Anabolic Effects of Recombinant Human Parathyroid Hormone (1-84) on Bone Histomorphometry in Overiectomized Rats / 대한내분비학회지

To evaluate the anabolic effects of human recombinant parathyroid hormone [hrPTH(1-84)], we examined effect of low-dose and high-dose of [hrPTH(1-84)] and estradiol on bone histomorphometry in ovariectomized rats. Sixty Sprague-Dawley female rats aged 8~10 weeks were used. Eight weeks after ovariectomy, or sham operation, rats were given daily sc injection of hrPTH (1-84), 30 pg/kg (OVX+L group), 150 pg/kg (OVX+H group), 17-estradiol (30 pg/kg, OVX+E group) or vehicle (OVX+V group) for 4 weeks. After double tetracycline labeling, all rats were killed at day 84. We completed the histomorphometric analysis of distal femoral metaphyseal cancellous bone for trabecular bone volume (TBV), mean trabecular plate thickness (MTPT), mean trabecular plate density (MTPD), mean trabecular plate separation (MTPS), mean osteoid seam width (OSW) and appositional rate (AR). The histomorphometric parameters (TBV, MTPT, OSW and AR) of trabecular bone mass in (OVX+E) group were higher than those in (OVX+V) group. The TBV of trabecular bone in PTH treated groups were higher than that in sham operated, (OVX+V) and (OVX+E) group. The histomorphometric parameters (TBV, MTPD, OSW and AR) of trabecular bone mass in (OVX+H) group showed a tendency to be higher than those in (OVX+L) group, but statistically not significant. In conclusion, Low dose (30 mg/kg) hrPTH (1-84) also shows a sufficient anabolic effect on trabecular bone.

Intermittent parathyroid hormone treatment can promote linear growth in the ovariectomized growing rat

To compare the effect of intermittent parathyroid hormone (PTH) treatment with that of estrogen treatment on epiphyseal growth in ovariectomized rats, 46 Sprague-Dawley female rats aged 9-10 weeks (about 200-220 g) were either ovariectomized or sham operated. From 6 weeks after ovariectomy (ovx), rats were daily injected with subcutaneous human recombinant PTH (1-84)-dosed 30 micrograms/kg (the low dose PTH-treated group) or 300 micrograms/kg (the high dose PTH-treated group), 17 beta-estradiol (the 17 beta-estradiol-treated group, 30 micrograms/kg) or vehicle (the ovx-alone group), 5 times a week for 4 weeks. The decalcified sections of the distal femoral epiphyseal plate were analyzed on light microscopy after H&E stain, and the lengths of the zones of proliferation, maturing and hypertrophic chondrocytes were measured. The length of the growth plate, the zone of proliferation and the zone of hypertrophic chondrocyte in the ovx-alone group were significantly shorter than those of the sham-operated group. The treatment of 17 beta-estradiol speeded up the differentiation of cells from proliferating chondrocytes to maturing and hypertrophic chondrocytes even though the length of the growth plate was comparable to that of the sham-operated group. Both low and high dose PTH treatments increased the length of the growth plate, and those lengths were comparable to that of the sham-operated group. The fractions of proliferating, maturing and hypertrophic zone in the low dose PTH-treated group were also comparable to those of the sham-operated group. However, high dose PTH treatment slowed down the differentiation of cells from proliferating chondrocytes to maturing and hypertrophic chondrocytes to a greater extent, and therefore the fraction of proliferating chondrocytes of the high dose PTH-treated group was larger than that of the low dose PTH-treated group (73.8 +/- 1.8 Vs 63.3 +/- 1.3%, p < 0.005). From these results, we showed that intermittent PTH treatment could promote linear growth in the ovariectomized growing rat. We propose that PTH may be an alternative drug candidate for promoting linear growth of long bones without the risk for early closure of the growth plate.