A single bisphosphonate infusion does not accelerate fracture healing in high tibial osteotomies

Abstract

BackgroundBisphosphonates increase the callus size and strength in animal fracture studies. In a human non-randomized pilot study of high tibial osteotomies in knee osteoarthritis, using the hemicallotasis (HCO) technique, bisphosphonates shortened the healing time by 12 days. In the present randomized study, we wanted to determine whether a single infusion of zoledronic acid reduces the time to clinical osteotomy healing. Results from the same trial, showing improved pin fixation with zoledronate, have been published separately.Methods46 consecutive patients (aged 35–65 years) were operated. At 4 weeks postoperatively, the patients were randomized to an intravenous infusion of either zoledronic acid or sodium chloride. Dual-energy X-ray absorptiometry (DEXA) was performed 10 weeks postoperatively. Radiographs were taken at 10 weeks and every second week until there was radiographic and clinical healing. Healing was evaluated blind, with extraction of the external fixator as the endpoint. At 1.5 years, an additional radiograph was taken and the hip-knee-ankle (HKA) angle measured to evaluate whether correction had been retained.ResultsAll osteotomies healed with no difference in healing time between the groups (77 (SD 7) days). Bone mineral density and bone mineral content, as assessed with DEXA, were similar between the groups. Radiographically, both groups had retained the acquired correction at the 1.5-year follow-up.InterpretationIn this randomized comparison, a single infusion of zoledronic acid increased the pin fixation of the external frame but did not shorten the healing time. In both groups, the external fixator was extracted almost 2 weeks earlier than in previous studies. The early extraction did not cause a loss of correction in either group.

Timing of the initiation of bisphosphonates after surgery for fracture healing: a systematic review and meta-analysis of randomized controlled trials

“…Figure 1 illustrates the process of study selection. Ten trials [25][26][27][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] were finally designed to evaluate the effect of the timing of BP initiation after surgery for fracture healing and fulfilled the inclusion criteria for published studies (including safety reports), including a large-scale multicultural RCT with a large number of reports written about it [26,27,[38][39][40][41][42][43][44][45][46].…”

“…Although there is no definitive evidence that BPs have different effects on various bone types, inherent differences in the structure and function of different bones and variations in reported delay/nonunion rates (all fractures healed for the distal radius [29,31], 2-16 % for hip [27,30,34,35,37,47], and 12-14 % for spine [25]) may suggest that these types of fractures may undergo differential healing processes. In the analysis of fracture healing time, two studies of distal radius [29,31], one of the hip [30], and one of knee [32,33] were included, and the result was consistent with many studies [30,32,42]. While in the analysis of the delay or nonunion of fracture healing, three studies including the hip [27,30,37,53] and one including the spine [25] were reviewed.…”

“…There was also variability in the type of fracture. Two of the studies included patients who had distal radius fractures [29,31], six involved hip fractures [27,30,34,35,37,47], one included spinal surgery [25], and one included keen surgery [32,33]. The more detailed characteristics of the included studies are listed in Table 1.…”

“…Four trials used alendronate [29,31,34,37], three trials used zoledronic [25,32,33,46], two trials used risedronate [30,35], and one trial used etidronate [36]; the schedule varied as reflected in Table 2. The control group included the delayed use of BPs or use placebo instead of BPs or no therapy.…”

“…Allocation concealment was reported as adequate in five trials [25,[31][32][33][34]46] and as high risk in three trials [29,32,33,35]. Few of the trials have been open label.…”