risk was noted with ZA vs. denosumab (IR, 46.87 vs. 39.03 per 1,000 person-years; HR, 1.19; 95% CI, 1.00-1.43).

Study details: In this new-user, active comparator study, patients (age, 50 years or more) without arrhythmia or advanced kidney disease who initiated ZA were propensity score matched (1:1) to patients initiating denosumab in separate osteoporosis (n = 16,235 pairs) and malignancy (7,732 pairs) cohorts.

Disclosures: No study sponsor was identified. SC Kim received research grants to the Brigham and Women’s Hospital from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb for unrelated studies. A close family member of SJ Cromer is employed by a Johnson & Johnson company. EW Yu received a research grant to the Massachusetts General Hospital from Amgen for unrelated studies. KM D'Silva and M Fischer reported no disclosures

Source: D'Silva KM et al. J Bone Miner Res. 2020 Nov 2. doi: 10.1002/jbmr.4174.

Key clinical point: Compared with denosumab, zoledronic acid (ZA) therapy for osteoporosis and possibly for malignancy-related bone disease is associated with modestly increased risk for incident atrial fibrillation (AFib) in the first year of treatment.

Major finding: In the osteoporosis cohort, the risk for AFib was higher with ZA vs. denosumab over 1 year (incidence rate [IR], 18.6 vs. 14.9 per 1,000 person-years; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.04-1.50). In the malignancy cohort, a nonsignificant trend toward an increased risk was noted with ZA vs. denosumab (IR, 46.87 vs. 39.03 per 1,000 person-years; HR, 1.19; 95% CI, 1.00-1.43).

Study details: In this new-user, active comparator study, patients (age, 50 years or more) without arrhythmia or advanced kidney disease who initiated ZA were propensity score matched (1:1) to patients initiating denosumab in separate osteoporosis (n = 16,235 pairs) and malignancy (7,732 pairs) cohorts.

Disclosures: No study sponsor was identified. SC Kim received research grants to the Brigham and Women’s Hospital from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb for unrelated studies. A close family member of SJ Cromer is employed by a Johnson & Johnson company. EW Yu received a research grant to the Massachusetts General Hospital from Amgen for unrelated studies. KM D'Silva and M Fischer reported no disclosures

Source: D'Silva KM et al. J Bone Miner Res. 2020 Nov 2. doi: 10.1002/jbmr.4174.

Key clinical point: Compared with denosumab, zoledronic acid (ZA) therapy for osteoporosis and possibly for malignancy-related bone disease is associated with modestly increased risk for incident atrial fibrillation (AFib) in the first year of treatment.

Major finding: In the osteoporosis cohort, the risk for AFib was higher with ZA vs. denosumab over 1 year (incidence rate [IR], 18.6 vs. 14.9 per 1,000 person-years; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.04-1.50). In the malignancy cohort, a nonsignificant trend toward an increased risk was noted with ZA vs. denosumab (IR, 46.87 vs. 39.03 per 1,000 person-years; HR, 1.19; 95% CI, 1.00-1.43).

Study details: In this new-user, active comparator study, patients (age, 50 years or more) without arrhythmia or advanced kidney disease who initiated ZA were propensity score matched (1:1) to patients initiating denosumab in separate osteoporosis (n = 16,235 pairs) and malignancy (7,732 pairs) cohorts.

Disclosures: No study sponsor was identified. SC Kim received research grants to the Brigham and Women’s Hospital from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb for unrelated studies. A close family member of SJ Cromer is employed by a Johnson & Johnson company. EW Yu received a research grant to the Massachusetts General Hospital from Amgen for unrelated studies. KM D'Silva and M Fischer reported no disclosures

Source: D'Silva KM et al. J Bone Miner Res. 2020 Nov 2. doi: 10.1002/jbmr.4174.

Adolescents who undergo sleeve gastrectomy have lower bone density and higher bone marrow fat at 1 year following surgery, new research shows.

“It’s almost paradoxical,” Miriam Bredella, MD, of Massachusetts General Hospital in Boston, told Medscape Medical News. “Despite marked loss of body fat, these children have more fat in their bones and decreased bone density.”

She explained that the dissected part of the stomach is filled with anabolic cells that are important for building bone mass. “When those cells are cut out, the body cannot produce the hormones for building up bone.” It’s a malabsorption problem, she added. “Cutting out parts of the stomach or gut leads to less absorption.”

It is well known that bariatric surgery in adults has long-term effects on bone, she said, but this is the first time it has been studied in children.

“Nobody thinks about bone loss in children, but it’s extremely important,” Bredella reports. “The adolescent years up to age 25 are when we accrue bone density, so if something happens during this critical time, it can lead to weak bones later in life.” In the case of these adolescents, peak bone mass is never reached.

To investigate the effects of sleeve gastrectomy on bone density and marrow adipose tissue in extremely obese teenagers, researchers at Massachusetts General Hospital and Harvard Medical School recruited 52 adolescents with a mean body mass index (BMI) of 45. They measured volumetric bone mineral density using quantitative computer tomography (QCT) of the lumbar spine.

“We used QCT instead of DEXA [dual energy x-ray absorptiometry] scan because it isn’t affected by changes in soft tissue; it’s less susceptible to extreme changes in body weight,” Bredella said. “With DEXA scan there are too many artifacts.”

Half of the group (n = 26) underwent surgery. At 1 year, those who underwent surgery lost an average of 34 kg (75 lb). Adolescents in the control group lost an average of 0.2 kg (0.5 lb) (P < .0001).

Both groups repeated the QCT scan at the 1-year follow-up. Researchers found a decrease in bone density in those who underwent sleeve gastrectomy vs. controls (P = .046).

In her presentation, Bredella showed the QCT of the L2 spine in a 17-year old female before surgery and 12 months later. Her volumetric bone mineral density decreased from 183 mg/cm³ to 146 mg/cm³.

“Sleeve gastrectomy in children is bad for bones,” Bradella said. “You have to take care of your bones. This is something people are not thinking about and it probably won’t be a problem when they’re young but will likely affect these patients with osteoporosis when they are older.”

Patients need to be aware of this, she warns, and take steps to combat the bone loss. “Drinking milk, taking vitamin D, and doing weight-bearing exercise may help increase the bone density,” she said.

The increased fat in the bone is also concerning, she said. “Increased fat in the bone is a phenomenon that we see in anorexic patients,” Bredella explained.

The body appears to store the fat in bone in case of need later on, she explained. “We know that in severe states of malnutrition the body has the ability to metabolize the fat in the bones.”

The obesity epidemic in America has given way to a 100-fold increase in sleeve gastrectomy procedures in teenagers between 2005 and 2014. “These patients need this surgery so they don›t die of cardiac arrest or diabetes,” she said. “But we need to make sure they get their bone mineral density checked frequently.”

“The results of this study are important,” Marc Michalsky, MD, Nationwide Children’s Hospital, Columbus, Ohio, told Medscape Medical News. “But they need to be put into context.”

“There is an impetus and argument to support bariatric surgery as it offers a significant reduction in BMI and an associated reversal and complete amelioration of obesity related diseases.”

What this study doesn’t address, he said, is whether this population will experience an increase in bone density-related fractures down the road.

“These results are a snapshot in time — a picture of one postoperative time point,” Michalsky pointed out. “Are we seeing a process that represents continued change in bone mineralization? It’s not unreasonable to assume that the radiological findings here may lead to real clinical impact, but we don’t know.”

Bredella and Michalsky have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Adolescents who undergo sleeve gastrectomy have lower bone density and higher bone marrow fat at 1 year following surgery, new research shows.

“It’s almost paradoxical,” Miriam Bredella, MD, of Massachusetts General Hospital in Boston, told Medscape Medical News. “Despite marked loss of body fat, these children have more fat in their bones and decreased bone density.”

She explained that the dissected part of the stomach is filled with anabolic cells that are important for building bone mass. “When those cells are cut out, the body cannot produce the hormones for building up bone.” It’s a malabsorption problem, she added. “Cutting out parts of the stomach or gut leads to less absorption.”

It is well known that bariatric surgery in adults has long-term effects on bone, she said, but this is the first time it has been studied in children.

“Nobody thinks about bone loss in children, but it’s extremely important,” Bredella reports. “The adolescent years up to age 25 are when we accrue bone density, so if something happens during this critical time, it can lead to weak bones later in life.” In the case of these adolescents, peak bone mass is never reached.

To investigate the effects of sleeve gastrectomy on bone density and marrow adipose tissue in extremely obese teenagers, researchers at Massachusetts General Hospital and Harvard Medical School recruited 52 adolescents with a mean body mass index (BMI) of 45. They measured volumetric bone mineral density using quantitative computer tomography (QCT) of the lumbar spine.

“We used QCT instead of DEXA [dual energy x-ray absorptiometry] scan because it isn’t affected by changes in soft tissue; it’s less susceptible to extreme changes in body weight,” Bredella said. “With DEXA scan there are too many artifacts.”

Half of the group (n = 26) underwent surgery. At 1 year, those who underwent surgery lost an average of 34 kg (75 lb). Adolescents in the control group lost an average of 0.2 kg (0.5 lb) (P < .0001).

Both groups repeated the QCT scan at the 1-year follow-up. Researchers found a decrease in bone density in those who underwent sleeve gastrectomy vs. controls (P = .046).

In her presentation, Bredella showed the QCT of the L2 spine in a 17-year old female before surgery and 12 months later. Her volumetric bone mineral density decreased from 183 mg/cm³ to 146 mg/cm³.

“Sleeve gastrectomy in children is bad for bones,” Bradella said. “You have to take care of your bones. This is something people are not thinking about and it probably won’t be a problem when they’re young but will likely affect these patients with osteoporosis when they are older.”

Patients need to be aware of this, she warns, and take steps to combat the bone loss. “Drinking milk, taking vitamin D, and doing weight-bearing exercise may help increase the bone density,” she said.

The increased fat in the bone is also concerning, she said. “Increased fat in the bone is a phenomenon that we see in anorexic patients,” Bredella explained.

The body appears to store the fat in bone in case of need later on, she explained. “We know that in severe states of malnutrition the body has the ability to metabolize the fat in the bones.”

The obesity epidemic in America has given way to a 100-fold increase in sleeve gastrectomy procedures in teenagers between 2005 and 2014. “These patients need this surgery so they don›t die of cardiac arrest or diabetes,” she said. “But we need to make sure they get their bone mineral density checked frequently.”

“The results of this study are important,” Marc Michalsky, MD, Nationwide Children’s Hospital, Columbus, Ohio, told Medscape Medical News. “But they need to be put into context.”

“There is an impetus and argument to support bariatric surgery as it offers a significant reduction in BMI and an associated reversal and complete amelioration of obesity related diseases.”

What this study doesn’t address, he said, is whether this population will experience an increase in bone density-related fractures down the road.

“These results are a snapshot in time — a picture of one postoperative time point,” Michalsky pointed out. “Are we seeing a process that represents continued change in bone mineralization? It’s not unreasonable to assume that the radiological findings here may lead to real clinical impact, but we don’t know.”

Bredella and Michalsky have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Adolescents who undergo sleeve gastrectomy have lower bone density and higher bone marrow fat at 1 year following surgery, new research shows.

“It’s almost paradoxical,” Miriam Bredella, MD, of Massachusetts General Hospital in Boston, told Medscape Medical News. “Despite marked loss of body fat, these children have more fat in their bones and decreased bone density.”

She explained that the dissected part of the stomach is filled with anabolic cells that are important for building bone mass. “When those cells are cut out, the body cannot produce the hormones for building up bone.” It’s a malabsorption problem, she added. “Cutting out parts of the stomach or gut leads to less absorption.”

It is well known that bariatric surgery in adults has long-term effects on bone, she said, but this is the first time it has been studied in children.

“Nobody thinks about bone loss in children, but it’s extremely important,” Bredella reports. “The adolescent years up to age 25 are when we accrue bone density, so if something happens during this critical time, it can lead to weak bones later in life.” In the case of these adolescents, peak bone mass is never reached.

To investigate the effects of sleeve gastrectomy on bone density and marrow adipose tissue in extremely obese teenagers, researchers at Massachusetts General Hospital and Harvard Medical School recruited 52 adolescents with a mean body mass index (BMI) of 45. They measured volumetric bone mineral density using quantitative computer tomography (QCT) of the lumbar spine.

“We used QCT instead of DEXA [dual energy x-ray absorptiometry] scan because it isn’t affected by changes in soft tissue; it’s less susceptible to extreme changes in body weight,” Bredella said. “With DEXA scan there are too many artifacts.”

Half of the group (n = 26) underwent surgery. At 1 year, those who underwent surgery lost an average of 34 kg (75 lb). Adolescents in the control group lost an average of 0.2 kg (0.5 lb) (P < .0001).

Both groups repeated the QCT scan at the 1-year follow-up. Researchers found a decrease in bone density in those who underwent sleeve gastrectomy vs. controls (P = .046).

In her presentation, Bredella showed the QCT of the L2 spine in a 17-year old female before surgery and 12 months later. Her volumetric bone mineral density decreased from 183 mg/cm³ to 146 mg/cm³.

“Sleeve gastrectomy in children is bad for bones,” Bradella said. “You have to take care of your bones. This is something people are not thinking about and it probably won’t be a problem when they’re young but will likely affect these patients with osteoporosis when they are older.”

Patients need to be aware of this, she warns, and take steps to combat the bone loss. “Drinking milk, taking vitamin D, and doing weight-bearing exercise may help increase the bone density,” she said.

The increased fat in the bone is also concerning, she said. “Increased fat in the bone is a phenomenon that we see in anorexic patients,” Bredella explained.

The body appears to store the fat in bone in case of need later on, she explained. “We know that in severe states of malnutrition the body has the ability to metabolize the fat in the bones.”

The obesity epidemic in America has given way to a 100-fold increase in sleeve gastrectomy procedures in teenagers between 2005 and 2014. “These patients need this surgery so they don›t die of cardiac arrest or diabetes,” she said. “But we need to make sure they get their bone mineral density checked frequently.”

“The results of this study are important,” Marc Michalsky, MD, Nationwide Children’s Hospital, Columbus, Ohio, told Medscape Medical News. “But they need to be put into context.”

“There is an impetus and argument to support bariatric surgery as it offers a significant reduction in BMI and an associated reversal and complete amelioration of obesity related diseases.”

What this study doesn’t address, he said, is whether this population will experience an increase in bone density-related fractures down the road.

“These results are a snapshot in time — a picture of one postoperative time point,” Michalsky pointed out. “Are we seeing a process that represents continued change in bone mineralization? It’s not unreasonable to assume that the radiological findings here may lead to real clinical impact, but we don’t know.”

Bredella and Michalsky have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Rheumatoid arthritis patients who are on both oral glucocorticoids (CGs) and proton pump inhibitors (PPIs) have an increased risk of osteoporotic fractures, according to a retrospective study of RA patients in the United Kingdom.

“Considering the increasing life expectancies and high consumption of PPIs among elderly patients, fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs,” wrote Shahab Abtahi, MD, of Maastricht (Netherlands) University Medical Centre and colleagues. The study was published in Annals of the Rheumatic Diseases.

To determine if concomitant use of the two medications – both already associated with osteoporotic fractures – would lead to a notable increase in fracture risk, the researchers conducted a population-based cohort study of RA patients aged 50 years or older who were diagnosed during 1997-2017. Patient data was gathered via the Clinical Practice Research Datalink, a primary care database of millions of U.K. medical records.

Patients with a recent history of GC/PPI use or those with a previous osteoporotic fracture were excluded from the study. Osteoporotic fractures were defined as fractures of the hip, vertebrae, humerus, forearm, pelvis, or rib. The study population included 12,351 patients, roughly two-thirds of whom were women, with a mean age of 68 years. Of the population, 4,254 patients were concomitant users of oral GCs and PPIs, compared with 3,138 patients who were not on either medication.

Among all patients, 1,411 osteoporotic fractures occurred, 264 of which occurred in the concomitant users group. After adjustments for age and sex, patients on both medications had a higher risk of fracture (adjusted hazard ratio, 1.93; 95% confidence interval, 1.65-2.27), compared to patients on oral GCs alone (aHR, 1.34; 95% CI, 1.12-1.59) or PPIs alone (aHR, 1.32; 95% CI, 1.14-1.54). After full adjustment, concomitant users again had a higher risk of fracture (aHR, 1.60; 95% CI, 1.35-1.89).

Regarding specific types of breaks, the concomitant users had a notably higher risk of hip (aHR, 1.45; 95% CI, 1.11-1.91), vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and rib fractures (aHR, 4.03; 95% CI, 2.13-7.63). No increased risk was found for either humerus or forearm fractures. The risk of fracture did not rise for concomitant users who had either increasing daily doses of PPI or a longer duration of use.

The authors noted their study’s potential limitations, including having access to data on prescriptions only, not the actual use of medication, and a lack of information in the medical records regarding biologic therapies or certain indicators of RA disease activity. In addition, there was a likelihood that some patients who were improving might have stopped taking the drugs and lessened their risk of fracture, though the researchers attempted to account for this by “adjusting our analyses for six indicators of RA severity, including analgesics and csDMARDs.”

Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.

SOURCE: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.

Rheumatoid arthritis patients who are on both oral glucocorticoids (CGs) and proton pump inhibitors (PPIs) have an increased risk of osteoporotic fractures, according to a retrospective study of RA patients in the United Kingdom.

“Considering the increasing life expectancies and high consumption of PPIs among elderly patients, fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs,” wrote Shahab Abtahi, MD, of Maastricht (Netherlands) University Medical Centre and colleagues. The study was published in Annals of the Rheumatic Diseases.

To determine if concomitant use of the two medications – both already associated with osteoporotic fractures – would lead to a notable increase in fracture risk, the researchers conducted a population-based cohort study of RA patients aged 50 years or older who were diagnosed during 1997-2017. Patient data was gathered via the Clinical Practice Research Datalink, a primary care database of millions of U.K. medical records.

Patients with a recent history of GC/PPI use or those with a previous osteoporotic fracture were excluded from the study. Osteoporotic fractures were defined as fractures of the hip, vertebrae, humerus, forearm, pelvis, or rib. The study population included 12,351 patients, roughly two-thirds of whom were women, with a mean age of 68 years. Of the population, 4,254 patients were concomitant users of oral GCs and PPIs, compared with 3,138 patients who were not on either medication.

Among all patients, 1,411 osteoporotic fractures occurred, 264 of which occurred in the concomitant users group. After adjustments for age and sex, patients on both medications had a higher risk of fracture (adjusted hazard ratio, 1.93; 95% confidence interval, 1.65-2.27), compared to patients on oral GCs alone (aHR, 1.34; 95% CI, 1.12-1.59) or PPIs alone (aHR, 1.32; 95% CI, 1.14-1.54). After full adjustment, concomitant users again had a higher risk of fracture (aHR, 1.60; 95% CI, 1.35-1.89).

Regarding specific types of breaks, the concomitant users had a notably higher risk of hip (aHR, 1.45; 95% CI, 1.11-1.91), vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and rib fractures (aHR, 4.03; 95% CI, 2.13-7.63). No increased risk was found for either humerus or forearm fractures. The risk of fracture did not rise for concomitant users who had either increasing daily doses of PPI or a longer duration of use.

The authors noted their study’s potential limitations, including having access to data on prescriptions only, not the actual use of medication, and a lack of information in the medical records regarding biologic therapies or certain indicators of RA disease activity. In addition, there was a likelihood that some patients who were improving might have stopped taking the drugs and lessened their risk of fracture, though the researchers attempted to account for this by “adjusting our analyses for six indicators of RA severity, including analgesics and csDMARDs.”

Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.

SOURCE: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.

Rheumatoid arthritis patients who are on both oral glucocorticoids (CGs) and proton pump inhibitors (PPIs) have an increased risk of osteoporotic fractures, according to a retrospective study of RA patients in the United Kingdom.

“Considering the increasing life expectancies and high consumption of PPIs among elderly patients, fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs,” wrote Shahab Abtahi, MD, of Maastricht (Netherlands) University Medical Centre and colleagues. The study was published in Annals of the Rheumatic Diseases.

To determine if concomitant use of the two medications – both already associated with osteoporotic fractures – would lead to a notable increase in fracture risk, the researchers conducted a population-based cohort study of RA patients aged 50 years or older who were diagnosed during 1997-2017. Patient data was gathered via the Clinical Practice Research Datalink, a primary care database of millions of U.K. medical records.

Patients with a recent history of GC/PPI use or those with a previous osteoporotic fracture were excluded from the study. Osteoporotic fractures were defined as fractures of the hip, vertebrae, humerus, forearm, pelvis, or rib. The study population included 12,351 patients, roughly two-thirds of whom were women, with a mean age of 68 years. Of the population, 4,254 patients were concomitant users of oral GCs and PPIs, compared with 3,138 patients who were not on either medication.

Among all patients, 1,411 osteoporotic fractures occurred, 264 of which occurred in the concomitant users group. After adjustments for age and sex, patients on both medications had a higher risk of fracture (adjusted hazard ratio, 1.93; 95% confidence interval, 1.65-2.27), compared to patients on oral GCs alone (aHR, 1.34; 95% CI, 1.12-1.59) or PPIs alone (aHR, 1.32; 95% CI, 1.14-1.54). After full adjustment, concomitant users again had a higher risk of fracture (aHR, 1.60; 95% CI, 1.35-1.89).

Regarding specific types of breaks, the concomitant users had a notably higher risk of hip (aHR, 1.45; 95% CI, 1.11-1.91), vertebrae (aHR, 2.84; 95% CI, 1.87-4.32), pelvis (aHR, 2.47; 95% CI, 1.41-4.34), and rib fractures (aHR, 4.03; 95% CI, 2.13-7.63). No increased risk was found for either humerus or forearm fractures. The risk of fracture did not rise for concomitant users who had either increasing daily doses of PPI or a longer duration of use.

The authors noted their study’s potential limitations, including having access to data on prescriptions only, not the actual use of medication, and a lack of information in the medical records regarding biologic therapies or certain indicators of RA disease activity. In addition, there was a likelihood that some patients who were improving might have stopped taking the drugs and lessened their risk of fracture, though the researchers attempted to account for this by “adjusting our analyses for six indicators of RA severity, including analgesics and csDMARDs.”

Two of the authors reported receiving research grants and speakers’ fees from various pharmaceutical companies. The others reported no conflicts of interest.

SOURCE: Abtahi S et al. Ann Rheum Dis. 2020 Dec 11. doi: 10.1136/annrheumdis-2020-218758.

Higher doses of vitamin D supplementation not only show no benefit in the prevention of falls in older adults at increased risk of falling, compared with the lowest doses, but they appear to increase the risk, new research shows.

Zbynek Pospisil/iStock/Getty Images

Based on the findings, supplemental vitamin D above the minimum dose of 200 IU/day likely has little benefit, lead author Lawrence J. Appel, MD, MPH, told this news organization.

“In the absence of any benefit of 1,000 IU/day versus 2,000 IU/day [of vitamin D supplementation] on falls, along with the potential for harm from doses above 1,000 IU/day, it is hard to recommend a dose above 200 IU/day in older-aged persons, unless there is a compelling reason,” asserted Dr. Appel, director of the Welch Center for Prevention, Epidemiology, and Clinical Research at Johns Hopkins Bloomberg School of Public Health in Baltimore.

“More is not always better – and it may even be worse,” when it comes to vitamin D’s role in the prevention of falls, he said.

The research, published in Annals of Internal Medicine, adds important evidence in the ongoing struggle to prevent falls, says Bruce R. Troen, MD, in an accompanying editorial.

“Falls and their deleterious consequences remain a substantial risk for older adults and a huge challenge for health care teams,” writes Dr. Troen, a physician-investigator with the Veterans Affairs Western New York Healthcare System.

However, commenting in an interview, Dr. Troen cautions: “There are many epidemiological studies that are correlative, not causative, that do show a likelihood for benefit [with vitamin D supplementation]. … Therefore, there’s no reason for clinicians to discontinue vitamin D in individuals because of this study.”

“If you’re monitoring an older adult who is frail and has multiple comorbidities, you want to know what their vitamin D level is [and] provide them an appropriate supplement if needed,” he emphasized.

Some guidelines already reflect the lack of evidence of any role of vitamin D supplementation in the prevention of falls, including those of the 2018 U.S. Preventive Services Task Force, which, in a reversal of its 2012 recommendation, now does not recommend vitamin D supplementation for fall prevention in older persons without osteoporosis or vitamin D deficiency, Dr. Appel and colleagues note.
 

No prevention of falls regardless of baseline vitamin D

As part of STURDY (Study to understand fall reduction and vitamin D in you), Dr. Appel and colleagues enrolled 688 community-dwelling participants who had an elevated risk of falling, defined as a serum 25-hydroxyvitamin D [25(OH)D] level of 25 to 72.5 nmol/L (10-29 ng/dL).

Participants were a mean age of 77.2 years and had a mean total 25(OH)D level of 55.3 nmol/L at enrollment.

They were randomized to one of four doses of vitamin D₃, including 200 IU/day (the control group), or 1,000, 2,000, or 4,000 IU/day.

The highest doses were found to be associated with worse – not better – outcomes including a shorter time to hospitalization or death, compared with the 1,000-IU/day group. The higher-dose groups were therefore switched to a dose of 1,000 IU/day or lower, and all participants were followed for up to 2 years.

Overall, 63% experienced falls over the course of the study, which, though high, was consistent with the study’s criteria of participants having an elevated fall risk.

Of the 667 participants who completed the trial, no benefit in prevention of falling was seen across any of the doses, compared with the control group dose of 200 IU/day, regardless of participants’ baseline vitamin D levels.

Safety analyses showed that even in the 1,000-IU/day group, a higher risk of first serious fall and first fall with hospitalization was seen compared with the 200-IU/day group.

A limitation is that the study did not have a placebo group, however, “200 IU/day is a very small dose, probably homeopathic,” Dr. Appel said. “It was likely close to a placebo,” he said.
 

Caveats: comorbidities, subgroups

In his editorial, Dr. Troen notes other studies, including VITAL (Vitamin D and Omega-3 Trial) also found no reduction in falls with higher vitamin D doses; however, that study did not show any significant risks with the higher doses.

He adds that the current study lacks information on subsets of participants.

“We don’t have enough information about the existing comorbidities and medications that these people are on to be able to pull back the layers. Maybe there is a subgroup that should not be getting 4,000 IU, whereas another subgroup may not be harmed and you may decide that patient can benefit,” he said.

Furthermore, the trial doesn’t address groups such as nursing home residents.

“I have, for instance, 85-year-olds with vitamin D levels of maybe 20 nmol/L with multiple medical issues, but levels that low were not included in the study, so this is a tricky business, but the bottom line is first, do no harm,” he said.

“We really need trials that factor in the multiple different aspects so we can come up, hopefully, with a holistic and interdisciplinary approach, which is usually the best way to optimize care for frail older adults,” he concluded.

The study received funding from the National Institute of Aging.
 

A version of this article originally appeared on Medscape.com.

Higher doses of vitamin D supplementation not only show no benefit in the prevention of falls in older adults at increased risk of falling, compared with the lowest doses, but they appear to increase the risk, new research shows.

Zbynek Pospisil/iStock/Getty Images

Based on the findings, supplemental vitamin D above the minimum dose of 200 IU/day likely has little benefit, lead author Lawrence J. Appel, MD, MPH, told this news organization.

“In the absence of any benefit of 1,000 IU/day versus 2,000 IU/day [of vitamin D supplementation] on falls, along with the potential for harm from doses above 1,000 IU/day, it is hard to recommend a dose above 200 IU/day in older-aged persons, unless there is a compelling reason,” asserted Dr. Appel, director of the Welch Center for Prevention, Epidemiology, and Clinical Research at Johns Hopkins Bloomberg School of Public Health in Baltimore.

“More is not always better – and it may even be worse,” when it comes to vitamin D’s role in the prevention of falls, he said.

The research, published in Annals of Internal Medicine, adds important evidence in the ongoing struggle to prevent falls, says Bruce R. Troen, MD, in an accompanying editorial.

“Falls and their deleterious consequences remain a substantial risk for older adults and a huge challenge for health care teams,” writes Dr. Troen, a physician-investigator with the Veterans Affairs Western New York Healthcare System.

However, commenting in an interview, Dr. Troen cautions: “There are many epidemiological studies that are correlative, not causative, that do show a likelihood for benefit [with vitamin D supplementation]. … Therefore, there’s no reason for clinicians to discontinue vitamin D in individuals because of this study.”

“If you’re monitoring an older adult who is frail and has multiple comorbidities, you want to know what their vitamin D level is [and] provide them an appropriate supplement if needed,” he emphasized.

Some guidelines already reflect the lack of evidence of any role of vitamin D supplementation in the prevention of falls, including those of the 2018 U.S. Preventive Services Task Force, which, in a reversal of its 2012 recommendation, now does not recommend vitamin D supplementation for fall prevention in older persons without osteoporosis or vitamin D deficiency, Dr. Appel and colleagues note.
 

No prevention of falls regardless of baseline vitamin D

As part of STURDY (Study to understand fall reduction and vitamin D in you), Dr. Appel and colleagues enrolled 688 community-dwelling participants who had an elevated risk of falling, defined as a serum 25-hydroxyvitamin D [25(OH)D] level of 25 to 72.5 nmol/L (10-29 ng/dL).

Participants were a mean age of 77.2 years and had a mean total 25(OH)D level of 55.3 nmol/L at enrollment.

They were randomized to one of four doses of vitamin D₃, including 200 IU/day (the control group), or 1,000, 2,000, or 4,000 IU/day.

The highest doses were found to be associated with worse – not better – outcomes including a shorter time to hospitalization or death, compared with the 1,000-IU/day group. The higher-dose groups were therefore switched to a dose of 1,000 IU/day or lower, and all participants were followed for up to 2 years.

Overall, 63% experienced falls over the course of the study, which, though high, was consistent with the study’s criteria of participants having an elevated fall risk.

Of the 667 participants who completed the trial, no benefit in prevention of falling was seen across any of the doses, compared with the control group dose of 200 IU/day, regardless of participants’ baseline vitamin D levels.

Safety analyses showed that even in the 1,000-IU/day group, a higher risk of first serious fall and first fall with hospitalization was seen compared with the 200-IU/day group.

A limitation is that the study did not have a placebo group, however, “200 IU/day is a very small dose, probably homeopathic,” Dr. Appel said. “It was likely close to a placebo,” he said.
 

Caveats: comorbidities, subgroups

In his editorial, Dr. Troen notes other studies, including VITAL (Vitamin D and Omega-3 Trial) also found no reduction in falls with higher vitamin D doses; however, that study did not show any significant risks with the higher doses.

He adds that the current study lacks information on subsets of participants.

“We don’t have enough information about the existing comorbidities and medications that these people are on to be able to pull back the layers. Maybe there is a subgroup that should not be getting 4,000 IU, whereas another subgroup may not be harmed and you may decide that patient can benefit,” he said.

Furthermore, the trial doesn’t address groups such as nursing home residents.

“I have, for instance, 85-year-olds with vitamin D levels of maybe 20 nmol/L with multiple medical issues, but levels that low were not included in the study, so this is a tricky business, but the bottom line is first, do no harm,” he said.

“We really need trials that factor in the multiple different aspects so we can come up, hopefully, with a holistic and interdisciplinary approach, which is usually the best way to optimize care for frail older adults,” he concluded.

The study received funding from the National Institute of Aging.
 

A version of this article originally appeared on Medscape.com.

Higher doses of vitamin D supplementation not only show no benefit in the prevention of falls in older adults at increased risk of falling, compared with the lowest doses, but they appear to increase the risk, new research shows.

Zbynek Pospisil/iStock/Getty Images

Based on the findings, supplemental vitamin D above the minimum dose of 200 IU/day likely has little benefit, lead author Lawrence J. Appel, MD, MPH, told this news organization.

“In the absence of any benefit of 1,000 IU/day versus 2,000 IU/day [of vitamin D supplementation] on falls, along with the potential for harm from doses above 1,000 IU/day, it is hard to recommend a dose above 200 IU/day in older-aged persons, unless there is a compelling reason,” asserted Dr. Appel, director of the Welch Center for Prevention, Epidemiology, and Clinical Research at Johns Hopkins Bloomberg School of Public Health in Baltimore.

“More is not always better – and it may even be worse,” when it comes to vitamin D’s role in the prevention of falls, he said.

The research, published in Annals of Internal Medicine, adds important evidence in the ongoing struggle to prevent falls, says Bruce R. Troen, MD, in an accompanying editorial.

“Falls and their deleterious consequences remain a substantial risk for older adults and a huge challenge for health care teams,” writes Dr. Troen, a physician-investigator with the Veterans Affairs Western New York Healthcare System.

However, commenting in an interview, Dr. Troen cautions: “There are many epidemiological studies that are correlative, not causative, that do show a likelihood for benefit [with vitamin D supplementation]. … Therefore, there’s no reason for clinicians to discontinue vitamin D in individuals because of this study.”

“If you’re monitoring an older adult who is frail and has multiple comorbidities, you want to know what their vitamin D level is [and] provide them an appropriate supplement if needed,” he emphasized.

Some guidelines already reflect the lack of evidence of any role of vitamin D supplementation in the prevention of falls, including those of the 2018 U.S. Preventive Services Task Force, which, in a reversal of its 2012 recommendation, now does not recommend vitamin D supplementation for fall prevention in older persons without osteoporosis or vitamin D deficiency, Dr. Appel and colleagues note.
 

No prevention of falls regardless of baseline vitamin D

As part of STURDY (Study to understand fall reduction and vitamin D in you), Dr. Appel and colleagues enrolled 688 community-dwelling participants who had an elevated risk of falling, defined as a serum 25-hydroxyvitamin D [25(OH)D] level of 25 to 72.5 nmol/L (10-29 ng/dL).

Participants were a mean age of 77.2 years and had a mean total 25(OH)D level of 55.3 nmol/L at enrollment.

They were randomized to one of four doses of vitamin D₃, including 200 IU/day (the control group), or 1,000, 2,000, or 4,000 IU/day.

The highest doses were found to be associated with worse – not better – outcomes including a shorter time to hospitalization or death, compared with the 1,000-IU/day group. The higher-dose groups were therefore switched to a dose of 1,000 IU/day or lower, and all participants were followed for up to 2 years.

Overall, 63% experienced falls over the course of the study, which, though high, was consistent with the study’s criteria of participants having an elevated fall risk.

Of the 667 participants who completed the trial, no benefit in prevention of falling was seen across any of the doses, compared with the control group dose of 200 IU/day, regardless of participants’ baseline vitamin D levels.

Safety analyses showed that even in the 1,000-IU/day group, a higher risk of first serious fall and first fall with hospitalization was seen compared with the 200-IU/day group.

A limitation is that the study did not have a placebo group, however, “200 IU/day is a very small dose, probably homeopathic,” Dr. Appel said. “It was likely close to a placebo,” he said.
 

Caveats: comorbidities, subgroups

In his editorial, Dr. Troen notes other studies, including VITAL (Vitamin D and Omega-3 Trial) also found no reduction in falls with higher vitamin D doses; however, that study did not show any significant risks with the higher doses.

He adds that the current study lacks information on subsets of participants.

“We don’t have enough information about the existing comorbidities and medications that these people are on to be able to pull back the layers. Maybe there is a subgroup that should not be getting 4,000 IU, whereas another subgroup may not be harmed and you may decide that patient can benefit,” he said.

Furthermore, the trial doesn’t address groups such as nursing home residents.

“I have, for instance, 85-year-olds with vitamin D levels of maybe 20 nmol/L with multiple medical issues, but levels that low were not included in the study, so this is a tricky business, but the bottom line is first, do no harm,” he said.

“We really need trials that factor in the multiple different aspects so we can come up, hopefully, with a holistic and interdisciplinary approach, which is usually the best way to optimize care for frail older adults,” he concluded.

The study received funding from the National Institute of Aging.
 

A version of this article originally appeared on Medscape.com.

Increasingly, bone health and fragility fracture prevention is one of the most important aspects of healthy aging that we, as women’s health care providers (HCPs), must be sure is part of our thought process in caring for women at midlife and beyond. Virtually all ObGyn HCPs are aware of breast health, both in terms of the clinical breast exam and imaging surveillance. The 5-year relative survival rate for “localized breast cancer” is 99%.¹ Most recent data on hip fracture, however, indicate that it is associated with a mortality in the first year of 21%!² We need to be sure that our patients understand this.

Previously, this column provided an update on osteoporosis. In 2016, I asked to change the focus to “Update on bone health” to highlight that simply relying on dual energy x-ray absorptiometry (DXA) testing of bone mass with arbitrary cutoffs for osteoporosis, osteopenia, and normal bone mass is not adequate for improving overall bone health. The addition of the FRAX fracture risk assessment tool, now widely employed, as well as the trabecular bone score (TBS), not widely employed, helps to refine the assessment of patients’ risk status. Further, issues such as sarcopenia, adequate dietary calcium and vitamin D supplementation, and fall prevention (improving balance, use of nonskid rugs in the bathroom, avoiding black ice when present, having nothing to slip on between the bed and the bathroom in the middle of the night, and so on) also are essential elements of “bone health.”

Finally, I cannot stress enough the importance of developing a good relationship with whatever facility one uses for DXA testing in order to maximize use of the reports and potential limitations. In addition, we should identify a metabolic bone specialist for referral of unusual cases or patients who require medications unlikely to be prescribed by us as ObGyns, and develop some familiarity with therapies that may be utilized.

Osteosarcopenia greatly enhances fall and fracture risk

Sepúlveda-Loyola W, Phu S, Bani Hassan E, et al. The joint occurrence of osteoporosis and sarcopenia (osteosarcopenia): definitions and characteristics. J Am Med Dir Assoc. 2020;21:220-225.

Tokeshi S, Eguchi Y, Suzuki M, et al. Relationship between skeletal muscle mass, bone mineral density, and trabecular bone score in osteoporotic vertebral compression fractures. Asian Spine J. 2020 Sep 3. doi: 10.31616/asj.2020.0045.

Kirk B, Zanker J, Duque G. Osteosarcopenia: epidemiology, diagnosis, and treatment—facts and numbers. J Cachexia Sarcopenia Muscle. 2020;11:609-618.

The topic of sarcopenia as defined by the concurrent presence of low muscle mass, physical performance, and strength has been discussed previously in this Update series.³ Now, osteosarcopenia, defined as the concomitant presence of osteoporosis or osteopenia combined with sarcopenia, seems to be an extremely important gauge of fracture risk, especially now as the population’s longevity has increased dramatically. This new syndrome is associated with higher disability and rates of fracture and falls in older people compared with either entity (the bone component or the sarcopenia component) alone.^4,5 In fact, in the 2016 ICD-10-CM, sarcopenia was finally recognized as a disease entity.

Severe sarcopenia is known to increase the risk for falls.⁶ Furthermore, evidence is increasing of cross talk between muscle and bone.⁴ The diagnostic criteria of osteopenia and osteoporosis are well established; however, absolute criteria for sarcopenia lack an international consensus.

Continue to: Assess for osteopenia/osteoporosis plus sarcopenia to determine those at greatest fracture risk...

Assess for osteopenia/osteoporosis plus sarcopenia to determine those at greatest fracture risk

Sepúlveda-Loyola and colleagues performed a cross-sectional analysis of 253 participants, of which 77% were women, average age 78, who presented for a “falls and fractures” risk assessment. T-scores were measured by DXA. In addition, the investigators measured components of sarcopenia, including physical performance (evaluated by hand grip strength, gait speed, timed up and go test, and 5-time sit to stand test) and dynamic and static balance. Falls in the previous year were self-reported, with 42% of participants having fallen once and 54%, more than once.

Results. Participants with osteosarcopenia had a statistically significant increased rate of falls of approximately threefold and an increased rate of fractures that was approximately fourfold when compared with osteopenia or osteoporosis alone.

Another important finding was that, despite the links between osteoporosis, fracture, and poor clinical outcomes, the investigators did not find differences in fracture rates in the osteopenic compared with the osteoporotic classifications. Their findings corroborated those of other studies that reported discrepancies in fractures and bone mineral density (BMD), with osteopenic older adults experiencing fracture rates similar to and in some cases greater than those diagnosed with osteoporosis.⁷

Thus, it appears that the use of T-scores that combine osteopenic and osteoporotic criteria into the osteosarcopenic category may be sufficient to capture individuals at the greatest risk of fracture.

Skeletal muscle mass plays a role in vertebral compression fractures

Tokeshi and colleagues conducted retrospective observational study to investigate the relationships between skeletal muscle mass, BMD, and TBS in individuals with osteoporotic vertebral compression fractures.

They evaluated 142 patients with an average age of 75; of these, 30% had radiographically diagnosed vertebral compression fractures (average age, 79) and 70% had no vertebral compression fractures (average age, 70). Body composition was measured using whole-body DXA; appendicular skeletal muscle mass index was determined as the sum of upper and lower extremities’ lean mass (kg/height in m² ). TBS was measured using the patented algorithm software on DXA scans for the lumbar vertebrae.

Results. The investigators found that the vertebral compression fracture group was statistically significantly older, had lower femur BMD, and had decreased leg muscle mass. The TBS was not identified as a risk factor.

Certain lifestyle factors add to risk of osteosarcopenia

In an editorial, Kirk and colleagues summarized the epidemiology, diagnosis, and treatment of osteosarcopenia. They concluded that this syndrome can be expected to grow in age-related and disease-related states as a consequence of immunosenescence coinciding with an increase in sedentary lifestyle, obesity, and fat infiltration of muscle and bone.

Increasingly, clinicians should screen for osteosarcopenia via imaging methods (DXA) to quantitate bone mass (as is currently done) and, increasingly, quantify muscle mass. In addition, assessment of muscle strength, easily done by testing grip strength, as well as functional capacity (gait speed), will become increasingly important.

Finally, the authors call for a more comprehensive geriatric assessment that includes medical history and risk factors as well as treatment (including osteoporosis drugs, where indicated), and progressive resistance and balance exercises. Nutritional recommendations, in terms of protein, vitamin D, and calcium, also are necessary. They anticipate that diagnosis and treatment of osteosarcopenia will become part of routine health care in the future.

Continue to: The denosumab discontinuation dilemma...

The denosumab discontinuation dilemma

Lyu H, Yoshida K, Zhao SS, et al. Delayed denosumab injections and fracture risk among patients with osteoporosis: a population-based cohort study. Ann Intern Med. 2020;173:516-526.

Tripto-Shkolnik L, Fund N, Rouach V, et al. Fracture incidence after denosumab discontinuation: real-world data from a large healthcare provider. Bone. 2020;130:115150.

Denosumab, marketed under the brand name Prolia, is a human monoclonal antibody that blocks the binding of RANK ligand and inhibits development and activity of osteoclast, thus decreasing bone resorption and increasing BMD. In the original pivotal clinical trial of denosumab, almost 7,900 women between the ages of 60 and 90 (average age, 73) with osteoporotic T-scores were enrolled.⁸ The women were randomly assigned to receive 60 mg of denosumab subcutaneously every 6 months or placebo for a total of 3 years. In that trial, the denosumabtreated group, relative to the placebo group, showed a statistically significant decrease in radiographic vertebral fracture, hip fracture, and nonvertebral fracture. 

An open-label extension study looked at denosumab use for a total of 10 years.⁹ That study found that denosumab treatment for up to 10 years was associated with low rates of adverse events, low fracture incidence compared with that observed during the original trial, and continued increases in BMD without plateau. Thus, denosumab appeared to be an extremely safe and effective agent for treating postmenopausal women with osteoporosis.

Denosumab cessation leads to rebound vertebral fractures

As opposed to bisphosphonates, denosumab does not incorporate into bone matrix, and bone turnover is not suppressed after cessation of its use. Reports have implied that denosumab discontinuation may lead to an increased risk of multiple vertebral fractures.¹⁰ One theory is that unlike atypical femoral fractures that seem to emerge from failure of microdamage repair in cortical bone with long-term antiresorptive treatment, denosumab rebound–associated vertebral fractures seem to originate from the synergy of rapid bone resorption and accelerated microdamage accumulation in trabecular bone triggered by the discontinuation of this highly potent reversible agent.¹¹

Post hoc analysis of the denosumab placebo-controlled trial and its extension reported that the vertebral fracture rate increased after denosumab discontinuation to the level observed in untreated patients.¹² Further, a majority of participants who did sustain vertebral fracture after discontinuing denosumab had multiple vertebral fractures, with the risk being greatest in participants who had a prior vertebral facture. This caused those authors to suggest that patients who discontinued denosumab should rapidly transition to an alternative antiresorptive treatment.

Effect of dose delays, discontinuation on vertebral fracture rate

Lyu and colleagues recently described their population-based cohort study of the United Kingdom’s Health Improvement Network primary care database between 2010 and 2019. They found that delayed administration of a subsequent denosumab dose by more than 16 weeks was associated with an increased risk for vertebral fracture compared with on-time dosing. They noted, however, that the evidence was insufficient to conclude that fracture risk at any other anatomic sites is increased with such a delay.

In a similar study, Tripto-Shkolnik and colleagues examined an Israeli database of 2.3 million members in a state-mandated health organization. They identified osteoporotic patients with at least 2 denosumab prescription dispenses and defined treatment discontinuation as a refill gap of 3 months or more. Fractures were identified by an osteoporosis registry, including fractures that occurred within 1 year from discontinuation in denosumab discontinuers as well as from the second year of treatment forward for persistent users. They identified 1,500 denosumab discontinuers (average age, 72) and 1,610 persistent users (average age also 72). At baseline, the groups were comparable in fracture history, smoking, and bone density.

In the discontinuation group, 0.8% had multiple vertebral fractures versus 0.1% in the persistent users (P = .006); the overall rate of fractures per 100 patient-years of follow-up was 3 times higher in the discontinuation group than in the persistent user group, and the rate of vertebral fractures was almost 5 times higher in the discontinuation group.

Continue to: Atypical femur fracture risk and bisphosphonate use...

Atypical femur fracture risk and bisphosphonate use

Black DM, Geiger EJ, Eastell R, et al. Atypical femur fracture risk versus fragility fracture prevention with bisphosphonates. N Engl J Med. 2020;383:743-753.

Since their introduction in the 1990s, bisphosphonates have been the mainstay of osteoporosis treatment. This category of medications inhibits osteoclast-mediated resorption and remodeling of bone. Various large, randomized, controlled trials have established the efficacy of bisphosphonates to increase BMD and decrease the risk of hip and vertebral fracture by as much as 40% to 70%.¹³

However, case reports of unusual fragility fractures in the subtrochanteric region and along the femoral diaphysis in patients treated with bisphosphonates started to appear approximately 15 years ago.¹⁴ Since then, concerns and publicity about these atypical fractures have led to substantial declines in bisphosphonate use clinically.

Bisphosphonate preventive benefits versus atypical fracture risk

Black and colleagues reviewed data on women 50 years and older who were enrolled in the Kaiser Permanente health care system in California. The total cohort included slightly more than 1 million women, of which almost 200,000 (17.9%) used bisphosphonates at any point from 2007–2017.

A total of 277 atypical femur fractures occurred. Among bisphosphonate users, there were 1.74 fractures per 10,000 patient-years. Overall, there were almost 59 fractures per 10,000 person-years. The incidence of atypical fractures was highest in women between the ages of 75 and 84 years, and the incidence diminished after age 85. Rates of atypical fractures increased as the duration of bisphosphonate use increased. In addition, rates of atypical fractures decreased with time since bisphosphonate discontinuation.

The rate of atypical fractures in women who had never received bisphosphonate therapy was 0.1 per 10,000 person-years. The number of fractures prevented for each fracture type far outweighed bisphosphonate-associated atypical fractures at all time points along the 10 years of study. In White women, for instance, at 3 years there were 541 clinical fractures prevented and 149 hip fractures prevented, while 2 bisphosphonate-associated atypical fractures occurred, all per 10,000 women.

Interestingly, in the Asian population at the same time point, 330 clinical fractures were prevented and 91 hip fractures were prevented, but 8 atypical fractures of the femur occurred, per 10,000 women. The authors further referenced an earlier Kaiser study that showed that 49% of 142 atypical femur fractures occurred in Asian patients who comprised only 10% of the study population.¹⁵

The authors concluded that the risk of atypical femur fracture increases with longer duration of bisphosphate use and rapidly decreases after bisphosphate discontinuation. Asian women have a higher risk than White women. With bisphosphonate treatment, the absolute risk of atypical femur fracture is very low compared with the reduction in the risk of hip and other fractures.

Continue to: Romosozumab increases BMD gains and improves T-scores...

Romosozumab increases BMD gains and improves T-scores

Cosman F, Lewiecki EM, Ebeling PR, et al. T-score as an indicator of fracture risk during treatment with romosozumab or alendronate in the ARCH trial. J Bone Miner Res. 2020;35:1333-1342

Romosozumab (Evenity) is a monoclonal antibody that binds and inhibits sclerostin, thus having the dual effect of increasing bone formation and decreasing bone resorption.¹⁶ It is administered for 1 year as monthly doses of 210 mg subcutaneously. Previous studies have shown that romosozumab produces large increases in lumbar spine and total hip BMD,¹⁷ reduces the risk of new vertebral and clinical fractures compared with placebo,¹⁶ and reduces the risk of vertebral, clinical, nonvertebral, and hip fractures compared with alendronate over a median treatment period of 33 months (the ARCH study).¹⁸

According to the package insert, romosozumab is indicated “for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy.”

Should T-score be a therapeutic target?

Cosman and colleagues performed a post hoc analysis of the ARCH trial specifically to evaluate mean BMD and corresponding mean T-score changes (and the relationships between T-scores) after 1 year of romosozumab or alendronate therapy and subsequent fracture incidence. The study is quite detailed with much numerical data and statistical analysis.

Basically, the ARCH trial randomly assigned patients with osteoporosis to receive either monthly subcutaneous romosozumab 210 mg or weekly oral alendronate 70 mg for 12 months. After the double-blind portion of the trial, all patients received open label weekly oral alendronate 70 mg through the end of study (24 months), although they were still blinded to the initial treatment assignment. In addition, patients received daily calcium and vitamin D supplements.

The data analysis found that 1 year of romosozumab led to larger BMD gains than alendronate therapy. Also, the T-score achieved with either therapy was directly related to subsequent fracture risk. The authors thus proposed that these data support the use of the T-score as a therapeutic target for patients with osteoporosis.

It is important to note that in the original ARCH study, the participants’ average age was 71 years and approximately one-third were older than 75. The average T-score was -2.7 at both the lumbar spine and femoral neck. Approximately 20% of patients had a pre-existing vertebral fracture, and approximately 20% had a previous nonvertebral fracture.

The authors of the current study, furthermore, found that mean BMD gains after 1 year of romosozumab treatment were more than twice those seen with alendronate at the total hip, femoral neck, and lumbar spine. These BMD changes resulted in a larger proportion of patients who achieved T-scores above the osteoporosis level at each of the skeletal sites after 1 year of therapy. Fewer fractures occurred during the second year and the entire open label period among patients who had received romosozumab first compared with those who received alendronate.●

Increasingly, bone health and fragility fracture prevention is one of the most important aspects of healthy aging that we, as women’s health care providers (HCPs), must be sure is part of our thought process in caring for women at midlife and beyond. Virtually all ObGyn HCPs are aware of breast health, both in terms of the clinical breast exam and imaging surveillance. The 5-year relative survival rate for “localized breast cancer” is 99%.¹ Most recent data on hip fracture, however, indicate that it is associated with a mortality in the first year of 21%!² We need to be sure that our patients understand this.

Previously, this column provided an update on osteoporosis. In 2016, I asked to change the focus to “Update on bone health” to highlight that simply relying on dual energy x-ray absorptiometry (DXA) testing of bone mass with arbitrary cutoffs for osteoporosis, osteopenia, and normal bone mass is not adequate for improving overall bone health. The addition of the FRAX fracture risk assessment tool, now widely employed, as well as the trabecular bone score (TBS), not widely employed, helps to refine the assessment of patients’ risk status. Further, issues such as sarcopenia, adequate dietary calcium and vitamin D supplementation, and fall prevention (improving balance, use of nonskid rugs in the bathroom, avoiding black ice when present, having nothing to slip on between the bed and the bathroom in the middle of the night, and so on) also are essential elements of “bone health.”

Finally, I cannot stress enough the importance of developing a good relationship with whatever facility one uses for DXA testing in order to maximize use of the reports and potential limitations. In addition, we should identify a metabolic bone specialist for referral of unusual cases or patients who require medications unlikely to be prescribed by us as ObGyns, and develop some familiarity with therapies that may be utilized.

Osteosarcopenia greatly enhances fall and fracture risk

Sepúlveda-Loyola W, Phu S, Bani Hassan E, et al. The joint occurrence of osteoporosis and sarcopenia (osteosarcopenia): definitions and characteristics. J Am Med Dir Assoc. 2020;21:220-225.

Tokeshi S, Eguchi Y, Suzuki M, et al. Relationship between skeletal muscle mass, bone mineral density, and trabecular bone score in osteoporotic vertebral compression fractures. Asian Spine J. 2020 Sep 3. doi: 10.31616/asj.2020.0045.

Kirk B, Zanker J, Duque G. Osteosarcopenia: epidemiology, diagnosis, and treatment—facts and numbers. J Cachexia Sarcopenia Muscle. 2020;11:609-618.

The topic of sarcopenia as defined by the concurrent presence of low muscle mass, physical performance, and strength has been discussed previously in this Update series.³ Now, osteosarcopenia, defined as the concomitant presence of osteoporosis or osteopenia combined with sarcopenia, seems to be an extremely important gauge of fracture risk, especially now as the population’s longevity has increased dramatically. This new syndrome is associated with higher disability and rates of fracture and falls in older people compared with either entity (the bone component or the sarcopenia component) alone.^4,5 In fact, in the 2016 ICD-10-CM, sarcopenia was finally recognized as a disease entity.

Severe sarcopenia is known to increase the risk for falls.⁶ Furthermore, evidence is increasing of cross talk between muscle and bone.⁴ The diagnostic criteria of osteopenia and osteoporosis are well established; however, absolute criteria for sarcopenia lack an international consensus.

Continue to: Assess for osteopenia/osteoporosis plus sarcopenia to determine those at greatest fracture risk...

Assess for osteopenia/osteoporosis plus sarcopenia to determine those at greatest fracture risk

Sepúlveda-Loyola and colleagues performed a cross-sectional analysis of 253 participants, of which 77% were women, average age 78, who presented for a “falls and fractures” risk assessment. T-scores were measured by DXA. In addition, the investigators measured components of sarcopenia, including physical performance (evaluated by hand grip strength, gait speed, timed up and go test, and 5-time sit to stand test) and dynamic and static balance. Falls in the previous year were self-reported, with 42% of participants having fallen once and 54%, more than once.

Results. Participants with osteosarcopenia had a statistically significant increased rate of falls of approximately threefold and an increased rate of fractures that was approximately fourfold when compared with osteopenia or osteoporosis alone.

Another important finding was that, despite the links between osteoporosis, fracture, and poor clinical outcomes, the investigators did not find differences in fracture rates in the osteopenic compared with the osteoporotic classifications. Their findings corroborated those of other studies that reported discrepancies in fractures and bone mineral density (BMD), with osteopenic older adults experiencing fracture rates similar to and in some cases greater than those diagnosed with osteoporosis.⁷

Thus, it appears that the use of T-scores that combine osteopenic and osteoporotic criteria into the osteosarcopenic category may be sufficient to capture individuals at the greatest risk of fracture.

Skeletal muscle mass plays a role in vertebral compression fractures

Tokeshi and colleagues conducted retrospective observational study to investigate the relationships between skeletal muscle mass, BMD, and TBS in individuals with osteoporotic vertebral compression fractures.

They evaluated 142 patients with an average age of 75; of these, 30% had radiographically diagnosed vertebral compression fractures (average age, 79) and 70% had no vertebral compression fractures (average age, 70). Body composition was measured using whole-body DXA; appendicular skeletal muscle mass index was determined as the sum of upper and lower extremities’ lean mass (kg/height in m² ). TBS was measured using the patented algorithm software on DXA scans for the lumbar vertebrae.

Results. The investigators found that the vertebral compression fracture group was statistically significantly older, had lower femur BMD, and had decreased leg muscle mass. The TBS was not identified as a risk factor.

Certain lifestyle factors add to risk of osteosarcopenia

In an editorial, Kirk and colleagues summarized the epidemiology, diagnosis, and treatment of osteosarcopenia. They concluded that this syndrome can be expected to grow in age-related and disease-related states as a consequence of immunosenescence coinciding with an increase in sedentary lifestyle, obesity, and fat infiltration of muscle and bone.

Increasingly, clinicians should screen for osteosarcopenia via imaging methods (DXA) to quantitate bone mass (as is currently done) and, increasingly, quantify muscle mass. In addition, assessment of muscle strength, easily done by testing grip strength, as well as functional capacity (gait speed), will become increasingly important.

Finally, the authors call for a more comprehensive geriatric assessment that includes medical history and risk factors as well as treatment (including osteoporosis drugs, where indicated), and progressive resistance and balance exercises. Nutritional recommendations, in terms of protein, vitamin D, and calcium, also are necessary. They anticipate that diagnosis and treatment of osteosarcopenia will become part of routine health care in the future.

Continue to: The denosumab discontinuation dilemma...

The denosumab discontinuation dilemma

Lyu H, Yoshida K, Zhao SS, et al. Delayed denosumab injections and fracture risk among patients with osteoporosis: a population-based cohort study. Ann Intern Med. 2020;173:516-526.

Tripto-Shkolnik L, Fund N, Rouach V, et al. Fracture incidence after denosumab discontinuation: real-world data from a large healthcare provider. Bone. 2020;130:115150.

Denosumab, marketed under the brand name Prolia, is a human monoclonal antibody that blocks the binding of RANK ligand and inhibits development and activity of osteoclast, thus decreasing bone resorption and increasing BMD. In the original pivotal clinical trial of denosumab, almost 7,900 women between the ages of 60 and 90 (average age, 73) with osteoporotic T-scores were enrolled.⁸ The women were randomly assigned to receive 60 mg of denosumab subcutaneously every 6 months or placebo for a total of 3 years. In that trial, the denosumabtreated group, relative to the placebo group, showed a statistically significant decrease in radiographic vertebral fracture, hip fracture, and nonvertebral fracture. 

An open-label extension study looked at denosumab use for a total of 10 years.⁹ That study found that denosumab treatment for up to 10 years was associated with low rates of adverse events, low fracture incidence compared with that observed during the original trial, and continued increases in BMD without plateau. Thus, denosumab appeared to be an extremely safe and effective agent for treating postmenopausal women with osteoporosis.

Denosumab cessation leads to rebound vertebral fractures

As opposed to bisphosphonates, denosumab does not incorporate into bone matrix, and bone turnover is not suppressed after cessation of its use. Reports have implied that denosumab discontinuation may lead to an increased risk of multiple vertebral fractures.¹⁰ One theory is that unlike atypical femoral fractures that seem to emerge from failure of microdamage repair in cortical bone with long-term antiresorptive treatment, denosumab rebound–associated vertebral fractures seem to originate from the synergy of rapid bone resorption and accelerated microdamage accumulation in trabecular bone triggered by the discontinuation of this highly potent reversible agent.¹¹

Post hoc analysis of the denosumab placebo-controlled trial and its extension reported that the vertebral fracture rate increased after denosumab discontinuation to the level observed in untreated patients.¹² Further, a majority of participants who did sustain vertebral fracture after discontinuing denosumab had multiple vertebral fractures, with the risk being greatest in participants who had a prior vertebral facture. This caused those authors to suggest that patients who discontinued denosumab should rapidly transition to an alternative antiresorptive treatment.

Effect of dose delays, discontinuation on vertebral fracture rate

Lyu and colleagues recently described their population-based cohort study of the United Kingdom’s Health Improvement Network primary care database between 2010 and 2019. They found that delayed administration of a subsequent denosumab dose by more than 16 weeks was associated with an increased risk for vertebral fracture compared with on-time dosing. They noted, however, that the evidence was insufficient to conclude that fracture risk at any other anatomic sites is increased with such a delay.

In a similar study, Tripto-Shkolnik and colleagues examined an Israeli database of 2.3 million members in a state-mandated health organization. They identified osteoporotic patients with at least 2 denosumab prescription dispenses and defined treatment discontinuation as a refill gap of 3 months or more. Fractures were identified by an osteoporosis registry, including fractures that occurred within 1 year from discontinuation in denosumab discontinuers as well as from the second year of treatment forward for persistent users. They identified 1,500 denosumab discontinuers (average age, 72) and 1,610 persistent users (average age also 72). At baseline, the groups were comparable in fracture history, smoking, and bone density.

In the discontinuation group, 0.8% had multiple vertebral fractures versus 0.1% in the persistent users (P = .006); the overall rate of fractures per 100 patient-years of follow-up was 3 times higher in the discontinuation group than in the persistent user group, and the rate of vertebral fractures was almost 5 times higher in the discontinuation group.

Continue to: Atypical femur fracture risk and bisphosphonate use...

Atypical femur fracture risk and bisphosphonate use

Black DM, Geiger EJ, Eastell R, et al. Atypical femur fracture risk versus fragility fracture prevention with bisphosphonates. N Engl J Med. 2020;383:743-753.

Since their introduction in the 1990s, bisphosphonates have been the mainstay of osteoporosis treatment. This category of medications inhibits osteoclast-mediated resorption and remodeling of bone. Various large, randomized, controlled trials have established the efficacy of bisphosphonates to increase BMD and decrease the risk of hip and vertebral fracture by as much as 40% to 70%.¹³

However, case reports of unusual fragility fractures in the subtrochanteric region and along the femoral diaphysis in patients treated with bisphosphonates started to appear approximately 15 years ago.¹⁴ Since then, concerns and publicity about these atypical fractures have led to substantial declines in bisphosphonate use clinically.

Bisphosphonate preventive benefits versus atypical fracture risk

Black and colleagues reviewed data on women 50 years and older who were enrolled in the Kaiser Permanente health care system in California. The total cohort included slightly more than 1 million women, of which almost 200,000 (17.9%) used bisphosphonates at any point from 2007–2017.

A total of 277 atypical femur fractures occurred. Among bisphosphonate users, there were 1.74 fractures per 10,000 patient-years. Overall, there were almost 59 fractures per 10,000 person-years. The incidence of atypical fractures was highest in women between the ages of 75 and 84 years, and the incidence diminished after age 85. Rates of atypical fractures increased as the duration of bisphosphonate use increased. In addition, rates of atypical fractures decreased with time since bisphosphonate discontinuation.

The rate of atypical fractures in women who had never received bisphosphonate therapy was 0.1 per 10,000 person-years. The number of fractures prevented for each fracture type far outweighed bisphosphonate-associated atypical fractures at all time points along the 10 years of study. In White women, for instance, at 3 years there were 541 clinical fractures prevented and 149 hip fractures prevented, while 2 bisphosphonate-associated atypical fractures occurred, all per 10,000 women.

Interestingly, in the Asian population at the same time point, 330 clinical fractures were prevented and 91 hip fractures were prevented, but 8 atypical fractures of the femur occurred, per 10,000 women. The authors further referenced an earlier Kaiser study that showed that 49% of 142 atypical femur fractures occurred in Asian patients who comprised only 10% of the study population.¹⁵

The authors concluded that the risk of atypical femur fracture increases with longer duration of bisphosphate use and rapidly decreases after bisphosphate discontinuation. Asian women have a higher risk than White women. With bisphosphonate treatment, the absolute risk of atypical femur fracture is very low compared with the reduction in the risk of hip and other fractures.

Continue to: Romosozumab increases BMD gains and improves T-scores...

Romosozumab increases BMD gains and improves T-scores

Cosman F, Lewiecki EM, Ebeling PR, et al. T-score as an indicator of fracture risk during treatment with romosozumab or alendronate in the ARCH trial. J Bone Miner Res. 2020;35:1333-1342

Romosozumab (Evenity) is a monoclonal antibody that binds and inhibits sclerostin, thus having the dual effect of increasing bone formation and decreasing bone resorption.¹⁶ It is administered for 1 year as monthly doses of 210 mg subcutaneously. Previous studies have shown that romosozumab produces large increases in lumbar spine and total hip BMD,¹⁷ reduces the risk of new vertebral and clinical fractures compared with placebo,¹⁶ and reduces the risk of vertebral, clinical, nonvertebral, and hip fractures compared with alendronate over a median treatment period of 33 months (the ARCH study).¹⁸

According to the package insert, romosozumab is indicated “for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy.”

Should T-score be a therapeutic target?

Cosman and colleagues performed a post hoc analysis of the ARCH trial specifically to evaluate mean BMD and corresponding mean T-score changes (and the relationships between T-scores) after 1 year of romosozumab or alendronate therapy and subsequent fracture incidence. The study is quite detailed with much numerical data and statistical analysis.

Basically, the ARCH trial randomly assigned patients with osteoporosis to receive either monthly subcutaneous romosozumab 210 mg or weekly oral alendronate 70 mg for 12 months. After the double-blind portion of the trial, all patients received open label weekly oral alendronate 70 mg through the end of study (24 months), although they were still blinded to the initial treatment assignment. In addition, patients received daily calcium and vitamin D supplements.

The data analysis found that 1 year of romosozumab led to larger BMD gains than alendronate therapy. Also, the T-score achieved with either therapy was directly related to subsequent fracture risk. The authors thus proposed that these data support the use of the T-score as a therapeutic target for patients with osteoporosis.

It is important to note that in the original ARCH study, the participants’ average age was 71 years and approximately one-third were older than 75. The average T-score was -2.7 at both the lumbar spine and femoral neck. Approximately 20% of patients had a pre-existing vertebral fracture, and approximately 20% had a previous nonvertebral fracture.

The authors of the current study, furthermore, found that mean BMD gains after 1 year of romosozumab treatment were more than twice those seen with alendronate at the total hip, femoral neck, and lumbar spine. These BMD changes resulted in a larger proportion of patients who achieved T-scores above the osteoporosis level at each of the skeletal sites after 1 year of therapy. Fewer fractures occurred during the second year and the entire open label period among patients who had received romosozumab first compared with those who received alendronate.●

Increasingly, bone health and fragility fracture prevention is one of the most important aspects of healthy aging that we, as women’s health care providers (HCPs), must be sure is part of our thought process in caring for women at midlife and beyond. Virtually all ObGyn HCPs are aware of breast health, both in terms of the clinical breast exam and imaging surveillance. The 5-year relative survival rate for “localized breast cancer” is 99%.¹ Most recent data on hip fracture, however, indicate that it is associated with a mortality in the first year of 21%!² We need to be sure that our patients understand this.

Previously, this column provided an update on osteoporosis. In 2016, I asked to change the focus to “Update on bone health” to highlight that simply relying on dual energy x-ray absorptiometry (DXA) testing of bone mass with arbitrary cutoffs for osteoporosis, osteopenia, and normal bone mass is not adequate for improving overall bone health. The addition of the FRAX fracture risk assessment tool, now widely employed, as well as the trabecular bone score (TBS), not widely employed, helps to refine the assessment of patients’ risk status. Further, issues such as sarcopenia, adequate dietary calcium and vitamin D supplementation, and fall prevention (improving balance, use of nonskid rugs in the bathroom, avoiding black ice when present, having nothing to slip on between the bed and the bathroom in the middle of the night, and so on) also are essential elements of “bone health.”

Finally, I cannot stress enough the importance of developing a good relationship with whatever facility one uses for DXA testing in order to maximize use of the reports and potential limitations. In addition, we should identify a metabolic bone specialist for referral of unusual cases or patients who require medications unlikely to be prescribed by us as ObGyns, and develop some familiarity with therapies that may be utilized.

Osteosarcopenia greatly enhances fall and fracture risk

Sepúlveda-Loyola W, Phu S, Bani Hassan E, et al. The joint occurrence of osteoporosis and sarcopenia (osteosarcopenia): definitions and characteristics. J Am Med Dir Assoc. 2020;21:220-225.

Tokeshi S, Eguchi Y, Suzuki M, et al. Relationship between skeletal muscle mass, bone mineral density, and trabecular bone score in osteoporotic vertebral compression fractures. Asian Spine J. 2020 Sep 3. doi: 10.31616/asj.2020.0045.

Kirk B, Zanker J, Duque G. Osteosarcopenia: epidemiology, diagnosis, and treatment—facts and numbers. J Cachexia Sarcopenia Muscle. 2020;11:609-618.

The topic of sarcopenia as defined by the concurrent presence of low muscle mass, physical performance, and strength has been discussed previously in this Update series.³ Now, osteosarcopenia, defined as the concomitant presence of osteoporosis or osteopenia combined with sarcopenia, seems to be an extremely important gauge of fracture risk, especially now as the population’s longevity has increased dramatically. This new syndrome is associated with higher disability and rates of fracture and falls in older people compared with either entity (the bone component or the sarcopenia component) alone.^4,5 In fact, in the 2016 ICD-10-CM, sarcopenia was finally recognized as a disease entity.

Severe sarcopenia is known to increase the risk for falls.⁶ Furthermore, evidence is increasing of cross talk between muscle and bone.⁴ The diagnostic criteria of osteopenia and osteoporosis are well established; however, absolute criteria for sarcopenia lack an international consensus.

Continue to: Assess for osteopenia/osteoporosis plus sarcopenia to determine those at greatest fracture risk...

Assess for osteopenia/osteoporosis plus sarcopenia to determine those at greatest fracture risk

Sepúlveda-Loyola and colleagues performed a cross-sectional analysis of 253 participants, of which 77% were women, average age 78, who presented for a “falls and fractures” risk assessment. T-scores were measured by DXA. In addition, the investigators measured components of sarcopenia, including physical performance (evaluated by hand grip strength, gait speed, timed up and go test, and 5-time sit to stand test) and dynamic and static balance. Falls in the previous year were self-reported, with 42% of participants having fallen once and 54%, more than once.

Results. Participants with osteosarcopenia had a statistically significant increased rate of falls of approximately threefold and an increased rate of fractures that was approximately fourfold when compared with osteopenia or osteoporosis alone.

Another important finding was that, despite the links between osteoporosis, fracture, and poor clinical outcomes, the investigators did not find differences in fracture rates in the osteopenic compared with the osteoporotic classifications. Their findings corroborated those of other studies that reported discrepancies in fractures and bone mineral density (BMD), with osteopenic older adults experiencing fracture rates similar to and in some cases greater than those diagnosed with osteoporosis.⁷

Thus, it appears that the use of T-scores that combine osteopenic and osteoporotic criteria into the osteosarcopenic category may be sufficient to capture individuals at the greatest risk of fracture.

Skeletal muscle mass plays a role in vertebral compression fractures

Tokeshi and colleagues conducted retrospective observational study to investigate the relationships between skeletal muscle mass, BMD, and TBS in individuals with osteoporotic vertebral compression fractures.

They evaluated 142 patients with an average age of 75; of these, 30% had radiographically diagnosed vertebral compression fractures (average age, 79) and 70% had no vertebral compression fractures (average age, 70). Body composition was measured using whole-body DXA; appendicular skeletal muscle mass index was determined as the sum of upper and lower extremities’ lean mass (kg/height in m² ). TBS was measured using the patented algorithm software on DXA scans for the lumbar vertebrae.

Results. The investigators found that the vertebral compression fracture group was statistically significantly older, had lower femur BMD, and had decreased leg muscle mass. The TBS was not identified as a risk factor.

Certain lifestyle factors add to risk of osteosarcopenia

In an editorial, Kirk and colleagues summarized the epidemiology, diagnosis, and treatment of osteosarcopenia. They concluded that this syndrome can be expected to grow in age-related and disease-related states as a consequence of immunosenescence coinciding with an increase in sedentary lifestyle, obesity, and fat infiltration of muscle and bone.

Increasingly, clinicians should screen for osteosarcopenia via imaging methods (DXA) to quantitate bone mass (as is currently done) and, increasingly, quantify muscle mass. In addition, assessment of muscle strength, easily done by testing grip strength, as well as functional capacity (gait speed), will become increasingly important.

Finally, the authors call for a more comprehensive geriatric assessment that includes medical history and risk factors as well as treatment (including osteoporosis drugs, where indicated), and progressive resistance and balance exercises. Nutritional recommendations, in terms of protein, vitamin D, and calcium, also are necessary. They anticipate that diagnosis and treatment of osteosarcopenia will become part of routine health care in the future.

Continue to: The denosumab discontinuation dilemma...

The denosumab discontinuation dilemma

Lyu H, Yoshida K, Zhao SS, et al. Delayed denosumab injections and fracture risk among patients with osteoporosis: a population-based cohort study. Ann Intern Med. 2020;173:516-526.

Tripto-Shkolnik L, Fund N, Rouach V, et al. Fracture incidence after denosumab discontinuation: real-world data from a large healthcare provider. Bone. 2020;130:115150.

Denosumab, marketed under the brand name Prolia, is a human monoclonal antibody that blocks the binding of RANK ligand and inhibits development and activity of osteoclast, thus decreasing bone resorption and increasing BMD. In the original pivotal clinical trial of denosumab, almost 7,900 women between the ages of 60 and 90 (average age, 73) with osteoporotic T-scores were enrolled.⁸ The women were randomly assigned to receive 60 mg of denosumab subcutaneously every 6 months or placebo for a total of 3 years. In that trial, the denosumabtreated group, relative to the placebo group, showed a statistically significant decrease in radiographic vertebral fracture, hip fracture, and nonvertebral fracture. 

An open-label extension study looked at denosumab use for a total of 10 years.⁹ That study found that denosumab treatment for up to 10 years was associated with low rates of adverse events, low fracture incidence compared with that observed during the original trial, and continued increases in BMD without plateau. Thus, denosumab appeared to be an extremely safe and effective agent for treating postmenopausal women with osteoporosis.

Denosumab cessation leads to rebound vertebral fractures

As opposed to bisphosphonates, denosumab does not incorporate into bone matrix, and bone turnover is not suppressed after cessation of its use. Reports have implied that denosumab discontinuation may lead to an increased risk of multiple vertebral fractures.¹⁰ One theory is that unlike atypical femoral fractures that seem to emerge from failure of microdamage repair in cortical bone with long-term antiresorptive treatment, denosumab rebound–associated vertebral fractures seem to originate from the synergy of rapid bone resorption and accelerated microdamage accumulation in trabecular bone triggered by the discontinuation of this highly potent reversible agent.¹¹

Post hoc analysis of the denosumab placebo-controlled trial and its extension reported that the vertebral fracture rate increased after denosumab discontinuation to the level observed in untreated patients.¹² Further, a majority of participants who did sustain vertebral fracture after discontinuing denosumab had multiple vertebral fractures, with the risk being greatest in participants who had a prior vertebral facture. This caused those authors to suggest that patients who discontinued denosumab should rapidly transition to an alternative antiresorptive treatment.

Effect of dose delays, discontinuation on vertebral fracture rate

Lyu and colleagues recently described their population-based cohort study of the United Kingdom’s Health Improvement Network primary care database between 2010 and 2019. They found that delayed administration of a subsequent denosumab dose by more than 16 weeks was associated with an increased risk for vertebral fracture compared with on-time dosing. They noted, however, that the evidence was insufficient to conclude that fracture risk at any other anatomic sites is increased with such a delay.

In a similar study, Tripto-Shkolnik and colleagues examined an Israeli database of 2.3 million members in a state-mandated health organization. They identified osteoporotic patients with at least 2 denosumab prescription dispenses and defined treatment discontinuation as a refill gap of 3 months or more. Fractures were identified by an osteoporosis registry, including fractures that occurred within 1 year from discontinuation in denosumab discontinuers as well as from the second year of treatment forward for persistent users. They identified 1,500 denosumab discontinuers (average age, 72) and 1,610 persistent users (average age also 72). At baseline, the groups were comparable in fracture history, smoking, and bone density.

In the discontinuation group, 0.8% had multiple vertebral fractures versus 0.1% in the persistent users (P = .006); the overall rate of fractures per 100 patient-years of follow-up was 3 times higher in the discontinuation group than in the persistent user group, and the rate of vertebral fractures was almost 5 times higher in the discontinuation group.

Continue to: Atypical femur fracture risk and bisphosphonate use...

Atypical femur fracture risk and bisphosphonate use

Black DM, Geiger EJ, Eastell R, et al. Atypical femur fracture risk versus fragility fracture prevention with bisphosphonates. N Engl J Med. 2020;383:743-753.

Since their introduction in the 1990s, bisphosphonates have been the mainstay of osteoporosis treatment. This category of medications inhibits osteoclast-mediated resorption and remodeling of bone. Various large, randomized, controlled trials have established the efficacy of bisphosphonates to increase BMD and decrease the risk of hip and vertebral fracture by as much as 40% to 70%.¹³

However, case reports of unusual fragility fractures in the subtrochanteric region and along the femoral diaphysis in patients treated with bisphosphonates started to appear approximately 15 years ago.¹⁴ Since then, concerns and publicity about these atypical fractures have led to substantial declines in bisphosphonate use clinically.

Bisphosphonate preventive benefits versus atypical fracture risk

Black and colleagues reviewed data on women 50 years and older who were enrolled in the Kaiser Permanente health care system in California. The total cohort included slightly more than 1 million women, of which almost 200,000 (17.9%) used bisphosphonates at any point from 2007–2017.

A total of 277 atypical femur fractures occurred. Among bisphosphonate users, there were 1.74 fractures per 10,000 patient-years. Overall, there were almost 59 fractures per 10,000 person-years. The incidence of atypical fractures was highest in women between the ages of 75 and 84 years, and the incidence diminished after age 85. Rates of atypical fractures increased as the duration of bisphosphonate use increased. In addition, rates of atypical fractures decreased with time since bisphosphonate discontinuation.

The rate of atypical fractures in women who had never received bisphosphonate therapy was 0.1 per 10,000 person-years. The number of fractures prevented for each fracture type far outweighed bisphosphonate-associated atypical fractures at all time points along the 10 years of study. In White women, for instance, at 3 years there were 541 clinical fractures prevented and 149 hip fractures prevented, while 2 bisphosphonate-associated atypical fractures occurred, all per 10,000 women.

Interestingly, in the Asian population at the same time point, 330 clinical fractures were prevented and 91 hip fractures were prevented, but 8 atypical fractures of the femur occurred, per 10,000 women. The authors further referenced an earlier Kaiser study that showed that 49% of 142 atypical femur fractures occurred in Asian patients who comprised only 10% of the study population.¹⁵

The authors concluded that the risk of atypical femur fracture increases with longer duration of bisphosphate use and rapidly decreases after bisphosphate discontinuation. Asian women have a higher risk than White women. With bisphosphonate treatment, the absolute risk of atypical femur fracture is very low compared with the reduction in the risk of hip and other fractures.

Continue to: Romosozumab increases BMD gains and improves T-scores...

Romosozumab increases BMD gains and improves T-scores

Cosman F, Lewiecki EM, Ebeling PR, et al. T-score as an indicator of fracture risk during treatment with romosozumab or alendronate in the ARCH trial. J Bone Miner Res. 2020;35:1333-1342

Romosozumab (Evenity) is a monoclonal antibody that binds and inhibits sclerostin, thus having the dual effect of increasing bone formation and decreasing bone resorption.¹⁶ It is administered for 1 year as monthly doses of 210 mg subcutaneously. Previous studies have shown that romosozumab produces large increases in lumbar spine and total hip BMD,¹⁷ reduces the risk of new vertebral and clinical fractures compared with placebo,¹⁶ and reduces the risk of vertebral, clinical, nonvertebral, and hip fractures compared with alendronate over a median treatment period of 33 months (the ARCH study).¹⁸

According to the package insert, romosozumab is indicated “for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy.”

Should T-score be a therapeutic target?

Cosman and colleagues performed a post hoc analysis of the ARCH trial specifically to evaluate mean BMD and corresponding mean T-score changes (and the relationships between T-scores) after 1 year of romosozumab or alendronate therapy and subsequent fracture incidence. The study is quite detailed with much numerical data and statistical analysis.

Basically, the ARCH trial randomly assigned patients with osteoporosis to receive either monthly subcutaneous romosozumab 210 mg or weekly oral alendronate 70 mg for 12 months. After the double-blind portion of the trial, all patients received open label weekly oral alendronate 70 mg through the end of study (24 months), although they were still blinded to the initial treatment assignment. In addition, patients received daily calcium and vitamin D supplements.

The data analysis found that 1 year of romosozumab led to larger BMD gains than alendronate therapy. Also, the T-score achieved with either therapy was directly related to subsequent fracture risk. The authors thus proposed that these data support the use of the T-score as a therapeutic target for patients with osteoporosis.

It is important to note that in the original ARCH study, the participants’ average age was 71 years and approximately one-third were older than 75. The average T-score was -2.7 at both the lumbar spine and femoral neck. Approximately 20% of patients had a pre-existing vertebral fracture, and approximately 20% had a previous nonvertebral fracture.

The authors of the current study, furthermore, found that mean BMD gains after 1 year of romosozumab treatment were more than twice those seen with alendronate at the total hip, femoral neck, and lumbar spine. These BMD changes resulted in a larger proportion of patients who achieved T-scores above the osteoporosis level at each of the skeletal sites after 1 year of therapy. Fewer fractures occurred during the second year and the entire open label period among patients who had received romosozumab first compared with those who received alendronate.●

Low-dose chest CT for lung cancer screening provides the opportunity to simultaneously screen patients for osteoporosis, detecting notably higher rates of osteoporosis in men than the traditional tool of DXA, research published in the Journal of Bone and Mineral Research shows.

“Our large-scale, multicenter study of bone density measured from routine low-dose CT scans demonstrated the great potential of using low-dose CT for the opportunistic screening of osteoporosis as an alternative to standard DXA scans,” said senior author Wei Tian, MD, of the Chinese Academy of Engineering and Peking University, in a press statement from the journal.

“Our study revealed the unexpectedly high prevalence of osteoporosis in men, which may impact on the management strategy of men in the future,” Dr. Tian added.

Josephine Therkildsen, MD, of Herning Hospital, Denmark, who has conducted similar research using cardiac CT scans, said the findings add important new insights into the issue of opportunistic screening.

“The results are highly interesting, as they show that low-dose CT-based opportunistic screening could identify a substantial number of patients with low lumbar bone mineral density (BMD) with the future potential to diagnose osteoporosis and initiate relevant treatment before a fracture occurs,” she told this news organization.

Perry J. Pickhardt, MD, chief of gastrointestinal imaging at the University of Wisconsin School of Medicine and Public Health in Madison, agrees. He said in an interview that CT scans of the chest and abdomen, commonly performed for a variety of clinical indications and widespread in most developed countries, can in fact be essential for the detection of a multitude of other concerns – yet are underused for those other purposes.

Use of CT in this way “would likely be very cost effective and clinically efficacious,” he said, adding: “We are seeing greatly increased interest in leveraging this extra information that is contained within every CT scan.” And, “Importantly, artificial intelligence advances now allow for automated approaches, which should allow for expanded use.”
 

Lung cancer CT scans shed light on osteoporosis prevalence

In the study, led by Xiaoguang Cheng, MD, PhD, of the department of radiology, Beijing Jishuitan Hospital, China, researchers examined lung cancer CT screening data from the prospective China Biobank Project to determine the prevalence of osteoporosis in China.

This included the thoracic low-dose CT scans of 69,095 adults, including 40,733 men and 28,362 women, taken between 2018 and 2019.

To screen for osteoporosis, they used quantitative CT software to evaluate lumbar spine (L1-L2) trabecular volume BMD (vBMD) and diagnostic criteria from the American College of Radiology. Using the vBMD measures from the CT imaging, they found the prevalence of osteoporosis among those over 50 years of age in the Chinese population to be 29% for women (49 million) and 13.5% for men (22.8 million).

Interestingly, the osteoporosis prevalence rate among women was comparable to estimates in the population derived from DXA (29.1%); however, the rate in men was twice that estimated from DXA scans (6.5%).

Decreases in trabecular vBMD with age were observed in both genders. However, declines were steeper among women, who had higher peak trabecular vBMD (185.4 mg/cm³), compared with men (176.6 mg/cm³) at age 30-34 years, but significantly lower measures (62.4 mg/cm³) than men (92.1 mg/cm³) at age 80 years.

The prevalence of osteoporosis in women increased from 2.8% at age 50-54 years to 79.8% at age 85 or older, while in men, the prevalence was 3.2% at age 50-54 years and 44.1% at age 85 or older.

“This is the first study to establish Chinese reference data for vBMD using opportunistic screening from low-dose chest CT in a large population cohort,” the authors write.

“The opportunistic screening of osteoporosis using low-dose CT is clinically feasible and requires no additional exposure to ionizing radiation.”

In addition, no additional equipment or patient time was required, suggesting that “this approach has potential for opportunistic screening for osteoporosis.”

They note, however, that further cohort studies are needed to assess clinical utility of this method.
 

CT ‘likely a more accurate measure’ of volumetric BMD

Dr. Pickhardt said the differences in osteoporosis prevalence observed between DXA and CT-derived measures in men likely reflect the greater accuracy of CT.

“DXA is a planar technique with a number of drawbacks,” he said in an interview. “CT provides a more direct volumetric measure and is likely a more accurate method for BMD assessment.”

He speculated that the greater differences between DXA versus CT seen in men than women “may relate to sex differences in cortical bone of vertebral bodies, which cannot be separated from the underlying trabecular bone with DXA (whereas CT directly measures the inner trabecular bone).” 

The authors note that, although areal BMD (aBMD) derived from DXA is required for osteoporosis diagnosis according to World Health Organization criteria, “trabecular vBMD derived from CT can be also used for diagnosis based on thresholds published by the American College of Radiology of 120 mg/cm³ and 80 mg/cm³ to define osteopenia and osteoporosis, respectively, thresholds that were subsequently confirmed for the Chinese population.”

Furthermore, vBMD has been shown in some studies to be more strongly related to fracture risk, compared with DXA aBMD measures.

Importantly, in another recent study involving 9,223 adults, Dr. Pickhardt and colleagues reported that bone and muscle biomarkers derived from CT were comparable to the Fracture Risk Assessment Tool score for the presymptomatic prediction of future osteoporotic fractures.

Dr. Pickhardt is an advisor to Bracco Imaging and Zebra Medical Vision. Dr. Therkildsen has reported no relevant financial relationships.

This article first appeared on Medscape.com.

Low-dose chest CT for lung cancer screening provides the opportunity to simultaneously screen patients for osteoporosis, detecting notably higher rates of osteoporosis in men than the traditional tool of DXA, research published in the Journal of Bone and Mineral Research shows.

“Our large-scale, multicenter study of bone density measured from routine low-dose CT scans demonstrated the great potential of using low-dose CT for the opportunistic screening of osteoporosis as an alternative to standard DXA scans,” said senior author Wei Tian, MD, of the Chinese Academy of Engineering and Peking University, in a press statement from the journal.

“Our study revealed the unexpectedly high prevalence of osteoporosis in men, which may impact on the management strategy of men in the future,” Dr. Tian added.

Josephine Therkildsen, MD, of Herning Hospital, Denmark, who has conducted similar research using cardiac CT scans, said the findings add important new insights into the issue of opportunistic screening.

“The results are highly interesting, as they show that low-dose CT-based opportunistic screening could identify a substantial number of patients with low lumbar bone mineral density (BMD) with the future potential to diagnose osteoporosis and initiate relevant treatment before a fracture occurs,” she told this news organization.

Perry J. Pickhardt, MD, chief of gastrointestinal imaging at the University of Wisconsin School of Medicine and Public Health in Madison, agrees. He said in an interview that CT scans of the chest and abdomen, commonly performed for a variety of clinical indications and widespread in most developed countries, can in fact be essential for the detection of a multitude of other concerns – yet are underused for those other purposes.

Use of CT in this way “would likely be very cost effective and clinically efficacious,” he said, adding: “We are seeing greatly increased interest in leveraging this extra information that is contained within every CT scan.” And, “Importantly, artificial intelligence advances now allow for automated approaches, which should allow for expanded use.”
 

Lung cancer CT scans shed light on osteoporosis prevalence

In the study, led by Xiaoguang Cheng, MD, PhD, of the department of radiology, Beijing Jishuitan Hospital, China, researchers examined lung cancer CT screening data from the prospective China Biobank Project to determine the prevalence of osteoporosis in China.

This included the thoracic low-dose CT scans of 69,095 adults, including 40,733 men and 28,362 women, taken between 2018 and 2019.

To screen for osteoporosis, they used quantitative CT software to evaluate lumbar spine (L1-L2) trabecular volume BMD (vBMD) and diagnostic criteria from the American College of Radiology. Using the vBMD measures from the CT imaging, they found the prevalence of osteoporosis among those over 50 years of age in the Chinese population to be 29% for women (49 million) and 13.5% for men (22.8 million).

Interestingly, the osteoporosis prevalence rate among women was comparable to estimates in the population derived from DXA (29.1%); however, the rate in men was twice that estimated from DXA scans (6.5%).

Decreases in trabecular vBMD with age were observed in both genders. However, declines were steeper among women, who had higher peak trabecular vBMD (185.4 mg/cm³), compared with men (176.6 mg/cm³) at age 30-34 years, but significantly lower measures (62.4 mg/cm³) than men (92.1 mg/cm³) at age 80 years.

The prevalence of osteoporosis in women increased from 2.8% at age 50-54 years to 79.8% at age 85 or older, while in men, the prevalence was 3.2% at age 50-54 years and 44.1% at age 85 or older.

“This is the first study to establish Chinese reference data for vBMD using opportunistic screening from low-dose chest CT in a large population cohort,” the authors write.

“The opportunistic screening of osteoporosis using low-dose CT is clinically feasible and requires no additional exposure to ionizing radiation.”

In addition, no additional equipment or patient time was required, suggesting that “this approach has potential for opportunistic screening for osteoporosis.”

They note, however, that further cohort studies are needed to assess clinical utility of this method.
 

CT ‘likely a more accurate measure’ of volumetric BMD

Dr. Pickhardt said the differences in osteoporosis prevalence observed between DXA and CT-derived measures in men likely reflect the greater accuracy of CT.

“DXA is a planar technique with a number of drawbacks,” he said in an interview. “CT provides a more direct volumetric measure and is likely a more accurate method for BMD assessment.”

He speculated that the greater differences between DXA versus CT seen in men than women “may relate to sex differences in cortical bone of vertebral bodies, which cannot be separated from the underlying trabecular bone with DXA (whereas CT directly measures the inner trabecular bone).” 

The authors note that, although areal BMD (aBMD) derived from DXA is required for osteoporosis diagnosis according to World Health Organization criteria, “trabecular vBMD derived from CT can be also used for diagnosis based on thresholds published by the American College of Radiology of 120 mg/cm³ and 80 mg/cm³ to define osteopenia and osteoporosis, respectively, thresholds that were subsequently confirmed for the Chinese population.”

Furthermore, vBMD has been shown in some studies to be more strongly related to fracture risk, compared with DXA aBMD measures.

Importantly, in another recent study involving 9,223 adults, Dr. Pickhardt and colleagues reported that bone and muscle biomarkers derived from CT were comparable to the Fracture Risk Assessment Tool score for the presymptomatic prediction of future osteoporotic fractures.

Dr. Pickhardt is an advisor to Bracco Imaging and Zebra Medical Vision. Dr. Therkildsen has reported no relevant financial relationships.

This article first appeared on Medscape.com.

Low-dose chest CT for lung cancer screening provides the opportunity to simultaneously screen patients for osteoporosis, detecting notably higher rates of osteoporosis in men than the traditional tool of DXA, research published in the Journal of Bone and Mineral Research shows.

“Our large-scale, multicenter study of bone density measured from routine low-dose CT scans demonstrated the great potential of using low-dose CT for the opportunistic screening of osteoporosis as an alternative to standard DXA scans,” said senior author Wei Tian, MD, of the Chinese Academy of Engineering and Peking University, in a press statement from the journal.

“Our study revealed the unexpectedly high prevalence of osteoporosis in men, which may impact on the management strategy of men in the future,” Dr. Tian added.

Josephine Therkildsen, MD, of Herning Hospital, Denmark, who has conducted similar research using cardiac CT scans, said the findings add important new insights into the issue of opportunistic screening.

“The results are highly interesting, as they show that low-dose CT-based opportunistic screening could identify a substantial number of patients with low lumbar bone mineral density (BMD) with the future potential to diagnose osteoporosis and initiate relevant treatment before a fracture occurs,” she told this news organization.

Perry J. Pickhardt, MD, chief of gastrointestinal imaging at the University of Wisconsin School of Medicine and Public Health in Madison, agrees. He said in an interview that CT scans of the chest and abdomen, commonly performed for a variety of clinical indications and widespread in most developed countries, can in fact be essential for the detection of a multitude of other concerns – yet are underused for those other purposes.

Use of CT in this way “would likely be very cost effective and clinically efficacious,” he said, adding: “We are seeing greatly increased interest in leveraging this extra information that is contained within every CT scan.” And, “Importantly, artificial intelligence advances now allow for automated approaches, which should allow for expanded use.”
 

Lung cancer CT scans shed light on osteoporosis prevalence

In the study, led by Xiaoguang Cheng, MD, PhD, of the department of radiology, Beijing Jishuitan Hospital, China, researchers examined lung cancer CT screening data from the prospective China Biobank Project to determine the prevalence of osteoporosis in China.

This included the thoracic low-dose CT scans of 69,095 adults, including 40,733 men and 28,362 women, taken between 2018 and 2019.

To screen for osteoporosis, they used quantitative CT software to evaluate lumbar spine (L1-L2) trabecular volume BMD (vBMD) and diagnostic criteria from the American College of Radiology. Using the vBMD measures from the CT imaging, they found the prevalence of osteoporosis among those over 50 years of age in the Chinese population to be 29% for women (49 million) and 13.5% for men (22.8 million).

Interestingly, the osteoporosis prevalence rate among women was comparable to estimates in the population derived from DXA (29.1%); however, the rate in men was twice that estimated from DXA scans (6.5%).

Decreases in trabecular vBMD with age were observed in both genders. However, declines were steeper among women, who had higher peak trabecular vBMD (185.4 mg/cm³), compared with men (176.6 mg/cm³) at age 30-34 years, but significantly lower measures (62.4 mg/cm³) than men (92.1 mg/cm³) at age 80 years.

The prevalence of osteoporosis in women increased from 2.8% at age 50-54 years to 79.8% at age 85 or older, while in men, the prevalence was 3.2% at age 50-54 years and 44.1% at age 85 or older.

“This is the first study to establish Chinese reference data for vBMD using opportunistic screening from low-dose chest CT in a large population cohort,” the authors write.

“The opportunistic screening of osteoporosis using low-dose CT is clinically feasible and requires no additional exposure to ionizing radiation.”

In addition, no additional equipment or patient time was required, suggesting that “this approach has potential for opportunistic screening for osteoporosis.”

They note, however, that further cohort studies are needed to assess clinical utility of this method.
 

CT ‘likely a more accurate measure’ of volumetric BMD

Dr. Pickhardt said the differences in osteoporosis prevalence observed between DXA and CT-derived measures in men likely reflect the greater accuracy of CT.

“DXA is a planar technique with a number of drawbacks,” he said in an interview. “CT provides a more direct volumetric measure and is likely a more accurate method for BMD assessment.”

He speculated that the greater differences between DXA versus CT seen in men than women “may relate to sex differences in cortical bone of vertebral bodies, which cannot be separated from the underlying trabecular bone with DXA (whereas CT directly measures the inner trabecular bone).” 

The authors note that, although areal BMD (aBMD) derived from DXA is required for osteoporosis diagnosis according to World Health Organization criteria, “trabecular vBMD derived from CT can be also used for diagnosis based on thresholds published by the American College of Radiology of 120 mg/cm³ and 80 mg/cm³ to define osteopenia and osteoporosis, respectively, thresholds that were subsequently confirmed for the Chinese population.”

Furthermore, vBMD has been shown in some studies to be more strongly related to fracture risk, compared with DXA aBMD measures.

Importantly, in another recent study involving 9,223 adults, Dr. Pickhardt and colleagues reported that bone and muscle biomarkers derived from CT were comparable to the Fracture Risk Assessment Tool score for the presymptomatic prediction of future osteoporotic fractures.

Dr. Pickhardt is an advisor to Bracco Imaging and Zebra Medical Vision. Dr. Therkildsen has reported no relevant financial relationships.

This article first appeared on Medscape.com.

New observational data are the first to support recommendations to continue osteoporosis medications during the COVID-19 pandemic, and even suggest that some agents may protect against the virus.

Findings from the cross-sectional study of 2,102 patients with osteoporosis, osteoarthritis, and/or fibromyalgia – so-called noninflammatory rheumatic conditions – during March 1 to May 3, 2020, were recently published in Aging by Josep Blanch-Rubió, MD, scientific clinical director of the Rheumatology Service, Hospital del Mar, Barcelona, and colleagues.

Patients taking denosumab, zoledronate, and calcium showed trends toward lower incidence of developing symptomatic presumed COVID-19 (polymerase chain reaction tests weren’t widely available at the time), as did those taking the antidepressant serotonin/norepinephrine inhibitor duloxetine.

Some analgesics, particularly pregabalin and most other antidepressants, were associated with higher incidences of COVID-19, while oral bisphosphonates, vitamin D, thiazide diuretics, antihypertensive drugs, and chronic nonsteroidal anti-inflammatory drugs had no effect on COVID-19 incidence.

These data are the first to support guidance issued in May 2020 by the American Society for Bone and Mineral Research and four other professional societies advising continuation of osteoporosis medications during the pandemic. That statement’s authors acknowledged that, lacking data, their recommendations were based primarily on expert opinion.

“There were guidelines without any scientific base. ... This is the first scientific evidence showing that indeed you should continue your osteoporosis treatment if you have COVID-19. This is the first study to provide scientific support for the guidelines,” study coauthor Rafael Maldonado, MD, PhD, of the Laboratory of Neuropharmacology, Universitat Pompeu Fabra, Barcelona, said in an interview.

And while the data don’t offer proof of benefit for any drug – all of the 95% confidence intervals crossed 1.0 – they do show trends that deserve further study, Dr. Maldonado said.

“What we observed is that there is no harm. Treatments should be continued.”

“But we obtained very interesting results with denosumab, zoledronate, calcium, and duloxetine. ... There is a clear tendency, and the message is we should promote studies to see if these four treatments provide benefit.”
 

Different mechanisms for each?

Asked to comment on the findings, Matthew T. Drake, MD, PhD, said in an interview, “I would agree that there’s no reason any of these medications should be stopped or discontinued since there’s no evidence that they make the risk for infection worse.”

“But how [some of them may] improve or reduce the infection risk in my mind is somewhat unclear. ... It’s hard to come up with a unifying explanation” because those mentioned as potentially beneficial “are fairly different,” he noted.

Dr. Drake, associate professor of medicine in the department of endocrinology at the Mayo Clinic, Rochester, Minn., said he agreed with the study authors that denosumab’s targeting of the RANK/RANKL system is a possible anti-COVID-19 mechanism for that drug because that system is involved in immune response.

Regarding zoledronate/zoledronic acid, both the Spanish authors and Dr. Drake pointed to a landmark study linking the intravenous drug to longer survival in patients with hip fracture. The study authors note that there could be several mechanisms for an overall survival benefit, but additionally, “zoledronate may make dendritic cells and their precursors less susceptible to SARS-CoV-2 infection, which could explain the beneficial effects here ... on COVID-19 incidence.”

And, the authors hypothesized, the reason for the lack of benefit with oral bisphosphonates might relate to the higher potency of the intravenous zoledronate. Dr. Drake added that its higher bioavailability may also play a role.

As for calcium, the authors suggest that the beneficial effect against COVID-19 could relate to its action in generating two immune cell types – T follicular helper cells and T follicular regulatory cells – which promote an appropriate immune response against infectious agents, including viruses.
 

Data supporting the guidelines

Of the 2,102 patients in the study by Blanch-Rubió and colleagues, 80.5% were women, and their mean age was 66.4 years. Overall, 63.7% had osteoarthritis, 43.5% had osteoporosis, and 27.2% had fibromyalgia. Treatments included vitamin D in 62%, calcium in 23.3%, denosumab in 12.6%, and intravenous zoledronate in 8.5%. Over half were taking analgesics and nearly a third antidepressants, with 9.9% taking duloxetine.

During the study period, 5.2%, or 109 individuals, were diagnosed with COVID-19 based on presenting for medical care with hallmark symptoms.

After adjustments for sex, age, diabetes, pulmonary disease, cardiovascular disease, chronic kidney disease, and active cancer or treatment, the relative risks for COVID-19 were 0.58 for denosumab, 0.62 for intravenous zoledronate, and 0.64 for calcium, all nonsignificant trends. No associations were found between COVID-19 and oral bisphosphonates, vitamin D, or thiazide diuretics. Increased but nonsignificant relative risks for COVID-19 were seen with analgesics, particularly pregabalin (1.55), gabapentin (1.39), and opioids (1.25).

Among antidepressants, there was a relative risk of 1.54 for selective serotonin reuptake inhibitors, 1.38 for amitriptyline, and 1.22 for all dual-action antidepressants together. In contrast, there was a negative association with the dual-action antidepressant duloxetine, with an adjusted relative risk of 0.68.

“The good news,” Dr. Drake said, “is that none of it appears bad.”

Dr. Blanch-Rubió has received grants or consulting fees from Amgen, Laboratorio Stada, Gedeon-Rhicter Ibérica, Lilly España, Pfizer, Gebro Pharma, and UCB Pharma. Dr. Maldonado has received research grants or consulting fees from Aelis, Almirall, Boehringer Ingelheim, BrainCo, Esteve, Ferrer, GlaxoSmithKline, Grünenthal, GW Pharmaceuticals, Janus, Lundbeck, Pharmaleads, Phytoplant, Rhodes, Sanofi, Spherium, Union de Pharmacologie Scientifique Appliquée, Upjohn, and Uriach. Dr. Drake has reported no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

New observational data are the first to support recommendations to continue osteoporosis medications during the COVID-19 pandemic, and even suggest that some agents may protect against the virus.

Findings from the cross-sectional study of 2,102 patients with osteoporosis, osteoarthritis, and/or fibromyalgia – so-called noninflammatory rheumatic conditions – during March 1 to May 3, 2020, were recently published in Aging by Josep Blanch-Rubió, MD, scientific clinical director of the Rheumatology Service, Hospital del Mar, Barcelona, and colleagues.

Patients taking denosumab, zoledronate, and calcium showed trends toward lower incidence of developing symptomatic presumed COVID-19 (polymerase chain reaction tests weren’t widely available at the time), as did those taking the antidepressant serotonin/norepinephrine inhibitor duloxetine.

Some analgesics, particularly pregabalin and most other antidepressants, were associated with higher incidences of COVID-19, while oral bisphosphonates, vitamin D, thiazide diuretics, antihypertensive drugs, and chronic nonsteroidal anti-inflammatory drugs had no effect on COVID-19 incidence.

These data are the first to support guidance issued in May 2020 by the American Society for Bone and Mineral Research and four other professional societies advising continuation of osteoporosis medications during the pandemic. That statement’s authors acknowledged that, lacking data, their recommendations were based primarily on expert opinion.

“There were guidelines without any scientific base. ... This is the first scientific evidence showing that indeed you should continue your osteoporosis treatment if you have COVID-19. This is the first study to provide scientific support for the guidelines,” study coauthor Rafael Maldonado, MD, PhD, of the Laboratory of Neuropharmacology, Universitat Pompeu Fabra, Barcelona, said in an interview.

And while the data don’t offer proof of benefit for any drug – all of the 95% confidence intervals crossed 1.0 – they do show trends that deserve further study, Dr. Maldonado said.

“What we observed is that there is no harm. Treatments should be continued.”

“But we obtained very interesting results with denosumab, zoledronate, calcium, and duloxetine. ... There is a clear tendency, and the message is we should promote studies to see if these four treatments provide benefit.”
 

Different mechanisms for each?

Asked to comment on the findings, Matthew T. Drake, MD, PhD, said in an interview, “I would agree that there’s no reason any of these medications should be stopped or discontinued since there’s no evidence that they make the risk for infection worse.”

“But how [some of them may] improve or reduce the infection risk in my mind is somewhat unclear. ... It’s hard to come up with a unifying explanation” because those mentioned as potentially beneficial “are fairly different,” he noted.

Dr. Drake, associate professor of medicine in the department of endocrinology at the Mayo Clinic, Rochester, Minn., said he agreed with the study authors that denosumab’s targeting of the RANK/RANKL system is a possible anti-COVID-19 mechanism for that drug because that system is involved in immune response.

Regarding zoledronate/zoledronic acid, both the Spanish authors and Dr. Drake pointed to a landmark study linking the intravenous drug to longer survival in patients with hip fracture. The study authors note that there could be several mechanisms for an overall survival benefit, but additionally, “zoledronate may make dendritic cells and their precursors less susceptible to SARS-CoV-2 infection, which could explain the beneficial effects here ... on COVID-19 incidence.”

And, the authors hypothesized, the reason for the lack of benefit with oral bisphosphonates might relate to the higher potency of the intravenous zoledronate. Dr. Drake added that its higher bioavailability may also play a role.

As for calcium, the authors suggest that the beneficial effect against COVID-19 could relate to its action in generating two immune cell types – T follicular helper cells and T follicular regulatory cells – which promote an appropriate immune response against infectious agents, including viruses.
 

Data supporting the guidelines

Of the 2,102 patients in the study by Blanch-Rubió and colleagues, 80.5% were women, and their mean age was 66.4 years. Overall, 63.7% had osteoarthritis, 43.5% had osteoporosis, and 27.2% had fibromyalgia. Treatments included vitamin D in 62%, calcium in 23.3%, denosumab in 12.6%, and intravenous zoledronate in 8.5%. Over half were taking analgesics and nearly a third antidepressants, with 9.9% taking duloxetine.

During the study period, 5.2%, or 109 individuals, were diagnosed with COVID-19 based on presenting for medical care with hallmark symptoms.

After adjustments for sex, age, diabetes, pulmonary disease, cardiovascular disease, chronic kidney disease, and active cancer or treatment, the relative risks for COVID-19 were 0.58 for denosumab, 0.62 for intravenous zoledronate, and 0.64 for calcium, all nonsignificant trends. No associations were found between COVID-19 and oral bisphosphonates, vitamin D, or thiazide diuretics. Increased but nonsignificant relative risks for COVID-19 were seen with analgesics, particularly pregabalin (1.55), gabapentin (1.39), and opioids (1.25).

Among antidepressants, there was a relative risk of 1.54 for selective serotonin reuptake inhibitors, 1.38 for amitriptyline, and 1.22 for all dual-action antidepressants together. In contrast, there was a negative association with the dual-action antidepressant duloxetine, with an adjusted relative risk of 0.68.

“The good news,” Dr. Drake said, “is that none of it appears bad.”

Dr. Blanch-Rubió has received grants or consulting fees from Amgen, Laboratorio Stada, Gedeon-Rhicter Ibérica, Lilly España, Pfizer, Gebro Pharma, and UCB Pharma. Dr. Maldonado has received research grants or consulting fees from Aelis, Almirall, Boehringer Ingelheim, BrainCo, Esteve, Ferrer, GlaxoSmithKline, Grünenthal, GW Pharmaceuticals, Janus, Lundbeck, Pharmaleads, Phytoplant, Rhodes, Sanofi, Spherium, Union de Pharmacologie Scientifique Appliquée, Upjohn, and Uriach. Dr. Drake has reported no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

New observational data are the first to support recommendations to continue osteoporosis medications during the COVID-19 pandemic, and even suggest that some agents may protect against the virus.

Findings from the cross-sectional study of 2,102 patients with osteoporosis, osteoarthritis, and/or fibromyalgia – so-called noninflammatory rheumatic conditions – during March 1 to May 3, 2020, were recently published in Aging by Josep Blanch-Rubió, MD, scientific clinical director of the Rheumatology Service, Hospital del Mar, Barcelona, and colleagues.

Patients taking denosumab, zoledronate, and calcium showed trends toward lower incidence of developing symptomatic presumed COVID-19 (polymerase chain reaction tests weren’t widely available at the time), as did those taking the antidepressant serotonin/norepinephrine inhibitor duloxetine.

Some analgesics, particularly pregabalin and most other antidepressants, were associated with higher incidences of COVID-19, while oral bisphosphonates, vitamin D, thiazide diuretics, antihypertensive drugs, and chronic nonsteroidal anti-inflammatory drugs had no effect on COVID-19 incidence.

These data are the first to support guidance issued in May 2020 by the American Society for Bone and Mineral Research and four other professional societies advising continuation of osteoporosis medications during the pandemic. That statement’s authors acknowledged that, lacking data, their recommendations were based primarily on expert opinion.

“There were guidelines without any scientific base. ... This is the first scientific evidence showing that indeed you should continue your osteoporosis treatment if you have COVID-19. This is the first study to provide scientific support for the guidelines,” study coauthor Rafael Maldonado, MD, PhD, of the Laboratory of Neuropharmacology, Universitat Pompeu Fabra, Barcelona, said in an interview.

And while the data don’t offer proof of benefit for any drug – all of the 95% confidence intervals crossed 1.0 – they do show trends that deserve further study, Dr. Maldonado said.

“What we observed is that there is no harm. Treatments should be continued.”

“But we obtained very interesting results with denosumab, zoledronate, calcium, and duloxetine. ... There is a clear tendency, and the message is we should promote studies to see if these four treatments provide benefit.”
 

Different mechanisms for each?

Asked to comment on the findings, Matthew T. Drake, MD, PhD, said in an interview, “I would agree that there’s no reason any of these medications should be stopped or discontinued since there’s no evidence that they make the risk for infection worse.”

“But how [some of them may] improve or reduce the infection risk in my mind is somewhat unclear. ... It’s hard to come up with a unifying explanation” because those mentioned as potentially beneficial “are fairly different,” he noted.

Dr. Drake, associate professor of medicine in the department of endocrinology at the Mayo Clinic, Rochester, Minn., said he agreed with the study authors that denosumab’s targeting of the RANK/RANKL system is a possible anti-COVID-19 mechanism for that drug because that system is involved in immune response.

Regarding zoledronate/zoledronic acid, both the Spanish authors and Dr. Drake pointed to a landmark study linking the intravenous drug to longer survival in patients with hip fracture. The study authors note that there could be several mechanisms for an overall survival benefit, but additionally, “zoledronate may make dendritic cells and their precursors less susceptible to SARS-CoV-2 infection, which could explain the beneficial effects here ... on COVID-19 incidence.”

And, the authors hypothesized, the reason for the lack of benefit with oral bisphosphonates might relate to the higher potency of the intravenous zoledronate. Dr. Drake added that its higher bioavailability may also play a role.

As for calcium, the authors suggest that the beneficial effect against COVID-19 could relate to its action in generating two immune cell types – T follicular helper cells and T follicular regulatory cells – which promote an appropriate immune response against infectious agents, including viruses.
 

Data supporting the guidelines

Of the 2,102 patients in the study by Blanch-Rubió and colleagues, 80.5% were women, and their mean age was 66.4 years. Overall, 63.7% had osteoarthritis, 43.5% had osteoporosis, and 27.2% had fibromyalgia. Treatments included vitamin D in 62%, calcium in 23.3%, denosumab in 12.6%, and intravenous zoledronate in 8.5%. Over half were taking analgesics and nearly a third antidepressants, with 9.9% taking duloxetine.

During the study period, 5.2%, or 109 individuals, were diagnosed with COVID-19 based on presenting for medical care with hallmark symptoms.

After adjustments for sex, age, diabetes, pulmonary disease, cardiovascular disease, chronic kidney disease, and active cancer or treatment, the relative risks for COVID-19 were 0.58 for denosumab, 0.62 for intravenous zoledronate, and 0.64 for calcium, all nonsignificant trends. No associations were found between COVID-19 and oral bisphosphonates, vitamin D, or thiazide diuretics. Increased but nonsignificant relative risks for COVID-19 were seen with analgesics, particularly pregabalin (1.55), gabapentin (1.39), and opioids (1.25).

Among antidepressants, there was a relative risk of 1.54 for selective serotonin reuptake inhibitors, 1.38 for amitriptyline, and 1.22 for all dual-action antidepressants together. In contrast, there was a negative association with the dual-action antidepressant duloxetine, with an adjusted relative risk of 0.68.

“The good news,” Dr. Drake said, “is that none of it appears bad.”

Dr. Blanch-Rubió has received grants or consulting fees from Amgen, Laboratorio Stada, Gedeon-Rhicter Ibérica, Lilly España, Pfizer, Gebro Pharma, and UCB Pharma. Dr. Maldonado has received research grants or consulting fees from Aelis, Almirall, Boehringer Ingelheim, BrainCo, Esteve, Ferrer, GlaxoSmithKline, Grünenthal, GW Pharmaceuticals, Janus, Lundbeck, Pharmaleads, Phytoplant, Rhodes, Sanofi, Spherium, Union de Pharmacologie Scientifique Appliquée, Upjohn, and Uriach. Dr. Drake has reported no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

Although the effects of vitamin K on blood coagulation are well-established, it is now clear that many extracellular proteins are carboxylated in a vitamin K-dependent manner, including bone matrix proteins such as osteocalcin and matrix gla protein. Previous studies have reported a relationship between vitamin K levels and bone density and fracture risk. However, optimal circulating vitamin K levels for skeletal health remain unknown. In this cross-sectional study of 374 women with post-menopausal osteoporosis, the authors assessed the relationship between vitamin K levels, vitamin K dependent bone-relevant circulating proteins, bone density, and fractures. In doing so, it was noted that women with prevalent fractures showed lower vitamin K levels than those without fractures. No relationship between vitamin K levels and bone density was noted. Interestingly, different serum levels of vitamin K were associated with optimal carboxylation of different vitamin K-dependent proteins: lower vitamin K levels are needed to support clotting factors than bone matrix proteins. Overall, this study suggests that higher intake is needed to obtain the full skeletal benefit of vitamin K versus its effects on coagulation. Future prospective studies are needed to test this intriguing hypothesis, and to further explore the relationship between vitamin K and bone quality.

For over 20 years, bisphosphonates have been first line therapy to increase bone density and reduce fracture risk in patients with osteoporosis. At present, multiple oral and intravenous bisphosphonates are approved for this indication by regulatory agencies worldwide. Several ‘next-generation’ bisphosphonates with optimized anti-resorptive and pharmacokinetic properties have been developed. Of these agents, minodronate is a particularly potent, third generation azaryl bisphosphonate that is currently approved for osteoporosis treatment in Japan. In this meta-analysis of 13 randomized controlled trials, the effects of minodronate were assessed versus other commonly-used osteoporosis medications. Compared with other drugs (alendronate, risedronate, raloxifene, or eldecalcitol), minodronate more potently suppressed serum bone resorption markers (NTX and TRAcP-5b) and, because bone formation and resorption are coupled, more potently suppressed the bone formation marker bone-specific alkaline phosphatase. In addition to these effects on serum markers, minodronate reduced vertebral fractures more than other medications. Across studies, no differences were noted between minodronate and comparators at the level of bone mineral density. Minodronate treatment is associated with a high incidence of gastrointestinal adverse effects than comparator medications. Taken together, these findings suggest that minodronate represents a potent, orally-available bisphosphonate for vertebral fracture reduction in patients with osteoporosis in Japan.

Chronic obstructive pulmonary disease (COPD) is well-known to be a risk factor for osteoporosis and fragility fractures. However, the interplay between inhaled corticosteroid use in COPD and skeletal outcomes remains unclear. While systemic glucocorticoid therapy clearly impairs bone mass and increases fracture risk, whether inhaled steroids have similar effects remain unknown. Furthermore, since inhaled corticosteroids can reduce lung inflammation and COPD flares, it is possible that, by controlling pulmonary disease, these agents may actually promote bone health. In this real-world retrospective Swedish cohort study, 9,651 COPD patients and 59,454 reference controls were identified. Matching using propensity scoring was performed to identify two populations (COPD and control) with similar characteristics other than the presence of COPD. As expected, COPD patients showed an increased rate of osteoporosis-related events versus controls over approximately 5 years of subsequent follow-up. Amongst COPD patients, high-dose inhaled corticosteroid treatment also increased risk of osteoporosis-related events compared to COPD patients on no or low-dose inhaled steroids. These findings confirm the known relationship between COPD and fracture risk, and suggest that extra attention should be paid to fracture risk in COPD patients receiving high-dose inhaled corticosteroids.

Wrist fractures are common in patients with osteoporosis. In addition to causing pain and triggering functional decline, the presence of a wrist fracture indicates an increased risk of additional fragility fractures in the near future. Most wrist fractures occur in the ultradistal radius, a skeletal site rich in trabecular bone. In contrast, wrist bone density by DXA is most commonly reported in the distal 1/3 radius, a region of the radius with more cortical bone. Abaloparatide is a PTHrP analog that increases bone density and reduces fracture risk. In this sub-analysis of the ACTIVE and ACTIVExtend randomized clinical trial, the effects of abaloparatide on wrist fractures and BMD at various regions of the wrist were assessed. Compared to placebo, abaloparatide treatment significantly increased ultradistal wrist BMD after 18 months of therapy. These gains were preserved during the subsequent extension study when patients were maintained on alendronate. Very few wrist fractures were noted during this study thus precluding robust statistical analysis of the effects of abaloparatide on wrist fracture risk. However, numerically fewer wrist fractures were noted in abaloparatide-treated patients versus controls. Taken together, these results highlight the potential importance of measuring ultradistal radius BMD for patients undergoing therapy with bone anabolic agents. Future studies are needed to better standardize methods for obtaining ultradistal radius BMD measurements and to define least significant change thresholds at this potentially-important skeletal site.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School

Although the effects of vitamin K on blood coagulation are well-established, it is now clear that many extracellular proteins are carboxylated in a vitamin K-dependent manner, including bone matrix proteins such as osteocalcin and matrix gla protein. Previous studies have reported a relationship between vitamin K levels and bone density and fracture risk. However, optimal circulating vitamin K levels for skeletal health remain unknown. In this cross-sectional study of 374 women with post-menopausal osteoporosis, the authors assessed the relationship between vitamin K levels, vitamin K dependent bone-relevant circulating proteins, bone density, and fractures. In doing so, it was noted that women with prevalent fractures showed lower vitamin K levels than those without fractures. No relationship between vitamin K levels and bone density was noted. Interestingly, different serum levels of vitamin K were associated with optimal carboxylation of different vitamin K-dependent proteins: lower vitamin K levels are needed to support clotting factors than bone matrix proteins. Overall, this study suggests that higher intake is needed to obtain the full skeletal benefit of vitamin K versus its effects on coagulation. Future prospective studies are needed to test this intriguing hypothesis, and to further explore the relationship between vitamin K and bone quality.

For over 20 years, bisphosphonates have been first line therapy to increase bone density and reduce fracture risk in patients with osteoporosis. At present, multiple oral and intravenous bisphosphonates are approved for this indication by regulatory agencies worldwide. Several ‘next-generation’ bisphosphonates with optimized anti-resorptive and pharmacokinetic properties have been developed. Of these agents, minodronate is a particularly potent, third generation azaryl bisphosphonate that is currently approved for osteoporosis treatment in Japan. In this meta-analysis of 13 randomized controlled trials, the effects of minodronate were assessed versus other commonly-used osteoporosis medications. Compared with other drugs (alendronate, risedronate, raloxifene, or eldecalcitol), minodronate more potently suppressed serum bone resorption markers (NTX and TRAcP-5b) and, because bone formation and resorption are coupled, more potently suppressed the bone formation marker bone-specific alkaline phosphatase. In addition to these effects on serum markers, minodronate reduced vertebral fractures more than other medications. Across studies, no differences were noted between minodronate and comparators at the level of bone mineral density. Minodronate treatment is associated with a high incidence of gastrointestinal adverse effects than comparator medications. Taken together, these findings suggest that minodronate represents a potent, orally-available bisphosphonate for vertebral fracture reduction in patients with osteoporosis in Japan.

Chronic obstructive pulmonary disease (COPD) is well-known to be a risk factor for osteoporosis and fragility fractures. However, the interplay between inhaled corticosteroid use in COPD and skeletal outcomes remains unclear. While systemic glucocorticoid therapy clearly impairs bone mass and increases fracture risk, whether inhaled steroids have similar effects remain unknown. Furthermore, since inhaled corticosteroids can reduce lung inflammation and COPD flares, it is possible that, by controlling pulmonary disease, these agents may actually promote bone health. In this real-world retrospective Swedish cohort study, 9,651 COPD patients and 59,454 reference controls were identified. Matching using propensity scoring was performed to identify two populations (COPD and control) with similar characteristics other than the presence of COPD. As expected, COPD patients showed an increased rate of osteoporosis-related events versus controls over approximately 5 years of subsequent follow-up. Amongst COPD patients, high-dose inhaled corticosteroid treatment also increased risk of osteoporosis-related events compared to COPD patients on no or low-dose inhaled steroids. These findings confirm the known relationship between COPD and fracture risk, and suggest that extra attention should be paid to fracture risk in COPD patients receiving high-dose inhaled corticosteroids.

Wrist fractures are common in patients with osteoporosis. In addition to causing pain and triggering functional decline, the presence of a wrist fracture indicates an increased risk of additional fragility fractures in the near future. Most wrist fractures occur in the ultradistal radius, a skeletal site rich in trabecular bone. In contrast, wrist bone density by DXA is most commonly reported in the distal 1/3 radius, a region of the radius with more cortical bone. Abaloparatide is a PTHrP analog that increases bone density and reduces fracture risk. In this sub-analysis of the ACTIVE and ACTIVExtend randomized clinical trial, the effects of abaloparatide on wrist fractures and BMD at various regions of the wrist were assessed. Compared to placebo, abaloparatide treatment significantly increased ultradistal wrist BMD after 18 months of therapy. These gains were preserved during the subsequent extension study when patients were maintained on alendronate. Very few wrist fractures were noted during this study thus precluding robust statistical analysis of the effects of abaloparatide on wrist fracture risk. However, numerically fewer wrist fractures were noted in abaloparatide-treated patients versus controls. Taken together, these results highlight the potential importance of measuring ultradistal radius BMD for patients undergoing therapy with bone anabolic agents. Future studies are needed to better standardize methods for obtaining ultradistal radius BMD measurements and to define least significant change thresholds at this potentially-important skeletal site.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School

Although the effects of vitamin K on blood coagulation are well-established, it is now clear that many extracellular proteins are carboxylated in a vitamin K-dependent manner, including bone matrix proteins such as osteocalcin and matrix gla protein. Previous studies have reported a relationship between vitamin K levels and bone density and fracture risk. However, optimal circulating vitamin K levels for skeletal health remain unknown. In this cross-sectional study of 374 women with post-menopausal osteoporosis, the authors assessed the relationship between vitamin K levels, vitamin K dependent bone-relevant circulating proteins, bone density, and fractures. In doing so, it was noted that women with prevalent fractures showed lower vitamin K levels than those without fractures. No relationship between vitamin K levels and bone density was noted. Interestingly, different serum levels of vitamin K were associated with optimal carboxylation of different vitamin K-dependent proteins: lower vitamin K levels are needed to support clotting factors than bone matrix proteins. Overall, this study suggests that higher intake is needed to obtain the full skeletal benefit of vitamin K versus its effects on coagulation. Future prospective studies are needed to test this intriguing hypothesis, and to further explore the relationship between vitamin K and bone quality.

For over 20 years, bisphosphonates have been first line therapy to increase bone density and reduce fracture risk in patients with osteoporosis. At present, multiple oral and intravenous bisphosphonates are approved for this indication by regulatory agencies worldwide. Several ‘next-generation’ bisphosphonates with optimized anti-resorptive and pharmacokinetic properties have been developed. Of these agents, minodronate is a particularly potent, third generation azaryl bisphosphonate that is currently approved for osteoporosis treatment in Japan. In this meta-analysis of 13 randomized controlled trials, the effects of minodronate were assessed versus other commonly-used osteoporosis medications. Compared with other drugs (alendronate, risedronate, raloxifene, or eldecalcitol), minodronate more potently suppressed serum bone resorption markers (NTX and TRAcP-5b) and, because bone formation and resorption are coupled, more potently suppressed the bone formation marker bone-specific alkaline phosphatase. In addition to these effects on serum markers, minodronate reduced vertebral fractures more than other medications. Across studies, no differences were noted between minodronate and comparators at the level of bone mineral density. Minodronate treatment is associated with a high incidence of gastrointestinal adverse effects than comparator medications. Taken together, these findings suggest that minodronate represents a potent, orally-available bisphosphonate for vertebral fracture reduction in patients with osteoporosis in Japan.

Chronic obstructive pulmonary disease (COPD) is well-known to be a risk factor for osteoporosis and fragility fractures. However, the interplay between inhaled corticosteroid use in COPD and skeletal outcomes remains unclear. While systemic glucocorticoid therapy clearly impairs bone mass and increases fracture risk, whether inhaled steroids have similar effects remain unknown. Furthermore, since inhaled corticosteroids can reduce lung inflammation and COPD flares, it is possible that, by controlling pulmonary disease, these agents may actually promote bone health. In this real-world retrospective Swedish cohort study, 9,651 COPD patients and 59,454 reference controls were identified. Matching using propensity scoring was performed to identify two populations (COPD and control) with similar characteristics other than the presence of COPD. As expected, COPD patients showed an increased rate of osteoporosis-related events versus controls over approximately 5 years of subsequent follow-up. Amongst COPD patients, high-dose inhaled corticosteroid treatment also increased risk of osteoporosis-related events compared to COPD patients on no or low-dose inhaled steroids. These findings confirm the known relationship between COPD and fracture risk, and suggest that extra attention should be paid to fracture risk in COPD patients receiving high-dose inhaled corticosteroids.

Wrist fractures are common in patients with osteoporosis. In addition to causing pain and triggering functional decline, the presence of a wrist fracture indicates an increased risk of additional fragility fractures in the near future. Most wrist fractures occur in the ultradistal radius, a skeletal site rich in trabecular bone. In contrast, wrist bone density by DXA is most commonly reported in the distal 1/3 radius, a region of the radius with more cortical bone. Abaloparatide is a PTHrP analog that increases bone density and reduces fracture risk. In this sub-analysis of the ACTIVE and ACTIVExtend randomized clinical trial, the effects of abaloparatide on wrist fractures and BMD at various regions of the wrist were assessed. Compared to placebo, abaloparatide treatment significantly increased ultradistal wrist BMD after 18 months of therapy. These gains were preserved during the subsequent extension study when patients were maintained on alendronate. Very few wrist fractures were noted during this study thus precluding robust statistical analysis of the effects of abaloparatide on wrist fracture risk. However, numerically fewer wrist fractures were noted in abaloparatide-treated patients versus controls. Taken together, these results highlight the potential importance of measuring ultradistal radius BMD for patients undergoing therapy with bone anabolic agents. Future studies are needed to better standardize methods for obtaining ultradistal radius BMD measurements and to define least significant change thresholds at this potentially-important skeletal site.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School

Key clinical point: Hypogonadism is a major risk factor for the development of fractures in men and women treated with glucocorticoid (GC).

Major finding: Major risk factors for vertebral fracture were hypogonadism (odds ratio [OR], 12.38; P = .01) and receiving GC boluses (OR 3.45; P = .01) and that for friability fracture were hypogonadism (OR, 7.03; P = .01) and a FRAX index greater than 20 (OR, 7.08; P = .02).

Study details: A cross-sectional study of 127 adults receiving chronic GC treatment for a rheumatological autoimmune disease.

Disclosures: This study was funded in part by the Societat Catalana de Reumatologia. The authors declared no conflicts of interest.

Citation: Florez H et al. RMD Open. 2020 Sep 10. doi: 10.1136/rmdopen-2020-001355.

Key clinical point: Hypogonadism is a major risk factor for the development of fractures in men and women treated with glucocorticoid (GC).

Major finding: Major risk factors for vertebral fracture were hypogonadism (odds ratio [OR], 12.38; P = .01) and receiving GC boluses (OR 3.45; P = .01) and that for friability fracture were hypogonadism (OR, 7.03; P = .01) and a FRAX index greater than 20 (OR, 7.08; P = .02).

Study details: A cross-sectional study of 127 adults receiving chronic GC treatment for a rheumatological autoimmune disease.

Disclosures: This study was funded in part by the Societat Catalana de Reumatologia. The authors declared no conflicts of interest.

Citation: Florez H et al. RMD Open. 2020 Sep 10. doi: 10.1136/rmdopen-2020-001355.

Key clinical point: Hypogonadism is a major risk factor for the development of fractures in men and women treated with glucocorticoid (GC).

Major finding: Major risk factors for vertebral fracture were hypogonadism (odds ratio [OR], 12.38; P = .01) and receiving GC boluses (OR 3.45; P = .01) and that for friability fracture were hypogonadism (OR, 7.03; P = .01) and a FRAX index greater than 20 (OR, 7.08; P = .02).

Study details: A cross-sectional study of 127 adults receiving chronic GC treatment for a rheumatological autoimmune disease.

Disclosures: This study was funded in part by the Societat Catalana de Reumatologia. The authors declared no conflicts of interest.

Citation: Florez H et al. RMD Open. 2020 Sep 10. doi: 10.1136/rmdopen-2020-001355.