Drug-induced prevention of gastrectomy- and ovariectomy-induced osteopaenia in the young female rat.
Journal article, 2002
Both ovariectomy (Ovx) and gastrectomy (Gx) induce osteopaenia in rats and humans. While the effect of Ovx has been ascribed to oestrogen deficiency, the underlying mechanism behind Gx is poorly understood. Alendronate, oestrogen and parathyroid hormone (PTH) are known to prevent the osteopaenia induced by Ovx in rats. The purpose of the present study was to determine whether alendronate, oestrogen or PTH could also prevent Gx-evoked osteopaenia. Rats were Ovx-, Gx-, or were sham-operated (Sham) and were then treated with alendronate (50 micro g/kg/day), oestrogen (10 micro g/kg/day) or PTH(1-84) (75 micro g/kg/day) for eight weeks. At sacrifice, serum PTH was unaffected by surgery (Ovx, 64+/-8 pg/ml; Gx, 75+/-13 pg/ml; Sham, 58+/-11 pg/ml). The bone mineral density (BMD) of the fifth lumbar vertebra (L5) was analysed. Ovx and Gx reduced the BMD (ash weight/Volume) of the L5 by 15+/-4% and 22+/-3% respectively. Trabecular BMD and the cortical bone mineral content (BMC) of the femur were assessed using peripheral computed tomography. Both Ovx and Gx markedly reduced trabecular BMD in the metaphyseal area of the distal femur (Ovx, -37+/-7%; Gx, -49+/-7%). The cortical BMC of the femur was only slightly reduced. Alendronate prevented trabecular bone loss after both Ovx and Gx, while oestrogen and PTH prevented trabecular bone loss after Ovx but not after Gx. In conclusion, the bisphosphonate alendronate prevented both Ovx- and Gx-induced trabecular bone loss. In contrast, PTH and oestrogen prevented Ovx-induced but not Gx-induced trabecular bone loss, suggesting that the mechanism behind the trabecular bone loss in Ovx rats differs from that in Gx rats. The results support the notion that the mechanism of action for the bone-sparing effect of these drugs differs. The ability of alendronate, and probably also other bisphosphonates, to prevent Gx-evoked osteopaenia in the rat might be of potential clinical interest when dealing with post-Gx osteopaenia in humans.
Humans
blood
prevention & control
Rats
blood
Metabolic
therapeutic use
Analysis of Variance
Postmenopausal
Rats
Tomography
therapeutic use
Animal
Osteoporosis
Models
blood
Animals
Gastrectomy
Bone Diseases
Recombinant Proteins
X-Ray Computed
Osteocalcin
Biological Markers
Parathyroid Hormone
Random Allocation
Bone Density
Sprague-Dawley
Female
Alendronate
blood
Ovariectomy
drug effects
Estradiol
Gastrins
therapeutic use
therapeutic use
Author
Niklas Andersson
University of Gothenburg
V V Surve
Daisy Lehto-Axtelius
Claes Ohlsson
University of Gothenburg
Rolf Håkanson
K Andersson
Birgitta Ryberg
Journal of Endocrinology
0022-0795 (ISSN) 14796805 (eISSN)
Vol. 175 3 695-703Subject Categories
MEDICAL AND HEALTH SCIENCES
PubMed
12475380