In a shift from previous recommendations, the American College of Physicians (ACP) now recommends that clinicians only use bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) for initial pharmacologic treatment to reduce the risk for fractures in postmenopausal women and men diagnosed with primary osteoporosis, according to an updated guideline published in the Annals of Internal Medicine. Denosumab is recommended as a second-line treatment in the updated guideline.
The guideline is based on a systematic review and network meta-analysis and updates the ACP’s 2017 guideline in which bisphosphonates or the RANK ligand inhibitor denosumab were also recommended as initial treatment to reduce the risk for fractures in women with osteoporosis. The revised recommendations are outlined in the Table.
Bisphosphonates have the most favorable balance between benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated, the ACP noted. Bisphosphonates also are less expensive than other pharmacologic treatments for osteoporosis and are available in generic oral and injectable formulations.
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Table. ACP Guideline on Pharmacologic Treatment of Osteoporosis
| Recommendation | GRADE |
| Use bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) as initial treatment to reduce the risk of fractures in postmenopausal women and men diagnosed with primary osteoporosis | Strong recommendation; high-certainty evidence |
| Use bisphosphonates as initial treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis | Conditional recommendation; low-certainty evidence |
| Use the RANK ligand inhibitor denosumab as a second-line pharmacologic treatment to reduce the risk of fractures in postmenopausal women and men diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates | Conditional recommendation; low-certainty evidence |
| Use the sclerostin inhibitor romosozumab or the recombinant PTH teriparatide followed by a bisphosphonate to reduce the risk of fractures only in women with primary osteoporosis at very high risk of fracture | Romosozumab: moderate-certainty evidence Teriparatide, low-certainty evidence |
| Use an individualized approach to decisions regarding use of bisphosphonates in women older than 65 years of age with osteopenia to reduce the risk of fractures | Conditional recommendation; low-certainty evidence |
Source: Qaseem.1
Current evidence suggests that increasing the duration of bisphosphonate therapy longer than 3 to 5 years reduced the risk of new vertebral fractures but not the risk of other fractures. Because of an increased risk for long-term harms with prolonged use, clinicians should consider stopping bisphosphonates after 5 years of treatment unless there is a strong indication to continue treatment, according to the ACP.
The RANK ligand inhibitor (denosumab) is recommended as a second-line pharmacologic treatment to reduce the risk of fractures in postmenopausal women and men with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates. The ACP suggests that clinicians use the sclerostin inhibitor (romosozumab) or recombinant PTH (teriparatide), followed by a bisphosphonate, to reduce the risk of fractures only in women with primary osteoporosis with very high risk of fracture.
The ACP continues to recommend prescribing generic osteoporosis medications whenever possible, encouraging treatment adherence and healthy lifestyle modifications, and estimating baseline risk for fracture based on an individualized assessment of bone density, history of fractures, response to prior treatments for osteoporosis, and multiple risk factors for fractures.
More research is needed on the benefits vs harms of osteoporosis treatment in premenopausal women, men, intersex persons, transgender persons after any transitioning treatment, residents of long-term care facilities, and people with multiple comorbid conditions and polypharmacy, according to the guideline authors.
Disclosures
Some of the study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Sources
1. Qaseem A, Hicks LA, Etxeandia-Ikobaltzeta I, Shamliyan T, Cooney TG; 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 Jan 3. doi:10.7326/M22-1034
2. American College of Physicians recommends bisphosphonates for initial treatment for osteoporosis in males and postmenopausal females diagnosed with primary osteoporosis. News release. American College of Physicians; January 3, 2023. Accessed January 4, 2023. https://www.acponline.org/acp-newsroom/american-college-of-physicians-recommends-bisphosphonates-for-initial-treatment-for-osteoporosis-in
