Anabolic Effect Of PTH Research Articles

Loss of the anabolic effect of parathyroid hormone on bone after discontinuation of hormone in rats

We have previously reported that low doses of hPTH 1–34 given daily to rats exert an anabolic effect on bone. The objective of this study was to determine if the anabolic effect of PTH was dependent upon continued daily administration of the hormone. Young, male rats were given daily subcutaneous injections of either vehicle or 8 μg/100g bw hPTH 1–34 for 12, 16, 20, or 24 days. Additional groups were treated with 8 μg/100g bw hPTH for 12 days followed by vehicle for the next 4, 8, or 12 days, or 8 μg/100g bw hPTH 1–34 for 16 days followed by 4 days of vehicle. We measured calcium (Ca), dry weight (DW), and hydroxyproline (Hyp) of the distal femur, percent of osteoblast (Ob.S/BS) and osteoclast (Oc.S/BS) surface, mineral apposition rate (MAR), double label surface (DLS/BS), and bone formation rate (BFR) in the metaphysis of the proximal tibia, and serum calcium and phosphate. Trabecular and cortical bone Ca and DW and the histologic measures of bone formation increased in all PTH-treated rats. Serum calcium and phosphate were comparable in all rats. The PTH-stimulated bone mass was lost 12 days after discontinuation of PTH. Discontinuation of PTH administration for 4, 8, or 12 days, respectively, resulted in a 72%, 68%, or 50% decrease in Ob.S/BS from the 2- to 3-fold increase associated with PTH treatment ( p < .05). Oc.S/BS increased compared to controls after 4 days of PTH withdrawal (NS), but was comparable to controls 8 days after withdrawal of PTH. The loss of new bone mass after discontinuation of hormone was due to an inhibition of PTH-stimulated bone formation and an initial transient phase of increased resorption. Thus, the anabolic effect of PTH was dependent upon daily administration of the hormone in our model.

Human parathyroid hormone-(1-34) increases bone mass in ovariectomized and orchidectomized rats.

In intact growing rats, intermittent administration of low doses of PTH increases bone mass. As gonadal hormones are considered to be essential for normal bone growth, the anabolic effect of PTH may be mediated or modified by these hormones. The objective of this research was to determine if the anabolic effect of PTH would be altered in female ovariectomized (OVX) and male orchidectomized (ORCHX) rats. Two weeks after ovariectomy, orchidectomy, or sham operations, 5-week-old rats (eight per group) were given daily sc injections of human PTH (1-34) (8 micrograms/100 g) or vehicle. After 12 days of treatment, all rats were killed; castration was confirmed, and sera, femurs, tibias, and kidneys were collected. Calcium (Ca) and dry weight (DW) of trabecular and cortical bone of distal half-femurs were measured. Female OVX rats were osteopenic compared to their sham-operated controls, as the bone mass of distal femurs decreased while body weight increased. In PTH-treated females, total bone Ca and DW per 100 g BW increased significantly by 16% and 21%, respectively, in sham-operated rats and by 21% and 25%, respectively, in OVX rats compared to the appropriate control values. ORCHX rats were also osteopenic, as the bone mass of distal femurs was significantly decreased compared to that in sham-operated males. However, as body weight also decreased, the bone mass per unit BW was not altered. In PTH-treated males, total bone Ca and DW per 100 g BW increased significantly by 34% and 25%, respectively, in sham-operated rats by 32% and 29%, respectively, in ORCHX rats compared to their appropriate control values. Serum Ca, creatinine, and alkaline phosphatase levels were normal and comparable in all rats. We conclude that PTH increased bone mass in control, OVX, and ORCHX rats, and the anabolic response to PTH is not dependent on gonadal hormones.

Indomethacin does not inhibit the anabolic effect of parathyroid hormone on the long bones of rats.

Chronic administration of parathyroid hormone, hPTH 1-34, increased bone mass in normocalcemic, young rats. Since PTH can stimulate prostaglandin E2 (PGE2) production in bone in vitro, and since PGE2 can stimulate bone formation, the anabolic effect of PTH could be mediated by PGE2. To test this hypothesis, experiments were done to determine if indomethacin, which blocks endogenous PG production, would inhibit the anabolic response of bone to PTH. In the first experiment, male Sprague-Dawley rats, 70-100 g, in groups of five, were treated for 12 days with either hPTH 1-34, 8 micrograms/100g/day; PTH vehicle; indomethacin, 2 mg/kg/day; or a combination of PTH and indomethacin. In the second experiment, groups of 6 rats each were given vehicle or hPTH 1-34, 8 micrograms/100g/day, in combination with indomethacin, 0, 1, 2, or 4 mg/kg/day. Subcutaneous injections of PTH wee given once daily and indomethacin was given orally in divided doses, twice a day. Rats were killed on day 12 in both experiments; their sera were analyzed and the trabecular and cortical bone of distal femurs processed to determine calcium (Ca) and hydroxyproline content and dry weight. PTH and indomethacin had no significant effect on serum Ca, phosphate, alkaline phosphatase, urea nitrogen and creatinine, or systemic and long-bone linear growth. In rats treated with PTH alone or in combination with indomethacin, bone Ca of distal femurs increased by 28-44%; dry weight by 29-41%, and hydroxyproline by 17-45%. Indomethacin alone had no effect on bone growth.(ABSTRACT TRUNCATED AT 250 WORDS)