Drug-induced prevention of gastrectomy- and ovariectomy-induced osteopaenia in the young female rat.
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.
Andersson
N
N
Department of Pharmacology, Institute of Physiological Sciences, Lund University, BMC F-13, S-221 84 Lund, Sweden.
Surve
V V
VV
Lehto-Axtelius
D
D
Ohlsson
C
C
Håkanson
R
R
Andersson
K
K
Ryberg
B
B
D019386:Alendronate / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000517:prevention & control*; D004958:Estradiol / Q000627:therapeutic use; D005260:Female; D005743:Gastrectomy; D005755:Gastrins / Q000097:blood; D006801:Humans; D023421:Models, Animal; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000097:blood / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed
D015415:Biomarkers; D005755:Gastrins; D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D015675:Osteocalcin; D004958:Estradiol; D019386:Alendronate