Latest ACP clinical guideline for the management of osteoporosis assesses benefits and harms of treatments
Presenter: Carolyn Crandall, MD, MS, David Geffen School of Medicine at University of California, Los Angeles.
More news you can use: current clinical guidelines in treatments for osteoporosis and acute pain. Presented April 28, 2023
The American College of Physicians (ACP) has updated its recommendations for the management of adult patients with low bone mass or primary osteoporosis. The guideline, summarized by Carolyn Crandall, MD, MS, from the David Geffen School of Medicine at University of California, Los Angeles, was based on an independent systematic review conducted by ACP Center for Evidence Review at the Portland Veteran Affairs Research Foundation.
Outcomes assessed were the benefits and harms of interventions. Benefits that were evaluated in randomized controlled trials (RCTs) were fracture risk reductions, prioritizing hip and clinical vertebral fracture and prioritizing interventions of at least 36 months duration. Estimates of harm were derived from RCTs and observational studies that included at least 1,000 patients.
Women with osteoporosis
The ACP recommends that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis (strong recommendation; high-certainty level of evidence). For postmenopausal women diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates, the ACP suggests that clinicians use the RANK ligand inhibitor denosumab as a second-line pharmacologic treatment to reduce the risk of fractures (conditional recommendation; moderate-certainty evidence).
Bisphosphonates were associated with 6 fewer hip fractures (high certainty) and denosumab with 4 fewer hip fractures (moderate certainty) compared with placebo per 1,000 patients treated. Raloxifene had no significant effect on hip fractures (moderate certainty).
For clinical vertebral fractures, bisphosphonates were associated with 18 fewer fractures (high certainty) and denosumab with 16 fewer (high certainty) versus placebo, with raloxifene showing no significant difference (moderate certainty).
With 36 or more months of use, various risks have been associated with treatments, including a higher risk of osteonecrosis of the jaw (in 0.01% to 0.3% of users) and atypical femoral or subtrochanteric fracture in observational studies (statistical heterogeneity, no estimate) with the use of bisphosphonates, and these risks were higher with a longer duration of treatment. Osteonecrosis of the jaw and atypical femoral or subtrochanteric fracture events with denosumab were evidenced only in extension trials, not RCTs, she said.
“Bisphosphonates had the most favorable balance among benefits, harms, patient values and preferences, and cost among the examined drugs in postmenopausal females with primary osteoporosis and should be used as first-line treatment,” Dr. Crandall said. “Denosumab also had a favorable long-term net benefit but bisphosphonates are much cheaper than other pharmacologic treatments and they’re available in generic formulations.”
The evidence suggests that the benefits of teriparatide or the sclerostin inhibitor romosozumab may outweigh the harms compared with placebo in older postmenopausal women (mean age > 74 years) with osteoporosis and very high risk for fracture. Teriparatide may have resulted in no difference in risk of serious adverse events, but probably increased the risk of withdrawal due to adverse events in RCTs (low to moderate certainty). Therefore, the ACP suggests that clinicians use romosozumab (moderate certainty of evidence) or teriparatide (low certainty) followed by a bisphosphonate to reduce the risk of fractures only in women with primary osteoporosis with very high risk of fracture (conditional recommendation).
Men with osteoporosis
The ACP suggests that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis (conditional recommendation; low-certainty evidence), and suggests denosumab as a second-line pharmacologic treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; low-certainty evidence).
Data are far less extensive for men with primary osteoporosis compared with women, leading the guideline committee to extrapolate results from RCTs that included women. No RCTs have been conducted with the outcomes of hip fracture or clinical vertebral fracture in a population of men with osteoporosis. One RCT comparing a bisphosphonate with placebo in this group found no significant difference in the rate of any clinical fracture at 36 months or longer. A comparison between bisphosphonates and placebo found that active treatment reduced the rate of radiographic vertebral fracture at 36 months or longer by 140 per 1,000 treated patients.
Persons with low bone density
The ACP suggests that clinicians take an individualized approach regarding whether to start pharmacologic treatment with a bisphosphonate in women 65 years or older with low bone mass (formerly called osteopenia) to reduce the risk of fractures (conditional recommendation; low-certainty evidence).
According to the guideline, no treatments significantly reduce hip fracture risk in individuals with low bone mass, and although bisphosphonates may reduce the risks of any clinical fracture and clinical vertebral fracture, the certainty of evidence for this statement is low. Similarly, zoledronic acid may also decrease the risk of any clinical and vertebral fractures, but the certainty of the evidence is low given that the findings were largely informed by a single RCT versus placebo in women age 65 years or older, some of whom had osteoporosis and a history of fractures, said Dr. Crandall.
Duration of bisphosphonate therapy
Increasing the duration of bisphosphonate therapy to longer than 5 years reduces the risk for new vertebral fractures but not for other fractures, and increases the risk of long-term harms. Clinicians should therefore consider stopping bisphosphonates after 5 years unless there is a strong indication for continuation, she said.
References
Qaseem A, Hicks LA, Etxeandia-Ikobaltzeta I, et al. Pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults: a living clinical guideline from the American College of Physicians. Ann Intern Med 2023; 176:224–238. doi: 10.7326/M22-1034
Qaseem A, Kansagara D, Lin JS, et al. The development of clinical guidelines and guidance statements by the Clinical Guidelines Committee of the American College of Physicians: update of methods. Ann Intern Med 2019; 170:863–870. doi: 10.7326/M18-3290
Disclosures
Carolyn Crandall, MD, MS, reports no relationships with entities whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.