Effects of raloxifene and alendronate on non-enzymatic collagen cross-links and bone strength in ovariectomized rabbits in sequential treatments after daily human parathyroid hormone (1-34) administration.

Abstract

The standard sequential treatment to follow human parathyroid hormone (hPTH) (1-34) therapy for osteoporosis has yet to be determined. The objective of this study was to compare the effects of raloxifene and alendronate treatments to follow daily hPTH(1-34) treatment on non-enzymatic collagen cross-links, bone mass, and bone strength in ovariectomized (OVX) rabbits. From 3months after ovariectomy, seven month-old female New Zealand white rabbits were given either vehicle or hPTH(1-34) (8μg/kg/day), once daily for 5months. After hPTH(1-34) treatment, the hPTH(1-34)-treated animals were divided into two groups, and given raloxifene (10mg/kg, daily) orally or alendronate (100μg/kg, twice weekly) subcutaneously for 5months. We evaluated bone mineral density (BMD), bone structural parameters, advanced glycation end product (AGE) content in collagen, and bone mechanical parameters including intrinsic parameters in the femur. Raloxifene (hPTH/RLX) and alendronate (hPTH/ALN) to follow hPTH(1-34) increased cortical thickness, maximum load, and maximum stress and decreased endocortical surface in the diaphysis, in addition to increasing total BMD in the distal metaphysis. Decreased trabecular AGE, pentosidine, and homocysteine contents and increased toughness and breaking energy were noted with hPTH/RLX treatment only. With hPTH/ALN treatment, no effects on non-enzymatic collagen cross-link AGEs were noted although increases in stiffness and elastic modulus were observed. These results suggest that sequential treatments with hPTH(1-34) and antiresorptive drugs (raloxifene and alendronate) have a beneficial effect on bone mass and biomechanical properties in OVX rabbits.