Federal advisers on December 17 overwhelmingly recommended an emergency clearance to Moderna Inc’s COVID-19 vaccine, while noting concerns about potential allergic reactions and the challenges of continuing testing of this medicine.

The US Food and Drug Administration (FDA) put Moderna’s application before its Vaccines and Related Biological Products Advisory Committee. The panel voted 20-0 on this question: “Based on the totality of scientific evidence available, do the benefits of the Moderna COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?” There was one abstention.

The FDA is not bound to act on the recommendations of its advisers, but the agency usually takes the panel’s advice. The FDA cleared the similar Pfizer-BioNTech vaccine on December 11 through an emergency use authorization (EUA), following a positive vote for the product at a December 10 advisory committee meeting. In this case, the FDA staff appeared to be pushing for a broad endorsement of the Moderna vaccine, for which the agency appears likely to soon also grant an EUA.

Marion Gruber, PhD, director of the Office of Vaccines Research and Review at FDA’s Center for Biologics Evaluation and Research, earlier rebuffed attempts by some of the panelists to alter the voting question. Some panelists wanted to make tweaks, including a rephrasing to underscore the limited nature of an EUA, compared with a more complete approval through the biologics license application (BLA) process.

FDA panelist Michael Kurilla, MD, PhD, of the National Institutes of Health was the only panelist to abstain from voting. He said he was uncomfortable with the phrasing of the question.

“In the midst of a pandemic and with limited vaccine supply available, a blanket statement for individuals 18 years and older is just too broad,” he said. “I’m not convinced that for all of those age groups the benefits do actually outweigh the risks.”

In general, though, there was strong support for Moderna’s vaccine. FDA panelist James Hildreth Sr, MD, PhD, of Meharry Medical College in Nashville, Tennessee spoke of the “remarkable achievement” seen in having two vaccines ready for clearance by December for a virus that only emerged as a threat this year.

Study data indicate the primary efficacy endpoint demonstrated vaccine efficacy (VE) of 94.1% (95% CI, 89.3% - 96.8%) for the Moderna vaccine, with 11 COVID-19 cases in the vaccine group and 185 COVID-19 cases in the placebo group, the FDA staff noted during the meeting.

The advisers and FDA staff also honed in on several key issues with COVID-19 vaccines, including the challenge of having people in the placebo groups of studies seek to get cleared vaccines. Also of concern to the panel were early reports of allergic reactions seen with the Pfizer product.

Doran L. Fink, MD, PhD, an FDA official who has been closely involved with the COVID-19 vaccines, told the panel that two healthcare workers in Alaska had allergic reactions minutes after receiving the Pfizer vaccine, one of which was a case of anaphylactic reaction that resulted in hospitalization.

In the United Kingdom, there were two cases reported of notable allergic reactions, leading regulators there to issue a warning that people who have a history of significant allergic reactions should not currently receive the Pfizer-BioNTech vaccine.

The people involved in these incidents have recovered or are recovering, Fink said. But the FDA expects there will be additional reports of allergic reactions to COVID-19 vaccines.

“These cases underscores the need to remain vigilant during the early phase of the vaccination campaign,” Fink said. “To this end, FDA is working with Pfizer to further revise factsheets and prescribing information for their vaccine to draw attention to CDC guidelines for post- vaccination monitoring and management of immediate allergic reactions.”

mRNA vaccines in the lead

An FDA emergency clearance for Moderna’s product would be another vote of confidence in a new approach to making vaccines. Both the Pfizer-BioNTech and Moderna vaccines provide the immune system with a kind of blueprint in the form of genetic material, mRNA. The mRNA sets the stage for the synthesis of the signature spike protein that the SARS-CoV-2 virus uses to attach to and infect human cells.

In a December 15 commentary for this news organization Michael E. Pichichero, MD, wrote that the “revolutionary aspect of mRNA vaccines is the speed at which they can be designed and produced.”

“This is why they lead the pack among the SARS-CoV-2 vaccine candidates and why the National Institute of Allergy and Infectious Diseases provided financial, technical, and/or clinical support. Indeed, once the amino acid sequence of a protein can be determined (a relatively easy task these days) it’s straightforward to synthesize mRNA in the lab — and it can be done incredibly fast,” he wrote.

The FDA allowed one waiver for panelist James K. Hildreth in connection with his personal relationship to a trial participant and his university’s participation in vaccine testing.

This article first appeared on Medscape.com.

Federal advisers on December 17 overwhelmingly recommended an emergency clearance to Moderna Inc’s COVID-19 vaccine, while noting concerns about potential allergic reactions and the challenges of continuing testing of this medicine.

The US Food and Drug Administration (FDA) put Moderna’s application before its Vaccines and Related Biological Products Advisory Committee. The panel voted 20-0 on this question: “Based on the totality of scientific evidence available, do the benefits of the Moderna COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?” There was one abstention.

The FDA is not bound to act on the recommendations of its advisers, but the agency usually takes the panel’s advice. The FDA cleared the similar Pfizer-BioNTech vaccine on December 11 through an emergency use authorization (EUA), following a positive vote for the product at a December 10 advisory committee meeting. In this case, the FDA staff appeared to be pushing for a broad endorsement of the Moderna vaccine, for which the agency appears likely to soon also grant an EUA.

Marion Gruber, PhD, director of the Office of Vaccines Research and Review at FDA’s Center for Biologics Evaluation and Research, earlier rebuffed attempts by some of the panelists to alter the voting question. Some panelists wanted to make tweaks, including a rephrasing to underscore the limited nature of an EUA, compared with a more complete approval through the biologics license application (BLA) process.

FDA panelist Michael Kurilla, MD, PhD, of the National Institutes of Health was the only panelist to abstain from voting. He said he was uncomfortable with the phrasing of the question.

“In the midst of a pandemic and with limited vaccine supply available, a blanket statement for individuals 18 years and older is just too broad,” he said. “I’m not convinced that for all of those age groups the benefits do actually outweigh the risks.”

In general, though, there was strong support for Moderna’s vaccine. FDA panelist James Hildreth Sr, MD, PhD, of Meharry Medical College in Nashville, Tennessee spoke of the “remarkable achievement” seen in having two vaccines ready for clearance by December for a virus that only emerged as a threat this year.

Study data indicate the primary efficacy endpoint demonstrated vaccine efficacy (VE) of 94.1% (95% CI, 89.3% - 96.8%) for the Moderna vaccine, with 11 COVID-19 cases in the vaccine group and 185 COVID-19 cases in the placebo group, the FDA staff noted during the meeting.

The advisers and FDA staff also honed in on several key issues with COVID-19 vaccines, including the challenge of having people in the placebo groups of studies seek to get cleared vaccines. Also of concern to the panel were early reports of allergic reactions seen with the Pfizer product.

Doran L. Fink, MD, PhD, an FDA official who has been closely involved with the COVID-19 vaccines, told the panel that two healthcare workers in Alaska had allergic reactions minutes after receiving the Pfizer vaccine, one of which was a case of anaphylactic reaction that resulted in hospitalization.

In the United Kingdom, there were two cases reported of notable allergic reactions, leading regulators there to issue a warning that people who have a history of significant allergic reactions should not currently receive the Pfizer-BioNTech vaccine.

The people involved in these incidents have recovered or are recovering, Fink said. But the FDA expects there will be additional reports of allergic reactions to COVID-19 vaccines.

“These cases underscores the need to remain vigilant during the early phase of the vaccination campaign,” Fink said. “To this end, FDA is working with Pfizer to further revise factsheets and prescribing information for their vaccine to draw attention to CDC guidelines for post- vaccination monitoring and management of immediate allergic reactions.”

mRNA vaccines in the lead

An FDA emergency clearance for Moderna’s product would be another vote of confidence in a new approach to making vaccines. Both the Pfizer-BioNTech and Moderna vaccines provide the immune system with a kind of blueprint in the form of genetic material, mRNA. The mRNA sets the stage for the synthesis of the signature spike protein that the SARS-CoV-2 virus uses to attach to and infect human cells.

In a December 15 commentary for this news organization Michael E. Pichichero, MD, wrote that the “revolutionary aspect of mRNA vaccines is the speed at which they can be designed and produced.”

“This is why they lead the pack among the SARS-CoV-2 vaccine candidates and why the National Institute of Allergy and Infectious Diseases provided financial, technical, and/or clinical support. Indeed, once the amino acid sequence of a protein can be determined (a relatively easy task these days) it’s straightforward to synthesize mRNA in the lab — and it can be done incredibly fast,” he wrote.

The FDA allowed one waiver for panelist James K. Hildreth in connection with his personal relationship to a trial participant and his university’s participation in vaccine testing.

This article first appeared on Medscape.com.

Federal advisers on December 17 overwhelmingly recommended an emergency clearance to Moderna Inc’s COVID-19 vaccine, while noting concerns about potential allergic reactions and the challenges of continuing testing of this medicine.

The US Food and Drug Administration (FDA) put Moderna’s application before its Vaccines and Related Biological Products Advisory Committee. The panel voted 20-0 on this question: “Based on the totality of scientific evidence available, do the benefits of the Moderna COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?” There was one abstention.

The FDA is not bound to act on the recommendations of its advisers, but the agency usually takes the panel’s advice. The FDA cleared the similar Pfizer-BioNTech vaccine on December 11 through an emergency use authorization (EUA), following a positive vote for the product at a December 10 advisory committee meeting. In this case, the FDA staff appeared to be pushing for a broad endorsement of the Moderna vaccine, for which the agency appears likely to soon also grant an EUA.

Marion Gruber, PhD, director of the Office of Vaccines Research and Review at FDA’s Center for Biologics Evaluation and Research, earlier rebuffed attempts by some of the panelists to alter the voting question. Some panelists wanted to make tweaks, including a rephrasing to underscore the limited nature of an EUA, compared with a more complete approval through the biologics license application (BLA) process.

FDA panelist Michael Kurilla, MD, PhD, of the National Institutes of Health was the only panelist to abstain from voting. He said he was uncomfortable with the phrasing of the question.

“In the midst of a pandemic and with limited vaccine supply available, a blanket statement for individuals 18 years and older is just too broad,” he said. “I’m not convinced that for all of those age groups the benefits do actually outweigh the risks.”

In general, though, there was strong support for Moderna’s vaccine. FDA panelist James Hildreth Sr, MD, PhD, of Meharry Medical College in Nashville, Tennessee spoke of the “remarkable achievement” seen in having two vaccines ready for clearance by December for a virus that only emerged as a threat this year.

Study data indicate the primary efficacy endpoint demonstrated vaccine efficacy (VE) of 94.1% (95% CI, 89.3% - 96.8%) for the Moderna vaccine, with 11 COVID-19 cases in the vaccine group and 185 COVID-19 cases in the placebo group, the FDA staff noted during the meeting.

The advisers and FDA staff also honed in on several key issues with COVID-19 vaccines, including the challenge of having people in the placebo groups of studies seek to get cleared vaccines. Also of concern to the panel were early reports of allergic reactions seen with the Pfizer product.

Doran L. Fink, MD, PhD, an FDA official who has been closely involved with the COVID-19 vaccines, told the panel that two healthcare workers in Alaska had allergic reactions minutes after receiving the Pfizer vaccine, one of which was a case of anaphylactic reaction that resulted in hospitalization.

In the United Kingdom, there were two cases reported of notable allergic reactions, leading regulators there to issue a warning that people who have a history of significant allergic reactions should not currently receive the Pfizer-BioNTech vaccine.

The people involved in these incidents have recovered or are recovering, Fink said. But the FDA expects there will be additional reports of allergic reactions to COVID-19 vaccines.

“These cases underscores the need to remain vigilant during the early phase of the vaccination campaign,” Fink said. “To this end, FDA is working with Pfizer to further revise factsheets and prescribing information for their vaccine to draw attention to CDC guidelines for post- vaccination monitoring and management of immediate allergic reactions.”

mRNA vaccines in the lead

An FDA emergency clearance for Moderna’s product would be another vote of confidence in a new approach to making vaccines. Both the Pfizer-BioNTech and Moderna vaccines provide the immune system with a kind of blueprint in the form of genetic material, mRNA. The mRNA sets the stage for the synthesis of the signature spike protein that the SARS-CoV-2 virus uses to attach to and infect human cells.

In a December 15 commentary for this news organization Michael E. Pichichero, MD, wrote that the “revolutionary aspect of mRNA vaccines is the speed at which they can be designed and produced.”

“This is why they lead the pack among the SARS-CoV-2 vaccine candidates and why the National Institute of Allergy and Infectious Diseases provided financial, technical, and/or clinical support. Indeed, once the amino acid sequence of a protein can be determined (a relatively easy task these days) it’s straightforward to synthesize mRNA in the lab — and it can be done incredibly fast,” he wrote.

The FDA allowed one waiver for panelist James K. Hildreth in connection with his personal relationship to a trial participant and his university’s participation in vaccine testing.

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.