ACP recommends bisphosphonates for men, postmenopausal women with primary osteoporosis

In an update to its guidance on primary osteoporosis, ACP recommended bisphosphonates as a first line of defense to reduce fracture risk in men and postmenopausal women.

The new guideline, published in Annals of Internal Medicine, is based on an updated systematic review of evidence that included 34 randomized clinical trials and 36 observational studies assessing the comparative effectiveness of various treatments.

Chelsea Ayers, MPH, a senior research associate at the Center to Improve Veteran Involvement in Care, VA Portland Health Care System, and colleagues found that, in men and postmenopausal women with primary osteoporosis, “bisphosphonates had the most favorable balance between benefits, harms, patient values and preferences,” according to an ACP press release.

Notably, ACP said that bisphosphonates also confer benefits in that they “are much cheaper than other pharmacologic treatments and are available in generic oral and injectable formulations.”

“Bone fractures resulting from osteoporosis are associated with serious morbidity and mortality, and people with a history of osteoporotic bone fractures are at much higher risk of future fractures,” Ryan D. Mire, MD, MACP, president of ACP, said in the release. “This guideline will help clinicians determine the best course of treatment for their patients to best avoid bone fractures.”

The recommendation of bisphosphonates for postmenopausal women is a strong recommendation based on high-certainty evidence, whereas the recommendation for men is conditional, with low-certainty evidence, according to ACP.

The organization noted that extending the duration of bisphosphonate therapy past 3 to 5 years might reduce the risk for new vertebral fractures but not others, although “there is an increased risk of long-term harms.” So, providers should consider stopping therapy after 5 years “unless there is a strong indication to continue treatment,” ACP said.

The guideline underscores the importance of adults with osteoporosis adhering to the “recommended pharmacologic treatments and healthy lifestyle modifications,” which include exercise and counseling for fall evaluation and prevention, according to the release.

ACP additionally recommended that clinicians use the RANK ligand inhibitor denosumab as a second-line treatment to reduce fracture risk in men and postmenopausal women who have contraindications or experienced adverse events from bisphosphonates.

In women who have a very high fracture risk, the ACP recommended the recombinant human parathyroid hormone teriparatide (low-certainty evidence) or the sclerostin inhibitor Evenity (romosozumab, Amgen; moderate-certainty evidence), followed by a bisphosphonate.

Finally, the ACP recommended that clinicians use “an individualized approach” when they are deciding whether to initiate bisphosphonate treatment in women aged older than 65 years with low bone mass.

In an accompanying editorial, Susan M. Ott, MD, of the Bone and Joint Center and a professor of medicine at the University of Washington in Seattle, wrote that evidence on bisphosphonates “may seem overwhelmingly positive, leading to strong recommendations for their use to treat osteoporosis, but the decision to start a bisphosphonate is actually not that easy.”

“A strong recommendation should be given only when future studies are unlikely to change it. Yet, data already suggest that, in patients with serious osteoporosis, treatment should start with anabolic medications because previous treatment with either bisphosphonates or denosumab will prevent the anabolic response of newer medications,” Ott wrote. “Fewer fractures are seen when the initial treatment is an anabolic medicine, which increases bone volume and not just bone density.”

Ott also wrote that “it is unfortunate that the review and recommendations do not address estrogen,” because it is “one of the most effective medications to prevent osteoporotic fractures.”

“Both observational studies and clinical trials show beneficial skeletal effects of estrogen; those with adequate power show fracture reduction,” Ott wrote. “In 1991, I reviewed all of the clinical and preclinical studies of estrogen for a conference of the Federal Drug Administration and was struck by finding that they all showed positive effects. It was the least controversial topic. Since then, observational studies have shown benefits of estrogen to the skeleton, even after three decades of use.”

References:

• American College of Physicians recommends bisphosphonates for initial treatment for osteoporosis in males and postmenopausal females diagnosed with primary osteoporosis. https://www.acponline.org/acp-newsroom/american-college-of-physicians-recommends-bisphosphonates-for-initial-treatment-for-osteoporosis-in. Published Jan. 3, 2023. Accessed Jan. 3, 2023.
• Ayers C, et al. Ann Intern Med. 2023;doi:10.7326/M22-0684.
• Ott SM, et al. Ann Intern Med. 2023;doi:10.7326/M22-3580.
• Qaseem A, et al. Ann Intern Med. 2023;doi:10.7326/M22-1034.