Maintenance of vertebral body bone mass and strength created by human parathyroid hormone treatment in ovariectomized rats

Abstract

The purpose of this cross-sectional study was to evaluate the effects of human parathyroid hormone (1–84) (hPTH) followed by maintenance administration of 17β-estradiol (E 2), risedronate (Ris), or a reduced dose of hPTH (LowPTH) on vertebral body bone mineral density (BMD) and bone strength in ovariectomized (ovx) rats. Eight groups of ovx (219 rats) and one group of intact female rats (48 rats) were left untreated for 11 weeks (age 3.5 months at the beginning). For the following 12 weeks, four ovx groups received subcutaneous injections of hPTH (75 μg/kg per day, 3 days/week) and four groups received vehicle. Treatments were then changed to: E 2 (10 μg/kg per day, 2 days/week); Ris (3 μg/kg per day, 3 days/week); LowPTH (25 μg/kg per day, 3 days/week); or vehicle for 36 weeks. Bone tissue was collected at weeks −11 (baseline), 0 (ovx effect), 12 (hPTH effect), 24, 36, and 48 (maintenance effect). The endpoints were vertebral body BMD, ultimate stress (Ultstr), and moduli of elasticity from compression tests (ModM), and from ultrasound tests (ModUS). Ovariectomy resulted in lower BMD ( p < 0.001). The hPTH treatment for 12 weeks restored BMD to the level of intact rats. Ultstr and ModUS followed a similar pattern, but the ovx-induced Ultstr was not significant ( p = 0.073, ModUS: p = 0.003), nor was the hPTH-induced increase in ModUS ( p = 0.131, Ultstr: p = 0.02). After hPTH withdrawal, BMD, Ultstr, and ModUS levels were not different from levels in ovx animals. In Ris-treated rats pretreated with hPTH, BMD (weeks 24 and 48, p < 0.002) and ModUS (week 24, p = 0.018) values were greater than in ovx animals. In LowPTH-treated rats pretreated with hPTH, BMD (weeks 24 and 48, p < 0.001) and Ultstr (week 48, p = 0.005) were greater than in ovx animals. In E 2-treated rats pretreated with hPTH, BMD was greater than in ovx rats at week 24 ( p = 0.009), but did not differ at weeks 36–48. Neither Ultstr nor ModUS in E 2-treated rats differed significantly from ovx rats at any timepoint. Of the agents and dosing regimens used, we conclude that the hPTH-related vertebral bone mass gain in ovx rats can be maintained for up to 36 weeks with risedronate and low-dose hPTH treatment. Bone strength is maintained by treatment with low-dose hPTH, but only partially maintained with risedronate.