When to Start a Bisphosphonate After Hip Fracture
A hip fracture patient who leaves without osteoporosis treatment faces a high early risk of a second fracture, and treatment started soon after surgery lowers that risk without slowing healing.
Key terminology
- Fragility fracture
- This fracture comes from a fall from standing height or less. Healthy bone would not break this way, so the fracture itself points to osteoporosis.
- Major osteoporotic fracture
- This term groups fractures of the hip, spine, wrist and proximal humerus. It is the outcome that fracture risk tools such as FRAX predict.
- Imminent fracture risk
- This term describes the spike in fracture risk in the first 1 to 2 years after a fragility fracture. It is the reason guidelines push to start treatment promptly.
- Bisphosphonate
- These drugs bind bone mineral and are taken up by osteoclasts, which then stop resorbing bone. Alendronate and risedronate are oral, and zoledronic acid is a yearly IV infusion.
- Delayed union
- This fracture is healing more slowly than expected for its site and type. It may still unite, unlike a nonunion, which has stopped healing.
- Fracture liaison service
- This hospital program uses a coordinator to find fracture patients and start their osteoporosis workup and treatment. It closes the gap between the fracture team and primary care.
- Post hoc analysis
- This analysis compares subgroups that a trial was not designed to compare. Its results raise hypotheses and cannot prove cause.
Takeaways
- A low-energy hip fracture is enough to diagnose osteoporosis, with or without a DXA scan. The National Bone Health Alliance counts a hip fracture in postmenopausal women and men ≥50 as osteoporosis regardless of BMD. Vertebral, proximal humerus, pelvic and some wrist fractures in a patient with osteopenia also qualify (Siris et al, Osteoporos Int 2014;25:1439-1443, PMID 24577348).
- Fracture risk is highest right after a first fragility fracture and then fades. In 18,872 Icelandic adults, risk of a second major osteoporotic fracture was 2.7-fold the population risk 1 year after the first and 1.4-fold at 10 years. This imminent fracture risk is the reason the ASBMR-led coalition recommends prompt treatment after a hip or vertebral fracture (Johansson et al, Osteoporos Int 2017;28:775-780, PMID 28028554; Conley et al, J Bone Miner Res 2020;35:36-52, PMID 31538675).
- Yearly IV zoledronic acid after hip fracture repair prevents the next fracture. HORIZON-RFT randomized 2,127 patients within 90 days of surgery, all on vitamin D and calcium. New clinical fractures were 8.6% vs 13.9% (35% reduction). The coalition lists oral alendronate or risedronate first line, with zoledronic acid or denosumab as alternatives (Lyles et al, N Engl J Med 2007;357:1799-1809, PMID 17878149; Conley et al, J Bone Miner Res 2020;35:36-52, PMID 31538675).
- Zoledronic acid given soon after hip fracture surgery does not delay healing. In HORIZON-RFT, delayed union occurred in 3.2% vs 2.7% with placebo (OR 1.17, not significant), with no interaction by timing, even within 2 weeks of repair. NSAID use was linked to delayed union (OR 2.55). A 2022 meta-analysis found no delay with a bisphosphonate started within 1 month of proximal femur fixation (low-level evidence) (Colón-Emeric et al, Osteoporos Int 2011;22:2329-2336, PMID 21153021; Tong et al, ANZ J Surg 2022;92:2840-2848, PMID 35655397).
- Most hip fracture patients never start osteoporosis treatment. In 96,887 US patients, only 28.5% used an osteoporosis drug within 12 months of discharge, and the rate fell from 40.2% in 2002 to 20.5% in 2011. A fracture liaison service raised the likelihood of starting treatment by up to 21% over usual care (Solomon et al, J Bone Miner Res 2014;29:1929-1937, PMID 24535775; Wu et al, Osteoporos Int 2018;29:1023-1047, PMID 29525971).
- Early bisphosphonates leave healing unchanged after wrist fracture fixation too. In an RCT of 50 women after volar plating, starting at 2 weeks vs 3 months gave union at 6.7 vs 6.8 weeks, with no difference in DASH, motion or grip. A meta-analysis of 10 RCTs (2,888 patients) found no difference in radiographic healing time or in delayed union or nonunion (OR 0.98) (Gong et al, J Bone Joint Surg Am 2012;94:1729-1736, PMID 22992762; Li et al, Osteoporos Int 2015;26:431-441, PMID 25266485).
- The clearest fracture benefit comes with a first infusion 2 weeks or more after surgery. Median time to the first HORIZON-RFT dose was about 6 weeks. A post hoc analysis by 2-week intervals found a hip BMD response and fewer clinical fractures and deaths when the first dose came 2 weeks or later. It is a subgroup analysis by a sponsor author, so it supports waiting about 2 weeks and cannot prove that earlier doses fall short (Eriksen et al, J Bone Miner Res 2009;24:1308-1313, PMID 19257818).
- Zoledronic acid lowered mortality after hip fracture in one trial, and pooled trials disagree. HORIZON-RFT reported deaths in 9.6% vs 13.3% (28% reduction). A 2010 meta-analysis of 8 trials found an 11% reduction (RR 0.89), and a 2019 meta-analysis of 38 trials found none (RR 0.98, zoledronate RR 0.88, 95% CI 0.68-1.13). The 2019 authors advise treating for fracture risk only (Lyles et al, N Engl J Med 2007;357:1799-1809, PMID 17878149; Bolland et al, J Clin Endocrinol Metab 2010;95:1174-1181, PMID 20080842; Cummings et al, JAMA Intern Med 2019;179:1491-1500, PMID 31424486).