Osteoporosis

Women treated with oral bisphosphonate drugs for osteoporosis for 5 years get no additional benefit – in terms of hip fracture risk – if the treatment is extended for another 5 years, new research shows.

Raycat/Getty Images

“We found that hip fracture risk in women did not differ if women stopped bisphosphonate use after 5 years or stayed on the medication for 10 years,” coauthor Joan C. Lo, MD, Kaiser Permanente Northern California, Oakland, said in an interview.

The new study, published Dec. 7 in JAMA Network Open, did show a small benefit in continuing the treatment through 7 years vs. 5 years, but it wasn’t clear if this was significant.

“Whether there is a benefit to staying on the drug for 7 years needs to be further studied in randomized trials,” Dr. Lo stressed.

It is well established that oral bisphosphonates are effective in reducing the risk for fracture within the first 3-5 years of treatment; however, evidence on the effects of treatment beyond 5 years is lacking.

The most recent guidance from the American Society of Bone and Mineral Research (ASBMR) on the issue, which were released in 2015, recommends continuation of bisphosphonates beyond 5 years for high-risk patients, but it recommends a “drug holiday” for low-risk patients.
 

Study adds important new evidence

However, that guidance acknowledges that data are limited regarding long-term use. This large new study adds important new evidence to the discussion, Robert A. Adler, MD, who was a member of the ASBMR Task Force for the recent guidance, said in an interview.

“[With the lack of recent research,] this new study from Kaiser Permanente is of great interest,” said Dr. Adler, chief of endocrinology and metabolism at Central Virginia Veterans Affairs Health Care System and professor of internal medicine and of epidemiology at Virginia Commonwealth University, Richmond.

“It is new data and suggests we might temper our enthusiasm for long-term treatment with bisphosphonates,” he said.

“Importantly, it is the first large observational trial and is closer to a real-world setting than a randomized controlled trial,” he said.

But, Dr. Adler emphasized: “The take-home message is that while this suggests that patients can probably be given a drug holiday for a couple of years ... they should be retested, and if they appear to be at an increased risk of fracture, they probably should restart again.

“Osteoporosis is a chronic disorder,” he emphasized. “It isn’t cured by any of our treatments, and as people get older, they are at a higher fracture risk.

“So we really need to follow our patients for a lifetime and reassess their fracture risk every couple of years – whether they are still on therapy or on a drug holiday.”
 

Possible that 7 years is better than 5 but remains to be proven

The new study involved data from Kaiser Permanente Northern and Southern California on 29,685 women who had completed 5 years of treatment with oral bisphosphonates, including alendronate, risedronate, or ibandronate, between 2002 and 2014.

Among the women, 11,105 (37%) continued taking the drugs beyond 5 years to 7 years, and 2,725 (9.2%) completed a total of 10 years of treatment.

Their median age was 71. Among those for whom bone mineral density data were available, 37% had osteoporosis after the first 5 years of treatment.

During these 5 years of treatment, 507 hip fractures occurred.

The cumulative incidence of hip fracture among for those who discontinued study therapy at entry, i.e., those who underwent treatment for 5 years, was 23.0 per 1,000 individuals.

After 7 years of treatment, the rate was 20.8 per 1000. For those who continued therapy for 10 years, the rate was 26.8 per 1000 individuals.

The rate in the 7-year treatment group was based on patients taking a 6-month drug holiday after the initial 5 years, but the results are hard to interpret, Dr. Lo said.

“It’s possible that 7 years is better than 5, but this is not a randomized trial, and some of the data analyses done in the study suggest more research should be done to look at a benefit after 7 years.

“At the end of the day, doctors and women need to decide at 5 years what an individual woman’s risk fracture risk is and determine if she should stay on the drug longer,” Dr. Lo emphasized.
 

Limitations: Subgroups not identified, adherence hard to assess

The uncertainty of any benefit of treatment with bisphosphonates beyond 5 years is further reflected in U.S. recommendations – the Food and Drug Administration has concluded on the basis of pooled data from the extension phase of major clinical trials that any advantages of treatment beyond 3-5 years are unclear.

Key limitations of the current study include the fact that the incidence of hip fracture was not evaluated in low-risk vs. high-risk subgroups; therefore, “these findings may not be applicable to older women at higher risk of osteoporotic fracture,” the authors wrote.

Furthermore, the study did not assess outcomes of fractures other than hip fractures, such as vertebral fractures, they noted.

Dr. Adler pointed out that another limitation is that adherence in the trial was defined as taking 60% of prescribed pills.

“I think this is the biggest weakness with the study,” he said. “Particularly with medications like oral bisphosphonates that don’t really make patients feel any different, it’s a real challenge to make sure patients continue to take these drugs properly.”

The findings should give some reassurance for patients who take a break from the drugs after 5 years. However, reassessment of their risk is critical, Dr. Adler reiterated.

The study was supported by a grant from the National Institute on Aging and the National Institute of Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health. The authors and Adler have disclosed no relevant financial relationships.

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

Women treated with oral bisphosphonate drugs for osteoporosis for 5 years get no additional benefit – in terms of hip fracture risk – if the treatment is extended for another 5 years, new research shows.

Raycat/Getty Images

“We found that hip fracture risk in women did not differ if women stopped bisphosphonate use after 5 years or stayed on the medication for 10 years,” coauthor Joan C. Lo, MD, Kaiser Permanente Northern California, Oakland, said in an interview.

The new study, published Dec. 7 in JAMA Network Open, did show a small benefit in continuing the treatment through 7 years vs. 5 years, but it wasn’t clear if this was significant.

“Whether there is a benefit to staying on the drug for 7 years needs to be further studied in randomized trials,” Dr. Lo stressed.

It is well established that oral bisphosphonates are effective in reducing the risk for fracture within the first 3-5 years of treatment; however, evidence on the effects of treatment beyond 5 years is lacking.

The most recent guidance from the American Society of Bone and Mineral Research (ASBMR) on the issue, which were released in 2015, recommends continuation of bisphosphonates beyond 5 years for high-risk patients, but it recommends a “drug holiday” for low-risk patients.
 

Study adds important new evidence

However, that guidance acknowledges that data are limited regarding long-term use. This large new study adds important new evidence to the discussion, Robert A. Adler, MD, who was a member of the ASBMR Task Force for the recent guidance, said in an interview.

“[With the lack of recent research,] this new study from Kaiser Permanente is of great interest,” said Dr. Adler, chief of endocrinology and metabolism at Central Virginia Veterans Affairs Health Care System and professor of internal medicine and of epidemiology at Virginia Commonwealth University, Richmond.

“It is new data and suggests we might temper our enthusiasm for long-term treatment with bisphosphonates,” he said.

“Importantly, it is the first large observational trial and is closer to a real-world setting than a randomized controlled trial,” he said.

But, Dr. Adler emphasized: “The take-home message is that while this suggests that patients can probably be given a drug holiday for a couple of years ... they should be retested, and if they appear to be at an increased risk of fracture, they probably should restart again.

“Osteoporosis is a chronic disorder,” he emphasized. “It isn’t cured by any of our treatments, and as people get older, they are at a higher fracture risk.

“So we really need to follow our patients for a lifetime and reassess their fracture risk every couple of years – whether they are still on therapy or on a drug holiday.”
 

Possible that 7 years is better than 5 but remains to be proven

The new study involved data from Kaiser Permanente Northern and Southern California on 29,685 women who had completed 5 years of treatment with oral bisphosphonates, including alendronate, risedronate, or ibandronate, between 2002 and 2014.

Among the women, 11,105 (37%) continued taking the drugs beyond 5 years to 7 years, and 2,725 (9.2%) completed a total of 10 years of treatment.

Their median age was 71. Among those for whom bone mineral density data were available, 37% had osteoporosis after the first 5 years of treatment.

During these 5 years of treatment, 507 hip fractures occurred.

The cumulative incidence of hip fracture among for those who discontinued study therapy at entry, i.e., those who underwent treatment for 5 years, was 23.0 per 1,000 individuals.

After 7 years of treatment, the rate was 20.8 per 1000. For those who continued therapy for 10 years, the rate was 26.8 per 1000 individuals.

The rate in the 7-year treatment group was based on patients taking a 6-month drug holiday after the initial 5 years, but the results are hard to interpret, Dr. Lo said.

“It’s possible that 7 years is better than 5, but this is not a randomized trial, and some of the data analyses done in the study suggest more research should be done to look at a benefit after 7 years.

“At the end of the day, doctors and women need to decide at 5 years what an individual woman’s risk fracture risk is and determine if she should stay on the drug longer,” Dr. Lo emphasized.
 

Limitations: Subgroups not identified, adherence hard to assess

The uncertainty of any benefit of treatment with bisphosphonates beyond 5 years is further reflected in U.S. recommendations – the Food and Drug Administration has concluded on the basis of pooled data from the extension phase of major clinical trials that any advantages of treatment beyond 3-5 years are unclear.

Key limitations of the current study include the fact that the incidence of hip fracture was not evaluated in low-risk vs. high-risk subgroups; therefore, “these findings may not be applicable to older women at higher risk of osteoporotic fracture,” the authors wrote.

Furthermore, the study did not assess outcomes of fractures other than hip fractures, such as vertebral fractures, they noted.

Dr. Adler pointed out that another limitation is that adherence in the trial was defined as taking 60% of prescribed pills.

“I think this is the biggest weakness with the study,” he said. “Particularly with medications like oral bisphosphonates that don’t really make patients feel any different, it’s a real challenge to make sure patients continue to take these drugs properly.”

The findings should give some reassurance for patients who take a break from the drugs after 5 years. However, reassessment of their risk is critical, Dr. Adler reiterated.

The study was supported by a grant from the National Institute on Aging and the National Institute of Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health. The authors and Adler have disclosed no relevant financial relationships.

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

Women treated with oral bisphosphonate drugs for osteoporosis for 5 years get no additional benefit – in terms of hip fracture risk – if the treatment is extended for another 5 years, new research shows.

Raycat/Getty Images

“We found that hip fracture risk in women did not differ if women stopped bisphosphonate use after 5 years or stayed on the medication for 10 years,” coauthor Joan C. Lo, MD, Kaiser Permanente Northern California, Oakland, said in an interview.

The new study, published Dec. 7 in JAMA Network Open, did show a small benefit in continuing the treatment through 7 years vs. 5 years, but it wasn’t clear if this was significant.

“Whether there is a benefit to staying on the drug for 7 years needs to be further studied in randomized trials,” Dr. Lo stressed.

It is well established that oral bisphosphonates are effective in reducing the risk for fracture within the first 3-5 years of treatment; however, evidence on the effects of treatment beyond 5 years is lacking.

The most recent guidance from the American Society of Bone and Mineral Research (ASBMR) on the issue, which were released in 2015, recommends continuation of bisphosphonates beyond 5 years for high-risk patients, but it recommends a “drug holiday” for low-risk patients.
 

Study adds important new evidence

However, that guidance acknowledges that data are limited regarding long-term use. This large new study adds important new evidence to the discussion, Robert A. Adler, MD, who was a member of the ASBMR Task Force for the recent guidance, said in an interview.

“[With the lack of recent research,] this new study from Kaiser Permanente is of great interest,” said Dr. Adler, chief of endocrinology and metabolism at Central Virginia Veterans Affairs Health Care System and professor of internal medicine and of epidemiology at Virginia Commonwealth University, Richmond.

“It is new data and suggests we might temper our enthusiasm for long-term treatment with bisphosphonates,” he said.

“Importantly, it is the first large observational trial and is closer to a real-world setting than a randomized controlled trial,” he said.

But, Dr. Adler emphasized: “The take-home message is that while this suggests that patients can probably be given a drug holiday for a couple of years ... they should be retested, and if they appear to be at an increased risk of fracture, they probably should restart again.

“Osteoporosis is a chronic disorder,” he emphasized. “It isn’t cured by any of our treatments, and as people get older, they are at a higher fracture risk.

“So we really need to follow our patients for a lifetime and reassess their fracture risk every couple of years – whether they are still on therapy or on a drug holiday.”
 

Possible that 7 years is better than 5 but remains to be proven

The new study involved data from Kaiser Permanente Northern and Southern California on 29,685 women who had completed 5 years of treatment with oral bisphosphonates, including alendronate, risedronate, or ibandronate, between 2002 and 2014.

Among the women, 11,105 (37%) continued taking the drugs beyond 5 years to 7 years, and 2,725 (9.2%) completed a total of 10 years of treatment.

Their median age was 71. Among those for whom bone mineral density data were available, 37% had osteoporosis after the first 5 years of treatment.

During these 5 years of treatment, 507 hip fractures occurred.

The cumulative incidence of hip fracture among for those who discontinued study therapy at entry, i.e., those who underwent treatment for 5 years, was 23.0 per 1,000 individuals.

After 7 years of treatment, the rate was 20.8 per 1000. For those who continued therapy for 10 years, the rate was 26.8 per 1000 individuals.

The rate in the 7-year treatment group was based on patients taking a 6-month drug holiday after the initial 5 years, but the results are hard to interpret, Dr. Lo said.

“It’s possible that 7 years is better than 5, but this is not a randomized trial, and some of the data analyses done in the study suggest more research should be done to look at a benefit after 7 years.

“At the end of the day, doctors and women need to decide at 5 years what an individual woman’s risk fracture risk is and determine if she should stay on the drug longer,” Dr. Lo emphasized.
 

Limitations: Subgroups not identified, adherence hard to assess

The uncertainty of any benefit of treatment with bisphosphonates beyond 5 years is further reflected in U.S. recommendations – the Food and Drug Administration has concluded on the basis of pooled data from the extension phase of major clinical trials that any advantages of treatment beyond 3-5 years are unclear.

Key limitations of the current study include the fact that the incidence of hip fracture was not evaluated in low-risk vs. high-risk subgroups; therefore, “these findings may not be applicable to older women at higher risk of osteoporotic fracture,” the authors wrote.

Furthermore, the study did not assess outcomes of fractures other than hip fractures, such as vertebral fractures, they noted.

Dr. Adler pointed out that another limitation is that adherence in the trial was defined as taking 60% of prescribed pills.

“I think this is the biggest weakness with the study,” he said. “Particularly with medications like oral bisphosphonates that don’t really make patients feel any different, it’s a real challenge to make sure patients continue to take these drugs properly.”

The findings should give some reassurance for patients who take a break from the drugs after 5 years. However, reassessment of their risk is critical, Dr. Adler reiterated.

The study was supported by a grant from the National Institute on Aging and the National Institute of Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health. The authors and Adler have disclosed no relevant financial relationships.

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

Bariatric surgery rates continue to climb in the setting of increasing obesity throughout the world. While effective at promoting weight loss, a growing body of literature has clearly demonstrated that bone loss and increased fracture risk occurs following bariatric surgery. However, major important questions remain regarding the impact of specific types of bariatric surgery on bone metabolism. Notably, most previous studies were not performed in a randomized manner with respect to the type of weight loss surgery. As such, indication bias exists with respect to current knowledge regarding how specific weight loss surgeries impact bone. Here, a randomized, triple-blind single center study in Norway assessed skeletal endpoints in patients with severe obesity and type 2 diabetes who were randomized to receive either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy weight loss surgery. The primary focus of this study, reported elsewhere, was to assess rates of diabetes remission. Areal bone mineral density in the hip and spine decreased significantly more one year after RYGB than after sleeve gastrectomy. The authors investigated serum bone turnover markers over time in these subjects. Both forms of bariatric surgery led to increases in bone formation and resorption markers, with higher levels of both markers seen after RYGB than sleeve gastrectomy. Importantly, these effects were independently associated with surgical procedure and not resultant weight change. Findings here strongly support the emerging notion that RYGB in particular is linked to high bone turnover and bone loss. While many hypotheses exist as to the underlying mechanism linking RYBG and bone loss, this remains an active and open area of investigation.

Denosumab, a neutralizing antibody against RANKL, is a potent antiresorptive agent that increases bone density and reduces fracture risk. In addition to its major role in osteoclast development, the paracrine-acting cytokine RANKL plays an important role in development and maintenance of the adaptive immune system. As such, a concern has been raised that denosumab treatment may increase risk of malignancies kept at bay by lymphoid surveillance. In this systematic review and meta-analysis of randomized controlled trials, the authors assessed risk of malignancy of denosumab versus comparator in 25 prospective randomized controlled trials. In these trials, >21,000 patients were analyzed who were treated for osteoporosis with either denosumab or control. The risk of malignancy was similar between osteoporosis denosumab dosing (60 mg every 6 months) and control. Drug exposure in these studies was up to 48 months. As such, additional post-marketing surveillance safety data are needed to address longer-term risks of malignancy. Nonetheless, these data are largely reassuring and provide additional evidence of the safety of denosumab therapy for osteoporosis.

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

Bariatric surgery rates continue to climb in the setting of increasing obesity throughout the world. While effective at promoting weight loss, a growing body of literature has clearly demonstrated that bone loss and increased fracture risk occurs following bariatric surgery. However, major important questions remain regarding the impact of specific types of bariatric surgery on bone metabolism. Notably, most previous studies were not performed in a randomized manner with respect to the type of weight loss surgery. As such, indication bias exists with respect to current knowledge regarding how specific weight loss surgeries impact bone. Here, a randomized, triple-blind single center study in Norway assessed skeletal endpoints in patients with severe obesity and type 2 diabetes who were randomized to receive either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy weight loss surgery. The primary focus of this study, reported elsewhere, was to assess rates of diabetes remission. Areal bone mineral density in the hip and spine decreased significantly more one year after RYGB than after sleeve gastrectomy. The authors investigated serum bone turnover markers over time in these subjects. Both forms of bariatric surgery led to increases in bone formation and resorption markers, with higher levels of both markers seen after RYGB than sleeve gastrectomy. Importantly, these effects were independently associated with surgical procedure and not resultant weight change. Findings here strongly support the emerging notion that RYGB in particular is linked to high bone turnover and bone loss. While many hypotheses exist as to the underlying mechanism linking RYBG and bone loss, this remains an active and open area of investigation.

Denosumab, a neutralizing antibody against RANKL, is a potent antiresorptive agent that increases bone density and reduces fracture risk. In addition to its major role in osteoclast development, the paracrine-acting cytokine RANKL plays an important role in development and maintenance of the adaptive immune system. As such, a concern has been raised that denosumab treatment may increase risk of malignancies kept at bay by lymphoid surveillance. In this systematic review and meta-analysis of randomized controlled trials, the authors assessed risk of malignancy of denosumab versus comparator in 25 prospective randomized controlled trials. In these trials, >21,000 patients were analyzed who were treated for osteoporosis with either denosumab or control. The risk of malignancy was similar between osteoporosis denosumab dosing (60 mg every 6 months) and control. Drug exposure in these studies was up to 48 months. As such, additional post-marketing surveillance safety data are needed to address longer-term risks of malignancy. Nonetheless, these data are largely reassuring and provide additional evidence of the safety of denosumab therapy for osteoporosis.

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

Bariatric surgery rates continue to climb in the setting of increasing obesity throughout the world. While effective at promoting weight loss, a growing body of literature has clearly demonstrated that bone loss and increased fracture risk occurs following bariatric surgery. However, major important questions remain regarding the impact of specific types of bariatric surgery on bone metabolism. Notably, most previous studies were not performed in a randomized manner with respect to the type of weight loss surgery. As such, indication bias exists with respect to current knowledge regarding how specific weight loss surgeries impact bone. Here, a randomized, triple-blind single center study in Norway assessed skeletal endpoints in patients with severe obesity and type 2 diabetes who were randomized to receive either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy weight loss surgery. The primary focus of this study, reported elsewhere, was to assess rates of diabetes remission. Areal bone mineral density in the hip and spine decreased significantly more one year after RYGB than after sleeve gastrectomy. The authors investigated serum bone turnover markers over time in these subjects. Both forms of bariatric surgery led to increases in bone formation and resorption markers, with higher levels of both markers seen after RYGB than sleeve gastrectomy. Importantly, these effects were independently associated with surgical procedure and not resultant weight change. Findings here strongly support the emerging notion that RYGB in particular is linked to high bone turnover and bone loss. While many hypotheses exist as to the underlying mechanism linking RYBG and bone loss, this remains an active and open area of investigation.

Denosumab, a neutralizing antibody against RANKL, is a potent antiresorptive agent that increases bone density and reduces fracture risk. In addition to its major role in osteoclast development, the paracrine-acting cytokine RANKL plays an important role in development and maintenance of the adaptive immune system. As such, a concern has been raised that denosumab treatment may increase risk of malignancies kept at bay by lymphoid surveillance. In this systematic review and meta-analysis of randomized controlled trials, the authors assessed risk of malignancy of denosumab versus comparator in 25 prospective randomized controlled trials. In these trials, >21,000 patients were analyzed who were treated for osteoporosis with either denosumab or control. The risk of malignancy was similar between osteoporosis denosumab dosing (60 mg every 6 months) and control. Drug exposure in these studies was up to 48 months. As such, additional post-marketing surveillance safety data are needed to address longer-term risks of malignancy. Nonetheless, these data are largely reassuring and provide additional evidence of the safety of denosumab therapy for osteoporosis.

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

Key clinical point: Use of loop diuretics and nonuse of direct oral anticoagulants (DOACs) were independently associated with an increased risk of osteoporosis in patients with chronic heart failure (CHF).

Major finding: Use of loop diuretics (odds ratio [OR], 2.70; P less than .01) and nonuse of DOACs (OR for DOAC use, 0.36; P = .01) were associated with an increased risk for osteoporosis. Patients with osteoporotic BMD at 2 or 3 sites had a significantly higher rate of a composite of death and heart failure hospitalization than patients without osteoporosis (hazard ratio, 3.45; P less than .01).

Study details: The data come from a single-center, retrospective study of 303 (osteoporosis: n = 122; nonosteoporosis: n = 181) patients diagnosed with CHF.

Disclosures: The study was supported by a Grant-in-Aid for Young Scientists (S Katano) from the Japan Society for the Promotion of Science, KAKENHI, Tokyo, Japan. The authors reported no conflicts of interest. Dr. T Miura is a member of the Circulation Journal’s editorial team.

Source: Katano S et al. Circ J. 2020 Oct 28. doi: 10.1253/circj.CJ-20-0593.

Key clinical point: Use of loop diuretics and nonuse of direct oral anticoagulants (DOACs) were independently associated with an increased risk of osteoporosis in patients with chronic heart failure (CHF).

Major finding: Use of loop diuretics (odds ratio [OR], 2.70; P less than .01) and nonuse of DOACs (OR for DOAC use, 0.36; P = .01) were associated with an increased risk for osteoporosis. Patients with osteoporotic BMD at 2 or 3 sites had a significantly higher rate of a composite of death and heart failure hospitalization than patients without osteoporosis (hazard ratio, 3.45; P less than .01).

Study details: The data come from a single-center, retrospective study of 303 (osteoporosis: n = 122; nonosteoporosis: n = 181) patients diagnosed with CHF.

Disclosures: The study was supported by a Grant-in-Aid for Young Scientists (S Katano) from the Japan Society for the Promotion of Science, KAKENHI, Tokyo, Japan. The authors reported no conflicts of interest. Dr. T Miura is a member of the Circulation Journal’s editorial team.

Source: Katano S et al. Circ J. 2020 Oct 28. doi: 10.1253/circj.CJ-20-0593.

Key clinical point: Use of loop diuretics and nonuse of direct oral anticoagulants (DOACs) were independently associated with an increased risk of osteoporosis in patients with chronic heart failure (CHF).

Major finding: Use of loop diuretics (odds ratio [OR], 2.70; P less than .01) and nonuse of DOACs (OR for DOAC use, 0.36; P = .01) were associated with an increased risk for osteoporosis. Patients with osteoporotic BMD at 2 or 3 sites had a significantly higher rate of a composite of death and heart failure hospitalization than patients without osteoporosis (hazard ratio, 3.45; P less than .01).

Study details: The data come from a single-center, retrospective study of 303 (osteoporosis: n = 122; nonosteoporosis: n = 181) patients diagnosed with CHF.

Disclosures: The study was supported by a Grant-in-Aid for Young Scientists (S Katano) from the Japan Society for the Promotion of Science, KAKENHI, Tokyo, Japan. The authors reported no conflicts of interest. Dr. T Miura is a member of the Circulation Journal’s editorial team.

Source: Katano S et al. Circ J. 2020 Oct 28. doi: 10.1253/circj.CJ-20-0593.

Key clinical point: Switching to denosumab (Dmab) from bisphosphonates (BP) or selective estrogen receptor modulator (SERM) significantly suppressed osteoporosis progression in postmenopausal women with type 2 diabetes (T2D).

Major finding: SERM-Dmab vs. SERM-SERM group showed significantly higher percentage change (P less than .04) in lumbar spine bone mineral density. BP-Dmab and SERM-Dmab groups showed a significantly lower percentage change in serum bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b compared with the BP-BP and SERM-SERM groups, respectively (P less than .05 for all).

Study details: The data come from a 24-week, prospective, parallel-group, observational study of 48 T2D postmenopausal patients with osteoporosis who were either switched from BP or SERM to Dmab (BP-Dmab group/SERM-Dmab group, respectively) or continued BP or SERM therapy (BP-BP group/SERM-SERM group, respectively).

Disclosures: The study received no financial support. A Nakamura, T Astumi, and H Miyoshi received honoraria for lectures and research funding from various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Miyoshi A et al. J Diabetes Investig. 2020 Nov 3. doi: 10.1111/jdi.13458.

Key clinical point: Switching to denosumab (Dmab) from bisphosphonates (BP) or selective estrogen receptor modulator (SERM) significantly suppressed osteoporosis progression in postmenopausal women with type 2 diabetes (T2D).

Major finding: SERM-Dmab vs. SERM-SERM group showed significantly higher percentage change (P less than .04) in lumbar spine bone mineral density. BP-Dmab and SERM-Dmab groups showed a significantly lower percentage change in serum bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b compared with the BP-BP and SERM-SERM groups, respectively (P less than .05 for all).

Study details: The data come from a 24-week, prospective, parallel-group, observational study of 48 T2D postmenopausal patients with osteoporosis who were either switched from BP or SERM to Dmab (BP-Dmab group/SERM-Dmab group, respectively) or continued BP or SERM therapy (BP-BP group/SERM-SERM group, respectively).

Disclosures: The study received no financial support. A Nakamura, T Astumi, and H Miyoshi received honoraria for lectures and research funding from various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Miyoshi A et al. J Diabetes Investig. 2020 Nov 3. doi: 10.1111/jdi.13458.

Key clinical point: Switching to denosumab (Dmab) from bisphosphonates (BP) or selective estrogen receptor modulator (SERM) significantly suppressed osteoporosis progression in postmenopausal women with type 2 diabetes (T2D).

Major finding: SERM-Dmab vs. SERM-SERM group showed significantly higher percentage change (P less than .04) in lumbar spine bone mineral density. BP-Dmab and SERM-Dmab groups showed a significantly lower percentage change in serum bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b compared with the BP-BP and SERM-SERM groups, respectively (P less than .05 for all).

Study details: The data come from a 24-week, prospective, parallel-group, observational study of 48 T2D postmenopausal patients with osteoporosis who were either switched from BP or SERM to Dmab (BP-Dmab group/SERM-Dmab group, respectively) or continued BP or SERM therapy (BP-BP group/SERM-SERM group, respectively).

Disclosures: The study received no financial support. A Nakamura, T Astumi, and H Miyoshi received honoraria for lectures and research funding from various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Miyoshi A et al. J Diabetes Investig. 2020 Nov 3. doi: 10.1111/jdi.13458.

Key clinical point: The prevalence of periapical lesions is significantly higher in patients with vs. without osteoporosis. Patients treated with bisphosphonates (BPs) have a lower prevalence of periapical lesions.

Major finding: The prevalence of periapical lesions in patients with osteoporosis was significantly higher compared with the general patient population in the hospital (odds ratio, 3.36; P less than .0001). Treatment with BPs was associated with a lower prevalence of periapical lesions than no treatment with BPs (P less than.0001).

Study details: Analysis of data from 1,644,953 individuals, including admitted patients as well as outpatients.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Katz J et al. J Endod. 2020 Oct 28. doi: 10.1016/j.joen.2020.10.019.

Key clinical point: The prevalence of periapical lesions is significantly higher in patients with vs. without osteoporosis. Patients treated with bisphosphonates (BPs) have a lower prevalence of periapical lesions.

Major finding: The prevalence of periapical lesions in patients with osteoporosis was significantly higher compared with the general patient population in the hospital (odds ratio, 3.36; P less than .0001). Treatment with BPs was associated with a lower prevalence of periapical lesions than no treatment with BPs (P less than.0001).

Study details: Analysis of data from 1,644,953 individuals, including admitted patients as well as outpatients.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Katz J et al. J Endod. 2020 Oct 28. doi: 10.1016/j.joen.2020.10.019.

Key clinical point: The prevalence of periapical lesions is significantly higher in patients with vs. without osteoporosis. Patients treated with bisphosphonates (BPs) have a lower prevalence of periapical lesions.

Major finding: The prevalence of periapical lesions in patients with osteoporosis was significantly higher compared with the general patient population in the hospital (odds ratio, 3.36; P less than .0001). Treatment with BPs was associated with a lower prevalence of periapical lesions than no treatment with BPs (P less than.0001).

Study details: Analysis of data from 1,644,953 individuals, including admitted patients as well as outpatients.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Katz J et al. J Endod. 2020 Oct 28. doi: 10.1016/j.joen.2020.10.019.

Key clinical point: Patients with impaired fasting glucose (IFG) and diabetes mellitus (DM) have a lower risk for incident osteoporosis.

Major finding: The risk of osteoporosis significantly decreased (P less than .001 for all) above the fourth quartile of fasting glucose levels in men and above the third quartile in women compared with the first quartile. The risk of osteoporosis was significantly lower (P less than .001 for all) with IFG (men: hazard ratio [HR], 0.84; women: HR, 0.93) and DM (men: HR, 0.77; women: HR, 0.75) compared with the normal glucose group.

Study details: The data come from a retrospective study of 96,626 patients.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Park SK et al. Bone. 2020 Oct 21. doi: 10.1016/j.bone.2020.115690.

Key clinical point: Patients with impaired fasting glucose (IFG) and diabetes mellitus (DM) have a lower risk for incident osteoporosis.

Major finding: The risk of osteoporosis significantly decreased (P less than .001 for all) above the fourth quartile of fasting glucose levels in men and above the third quartile in women compared with the first quartile. The risk of osteoporosis was significantly lower (P less than .001 for all) with IFG (men: hazard ratio [HR], 0.84; women: HR, 0.93) and DM (men: HR, 0.77; women: HR, 0.75) compared with the normal glucose group.

Study details: The data come from a retrospective study of 96,626 patients.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Park SK et al. Bone. 2020 Oct 21. doi: 10.1016/j.bone.2020.115690.

Key clinical point: Patients with impaired fasting glucose (IFG) and diabetes mellitus (DM) have a lower risk for incident osteoporosis.

Major finding: The risk of osteoporosis significantly decreased (P less than .001 for all) above the fourth quartile of fasting glucose levels in men and above the third quartile in women compared with the first quartile. The risk of osteoporosis was significantly lower (P less than .001 for all) with IFG (men: hazard ratio [HR], 0.84; women: HR, 0.93) and DM (men: HR, 0.77; women: HR, 0.75) compared with the normal glucose group.

Study details: The data come from a retrospective study of 96,626 patients.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Park SK et al. Bone. 2020 Oct 21. doi: 10.1016/j.bone.2020.115690.

Key clinical point: Psoriasis was associated with an elevated risk of osteoporosis in individuals aged 40 years or older.

Major finding: In study 1 (a follow-up study), the psoriasis group had a significantly higher risk of osteoporosis than the control group (adjusted hazard ratio, 1.09; P less than .001). In study 2 (a nested case-control study), the osteoporosis group had a significantly higher prevalence of psoriasis than the control group (adjusted odds ratio, 1.21; P less than .001).

Study details: A total of 25,306 patients with psoriasis were matched (1:4) to 101,224 controls (study 1) and 79,212 patients with osteoporosis were matched (1:1) to 79,212 controls (study 2).

Disclosures: The work was supported in part by a research grant from the National Research Foundation of Korea. The authors reported no conflicts of interest.

Source: Lee JW et al. Osteoporos Int. 2020 Nov 5. doi: 10.1007/s00198-020-05724-2.

Key clinical point: Psoriasis was associated with an elevated risk of osteoporosis in individuals aged 40 years or older.

Major finding: In study 1 (a follow-up study), the psoriasis group had a significantly higher risk of osteoporosis than the control group (adjusted hazard ratio, 1.09; P less than .001). In study 2 (a nested case-control study), the osteoporosis group had a significantly higher prevalence of psoriasis than the control group (adjusted odds ratio, 1.21; P less than .001).

Study details: A total of 25,306 patients with psoriasis were matched (1:4) to 101,224 controls (study 1) and 79,212 patients with osteoporosis were matched (1:1) to 79,212 controls (study 2).

Disclosures: The work was supported in part by a research grant from the National Research Foundation of Korea. The authors reported no conflicts of interest.

Source: Lee JW et al. Osteoporos Int. 2020 Nov 5. doi: 10.1007/s00198-020-05724-2.

Key clinical point: Psoriasis was associated with an elevated risk of osteoporosis in individuals aged 40 years or older.

Major finding: In study 1 (a follow-up study), the psoriasis group had a significantly higher risk of osteoporosis than the control group (adjusted hazard ratio, 1.09; P less than .001). In study 2 (a nested case-control study), the osteoporosis group had a significantly higher prevalence of psoriasis than the control group (adjusted odds ratio, 1.21; P less than .001).

Study details: A total of 25,306 patients with psoriasis were matched (1:4) to 101,224 controls (study 1) and 79,212 patients with osteoporosis were matched (1:1) to 79,212 controls (study 2).

Disclosures: The work was supported in part by a research grant from the National Research Foundation of Korea. The authors reported no conflicts of interest.

Source: Lee JW et al. Osteoporos Int. 2020 Nov 5. doi: 10.1007/s00198-020-05724-2.

Key clinical point: Romosozumab followed by denosumab results in significant bone mineral density (BMD) gains and numerically lower vertebral fractures in postmenopausal Japanese women with osteoporosis at high risk of fracture vs. placebo followed by denosumab through 36 months of follow-up.

Major finding: At 12, 24, and 36 months, the incidence of new vertebral fractures was lower with romosozumab/denosumab vs. placebo/denosumab (relative risk reduction at all timepoints: 84%; P = .056). BMD increase at 12, 24, and 36 months were greater with romosozumab/denosumab vs. placebo/denosumab (lumbar spine: 16.3%, 21.5%, and 23.2% vs. 0.4%, 8.1%, and 10.4%; total hip: 4.9%, 7.9%, and 8.9% vs. 0.4%, 2.8%, and 4.1%; femoral neck: 4.8%, 7.6%, and 8.1% vs. 0.3%, 3.3%, and 3.7%, respectively; all P less than .001).

Study details: This post hoc analysis of phase 3 FRAME study included 187 postmenopausal Japanese women with osteoporosis at high risk of fracture (romosozumab/denosumab group, n = 91; placebo/denosumab group, n = 96).

Disclosures: This study was funded by Amgen Inc., Astellas, and UCB Pharma. A Miyauchi received consulting fees from Amgen, Astellas BioPharma K.K., and Teijin Pharma. E Hamaya, K Nishi, and J Shimauchi are employees of Amgen K.K., Japan, and E Hamaya holds stock in Amgen Inc. W Yang is an employee of Amgen Inc., USA. C Libanati is an employee of UCB Pharma, Belgium, and holds stock in UCB Pharma. C Tolman is an employee of Amgen and holds stock in Amgen.

Source: Miyauchi A et al. J Bone Miner Metab. 2020 Oct 15. doi: 10.1007/s00774-020-01147-5.

Key clinical point: Romosozumab followed by denosumab results in significant bone mineral density (BMD) gains and numerically lower vertebral fractures in postmenopausal Japanese women with osteoporosis at high risk of fracture vs. placebo followed by denosumab through 36 months of follow-up.

Major finding: At 12, 24, and 36 months, the incidence of new vertebral fractures was lower with romosozumab/denosumab vs. placebo/denosumab (relative risk reduction at all timepoints: 84%; P = .056). BMD increase at 12, 24, and 36 months were greater with romosozumab/denosumab vs. placebo/denosumab (lumbar spine: 16.3%, 21.5%, and 23.2% vs. 0.4%, 8.1%, and 10.4%; total hip: 4.9%, 7.9%, and 8.9% vs. 0.4%, 2.8%, and 4.1%; femoral neck: 4.8%, 7.6%, and 8.1% vs. 0.3%, 3.3%, and 3.7%, respectively; all P less than .001).

Study details: This post hoc analysis of phase 3 FRAME study included 187 postmenopausal Japanese women with osteoporosis at high risk of fracture (romosozumab/denosumab group, n = 91; placebo/denosumab group, n = 96).

Disclosures: This study was funded by Amgen Inc., Astellas, and UCB Pharma. A Miyauchi received consulting fees from Amgen, Astellas BioPharma K.K., and Teijin Pharma. E Hamaya, K Nishi, and J Shimauchi are employees of Amgen K.K., Japan, and E Hamaya holds stock in Amgen Inc. W Yang is an employee of Amgen Inc., USA. C Libanati is an employee of UCB Pharma, Belgium, and holds stock in UCB Pharma. C Tolman is an employee of Amgen and holds stock in Amgen.

Source: Miyauchi A et al. J Bone Miner Metab. 2020 Oct 15. doi: 10.1007/s00774-020-01147-5.

Key clinical point: Romosozumab followed by denosumab results in significant bone mineral density (BMD) gains and numerically lower vertebral fractures in postmenopausal Japanese women with osteoporosis at high risk of fracture vs. placebo followed by denosumab through 36 months of follow-up.

Major finding: At 12, 24, and 36 months, the incidence of new vertebral fractures was lower with romosozumab/denosumab vs. placebo/denosumab (relative risk reduction at all timepoints: 84%; P = .056). BMD increase at 12, 24, and 36 months were greater with romosozumab/denosumab vs. placebo/denosumab (lumbar spine: 16.3%, 21.5%, and 23.2% vs. 0.4%, 8.1%, and 10.4%; total hip: 4.9%, 7.9%, and 8.9% vs. 0.4%, 2.8%, and 4.1%; femoral neck: 4.8%, 7.6%, and 8.1% vs. 0.3%, 3.3%, and 3.7%, respectively; all P less than .001).

Study details: This post hoc analysis of phase 3 FRAME study included 187 postmenopausal Japanese women with osteoporosis at high risk of fracture (romosozumab/denosumab group, n = 91; placebo/denosumab group, n = 96).

Disclosures: This study was funded by Amgen Inc., Astellas, and UCB Pharma. A Miyauchi received consulting fees from Amgen, Astellas BioPharma K.K., and Teijin Pharma. E Hamaya, K Nishi, and J Shimauchi are employees of Amgen K.K., Japan, and E Hamaya holds stock in Amgen Inc. W Yang is an employee of Amgen Inc., USA. C Libanati is an employee of UCB Pharma, Belgium, and holds stock in UCB Pharma. C Tolman is an employee of Amgen and holds stock in Amgen.

Source: Miyauchi A et al. J Bone Miner Metab. 2020 Oct 15. doi: 10.1007/s00774-020-01147-5.

Key clinical point: Treatment with denosumab in an osteoporosis dosage is not associated with an increased risk of malignancy with drug exposure of up to 48 months.

Major finding: The risk of malignancy was similar between denosumab (60 mg every 6 months, up to 48 months) and other comparators (absolute risk difference, 0%; risk ratio, 1.08; 95% confidence interval, 0.94-1.24).

Study details: Meta-analysis of 25 randomized controlled trials including 21,523 patients with osteoporosis (10,721 treated with denosumab and 10,802 treated with a comparator).

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Rosenberg D et al. Osteoporos Int. 2020 Nov 3. doi: 10.1007/s00198-020-05704-6.

Key clinical point: Treatment with denosumab in an osteoporosis dosage is not associated with an increased risk of malignancy with drug exposure of up to 48 months.

Major finding: The risk of malignancy was similar between denosumab (60 mg every 6 months, up to 48 months) and other comparators (absolute risk difference, 0%; risk ratio, 1.08; 95% confidence interval, 0.94-1.24).

Study details: Meta-analysis of 25 randomized controlled trials including 21,523 patients with osteoporosis (10,721 treated with denosumab and 10,802 treated with a comparator).

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Rosenberg D et al. Osteoporos Int. 2020 Nov 3. doi: 10.1007/s00198-020-05704-6.

Key clinical point: Treatment with denosumab in an osteoporosis dosage is not associated with an increased risk of malignancy with drug exposure of up to 48 months.

Major finding: The risk of malignancy was similar between denosumab (60 mg every 6 months, up to 48 months) and other comparators (absolute risk difference, 0%; risk ratio, 1.08; 95% confidence interval, 0.94-1.24).

Study details: Meta-analysis of 25 randomized controlled trials including 21,523 patients with osteoporosis (10,721 treated with denosumab and 10,802 treated with a comparator).

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Rosenberg D et al. Osteoporos Int. 2020 Nov 3. doi: 10.1007/s00198-020-05704-6.

Key clinical point: Exposure to oral (OCS) and inhaled (ICS) corticosteroid is associated with an increased risk for osteoporosis and fragility fracture (FF) in patients with asthma.

Major finding: Patients receiving more OCS prescriptions (9 or more vs. 0) were at a greater risk for osteoporosis (adjusted odds ratio [aOR], 4.50; 95% confidence interval [CI], 3.21-6.11) and FF (aOR, 2.16; 95% CI, 1.56-3.38). Among patients receiving more ICS prescriptions (11 or more vs. 0), the aORs for osteoporosis and FF were 1.60 (95% CI, 1.22-2.10) and 1.31 (95% CI, 1.02-1.68), respectively.

Study details: Two UK population-based nested case-control studies included 1,564 patients with asthma and osteoporosis (3,313 control participants) and 2,131 with asthma and FF (4,421 control participants).

Disclosures: The study was funded by a research award from the British Medical Association. The authors declared no conflicts of interest.

Source: Chalitsios CV et al. Thorax. 2020 Oct 21. doi: 10.1136/thoraxjnl-2020-215664.

Key clinical point: Exposure to oral (OCS) and inhaled (ICS) corticosteroid is associated with an increased risk for osteoporosis and fragility fracture (FF) in patients with asthma.

Major finding: Patients receiving more OCS prescriptions (9 or more vs. 0) were at a greater risk for osteoporosis (adjusted odds ratio [aOR], 4.50; 95% confidence interval [CI], 3.21-6.11) and FF (aOR, 2.16; 95% CI, 1.56-3.38). Among patients receiving more ICS prescriptions (11 or more vs. 0), the aORs for osteoporosis and FF were 1.60 (95% CI, 1.22-2.10) and 1.31 (95% CI, 1.02-1.68), respectively.

Study details: Two UK population-based nested case-control studies included 1,564 patients with asthma and osteoporosis (3,313 control participants) and 2,131 with asthma and FF (4,421 control participants).

Disclosures: The study was funded by a research award from the British Medical Association. The authors declared no conflicts of interest.

Source: Chalitsios CV et al. Thorax. 2020 Oct 21. doi: 10.1136/thoraxjnl-2020-215664.

Key clinical point: Exposure to oral (OCS) and inhaled (ICS) corticosteroid is associated with an increased risk for osteoporosis and fragility fracture (FF) in patients with asthma.

Major finding: Patients receiving more OCS prescriptions (9 or more vs. 0) were at a greater risk for osteoporosis (adjusted odds ratio [aOR], 4.50; 95% confidence interval [CI], 3.21-6.11) and FF (aOR, 2.16; 95% CI, 1.56-3.38). Among patients receiving more ICS prescriptions (11 or more vs. 0), the aORs for osteoporosis and FF were 1.60 (95% CI, 1.22-2.10) and 1.31 (95% CI, 1.02-1.68), respectively.

Study details: Two UK population-based nested case-control studies included 1,564 patients with asthma and osteoporosis (3,313 control participants) and 2,131 with asthma and FF (4,421 control participants).

Disclosures: The study was funded by a research award from the British Medical Association. The authors declared no conflicts of interest.

Source: Chalitsios CV et al. Thorax. 2020 Oct 21. doi: 10.1136/thoraxjnl-2020-215664.