Summary
Disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) may impair mineralization and reduce turnover of bone. However, its administration has been shown to lead to an accumulation of osteoid in both man and the rat. Using rats, the effects of surgical parathyroidectomy and administration of EHDP (30 mg EHDP/kg body weight by subcutaneous injection daily for 5 days) upon bone composition, uptake of3H-proline into hydroxyproline in bone and the subsequent urinary excretion of labelled and unlabelled hydroxyproline have been compared. Both parathyroidectomized (PTX) rats and EHDP-treated animals accumulated more hydroxyproline in bone and excreted less total urinary hydroxyproline than sham-PTX control animals, the changes induced by EHDP being of greater magnitude than those induced by surgical parathyroidectomy. Skeletal buildup of hydroxyproline was associated with decreased catabolism of mature collagen rather than enhanced synthesis of hydroxyproline in bone. EHDP administration, although decreasing urinary excretion of newly synthesised hydroxyproline, did not alter the skeletal synthesis of hydroxyproline as measured by uptake of3H-proline. In all parameters measured, responses to EHDP were similar in PTX and sham-PTX rats. It is concluded that depression of parathyroid hormone mediated bone turnover may have contributed to, but did not fully account for, the lowering of bone turnover and changes in bone composition induced by EHDP in sham-PTX rats in the present experiment.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bergman, I., Loxley, R.: The determination of hydroxyproline in urine hydrolysates. Clinica chim. Acta27, 347–349 (1970)
Briggs, A.P.: Some applications of the colorimetric phosphate method. J. biol. Chem.49, 255–264 (1924)
Firschein, H.E.: Collagen and mineral dynamics in bone. Clin. Orthop. Related Res.66, 212–225 (1969)
Flanagan, R., Nichols, G.: Bone matrix turnover and balance in vitro. I. The effects of parathyroid hormone and thyrocalcitonin. J. clin. Invest.48, 595–606 (1969)
Gasser, A.G., Morgan, D.B., Fleisch, H.A., Richelle, L.J.: The influence of two diphosphonates on calcium metabolism in the rat. Clin. Sci.43, 31–45 (1972)
Goulding, A., Malthus, R.S.: Effect of dietary magnesium on the development of nephrocalcinosis in rats. J. Nutr.97, 353–358 (1969)
Goulding, A., Malthus, R.S.: Effects of parathyroidectomy on the development of nephrocalcinosis and calcium, phosphorus and magnesium balance in rats. J. Endocr.49, 29–37 (1971)
Goulding, A., McChesney, R., Malthus, R.S.: Diminished urinary excretion of cyclic AMP by rats given disodium ethane-1-hydroxy-1,1-diphosphonate. J. Endocr.65, 145–146 (1975)
Guncaga, J., Lauffenburger, Th., Lentner, C., Dambacher, M.A., Haas, H.G.: Diphosphonate treatment of Paget's disease of bone. Horm. Metab. Res.6, 62–69 (1974).
Haddad, J.G., Couranz, S., Avioli, L.V.: Nondialyzable urinary hydroxyproline as an index of bone collagen formation. J. clin. Endocr. Metab.30, 282–287 (1970)
Kalu, D.N.: Evaluation of a new technique for measuring bone formation. Med. Lab. Technol.32, 91–98 (1975)
Kivirikko, K.I.: Urinary excretion of hydroxyproline in health and disease. Int. Rev. Conn. Tiss. Res.5, 93–163 (1970)
Laitinen, O.: Parathyroid-induced changes in collagen and calcium metabolism in vivo. Endocrinology80, 815–824 (1967)
Jowsey, J., Riggs, B.L., Kelly, P.J., Hoffman, D.L., Bordier, P.: The treatment of osteoporosis with disodium ethane-1-hydroxy-1,1-diphosphonate. J. Lab. clin. Med.78, 574–584 (1971)
Meunier, P., Chapuy, M.C., Courpron, P., Vignon, E., Edouard, C., Bernard, J.: Effets cliniques, biologiques et histologiques de l'éthane-1-hydroxy-1,1-diphosphonate (EHDP) dans la maladie de Paget. Rev. Rhum. Mal Osteo-artic.42, 699–705 (1975)
Miller, S.C., Jee, W.S.S.: Ethane-1-hydroxy-1,1-diphosphonate (EHDP) effects on growth and modeling of the rat tibia. Calcif. Tiss. Res.18, 215–231 (1975)
Minkin, C., Rabadjija, Goldhaber, P.: Bone remodeling in vitro: the effects of two diphosphonates on osteoid synthesis and bone resorption in mouse calvaria. Calcif. Tiss. Res.14, 161–168 (1974)
Rosenblum, I.Y.: The effects of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on mineral and organic components of rat bone. Calcif. Tiss. Res.16, 239–250 (1974)
Russell, R.G.G., Muhlbauer, R.C., Bisaz, S., Williams, D.A., Fleisch, H.A.: The influence of pyrophosphates, condensed phosphates, phosphonates, and other phosphate compounds on the dissolution of hydroxyapatite in vitro and on bone resorption induced by parathyroid hormone in tissue culture and in thyroparathyroidectomized rats. Calcif. Tiss. Tes.6, 183–196 (1970)
Russell, R.G.G., Kislig, A., Casey, P.A., Fleisch, H.: Effect of diphosphonates and calcitonin on the chemistry and quantitative histology of rat bone. Calcif. Tiss. Res.11, 179–195 (1973)
Russell, R.G.G., Smith, R., Preston, C., Walton, R.J., Woods, C.G.: Diphosphonates in Paget's disease. Lancet1974 I, 894–898
Schenk, R., Merz, W.A., Muhlbauer, R., Russell, R.G.G., Fleisch, H.: Effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) and dichloromethylene diphosphonate (Cl2MDP) on the calcification and resorption of cartilage and bone in the tibial epiphysis and metaphysis of rats. Calcif. Tiss. Res.11, 196–214 (1973)
Turner, J.C.: Tritium counting with the Triton X-100 scintillant. Int. J. Radiat. Biol.20, 499–505 (1969)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Goulding, A., McChesney, R. Comparison of effects of parathyroidectomy and ethane-1-hydroxy-1,1-diphosphonate (EHDP) administration upon bone synthesis of hydroxyproline and urinary excretion of hydroxyproline in rats. Calc. Tis Res. 23, 115–119 (1977). https://doi.org/10.1007/BF02012775
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02012775