Effects of a weekly injection of human parathyroid hormone (1-34) and withdrawal on bone mass, strength, and turnover in mature ovariectomized rats

Abstract

One hundred fifteen Wistar rats, 7 months of age, were ovariectomized (ovx) or sham-operated to evaluate the effects of a weekly injection of human parathyroid hormone (hPTH) and withdrawal on the bone mass, strength, and turnover in mature ovariectomized rats. At 3 months, ovx rats were given a weekly injection of hPTH(1-34) at the respective doses of 0 (vehicle), 10, and 90 microg/kg body weight (BW) for 3 months. Then, hPTH-treated rats were divided into two groups each: continuously treated groups, and the groups treated with vehicle only for another 3 months. Weekly hPTH injections at doses of 10 or 90 microg/kg BW maintained the lumbar BMD values and increased the values of the femoral cortical bone, increasing the bone formation rates in the trabecular, endocortical, and periosteal envelopes. Trabecular osteoclasts were increased in the 90 microg/kg dose group. Trabecular bone surface relative to the volume was decreased by hPTH. The compressive load of the lumbar bone and the bending moment of the midfemur were increased. The lumbar compressive load values, corrected for BMD and volume, and the moment of inertia of the midfemur were also increased. The intracortical porosity values were not increased by the treatment. After withdrawal of hPTH treatment, the BMD values in both the lumbar and the midfemur were reduced to ovx control levels. The bone mass stimulated by the 90 microg/kg dose was reduced faster than that by the 10 microg/kg dose. However, the parameters of bone strength were still larger than those of the ovx controls after cessation of the hPTH treatment. Thus, a weekly hPTH injection effectively stimulated the bone formation in both the trabecular and cortical bone, leading to positive effects on mass and structure of the bone. These data suggest the possibility of benefits of both a lower frequency of hPTH injections as well as high-frequency injections for human osteoporotics.