Osteoporosis

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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