Abstract
The administration of 4 mg/kg/day of dichloromethane diphosphonate (Cl2MDP) subcutaneously to pregnant cows fed a low-calcium diet significantly reduced bone resorption as indicated by microradiographic evaluation of endosteal surfaces of cross sections of ribs. Plasma parathyroid hormone levels were similar between Cl2MDP-treated and control cows prepartum, during EDTA infusions, and near parturition. Ultrastructurally, chief cells of the parathyroid glands of both groups of cows were in the active stage of the secretory cycle. The chronically stimulated chief cell from cows administered Cl2MDP had a large cytoplasmic area containing many lipofuscin granules and lysosomal bodies and a few secretory granules near the large Golgi apparatus or aligned along the plasma membrane. Uptake of calcium 45 by the duodenal mucosa incubated in vitro was greater in Cl2MDP-treated cows compared to control cows. The administration of Cl2MDP significantly reduced rapidly mobilization calcium reserves. Following an intravenous EDTA infusion and the spontaneous calcium drain associated with parturition and the beginning of lactation, Cl2MDP-treated cows developed severe hypocalcemia. The rapid mobilization of calcium reserves in cows administered Cl2MDP prepartum was impaired mainly because of diminished resorption of bone despite adequate parathyroid hormone secretion in response to severe postpartal or EDTA-induced hypocalcemia.
Full text
PDF

















Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Black H. E., Capen C. C., Arnaud C. D. Ultrastructure of parathyroid glands and plasma immunoreactive parathyroid hormone in pregnant cows fed normal and high calcium diets. Lab Invest. 1973 Aug;29(2):173–185. [PubMed] [Google Scholar]
- Black H. E., Capen C. C. Urinary and plasma hydroxyproline during pregnancy, parturition and lactation in cows with parturient hypocalcemia. Metabolism. 1971 Apr;20(4):337–344. doi: 10.1016/0026-0495(71)90095-3. [DOI] [PubMed] [Google Scholar]
- Bonjour J. P., Fleisch H., Copp D. H. Influence of a diphosphonate on serum calcium homeostasis. Proc Soc Exp Biol Med. 1973 Jun;143(2):404–407. doi: 10.3181/00379727-143-37331. [DOI] [PubMed] [Google Scholar]
- CLARKE J. T. Colorimetric determination and distribution of urinary creatinine and creatine. Clin Chem. 1961 Aug;7:371–383. [PubMed] [Google Scholar]
- Cooper C. W., Hirsch P. F., Toverud S. U., Munson P. L. An improved method for the biological assay of thyrocalcitonin. Endocrinology. 1967 Sep;81(3):610–616. doi: 10.1210/endo-81-3-610. [DOI] [PubMed] [Google Scholar]
- Fleisch H., Russell R. G., Francis M. D. Diphosphonates inhibit hydroxyapatite dissolution in vitro and bone resorption in tissue culture and in vivo. Science. 1969 Sep 19;165(3899):1262–1264. doi: 10.1126/science.165.3899.1262. [DOI] [PubMed] [Google Scholar]
- Francis M. D. The inhibition of calcium hydroxypatite crystal growth by polyphosphonates and polyphosphates. Calcif Tissue Res. 1969;3(2):151–162. doi: 10.1007/BF02058658. [DOI] [PubMed] [Google Scholar]
- Gasser A. B., Morgan D. B., Fleisch H. A., Richelle L. J. The influence of two diphosphonates on calcium metabolism in the rat. Clin Sci. 1972 Jul;43(1):31–45. doi: 10.1042/cs0430031. [DOI] [PubMed] [Google Scholar]
- JOWSEY J., PHIL D., KELLY P. J., RIGGS B. L., BIANCO A. J., Jr, SCHOLZ D. A., GERSHON-COHEN J. QUANTITATIVE MICRORADIOGRAPHIC STUDIES OF NORMAL AND OSTEOPOROTIC BONE. J Bone Joint Surg Am. 1965 Jun;47:785–806. [PubMed] [Google Scholar]
- Kivirikko K. I., Laitinen O., Prockop D. J. Modifications of a specific assay for hydroxyproline in urine. Anal Biochem. 1967 May;19(2):249–255. doi: 10.1016/0003-2697(67)90160-1. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Martin D. L., Deluca H. F. Calcium transport and the role of vitamin D. Arch Biochem Biophys. 1969 Oct;134(1):139–148. doi: 10.1016/0003-9861(69)90260-4. [DOI] [PubMed] [Google Scholar]
- Melson G. L., Chase L. R., Aurbach G. D. Parathyroid hormone-sensitive adenyl cyclase in isolated renal tubules. Endocrinology. 1970 Mar;86(3):511–518. doi: 10.1210/endo-86-3-511. [DOI] [PubMed] [Google Scholar]
- Morgan D. B., Gasser A., Largiadér U., Jung A., Fleisch H. Effects of a diphophonate on calcium metabolism in calcium-deprived rats. Am J Physiol. 1975 Jun;228(6):1750–1756. doi: 10.1152/ajplegacy.1975.228.6.1750. [DOI] [PubMed] [Google Scholar]
- Morgan D. B., Monod A., Russel R. G., Fleisch H. Influence of dichloromethylene diphosphonate (Cl2MDP) and calcitonin on bone resorption, lactate production and phosphatase and pyrophosphatase content of mouse calvaria treated with parathyroid hormone in vitro. Calcif Tissue Res. 1973 Dec 31;13(4):287–294. doi: 10.1007/BF02015418. [DOI] [PubMed] [Google Scholar]
- Pilczyk R., Sutcliffe H., Martin T. J. Effects of pyrophosphate and diphosphonates on parathyroid hormone- and fluoride-stimulated adenylate cyclase activity. FEBS Lett. 1972 Aug 1;24(2):225–228. doi: 10.1016/0014-5793(72)80772-5. [DOI] [PubMed] [Google Scholar]
- Recker R. R., Hassing G. S., Lau J. R., Saville P. D. The hyperphosphatemic effect of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP TM ): renal handling of phosphorus and the renal response to parathyroid hormone. J Lab Clin Med. 1973 Feb;81(2):258–266. [PubMed] [Google Scholar]
- Reynolds J. J., Minkin C., Morgan D. B., Spycher D., Fleisch H. The effect of two diphosphonates on the resorption of mouse calvaria in vitro. Calcif Tissue Res. 1972;10(4):302–313. doi: 10.1007/BF02012561. [DOI] [PubMed] [Google Scholar]
- Russell R. G., Mühlbauer R. C., Bisaz S., Williams D. A., Fleisch H. The influence of pyrophosphate, 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 thyroparathyroidectomised rats. Calcif Tissue Res. 1970;6(3):183–196. doi: 10.1007/BF02196199. [DOI] [PubMed] [Google Scholar]
- Segre G. V., Tregear G. W., Potts J. T., Jr Development and application of sequence-specific radioimmunoassays for analysis of the metabolism of parathyroid hormone. Methods Enzymol. 1975;37:38–66. doi: 10.1016/s0076-6879(75)37005-5. [DOI] [PubMed] [Google Scholar]
- Steiner A. L., Kipnis D. M., Utiger R., Parker C. Radioimmunoassay for the measurement of adenosine 3',5'-cyclic phosphate. Proc Natl Acad Sci U S A. 1969 Sep;64(1):367–373. doi: 10.1073/pnas.64.1.367. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Talmage R. V. Effect of fasting and parathyroid hormone injection on plasma 45Ca concentrations in rats. Calcif Tissue Res. 1975;17(2):103–112. doi: 10.1007/BF02547283. [DOI] [PubMed] [Google Scholar]
- Wasserman R. H., Corradino R. A., Taylor A. N. Vitamin D-dependent calcium-binding protein. Purification and some properties. J Biol Chem. 1968 Jul 25;243(14):3978–3986. [PubMed] [Google Scholar]
- Yarrington J. T., Capen C. C., Black H. E., Re R., Potts J. T., Jr, Geho W. B. Experimental parturient hypocalcemia in cows following prepartal chemical inhibition of bone resportion. Am J Pathol. 1976 Jun;83(3):569–588. [PMC free article] [PubMed] [Google Scholar]