Bisphosphonate-induced reductions in rat femoral bone energy absorption and toughness are testing rate-dependent

Abstract

Bisphosphonates have been used for years to suppress bone turnover and reduce fracture risk. Bisphosphonates have recently been associated with atypical femoral fractures, which are catastrophic, low trauma, brittle fractures that appear to occur more frequently than in untreated individuals. Previous work using a dog model has demonstrated bisphosphonate-induced reductions in bone toughness (the inverse of brittleness), yet data are lacking to show this occurs in rodents. The goal of this study was to determine if bisphosphonate-induced alterations in toughness could be quantified in rats. At 26 weeks of age, skeletally mature rats (n = 32 total) were given an injection of either zoledronate (100 μg/kg body weight) or vehicle (0.5 ml saline). Five weeks post-injection, both femora were collected and analyzed for geometry and mechanical properties. To assess the effect of testing rate on the biomechanical outcomes, the left femora were broken at 2 mm/min, while the right femora were broken at 20 mm/min. The results showed a significantly lower energy to failure in zoledronate-treated animals compared to vehicle at the slow testing rate (-15%, p < 0.05) with no difference at the faster rate. While there was not a significant interaction between drug and testing rate for toughness to fracture (p = 0.07), toughness between ultimate stress and fracture was significantly lower with zoledronate only at the slow rate (-40%, p < 0.05). These data document that bisphosphonate-induced reductions in energy absorption and toughness can be quantified in rats yet they are highly dependent on testing rate.