Summary

The 2023 ACP living guideline updates pharmacologic management of primary osteoporosis and low bone mass in adults. Bisphosphonates are recommended as first-line therapy in both postmenopausal females and males with osteoporosis, with denosumab as second-line for bisphosphonate intolerance. Anabolic agents (romosozumab or teriparatide) followed by a bisphosphonate are reserved for females at very high fracture risk, while estrogen, estrogen-progestin, and SERMs are not recommended for treatment of osteoporosis.

Key Recommendations

Use a bisphosphonate (alendronate, risedronate, or zoledronate) as initial pharmacologic therapy to reduce fracture risk in postmenopausal females with primary osteoporosis.
Use a bisphosphonate as initial pharmacologic therapy to reduce fracture risk in males with primary osteoporosis.
Use denosumab (RANK ligand inhibitor) as second-line therapy in adults with primary osteoporosis who have contraindications to or adverse effects from bisphosphonates.
Use a sclerostin inhibitor (romosozumab) or recombinant PTH (teriparatide), followed by a bisphosphonate, in females with primary osteoporosis at very high risk of fracture.
Individualize the decision whether to start pharmacologic treatment in females ≥65 years with low bone mass (osteopenia) based on patient preferences, fracture risk, benefits/harms, and costs.
Do not use estrogen alone, estrogen plus progestin, or raloxifene (SERM) to treat osteoporosis in postmenopausal females.
Bisphosphonates have the most favorable balance of benefits, harms, and cost among osteoporosis pharmacotherapies and should be first-line in nearly all candidates.

Thresholds & Doses

Age ≥65 years — threshold defining the population for individualized treatment decisions in females with osteopenia/low bone mass
Anabolic agents (romosozumab, teriparatide) — reserved for females at very high fracture risk, then transition to bisphosphonate

Citations

ACP 2023 Recommendation 1 — bisphosphonates as initial therapy in postmenopausal females with primary osteoporosis
ACP 2023 Recommendation 1a — bisphosphonates as initial therapy in males with primary osteoporosis
ACP 2023 Recommendation 2 — RANK ligand inhibitor (denosumab) as second-line therapy
ACP 2023 Recommendation 3 — sclerostin inhibitor or recombinant PTH in females with very high fracture risk
ACP 2023 Recommendation 4 — individualized decision-making for women >65 with low bone mass/osteopenia
ACP 2023 Recommendation 5 — estrogen, estrogen plus progestin, and SERMs not recommended for osteoporosis treatment in postmenopausal women
Annals of Internal Medicine, ACP Living Guideline (M22-1034) — full guideline text and evidence review