Clinical Edge Journal Scan

Key clinical point: Bronchoscopy was safe for most patients with malignant hematologic disorders with careful monitoring and use of sedatives, particularly midazolam.

Major finding: A total of 12 out of 272 patients (3.8%) experienced prolonged oxygen desaturation; 7 of these recovered and 5 died from lung lesion deterioration. However, midazolam reduced the risk of prolonged oxygen desaturation in the study population.

Study details: The data come from a review of 316 bronchoscopies in 282 adults with malignant hematologic disorders and pulmonary infiltrates who were treated at a single center.

Disclosures: Lead author Dr. Uruga disclosed grant support from Okinaka Memorial Institute for Medical Research.

Citation: Uruga H et al. BMC Pulm Med. 2020 Sep 11. doi: 10.1186/s12890-020-01283-8.

Key clinical point: Bronchoscopy was safe for most patients with malignant hematologic disorders with careful monitoring and use of sedatives, particularly midazolam.

Major finding: A total of 12 out of 272 patients (3.8%) experienced prolonged oxygen desaturation; 7 of these recovered and 5 died from lung lesion deterioration. However, midazolam reduced the risk of prolonged oxygen desaturation in the study population.

Study details: The data come from a review of 316 bronchoscopies in 282 adults with malignant hematologic disorders and pulmonary infiltrates who were treated at a single center.

Disclosures: Lead author Dr. Uruga disclosed grant support from Okinaka Memorial Institute for Medical Research.

Citation: Uruga H et al. BMC Pulm Med. 2020 Sep 11. doi: 10.1186/s12890-020-01283-8.

Key clinical point: Bronchoscopy was safe for most patients with malignant hematologic disorders with careful monitoring and use of sedatives, particularly midazolam.

Major finding: A total of 12 out of 272 patients (3.8%) experienced prolonged oxygen desaturation; 7 of these recovered and 5 died from lung lesion deterioration. However, midazolam reduced the risk of prolonged oxygen desaturation in the study population.

Study details: The data come from a review of 316 bronchoscopies in 282 adults with malignant hematologic disorders and pulmonary infiltrates who were treated at a single center.

Disclosures: Lead author Dr. Uruga disclosed grant support from Okinaka Memorial Institute for Medical Research.

Citation: Uruga H et al. BMC Pulm Med. 2020 Sep 11. doi: 10.1186/s12890-020-01283-8.

Key clinical point: Adults with end-stage renal disease who underwent dialysis for at least six months were at significantly increased risk for MDS compared with healthy controls.

Major finding: Patients with chronic renal failure who underwent dialysis were significantly more likely to develop myelodysplastic syndrome compared to healthy controls (subdistribution hazard ratio 1.60); older age also was significantly associated with increased MDS risk (sHR 1.03).

Study details: The data come from a study of 74,712 adults with chronic renal failure diagnoses between 1997 and 2013 who underwent dialysis, and matched controls. Participants were follow from index date to the first occurrence of MDS, withdrawal from the NHI program, or the last day of 2013.

Disclosures: The study used the National Health Insurance Research Database established by the National Health Research Institutes with the authorization of the Bureau of National Health Insurance, Ministry of Health and Welfare of Taiwan. The researchers had no financial conflicts to disclose.

Citation: Chang M-Y et al. Sci Rep. 2020 Sept 23. doi: 10.1038/s41598-020-72568-5.

Key clinical point: Adults with end-stage renal disease who underwent dialysis for at least six months were at significantly increased risk for MDS compared with healthy controls.

Major finding: Patients with chronic renal failure who underwent dialysis were significantly more likely to develop myelodysplastic syndrome compared to healthy controls (subdistribution hazard ratio 1.60); older age also was significantly associated with increased MDS risk (sHR 1.03).

Study details: The data come from a study of 74,712 adults with chronic renal failure diagnoses between 1997 and 2013 who underwent dialysis, and matched controls. Participants were follow from index date to the first occurrence of MDS, withdrawal from the NHI program, or the last day of 2013.

Disclosures: The study used the National Health Insurance Research Database established by the National Health Research Institutes with the authorization of the Bureau of National Health Insurance, Ministry of Health and Welfare of Taiwan. The researchers had no financial conflicts to disclose.

Citation: Chang M-Y et al. Sci Rep. 2020 Sept 23. doi: 10.1038/s41598-020-72568-5.

Key clinical point: Adults with end-stage renal disease who underwent dialysis for at least six months were at significantly increased risk for MDS compared with healthy controls.

Major finding: Patients with chronic renal failure who underwent dialysis were significantly more likely to develop myelodysplastic syndrome compared to healthy controls (subdistribution hazard ratio 1.60); older age also was significantly associated with increased MDS risk (sHR 1.03).

Study details: The data come from a study of 74,712 adults with chronic renal failure diagnoses between 1997 and 2013 who underwent dialysis, and matched controls. Participants were follow from index date to the first occurrence of MDS, withdrawal from the NHI program, or the last day of 2013.

Disclosures: The study used the National Health Insurance Research Database established by the National Health Research Institutes with the authorization of the Bureau of National Health Insurance, Ministry of Health and Welfare of Taiwan. The researchers had no financial conflicts to disclose.

Citation: Chang M-Y et al. Sci Rep. 2020 Sept 23. doi: 10.1038/s41598-020-72568-5.

Key clinical point: Several long noncoding RNAs (lncRNAs) were strongly associated with disease pathogenesis and prognosis in myelodysplastic syndrome (MDS) patients.

Major finding: Based on genome-wide profiling, lncRNA gene networks with expression of H19, WT1-AS, TCL6, and LEF1-AS1 were associated with higher-risk MDS; of these, H19 also showed promise as a therapeutic target because of its strong predictive value for lower complete remission rate of induction therapy in AML in the presence of H19 overexpression. 

Study details: The data come from a study of genetic profiling including 54 patients with MDS, 14 patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and 9 healthy donors.

Disclosures: The study was supported by the Project for Conceptual Development of Research Organization from the Ministry of Health of the Czech Republic. The researchers had no financial conflicts to disclose.

Citation: Szikszai K et al. Cancers. 2020 Sept 23. doi: 10.3390/cancers12102726.

Key clinical point: Several long noncoding RNAs (lncRNAs) were strongly associated with disease pathogenesis and prognosis in myelodysplastic syndrome (MDS) patients.

Major finding: Based on genome-wide profiling, lncRNA gene networks with expression of H19, WT1-AS, TCL6, and LEF1-AS1 were associated with higher-risk MDS; of these, H19 also showed promise as a therapeutic target because of its strong predictive value for lower complete remission rate of induction therapy in AML in the presence of H19 overexpression. 

Study details: The data come from a study of genetic profiling including 54 patients with MDS, 14 patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and 9 healthy donors.

Disclosures: The study was supported by the Project for Conceptual Development of Research Organization from the Ministry of Health of the Czech Republic. The researchers had no financial conflicts to disclose.

Citation: Szikszai K et al. Cancers. 2020 Sept 23. doi: 10.3390/cancers12102726.

Key clinical point: Several long noncoding RNAs (lncRNAs) were strongly associated with disease pathogenesis and prognosis in myelodysplastic syndrome (MDS) patients.

Major finding: Based on genome-wide profiling, lncRNA gene networks with expression of H19, WT1-AS, TCL6, and LEF1-AS1 were associated with higher-risk MDS; of these, H19 also showed promise as a therapeutic target because of its strong predictive value for lower complete remission rate of induction therapy in AML in the presence of H19 overexpression. 

Study details: The data come from a study of genetic profiling including 54 patients with MDS, 14 patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and 9 healthy donors.

Disclosures: The study was supported by the Project for Conceptual Development of Research Organization from the Ministry of Health of the Czech Republic. The researchers had no financial conflicts to disclose.

Citation: Szikszai K et al. Cancers. 2020 Sept 23. doi: 10.3390/cancers12102726.

Key clinical point: Ferroptosis, a distinct form of regulated cell death process involving iron-dependent lipid peroxidation, may impact the action of chemotherapy drug decitabine.

Major finding: The level of GSH and the activity of GPX4 decreased, whereas the ROS level increased in MDS cells upon treatment with decitabine, which could be reversed by ferrostatin-1.

Study details: The data come from a review of cell viability assays, reactive oxygen species assays, gluthiathone assays, and

Disclosures: The study was supported in part by the National Natural Science Foundation of China, Key Technology Research and Development Program of Tianjin, Application Bases and Advanced Technology Research Program of Tianjin, and Key National Natural Science Foundation of Tianjin. The researchers had no financial conflicts to disclose.

Citation: Lv Q et al. Front. Oncol. 2020 Sept 2. doi: 10.3389/fonc.2020.01656.

Key clinical point: Ferroptosis, a distinct form of regulated cell death process involving iron-dependent lipid peroxidation, may impact the action of chemotherapy drug decitabine.

Major finding: The level of GSH and the activity of GPX4 decreased, whereas the ROS level increased in MDS cells upon treatment with decitabine, which could be reversed by ferrostatin-1.

Study details: The data come from a review of cell viability assays, reactive oxygen species assays, gluthiathone assays, and

Disclosures: The study was supported in part by the National Natural Science Foundation of China, Key Technology Research and Development Program of Tianjin, Application Bases and Advanced Technology Research Program of Tianjin, and Key National Natural Science Foundation of Tianjin. The researchers had no financial conflicts to disclose.

Citation: Lv Q et al. Front. Oncol. 2020 Sept 2. doi: 10.3389/fonc.2020.01656.

Key clinical point: Ferroptosis, a distinct form of regulated cell death process involving iron-dependent lipid peroxidation, may impact the action of chemotherapy drug decitabine.

Major finding: The level of GSH and the activity of GPX4 decreased, whereas the ROS level increased in MDS cells upon treatment with decitabine, which could be reversed by ferrostatin-1.

Study details: The data come from a review of cell viability assays, reactive oxygen species assays, gluthiathone assays, and

Disclosures: The study was supported in part by the National Natural Science Foundation of China, Key Technology Research and Development Program of Tianjin, Application Bases and Advanced Technology Research Program of Tianjin, and Key National Natural Science Foundation of Tianjin. The researchers had no financial conflicts to disclose.

Citation: Lv Q et al. Front. Oncol. 2020 Sept 2. doi: 10.3389/fonc.2020.01656.

Key clinical point: In a population of MDS patients with COVID-19 symptoms who underwent laboratory testing, 20.6% had confirmed cases.

Major finding: At the time of this analysis, 33 of 63 COVID-19 positive MDS patients were alive, suggesting a higher lethality rate in this population compared to the population at large.

Study details: The data come from a review of 5,326 adults with myelodysplastic syndromes who were symptomatic for COVID-19 between February 24 and April 28, 2020; 305 MDS patients underwent laboratory testing to confirm the infection.

Disclosures: The study was received no outside funding. The researchers had no financial conflicts to disclose.

Citation: Mossuto S et al. HemaSphere. 2020 Oct. doi: 10.1097/HS9.0000000000000483.

Key clinical point: In a population of MDS patients with COVID-19 symptoms who underwent laboratory testing, 20.6% had confirmed cases.

Major finding: At the time of this analysis, 33 of 63 COVID-19 positive MDS patients were alive, suggesting a higher lethality rate in this population compared to the population at large.

Study details: The data come from a review of 5,326 adults with myelodysplastic syndromes who were symptomatic for COVID-19 between February 24 and April 28, 2020; 305 MDS patients underwent laboratory testing to confirm the infection.

Disclosures: The study was received no outside funding. The researchers had no financial conflicts to disclose.

Citation: Mossuto S et al. HemaSphere. 2020 Oct. doi: 10.1097/HS9.0000000000000483.

Key clinical point: In a population of MDS patients with COVID-19 symptoms who underwent laboratory testing, 20.6% had confirmed cases.

Major finding: At the time of this analysis, 33 of 63 COVID-19 positive MDS patients were alive, suggesting a higher lethality rate in this population compared to the population at large.

Study details: The data come from a review of 5,326 adults with myelodysplastic syndromes who were symptomatic for COVID-19 between February 24 and April 28, 2020; 305 MDS patients underwent laboratory testing to confirm the infection.

Disclosures: The study was received no outside funding. The researchers had no financial conflicts to disclose.

Citation: Mossuto S et al. HemaSphere. 2020 Oct. doi: 10.1097/HS9.0000000000000483.

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.

Key clinical point: Abaloparatide/alendronate treatment shows numerically lower risks for wrist fractures compared with placebo/alendronate, suggesting a potential correlation between ultradistal (UD) radius bone mineral density (BMD) and wrist fracture.

Major finding: BMD gains at the UD radius following treatment with abaloparatide in ACTIVE were maintained over the subsequent 24 months of treatment with alendronate in ACTIVExtend (cumulative month 43 treatment difference, 0.89%; P = .20). Conversely, UD radius BMD in the placebo group during ACTIVE decreased to below ACTIVE baseline.

Study details: The data come from a subanalysis of the phase 3 ACTIVExtend trial.

Disclosures: Funding for this study was provided by Radius Health, Inc. NB Watts, RK Dore, and MS LeBoff reported ties with various pharmaceutical companies. B Mitlak and Y Wang were employees of and own company stock in Radius Health, Inc. G Hattersley was a former employee of and a consultant to Radius Health, Inc. TD Rozental is the Editor in Chief of the Journal of Hand Surgery Global Online. S Baim reported no conflicts of interest.

Citation: Watts NB et al. Osteoporos Int. 2020 Sep 15. doi: 10.1007/s00198-020-05555-1.

Key clinical point: Abaloparatide/alendronate treatment shows numerically lower risks for wrist fractures compared with placebo/alendronate, suggesting a potential correlation between ultradistal (UD) radius bone mineral density (BMD) and wrist fracture.

Major finding: BMD gains at the UD radius following treatment with abaloparatide in ACTIVE were maintained over the subsequent 24 months of treatment with alendronate in ACTIVExtend (cumulative month 43 treatment difference, 0.89%; P = .20). Conversely, UD radius BMD in the placebo group during ACTIVE decreased to below ACTIVE baseline.

Study details: The data come from a subanalysis of the phase 3 ACTIVExtend trial.

Disclosures: Funding for this study was provided by Radius Health, Inc. NB Watts, RK Dore, and MS LeBoff reported ties with various pharmaceutical companies. B Mitlak and Y Wang were employees of and own company stock in Radius Health, Inc. G Hattersley was a former employee of and a consultant to Radius Health, Inc. TD Rozental is the Editor in Chief of the Journal of Hand Surgery Global Online. S Baim reported no conflicts of interest.

Citation: Watts NB et al. Osteoporos Int. 2020 Sep 15. doi: 10.1007/s00198-020-05555-1.

Key clinical point: Abaloparatide/alendronate treatment shows numerically lower risks for wrist fractures compared with placebo/alendronate, suggesting a potential correlation between ultradistal (UD) radius bone mineral density (BMD) and wrist fracture.

Major finding: BMD gains at the UD radius following treatment with abaloparatide in ACTIVE were maintained over the subsequent 24 months of treatment with alendronate in ACTIVExtend (cumulative month 43 treatment difference, 0.89%; P = .20). Conversely, UD radius BMD in the placebo group during ACTIVE decreased to below ACTIVE baseline.

Study details: The data come from a subanalysis of the phase 3 ACTIVExtend trial.

Disclosures: Funding for this study was provided by Radius Health, Inc. NB Watts, RK Dore, and MS LeBoff reported ties with various pharmaceutical companies. B Mitlak and Y Wang were employees of and own company stock in Radius Health, Inc. G Hattersley was a former employee of and a consultant to Radius Health, Inc. TD Rozental is the Editor in Chief of the Journal of Hand Surgery Global Online. S Baim reported no conflicts of interest.

Citation: Watts NB et al. Osteoporos Int. 2020 Sep 15. doi: 10.1007/s00198-020-05555-1.

Key clinical point: Use of high-dose inhaled corticosteroids (ICS) significantly increased the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD).

Major finding: Patients with COPD using ICS were at an increased risk for any osteoporosis-related event (high dose: risk ratio [RR], 1.52; 95% confidence interval [CI], 1.24-1.82] and low dose: RR, 1.27; 95% CI, 1.13-1.56) compared with those not using ICS.

Study details: The data come from ARCTIC study of 9,651 patients with COPD and 59,454 matched reference controls.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. C Janson, K Lisspers, B Ställberg, G Johansson, and K Larsson reported relationships with various pharmaceutical companies, including Novartis. FS Gutzwiller and K Mezzi are employees of Novartis. L Mindeholm is a consultant to Novartis Institutes for Biomedical Research and holds stocks in Novartis. BK Bjerregaard and L Jorgensen are employees of IQVIA and have received remuneration in relation to statistical analyses.

Citation: Janson C et al. Eur Respir J. 2020 Sep 24. doi: 10.1183/13993003.00515-2020.

Key clinical point: Use of high-dose inhaled corticosteroids (ICS) significantly increased the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD).

Major finding: Patients with COPD using ICS were at an increased risk for any osteoporosis-related event (high dose: risk ratio [RR], 1.52; 95% confidence interval [CI], 1.24-1.82] and low dose: RR, 1.27; 95% CI, 1.13-1.56) compared with those not using ICS.

Study details: The data come from ARCTIC study of 9,651 patients with COPD and 59,454 matched reference controls.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. C Janson, K Lisspers, B Ställberg, G Johansson, and K Larsson reported relationships with various pharmaceutical companies, including Novartis. FS Gutzwiller and K Mezzi are employees of Novartis. L Mindeholm is a consultant to Novartis Institutes for Biomedical Research and holds stocks in Novartis. BK Bjerregaard and L Jorgensen are employees of IQVIA and have received remuneration in relation to statistical analyses.

Citation: Janson C et al. Eur Respir J. 2020 Sep 24. doi: 10.1183/13993003.00515-2020.

Key clinical point: Use of high-dose inhaled corticosteroids (ICS) significantly increased the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD).

Major finding: Patients with COPD using ICS were at an increased risk for any osteoporosis-related event (high dose: risk ratio [RR], 1.52; 95% confidence interval [CI], 1.24-1.82] and low dose: RR, 1.27; 95% CI, 1.13-1.56) compared with those not using ICS.

Study details: The data come from ARCTIC study of 9,651 patients with COPD and 59,454 matched reference controls.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. C Janson, K Lisspers, B Ställberg, G Johansson, and K Larsson reported relationships with various pharmaceutical companies, including Novartis. FS Gutzwiller and K Mezzi are employees of Novartis. L Mindeholm is a consultant to Novartis Institutes for Biomedical Research and holds stocks in Novartis. BK Bjerregaard and L Jorgensen are employees of IQVIA and have received remuneration in relation to statistical analyses.

Citation: Janson C et al. Eur Respir J. 2020 Sep 24. doi: 10.1183/13993003.00515-2020.

Key clinical point: Minodronate demonstrated better efficacy than alendronate, risedronate, raloxifene, or eldecalcitol in patients with osteoporosis.

Major finding: Compared with other drugs, minodronate significantly decreased N-telopeptide of type I collagen/creatinine (weighted mean difference [WMD], −13.669; 95% confidence interval [CI], −23.108 to −4.229), bone alkaline phosphatase (WMD, −1.26; 95% CI: −2.04 to −0.47), and tartrate-resistant acid phosphatase 5b (WMD, −154.11; 95% CI, −277.85 to −30.37).

Study details: A meta-analysis of 13 randomized controlled trials including 3,740 patients with osteoporosis.

Disclosures: This study received no financial support. The authors declared no conflicts of interest.

Citation: Liu Q et al. 2020 Oct 2. doi: 10.1097/MD.0000000000022542.

Key clinical point: Minodronate demonstrated better efficacy than alendronate, risedronate, raloxifene, or eldecalcitol in patients with osteoporosis.

Major finding: Compared with other drugs, minodronate significantly decreased N-telopeptide of type I collagen/creatinine (weighted mean difference [WMD], −13.669; 95% confidence interval [CI], −23.108 to −4.229), bone alkaline phosphatase (WMD, −1.26; 95% CI: −2.04 to −0.47), and tartrate-resistant acid phosphatase 5b (WMD, −154.11; 95% CI, −277.85 to −30.37).

Study details: A meta-analysis of 13 randomized controlled trials including 3,740 patients with osteoporosis.

Disclosures: This study received no financial support. The authors declared no conflicts of interest.

Citation: Liu Q et al. 2020 Oct 2. doi: 10.1097/MD.0000000000022542.

Key clinical point: Minodronate demonstrated better efficacy than alendronate, risedronate, raloxifene, or eldecalcitol in patients with osteoporosis.

Major finding: Compared with other drugs, minodronate significantly decreased N-telopeptide of type I collagen/creatinine (weighted mean difference [WMD], −13.669; 95% confidence interval [CI], −23.108 to −4.229), bone alkaline phosphatase (WMD, −1.26; 95% CI: −2.04 to −0.47), and tartrate-resistant acid phosphatase 5b (WMD, −154.11; 95% CI, −277.85 to −30.37).

Study details: A meta-analysis of 13 randomized controlled trials including 3,740 patients with osteoporosis.

Disclosures: This study received no financial support. The authors declared no conflicts of interest.

Citation: Liu Q et al. 2020 Oct 2. doi: 10.1097/MD.0000000000022542.