Cp. Jerome et al., Effect of treatment for 6 months with human parathyroid hormone (1-34) peptide in ovariectomized cynomolgus monkeys (Macaca fascicularis), BONE, 25(3), 1999, pp. 301-309
A potential negative side effect of intermittent parathyroid hormone (PTH)
therapy to treat osteoporosis is the lass of cortical bone concomitant with
increased cancellous bone mass. We addressed this issue by studying the ef
fects of PTH on whole-body, axial, and appendicular bone mass in an animal
model with haversian cortical bone remodeling. Ovariectomized, young adult
female cynomolgus monkeys were assigned to placebo (n = 9) or PTH groups (n
= 10), The PTH group received 10 mu g/kg synthetic human PTH(134) peptide
by subcutaneous injection, 3 days/week for 6 months, and the placebo group
received vehicle. Multiple endpoints of bone mass, strength, and turnover i
n the axial and appendicular skeleton were assessed, including dual-energy
X-ray absorptiometry (DEXA), quantitative computed tomography (qCT), analys
is of serum (calcium, phosphorus, alkaline phosphatase, osteocalcin, and ta
rtrate-resistant acid phosphatase) and urinary (calcium and creatinine) bio
markers, histomorphometry, and biomechanical testing, Compared with placebo
-treated animals, PTH-treated monkeys had no change in whole-body bone mass
, but a 6.7% increase in spinal areal bone mineral density (aBMD) was obser
ved. Cortical bone mass measured by qCT at appendicular sites was not affec
ted by PTH treatment, but there were significant increases in cancellous bo
ne mass in the proximal tibia, and a similar trend in the distal radius. Sm
all, transient increases in serum and urinary calcium were observed, but th
ere were no treatment-related effects on other biochemical endpoints. Incre
ased bone formation rate (BFR/BV) in the midradius and midfemur was accompa
nied by a nonsignificant increase in midfemur porosity. Increased vertebral
cancellous bone volume (BV/TV) was associated with greater trabecular and
interstitial thickness with no effect on wall thickness, Increases in bone
strength were observed in both axial (vertebral maximum stress and load at
fracture) and appendicular (femoral neck fracture load) skeleton, Together,
these results indicate that PTH therapy in the cynomolgus monkey results i
n a net gain of spinal and appendicular cancellous bone mass with no advers
e effect on cortical bone. (C) 1999 by Elsevier Science Inc. All rights res
erved.