Positive alterations of viscoelastic and geometric properties in ovariectomized rat femurs with concurrent administration of ibandronate and PTH

Besides bone mineral density (BMD), structural and nano-level viscoelastic properties of bone are also crucial determinants of bone strength. However, treatment induced viscosity changes in osteoporotic bone have seldom been characterized. In this study, the effects of anabolic, antiresorptive and concurrent treatments on ovariectomized rat bones were thoroughly analyzed using multiple bone strength parameters. A total of 52 female Sprague-Dawley rats of 3 months age were divided into 5 groups and subjected to sham (SHM group) or ovariectomy surgery (OVX, PTH, IBN and COM groups). Weekly low-dose parathyroid hormone (PTH) and/or ibandronate or its vehicle was administered subcutaneously to the respective groups starting from 4th week post-surgery. Four rats per group were euthanized every 4 weeks and their femurs were harvested. The BMD, micro-architectural parameters, cortical bone geometry and viscoelastic parameters were measured at the distal femoral metaphysis. Our results showed that PTH, ibandronate or its concurrent treatment can effectively reverse ovariectomy induced deteriorations in both trabecular and cortical bone. Different drugs had selective effects especially in preserving geometric and viscoelastic properties of the bone. The concurrent administration of PTH and ibandronate was shown to offer an added advantage in preserving mean BMD and had a positive effect on cortical bone geometry, resulting from an increased periosteal formation and a decreased endocortical resorption. Viscosity (η) was prominently restored in combined treatment group. It is in accordance with an observed denser alignment of collagen fibers and hydroxyapatite crystal matrix with fewer pores, which may play an important role in hindering fracture propagation.

► We studied the effect of hPTH and/or ibandronate treatments on ovariectomized rat femurs using geometric, densitometric and viscoelastic parameters. ► Different drugs had selective effects in preserving geometric and nano-level viscoelastic properties of cortical bone. ► Concurrent treatment offers an advantage in restoring mean BMD and cortical geometry as compared to monotherapy. ► Concurrent treatment causes prominent increase in viscosity which complies with denser alignment of collagen matrix and hydroxyapatite crystals. ► Nanoindentation measured viscosity is postulated to be a potential determinant of bone quality.