E. Samnegard et al., Maintenance of vertebral body bone mass and strength created by human parathyroid hormone treatment in ovariectomized rats, BONE, 28(4), 2001, pp. 414-422
The purpose of this cross-sectional study was to evaluate the effects of hu
man parathyroid hormone (1-84) (hPTH) followed by maintenance administratio
n of 17 beta -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, Fight groups of ovx (219 rats) and one group of
intact female rats (48 rats) were left untreated for 11 weeks (age 3.5 mon
ths at the beginning). For the following 12 weeks, four ovx groups received
subcutaneous injections of hPTH (75 mug/kg per day, 3 days/week) and four
groups received vehicle. Treatments were then changed to: E-2 (10 mug/kg pe
r day, 2 days/week); Ris (3 mug/kg per day, 3 days/week); LowPTH (25 mug/kg
per day, 3 days/ week); or vehicle for 36 weeks. Bone tissue was collected
at weeks -11 (bascline), 0 (ovx effect), 12 (hPTH effect), 24, 36, and 48
(maintenance effect), The endpoints were vertebral body BMD, ultimate stres
s (Ultstr), and moduli of elasticity from compression tests (ModM), and fro
m 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. U
ltstr 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 inc
rease in ModUS (p = 0.131, Ultstr: p = 0.02). After hPTH withdrawal, BMD, U
ltstr, and ModUS levels were not different from levels in ovx animals. In R
is-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 LowP
TH-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-treate
d 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 t
he agents and dosing regimens used, we conclude that the hPTH-related verte
bral bone mass gain in ovx rats can be maintained for up to 36 weeks with r
isedronate and low-dose hPTH treatment. Bone strength is maintained by trea
tment with low-dose hPTH, but only partially maintained with risedronate. (
Bone 28:414-422; 2001) (C) 2001 by Elsevier Science Inc. All rights reserve
d.