Effects of single and concurrent intermittent administration of human parathyroid hormone and bisphosphonate cimadronate on bone mineral densities of femur in ovariectomized rats

This study compared the single administration of human parathyroid hormone [hPTH(1-34)] or bisphosphonate cimadronate (YM-175), and concurrent therapy with both of these agents for restoration of lost bone mineral density (BMD) in ovariectomized (OVX) rats. Animals were untreated for 4 weeks after surgery, and then injected s.c. with vehicle (OVX+V), hPTH(l-34) (30g/kg) (OVX+P), YM-175 (5g/kg) (OVX+Y), or a combination of these two (OVX+P+Y), 3 days a week, for 8 weeks, and killed. BMD of distal, middle, and total femur were determined by dual-energy X-ray absorptiometry (DXA). BMD of distal and total femur, but not of midfemur, decreased at both 4 weeks and 12 weeks after ovariectomy. In the distal femoral BMD, although OVX+Y failed to restore lost BMD in OVX rats, either OVX+P or OVX+P+Y could reverse BMD lost due to OVX. Midfemoral BMD was unchanged through OVX or both single treatments, whereas this parameter was increased only in OVX+P+Y. These results suggest that concurrent treatment with PTH and YM-175 results in a bone anabolic effect not only in cancellous bone but also in cortical bone.