The effects of intermittent administration of human parathyroid hormone (1–34) on streptozotocin-induced diabetic rats

Abstract

Intermittent administration of low doses of human parathyroid hormone (h-PTH) has been reported to exhibit an anabolic effect on bone, increasing its mass. We investigated the effects of intermittent administration of h-PTH on bone changes in streptozotocin-(STZ-) induced diabetes mellitus (DM) rats by measuring bone mineral density and bone mineral contents and by bone histomorphometry. Wistar rats, 7-8 months old, were used. Osteoporosis was induced by diabetes mellitus, which was established by an intraperitoneal injection of STZ. Rats were separated into five groups: shaminjected, baseline control, vehicle-only-administered, and low-dose (6.0~g/kg) or high-dose (60.0Fg/kg) h-PTHadministered groups, h-PTH or vehicle was injected subcutaneously six times a week for 4 weeks beginning 9 weeks after STZ administration. Bone mineral density and mineral contents were significantly lower in the baseline control and vehicle groups than in the control group. The PTH-administered groups showed higher values compared with both vehicle and baseline control groups. In bone histomorphometry, both bone volume and bone formation in the STZ group were markedly reduced. The h-PTH-administered rats showed increase in both bone volume and bone formation, which are related parameters, but administration of h-PTH did not alter the extent of eroded surface. Our results suggest that intermittent administration of h-PTH is effective in activating bone formation and in preventing further bone loss in osteoporosis developed by STZ-induced DM.

Histomorphometric Evaluation of the Recovering Effect of Human Parathyroid Hormone (1–34) on Bone Structure and Turnover in Streptozotocin-Induced Diabetic Rats

“…In the present study, diabetes markedly inhibited bone formation rate, resulting in low turnover osteopenia, as previously reported [8,[10][11][12][13][14]26]. h-PTH increased bone mass by stimulating the bone formation rate against diabetes.…”

“…Bone histomorphometry was performed with a semiautomatic graphic system as previously described [25,26,[29][30][31]. Measurements were obtained in areas 390 m from the lowest point of the growth plate-metaphyseal junctions in the caudal direction to exclude primary spongiosa, as well as 390 m from endocortical surfaces.…”

“…To date, there has been only one report of h-PTH in diabetic rats with bone loss [26]. However, PTH treatment for trabecular disconnectivity caused by bone loss with low bone turnover has not been sufficiently evaluated.…”

Treatment of bone fragility in patients with diabetes: antiresorptive versus anabolic?

“…In studies of insulin-deficient mouse models that show a reduced BMD phenotype, treatment with intermittent PTH results in increased BMD and bone formation rate [34,35]. Similarly, intermittent PTH administration in mice with diabetes has been demonstrated to improve trabecular bone structure and strength through the anabolic effects of PTH on osteoblast differentiation and improved osteoblast survival [36].…”

Preventive effects of intermittent administration of human parathyroid hormone on steroid-induced osteopenia in rats

“…The author's colleagues have discussed the anabolic effects on bone of the intermittent administration of human-PTH (h-PTH) in ovariectomized, streptozotocin-induced diabetes mellitus, and steroid-induced osteopenia rats. 16,23 Restoring bone mass clinically in established osteoporosis is very difficult, regardless of whether the osteoporosis is involutional or secondary. Steroidinduced osteoporosis, a form of secondary osteoporosis, is a serious condition in young patients who have taken steroids for a long period.…”