Systemic Pamidronate (APD) administration potentially modulates local bone cellular activities and accordingly alters bone defect healing (intramembranous ossification). Metaphyseal tibia bone defects were created in 6-month-old female rats, which were injected with APD (0.1 mg/kg-5 d/w) or vehicle for 2 or 4 weeks. Bone samples were analysed by micro-computed tomography, histomorphometry and nano-indentation in metaphyseal 2nd spongiosa (MC), a region close to the defect (CDC), within the healing defect (DC) and in cortical defect bridging region. In cortical and trabecular healing zone, a blurry tetracycline labelling was observed at week-2 in both groups, indicating rapid bone formation while osteoid thickness and surfaces remained unaltered; interestingly bone formation was maintained in APD group. In contrast, bone formation rate in MC and CDC was decreased in APD group (~-60% each, p<.001) at the same time point. At week-4 osteoid surfaces and bone formation rate were lower in APD group independently of the trabecular sites while mineral apposition rate was also lower in APD group at cortical compartment. As expected, APD reduced active osteoclast surfaces at weeks-2 independently of the site (~-40%, p<.001). At weeks-4, bone resorption was even more decreased in all trabecular compartments (MC and CDC: -60%, p<.001, DC: -40%, p<.001) while it tended to be increased at the periost and decrease at endost. This resulted in higher trabeculare bone mass in APD group at the two time points and in a trabecularised cortical-shell in the APD group at week-4. Nano-indentation tests demonstrated an improvement of bone material level properties at week-4 in APD treated rats as evaluated at CDC (higher hardness) and cortical bridge (higher hardness and elasticity). Inside the healing zone, APD decreases resorption and maintained formation during bone modelling phase (i.e. first 2-weeks) leading to a positive bone balance, then inhibits bone remodelling and improves bone material level properties.
Disclosure: The authors declared no competing interests.