Updated U.S. guidelines for treatment of osteoporosis or low bone mass

The American College of Physicians has updated its recommendations for the pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults. The guidelines were last published in 2017. The update is based on the best available evidence of the benefits and harms of treatments, with consideration given to patient values, preferences and treatment costs. Primary osteoporosis refers to osteoporosis that is not secondary to a separate condition or medication. It is characterized by decreasing bone mass and bone density and reduced bone strength, leading to a higher risk for fracture. The guidelines provide three main recommendations for females: Bisphosphonates (alendronate, risedronate or zoledronic acid) should be used for initial pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis (strong recommendation; high-certainty evidence). Denosumab, a RANK ligand inhibitor, is suggested as a second-line pharmacologic treatment. It should be used to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis who have contraindications to or experience adverse effects with bisphosphonates (conditional recommendation; moderate-certainty evidence). The sclerostin inhibitor (romosozumab, moderate-certainty evidence) or recombinant parathyroid hormone (teriparatide; low-certainty evidence), followed by a bisphosphonate, is suggested to reduce the risk of fractures only in females with primary osteoporosis with very high risk of fracture (conditional recommendation). The rationale for these recommendations stems from the finding that bisphosphonates have the most favourable 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. Denosumab also has a favourable long-term net benefit, but bisphosphonates are much cheaper than other pharmacologic treatments and are available in generic formulations. Evidence shows that the benefits of teriparatide or romosozumab may outweigh the harms compared with placebo in a select population of postmenopausal females (mean age > 74 years) with osteoporosis and very high risk for fracture. Bisphosphonates and denosumab are associated with higher risk for osteonecrosis of the jaw and atypical femoral fractures, while romosozumab is associated with adverse cardiovascular events. The long-term safety of teriparatide in humans is unknown. The guidelines provide two main recommendations for males: Bisphosphonates are suggested for initial pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis (conditional recommendation; low-certainty evidence). Denosumab is suggested as a second-line pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis who have contraindications to or experience adverse effects with bisphosphonates (conditional recommendation; low-certainty evidence). The rationale for these recommendations stems from the finding that there is no evidence suggesting differences in treatment benefits and harms by sex. Bisphosphonates are approved for males with primary osteoporosis based on improvement in bone mineral density, and denosumab is approved for males with secondary osteoporosis based on the reduction in the risk for vertebral fractures. Clinical considerations in prescribing pharmacologic treatment Clinicians should prescribe generic medications, if possible, rather than more expensive brand-name medications. Clinicians treating postmenopausal females with osteoporosis should encourage adherence to recommended drug treatments and healthy lifestyle modifications, including exercise, and counselling for evaluation and prevention of falls. Adequate calcium and vitamin D intake should be part of fracture prevention in all postmenopausal females with low bone mass or osteoporosis. Clinicians should assess baseline risk for fracture based on individualized assessment of bone density, history of fractures, response to prior treatments for osteoporosis, and multiple risk factors for fractures in postmenopausal females with primary osteoporosis. Current evidence suggests that increasing the duration of bisphosphonate therapy to longer than five years probably reduces risk for new vertebral fractures but not risk for other fractures, and this is at the expense of increased risk for long-term harms. Therefore, clinicians should consider stopping bisphosphonate treatment after five years unless the patient has a strong indication for treatment continuation. The decision to temporarily discontinue treatment (i.e., a drug holiday) should be individualized and based on baseline risk for fractures, type of medication and its half-life in bone, duration of discontinuation, benefits and harms of discontinuation, and higher risk for fracture due to drug discontinuation. Females initially treated with an anabolic agent should be offered an antiresorptive agent after discontinuation to preserve gains and because of serious risk for rebound and multiple vertebral fractures. Older postmenopausal females with primary osteoporosis who are at increased risk for falls and other adverse events due to polypharmacy or drug interactions need individualized treatment based on comorbidities and concomitant medications associated with higher risk for falls/fractures. The guidelines also address evidence gaps, including areas with inconclusive or no evidence, as well as future research needs. Reference 1. Qaseem A, Hicks LA, Etxeandia-Ikobaltzeta I, et al; Clinical Guidelines Committee of the American College of Physicians. 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;176:224-38. (accessed March 9, 2023).

Updated U.S. guidelines for treatment of osteoporosis or low bone mass

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