Abstract
This study investigates whether bisphosphonate-treated rats are still able to adapt to low calcium supply through an increase in bone resorption assessed by measuring the urinary excretion of [3H]-tetracycline from chronically prelabeled rats. First it was shown that in this model, parathyroid hormone was responsible for the increase in bone resorption on the low calcium diet. In the second part, animals were treated with the three bisphosphonates—clodronate, alendronate, and ibandronate—given in two doses. Animals receiving a dose that already strongly inhibits bone resorption were still able to respond to a low calcium diet by increasing bone resorption, showing the potency of the latter as a stimulator of bone resorption. Higher doses were, however, able to blunt this response. As soon as the treatment was discontinued, this increase in bone resorption resumed with clodronate but not with alendronate or ibandronate.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Fleisch H, Russell RGG, Francis MD (1969) Diphosphonates inhibit hydroxyapatite dissolution in vitro and bone resorption in tissue culture and in vivo. Science 165:1262–1264
Fleisch H (1995) Bisphosphonates in bone disease: from the laboratory to the patient, 2nd ed. The Parthenon Publishing Group Inc., London, New York
Kanis JA (1991) Drugs used for the treatment of Paget's disease. In: Kanis JA. Pathophysiology and treatment of Paget's disease of bone. Martin Dunitz Ltd, London, pp 159–216
Fleisch H (1991) Bisphosphonates. Pharmacology and use in the treatment of tumour-induced hypercalcaemic and metastatic bone disease. Drugs 42:919–944
Watts NB, Harris ST, Genant HK, Wasnich RD, Miller PD, Jackson RD, Licata AA, Ross P, Woodson GC, Yanover MJ, Mysiw WJ, Kohse L, Rao MB, Steiger P, Richmond B, Chesnut CH III (1990) Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. N Engl J Med 323:73–79
Adami S, Baroni MC, Broggini M, Carretelli L, Caruso I, Gnessi L, Laurenzi M, Lombardi A, Norbiato G, Ortolani S, Ricerca E, Romanini L, Subrizi S, Weinberg J, Yates AJ (1993) Treatment of postmenopausal osteoporosis with continuous daily oral alendronate in comparison with either placebo or intranasal salmon calcitonin. Osteoporosis Int (suppl 3):S21–27
Reid IR, Wattie DJ, Evans MC, Gamble GD, Stapleton JP, Cornish J (1994) Continuous therapy with pamidronate, a potent bisphosphonate, in postmenopausal osteoporosis. J Clin Endocrinol Metab 79:1595–1599
Chesnut CH, McClung MR, Ensrud KE, Bell NH, Genant HK, Harris ST, Singer FR, Stock JL, Yood RA, Delmas PD, Kher U, Pryor-Tillotson S, Santora AC (1995) Alendronate treatment of the postmenopausal osteoporotic woman: effect of multiple dosages on bone mass and bone remodeling. Am J Med 99:144–152
Liberman UA, Weiss SR, Bröll J, Minne HW, Quan H, Bell NH, Rodrigues-Portales J, Downs RW, Dequeker J, Favus M, Seeman E, Recker RR, Capizzi T, Santora AC, Lombardi A, Shah RV, Hirsch LJ, Karpf DB (1995) Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med 333:1437–1443
Klein L, Jackman K (1976) Assay of bone resorption in vivo with 3H-tetracycline. Calcif Tissue Res 20:275–290
Klein L, Wong KM, Simmelink JW (1985) Biochemical and autoradiographic evaluation of bone turnover in prelabeled dogs and rabbits on normal and calcium-deficient diets. Bone 6:395–399
Mühlbauer RC, Fleisch H (1990) A method for continual monitoring of bone resorption in rats: evidence for a diurnal rhythm. Am J Physiol 258:R679-R689
Mühlbauer RC, Fleisch H (1990) The diurnal rhythm of bone resorption in the rat. Effect of feeding habits and pharmacological inhibitors. J Clin Invest 95:1933–1940
Trechsel U, Stutzer A, Fleisch H (1987) Hypercalcemia induced with an arotinoid in thyroparathyroidectomized rats. A new model to study bone resorption in vivo. J Clin Invest 80:1679–1686
Mühlbauer RC, Bauss F, Schenk R, Janner M, Bosies E, Strein K, Fleisch H (1991) BM 21.0955, a potent new bisphosphonate to inhibit bone resorption. J Bone Miner Res 6:1003–1011
Mühlbauer RC, Bonjour JP, Fleisch H (1977) Tubular localization of adaptation to dietary phosphate in rats. Am J Physiol 233:F342-F348
Wong KM, Singer L, Ophaug RH (1980) Metabolic aspects of bone resorption in calcium-deficient lactating rats. Calcif Tissue Int 32:213–219
Kalu DN, Hadji-Georgopoulos A, Sarr MG, Solomon BA, Foster GV (1974) The role of parathyroid hormone in the maintenance of plasma calcium levels in rats. Endocrinology 95:1156–1165
Haldimann B, Bonjour JP, Fleisch H, (1977) Role of parathyroid hormone in regulation of main calcium fluxes in rats. Am J Physiol 232:E535-E541
Inomata N, Akiyama M, Kubota N, Jüppner H (1995) Characterization of a novel parathyroid hormone (PTH) receptor with specificity for the carboxyl-terminal region of PTH-(1-84). Endocrinology 136:4732–4740
Gasser AB, Morgan DB, Fleisch HA, Richelle LJ (1972) The influence of two diphosphonates on calcium metabolism in the rat. Clin Sci 43:31–45
Morgan DB, Gasser A, Largiadèr U, Jung A, Fleisch H (1975) Effects of a diphosphonate on calcium metabolism in calcium-deprived rats. Am J Physiol 228:1750–1756
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
Adami S, Bolzicco GP, Rizzo A, Salvagno G, Bertoldo F, Rossini M, Suppi R, Lo Cascio V (1987) The use of dichloromethylene bisphosphonate and aminobutane bisphosphonate in hypercalcemia of malignancy. Bone Miner 2:395–404
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Antic, V.N., Fleisch, H. & Mühlbauer, R.C. Effect of bisphosphonates on the increase in bone resorption induced by a low calcium diet. Calcif Tissue Int 58, 443–448 (1996). https://doi.org/10.1007/BF02509445
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02509445