The effects of combined human parathyroid hormone (1-34) and zoledronic acid treatment on fracture healing in osteoporotic rats

Abstract

Ovariectomized (OVX) rats with tibial fracture received vehicle, ZA, PTH, or ZA plus PTH treatment for 4 and 8 weeks. Bone metabolism, callus formation, and the mass of undisturbed bone tissue were evaluated by serum analysis, histology, immunohistochemistry, radiography, micro-computerized tomography, and biomechanical test. Previous studies have demonstrated the effect of ZA or PTH on osteoporotic fracture healing. However, reports about effects of ZA plus PTH on callus formation of osteoporotic fracture were limited. This study was designed to investigate the impact of combined treatment with ZA and PTH on fracture healing in OVX rats. Twelve weeks after bilateral ovariectomy, all rats underwent unilateral transverse osteotomy on tibiae. Animals then randomly received vehicle, ZA (1.5 μg/kg weekly), PTH (60 μg/kg, three times a week), or ZA plus PTH until death at 4 and 8 weeks. The blood and bilateral tibiae of rats were harvested for evaluation. All treatments increased callus formation and strength other than the control; ZA + PTH showed the strongest effects on percent bone volume (BV/TV), trabecular thickness, total fluorescence-marked callus area, and biomechanical strength. Additionally, inhibited RANKL and enhanced osteoprotegerin expression were observed in the ZA + PTH group. But no difference in bone mineral density and BV/TV of the contralateral tibiae was observed between treated groups. Findings in this study suggested an additive effect of ZA and PTH on fracture healing in OVX rats, and this additive effect was specific to callus formation, not to undisturbed bone tissue.