Summary
To prevent the high turnover bone remodeling associated with acute estrogen deficiency, the bisphosphonate [2-(2-pyridinyl) ethylidene-BP] (2-PEBP) was administered to oophorectomized (OX) rats. Three groups of 15 rats each (250 g) were studied. Group (Gp) A was sham operated, Gp B was OX, and Gp C received 2-PEBP (1.72 mg/kg/day) intraperitoneally for 3 days commencing 4 days postoophorectomy. Oophorectomy was confirmed with serum estradiol measurements. Blood samples were collected on days −7, 0, 7, 14, 21, and 28 for ionized calcium (Ca2+), PTH, and serum bone gla protein (BGP). Rats received tetracycline for bone histomorphometric labeling. All results were compared to Gp A. Body weight increased significantly in Gps B and C (P<0.005 by day 28). There was no significant difference in Ca2+, and PTH levels in Gps B and C were similar to Gp A. BGP levels were significantly higher on day 28 in Gp B (P<0.05). In Gp C, BGP levels were significantly decreased on days 7,21, and 28 (P<0.03). Gp B revealed increased bone turnover without loss of bone volume (BV/TV). BV/TV was significantly increased in Gp C despite a decrease in parameters of bone formation and normal osteoclast number. In conclusion, 2-PEBP in the OX rat inhibited bone resorption more than formation with resultant hyperostosis. Serum BGP appeared to be a good marker of the changes observed on bone histomorphometry.
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References
Fleisch H (1983) Bisphosphonates: mechanisms of action and clinical applications. In: Peck W (ed). Bone and mineral research annual. I. Elsevier, Amsterdam, pp 319–357
Meunier PJ, Alexandre C, Edouard C, Mathieu L, Chapuy MC, Bressot C, Vigrion E, Trechsel U (1979) Effects of disodium dichloromethylenediphosphanate on Paget's disease of bone. Lancet 2:489–492
Hasling C, Charles P, Mosekilde L (1986) Etidronate disodium for treating hypercalcemia of malignancy: a doubleblind, placebo-controlled study. Eur J Clin Invest 16(5)433–437
Minaire P, Berard E, Meunier PJ, Edouard C, Goedert G, Pilonchery G (1981) Effects of disodium dichloromethylene diphosphonate on bone loss in paraplegic patients. J Clin Invest 68:1086–1092
Storm T, Thamsborg G, Sorensen OH, Lund B (1987) The effect of etidronate therapy in postmenopausal women: preliminary results. In: Christianse C (ed) Osteoporosis 1987. Osteopress Aps, Denmark, pp 20–24
Stutzer A, Trechsel U, Fleisch H, Schenk R (1987) Effect of bisphosphonates on osteoclast number and bone resorption in the rat (abstract 266) J Bone Min Res 2:S1
Lowik CWGM, Van der Pluijm G, Van der Wee-Pals LJA, Bloys van Treslong-de-Groot H, Bijvoet OLM (1988), Migration and phenotypic transformation of osteoclast precursors into mature osteoclasts: the effect of a bisphosphonate. J Bone Min Res 3:185–192
Reynolds JJ, Minkin C, Morgan DB, Spycher D, Fleisch H (1972) The effect of two diphosphonates on the resorption of mouse calvaria in vitro. Calcif Tissue Res. 10:302–313
Frijlink WB, TeVelde J, Bijvoet OLM, Heynen G (1979) Treatment of Paget's disease with (3 amino-1 hydroxypropylidene)-1, 1-bisphosphonate (APD). Lancet 1:799–803
Reitsma PH, Bijvoet OLM, Verlinden-Ooms H, Van der Wee-Pals LJA (1980) Kinetic studies of bone and mineral metabolism during treatment with (3 amino-1-hydroxy-propylidene)-1, 1-bisphosphonate (APD) in rats. Calcif Tissue Int 32:145–147
Schenk R, Eggli P, Fleisch H, Rosini S (1986) Quantitative morphometric evaluation of the inhibitory activity of new amino bisphosphonates on bone resorption in the rat. Calcif Tissue Int 38:342–349
Stutzer A, Fleisch H, Trechsel U (1988) Short- and long-term effects of a single dose of bisphosphonates on retinoid-induced bone resorption in thyroparathyroidectomized rats. Calcif Tissue Int 43:294–299
Ismail F, Epstein S, Fallon MD, Thomas SB, Reinhardt TA (1988) Serum bone gla protein and the vitamin D endocrine system in the oophorectomized rat. Endocrinology 122:624–630
Price PA, Lothringer JW, Nishimoto SK (1980) Absence of the vitamin K-dependent bone protein in fetal rat mineral. J Biol Chem 255:2938–2942
Jowell PS, Epstein S, Fallon MD, Reinhardt TA, Ismail F (1987) 1,25 dihydroxyvitamin D3 modulates glucocorticoid-induced alteration in serum bone gla protein and bone histmorphometry. Endocrinology 120:531–536
Movsowitz C, Epstein S, Fallon MD, Ismail F, Thomas SB (1988) Cyclosporin A in vivo produces severe osteopenia in the rat: effect of dose and duration of administration. Endocrinology 123: 2571–2577
Toverud SU, Boass A, Gardner SC, Endress DB (1986) Circulating parathyroid hormone concentrations in normal and vitamin D-deprived rat pups determined with N-terminal-specific radioimmunoassay. Bone Mineral 1:145–155
Glowacki J, Rey C, Cox KA, Lian J (1988) The role of osteocalcin in osteoclast differentiation. 2nd Intl Workshop on Cells and Cytokines in Bone and Cartilage (abstract 120) Calcif Tissue Int
Wronski TJ, Schenck PA, Cintron M, Walsh CC (1987) Effect of body weight on osteopenia in ovariectomized rats. Calcif Tissue Int 40:155–159
Bevans J, Johnson K, Slough C, Benedict J, Fleisch H, Black J (1985) Skeletal effects of 2-(2-pyridinyl) ethylidene bisphosphonate in acute and subchronic rat studies. Calcif Tissue Int 38:31
Kozak S, Rizzoli R, Trechsel U, Fleisch H (1987) Effect of a single injection of 2 new bisphosphonates on the hypercalcemia and hypercalciuria induced by Walker CA256/B thyroparathyroidectomized rats. Cancer Res 47:6193–6197
Guaitani A, Geddes A, Boyce R, Filippeschi S, Bassani D (1987) Effect of bisphosphonate derivatives on animal models of bone cancer. 9th Ann Scientific Meeting American Soc for Bone and Min Res, Indianapolis, IN
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Movsowitz, C., Epstein, S., Fallon, M. et al. Hyperstosis induced by the bisphosphanate (2-PEBP) in the oophoretomized rat. Calcif Tissue Int 46, 195–199 (1990). https://doi.org/10.1007/BF02555044
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DOI: https://doi.org/10.1007/BF02555044