Effects of different anti-osteoporosis medications on re-fracture risk, bone mineral density, and functional recovery following hip fragility fracture surgery: a systematic review and network meta-analysis

Abstract

Patients undergoing surgery for fragility hip fracture remain at high risk of refracture and poor functional recovery. This study compared the effects of commonly used anti-osteoporosis medications on postoperative outcomes. PubMed, Embase, Web of Science, and the Cochrane Library were searched from January 1, 2015, to April 15, 2026. Randomized and non-randomized comparative studies were eligible. Bayesian random-effects consistency-model network meta-analyses assessed refracture, hip bone mineral density expressed as g/cm 2 or T-scores, Harris Hip Score, and visual analog scale scores. Leave-one-out sensitivity analyses were conducted for all outcomes. For HHS and VAS, RCT-only analyses were performed when the available RCTs formed connected networks, and analyses restricted to exactly 12 months of follow-up were conducted where feasible. The certainty of evidence was assessed using the GRADE approach. Eighteen studies involving 2,414 patients were included. Comparative effects varied by outcome and follow-up duration, with no consistent evidence of treatment superiority. Ranking patterns suggested relatively favorable signals for ZOL and DEN in 12-month hip refracture, ZOL and ALN in 12-month overall refracture, and TPTD and DEN in 24-month overall refracture, but were interpreted as descriptive summaries. BMD ranking patterns varied according to reporting format, and no clear differences were found for BMD, HHS, or VAS. Leave-one-out sensitivity analyses showed broadly stable findings, and the additional RCT-only and exact 12-month analyses for HHS and VAS were generally consistent with the primary analyses. GRADE assessments indicated limited certainty of evidence across outcomes. Anti-osteoporosis medications showed outcome- and time-specific efficacy patterns, but no consistent superiority was demonstrated. ZOL, DEN, and ALN showed relatively favorable signals for some early refracture outcomes, whereas TPTD showed a more favorable pattern for longer-term bone mass restoration. Given the limited and predominantly low-certainty evidence, these findings should be interpreted as contextual efficacy signals rather than treatment recommendations. https://www.crd.york.ac.uk/PROSPERO/view/CRD420261363237 , identifier CRD420261363237.