Influence of Bisphosphonates on the Bone Healing Biology and Clinical Outcomes in Acute Fractures: A Systematic Review of Literature

Bisphosphonates (BPs) are widely used antiresorptive agents for osteoporosis and fracture prevention, but their influence on fracture healing remains controversial. Concerns exist regarding potential delays in union, while other studies suggest neutral or even beneficial effects. A systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines. PubMed, Scopus, Embase, and Web of Science were searched up to December 2024 for randomized-controlled trials (RCTs) and cohort studies evaluating the effect of bisphosphonates on fracture healing. Outcomes included time to union, union rates, delayed union, non-union, revision surgery, pain, functional outcomes, and bone turnover markers. Risk of bias was assessed using RoB 2 and the Newcastle–Ottawa Scale. Twenty-two studies (14 RCTs, 8 cohort studies) comprising 12,371 patients were included. Bisphosphonates showed no significant effect on time to union (MD = 0.07 weeks, 95% CI − 0.54–0.68), nor on union rates at 6, 12, or 24 months. The risk of delayed union was unaffected (RR = 1.08, 95% CI 0.80–1.46), while the risk of non-union may be reduced (RR = 0.48, 95% CI 0.26–0.89), although conflicting findings in specific fracture types warrants cautious interpretation. Revision surgery rates did not differ between groups (RR = 0.61, 95% CI 0.08–4.55). Pain outcomes (VAS) showed a non-significant trend toward reduction, whereas Oswestry Disability Index (ODI) scores improved with bisphosphonates (MD = − 3.37, p = 0.001). Bisphosphonate usage did not affect bone resorption and formation biomarkers (p = 0.05). Bisphosphonates appear safe for fracture healing and may reduce non-union risk in select cases. However, effects vary by fracture type, timing, and study design. Evidence remains heterogeneous, and conclusions should be drawn cautiously. Further high-quality trials are needed to confirm safety and efficacy across diverse clinical settings.