Effect of Alendronic Acid on Fracture Healing: A Multicenter Randomized Placebo-Controlled Trial

Abstract

There is a concern that bisphosphonates may impair fracture healing because of their inhibitory effects on bone turnover. Here we evaluated the effects of early bisphosphonate therapy on fracture healing and functional outcome following a fracture of the distal radius. The fracture and bisphosphonates (FAB) trial was a double-blind, randomized, placebo-controlled trial involving 15 trauma centers in the United Kingdom. We enrolled 421 bisphosphonate-naive patients aged !50 years with a radiographically confirmed fracture of the distal radius and randomized them in a 1:1 ratio to receive alendronic acid 70 mg once weekly (n ¼ 215) or placebo (n ¼ 206) within 14 days of the fracture. The primary outcome measure was the proportion of fractures that had radiologically united at 4 weeks as assessed by an observer, blinded to treatment allocation. Secondary outcomes included the Disabilities of the Arm Shoulder and Hand (DASH) questionnaire, range of wrist movement and grip strength, pain and analgesia requirements, and the rate of malunion. The mean AE SD age of participants was 63 AE 8.5 years and 362 (86%) were female. At 4 weeks, 48 of 202 (23.8%) fractures had united in the alendronic acid group compared with 52 of 187 (27.8%) in the placebo group (observed absolute proportion difference 4.0%; 95% CI, -4.7% to 12.8%; p ¼ 0.36). The absolute proportion difference between groups based on imputed data was 4.5% (95% CI, -4.7% to 13.8%; p ¼ 0.30). There was no significant difference in the proportion of fractures that had united at any other time point and no differences in the DASH score, pain at the fracture site, grip strength, or any other clinical outcome. We conclude that among patients aged 50 years and above with a distal radius

Bisphosphonate use in the horse: what is good and what is not?

“…The fracture and bisphosphonates (FAB) trial was a double-blind, randomized, placebo-controlled trial involving 15 trauma centers across the United Kingdom that enrolled 421 bisphosphonate-naive patients aged ≥50 years with a radiographically confirmed fracture of the distal radius and randomized them in a 1:1 ratio to receive alendronate 70 mg once weekly (n = 215) or placebo (n = 206) within 14 days of the fracture. Administration of this highly potent N-containing BP did not affect fracture healing or clinical parameters [49]. Collectively, these data would contradict the anecdotal claims of many veterinary practitioners that the BPs mechanism of action disrupts the natural bone healing process.…”

“…1) treatment began within 90 days after hip fracture and no evidence of any delayed healing if treatment began within 2 weeks. More recently, the effects of early BP therapy on fracture healing and functional outcome following a fracture of the distal radius in osteoporotic patients was evaluated [49]. The fracture and bisphosphonates (FAB) trial was a double-blind, randomized, placebo-controlled trial involving 15 trauma centers across the United Kingdom that enrolled 421 bisphosphonate-naive patients aged ≥50 years with a radiographically confirmed fracture of the distal radius and randomized them in a 1:1 ratio to receive alendronate 70 mg once weekly (n = 215) or placebo (n = 206) within 14 days of the fracture.…”

Response to: Effects of Alendronic Acid on Fracture Healing

“…(1) As Fung correctly states, the fracture and bisphosphonates (FAB) study showed that alendronic acid did not have a clinically important effect on fracture healing or patient-reported outcomes in patients who were bisphosphonate naïve for the previous 2 years. (1) As Fung correctly states, the fracture and bisphosphonates (FAB) study showed that alendronic acid did not have a clinically important effect on fracture healing or patient-reported outcomes in patients who were bisphosphonate naïve for the previous 2 years.…”

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We thank Dr Fung for his interest in our article that was recently published in JBMR. (1) As Fung correctly states, the fracture and bisphosphonates (FAB) study showed that alendronic acid did not have a clinically important effect on fracture healing or patient-reported outcomes in patients who were bisphosphonate naïve for the previous 2 years. We do not agree with the implication that the absence of data on biochemical markers of bone turnover in our study is a limitation.

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Early Alendronate Can Be Safe during Fracture Healing?

“…To the Editor I read the article by Duckworth and colleagues (1) with great interest, especially as the JBMR June 2019 cover highlights "Alendronate Safe During Fracture Healing." The study shows that early use of alendronate, starting around 10 days after fracture, does not affect healing at 2, 4, 6, and 8 weeks and presumably also at 24 weeks.…”