Hormone–bisphosphonate combination improves postmenopausal bone density; fracture superiority remains uncertain

A systematic review and network meta-analysis published in Menopause compared systemic menopausal hormone therapy (MHT), bisphosphonates, calcitonin, and combined regimens in postmenopausal women. Researchers searched four databases through April 14, 2026, and included 16 randomized controlled trials involving 2,861 women. Outcomes included site-specific bone mineral density (BMD), fractures, and selected adverse events.

All active regimens increased lumbar spine BMD compared with control. The largest mean differences were reported for MHT plus calcitonin (12.24%; 95% CI, 7.46–17.01) and MHT plus bisphosphonates (9.71%; 95% CI, 6.99–12.42), although calcitonin estimates relied on limited evidence. MHT plus bisphosphonates had the most favorable hip-region BMD profile, with mean differences versus control of 4.87% at the femoral neck (95% CI, 2.66–7.07) and 6.65% at the femoral trochanter (95% CI, 5.12–8.17).

MHT plus bisphosphonates was associated with fewer fractures of any type versus control (risk ratio, 0.51; 95% CI, 0.28–0.93). However, fracture events were sparse and often not prespecified efficacy outcomes. MHT alone and combined with bisphosphonates increased risks of breast pain and vaginal spotting or bleeding. The BMD findings therefore do not establish superior fracture prevention with combination therapy, and long-term safety remains uncertain.