In updated recommendations on pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults, the American College of Physicians (ACP) incorporates results of a network meta-analysis, considers new evidence on the efficacy of human parathyroid hormone (PTH)–related peptides and sclerostin inhibitors, and adds key questions on values and preferences and the cost of interventions. The text of the new recommendations is as follows:
- Recommendation 1a: ACP recommends that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis (strong recommendation; high-certainty evidence).
- Recommendation 1b: ACP suggests that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis (conditional recommendation; low-certainty evidence).
- Recommendation 2a: ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; moderate-certainty evidence).
- Recommendation 2b: ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) 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 of bisphosphonates (conditional recommendation; low-certainty evidence).
- Recommendation 3: ACP suggests that clinicians use the sclerostin inhibitor (romosozumab, moderate-certainty evidence) or recombinant PTH (teriparatide, low-certainty evidence), followed by a bisphosphonate, to reduce the risk of fractures only in females with primary osteoporosis with very high risk of fracture (conditional recommendation).
- Recommendation 4: ACP suggests that clinicians take an individualized approach regarding whether to start pharmacologic treatment with a bisphosphonate in females over the age of 65 with low bone mass (osteopenia) to reduce the risk of fractures (conditional recommendation; low-certainty evidence).
Clinical Evidence: “Bisphosphonates and denosumab reduced hip, clinical and radiographic vertebral, and other clinical fractures in postmenopausal females with osteoporosis (moderate to high [certainty of evidence (CoE)],” report authors of the living systematic review and network meta-analysis of 34 randomized controlled trials and 36 observational studies that supports the ACP recommendations. “Bisphosphonates for 36 months or more may increase the risk for atypical femoral fractures and osteonecrosis of the jaw, but the absolute risks were low. Abaloparatide and teriparatide reduced clinical and radiographic vertebral fractures but increased the risk for withdrawals due to adverse events (moderate to high CoE). Raloxifene and bazedoxifene for 36 months or more reduced radiographic vertebral but not clinical fractures (low to moderate CoE). Abaloparatide, teriparatide, and sequential romosozumab, then alendronate, may be more effective than bisphosphonates in reducing clinical fractures for 17 to 24 months in older postmenopausal females at very high fracture risk (low to moderate CoE). Bisphosphonates may reduce clinical fractures in older females with low bone mass (low CoE) and radiographic vertebral fractures in males with osteoporosis (low to moderate CoE).”
Editorial: An editorialist closes with these elements of an “optimistic view for future osteoporosis treatments”: “Less-expensive anabolic medicines that would vastly improve the cost–benefit ratio, anabolic medications that could be recycled for continuing bone gains, a transdermal form of a selective estrogen receptor modulator that could stabilize bone for decades in women whose bone density is below average but not yet in the osteoporotic range, and senolytic medications that would effectively improve osteoblast survival and slow down the relentless aging that makes treating osteoporosis so challenging.”