Objective: Bisphosphonates are widely used to treat diseases of disproportionate bone resorption; however, possible side-effects include bisphosphonate-related osteonecrosis of the jaw (BRONJ). The susceptibility of various skeletal sites to BRONJ has been hypothesized to be related to the level of site-specific bone remodeling. Little is known about the physiologic trabecular bone remodeling (TBR) in the mandibular condyle of aged dogs or the effects of bisphosphonates on this TBR. The objectives of this study were to quantify and compare TBR in the mandibular condyle and vertebra of aged (2- to 3-year old) dogs and to evaluate the effects of short-term zoledronic acid on TBR.
Methods: Seven (3 untreated, NT; 4 treated with 4 doses of 0.1 mg/kg/month zoledronic acid, ZOL) dogs were given a pair of calcein labels. Mineral apposition rate (MAR, μm/d), mineralizing surface (MS/BS, %), bone formation rate (BFR/BS, μm3/μm2/d), and micro-architectural histomorphometric parameters were quantified from undecalcified specimen (n=56; 4 condyle and 4 vertebra sections/dog) using histomorphometric methods and analyzed statistically (ANOVA, Tukey test, p<0.05). BFR/BS was the main variable of interest as it describes TBR.
Results: TBR in NT group was significantly higher (>9-fold, p=0.0002) in the vertebra (BFR/BS 0.19+0.06) than the mandibular condyle (BFR/BS 0.020+0.012). In ZOL group, BFR/BS in both skeletal sites was reduced to similar absolute levels (vertebra 0.008+0.010; mandibular condyle 0.007+0.012). BFR/BS in the vertebra was significantly reduced (-0.18; 96% reduction, p=0.0006), while it was not in the mandibular condyle (-0.014; 67% reduction, p=0.9).
Conclusions: Physiologic TBR in aged dogs is vastly different in the mandibular condyle than in the vertebrae. This higher level of TBR in the vertebrae leads to greater reduction by short-term ZA treatment.