Abstract
The daily subcutaneous administration of (dichloromethylene)diphosphonate (clodronate) to 3-day-old normal inbred Wistar-Furth rats for 30 days produces osteopetrotic bone lesions resembling those of the osteopetrotic mutants. Furthermore, tooth eruption is prevented, growth slows down, and signs of runt disease appear. The weight of the thymus is decreased, and T cells from the thymus and spleen respond weakly to mitogens. These thymic disorders associated with defective bone resorption are very similar to those previously reported in the osteopetrotic mutant op rat and support the hypothesis of a link between the thymus and normal bone modeling and remodeling.
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- Bone H. G., 3rd, Zerwekh J. E., Britton F., Pak C. Y. Treatment of calcium urolithiasis with diphosphonate: efficacy and hazards. J Urol. 1979 May;121(5):568–571. doi: 10.1016/s0022-5347(17)56883-4. [DOI] [PubMed] [Google Scholar]
- Douglas D. L., Duckworth T., Russell R. G., Kanis J. A., Preston C. J., Preston F. E., Prenton M. A., Woodhead J. S. Effect of dichloromethylene diphosphonate in Paget's disease of bone and in hypercalcaemia due to primary hyperparathyroidism or malignant disease. Lancet. 1980 May 17;1(8177):1043–1047. doi: 10.1016/s0140-6736(80)91496-8. [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., Russell R. G., Fleisch H. Diphosphonates inhibit formation of calcium phosphate crystals in vitro and pathological calcification in vivo. Science. 1969 Sep 19;165(3899):1264–1266. doi: 10.1126/science.165.3899.1264. [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]
- Hoover R., Fraumeni J. F., Jr Risk of cancer in renal-transplant recipients. Lancet. 1973 Jul 14;2(7820):55–57. doi: 10.1016/s0140-6736(73)93256-x. [DOI] [PubMed] [Google Scholar]
- Horton J. E., Oppenheim J. J., Mergenhagen S. E., Raisz L. G. Macrophage-lymphocyte synergy in the production of osteoclast activating factor. J Immunol. 1974 Oct;113(4):1278–1287. [PubMed] [Google Scholar]
- Horton J. E., Raisz L. G., Simmons H. A., Oppenheim J. J., Mergenhagen S. E. Bone resorbing activity in supernatant fluid from cultured human peripheral blood leukocytes. Science. 1972 Sep 1;177(4051):793–795. doi: 10.1126/science.177.4051.793. [DOI] [PubMed] [Google Scholar]
- Labat M. L., Hurley L. S., Milhaud G. Mesure des principaux paramètres du métabolisme calcique chez le rat ostópétrotique à différentes étapes de la maladie. C R Acad Sci Hebd Seances Acad Sci D. 1975 Feb 24;280(8):995–998. [PubMed] [Google Scholar]
- Milhaud G., Labat M. L., Graf B., Thillard M. J. Guérison de l'ostéopétrose congénitale du rat "op" par greffe de thymus. C R Acad Sci Hebd Seances Acad Sci D. 1976 Sep 20;283(5):531–533. [PubMed] [Google Scholar]
- Milhaud G., Labat M. L., Litwin I., Moricard Y., Moutier R., Rimbaut C., Buffe D., Juster M. Osteopetro-rickets: a new congenital bone disorder. Metab Bone Dis Relat Res. 1981;3(2):91–97. doi: 10.1016/0221-8747(81)90026-6. [DOI] [PubMed] [Google Scholar]
- Milhaud G., Labat M. L., Parant M., Damais C., Chedid L. Immunological defect and its correction in the osteopetrotic mutant rat. Proc Natl Acad Sci U S A. 1977 Jan;74(1):339–342. doi: 10.1073/pnas.74.1.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paupe J., Nézeloff C., Denan B., Vialatte J. L'ostéopétrose avec rachitisme. A propos d'un cas avec étude anatomo-pathologique. Ann Pediatr (Paris) 1967 Oct 2;14(10):2451–2461. [PubMed] [Google Scholar]
- Raisz L. G., Simmons H. A., Gworek S. C., Eilon G. Studies on congenital osteopetrosis in microphthalmic mice using organ cultures: impairment of bone resorption in response to physiologic stimulators. J Exp Med. 1977 Apr 1;145(4):857–865. doi: 10.1084/jem.145.4.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reeve J., Arlot M., Bernat M., Charhon S., Edouard C., Slovik D., Vismans F. J., Meunier P. J. Calcium-47 kinetic measurements of bone turnover compared to bone histomorphometry in osteoporosis: the influence of human parathyroid fragment (hPTH 1-34) therapy. Metab Bone Dis Relat Res. 1981;3(1):23–30. doi: 10.1016/s0221-8747(81)80019-7. [DOI] [PubMed] [Google Scholar]
- Reynolds J. J., Murphy H., Mühlbauer R. C., Morgan D. B., Fleisch H. Inhibition by diphosphonates of bone resorption in mice and comparison with grey-lethal osteopetrosis. Calcif Tissue Res. 1973;12(1):59–71. doi: 10.1007/BF02013722. [DOI] [PubMed] [Google Scholar]
- Russell R. G., Smith R., Bishop M. C., Price D. A. Treatment of myositis ossificans progressiva with a diphosphonate. Lancet. 1972 Jan 1;1(7740):10–11. doi: 10.1016/s0140-6736(72)90004-9. [DOI] [PubMed] [Google Scholar]
- Sarkar B. C., Chauhan U. P. A new method for determining micro quantities of calcium in biological materials. Anal Biochem. 1967 Jul;20(1):155–166. doi: 10.1016/0003-2697(67)90273-4. [DOI] [PubMed] [Google Scholar]
- Simmons D. J., Simmons R. L. Skeletal changes in murine runt disease. Am J Anat. 1967 Jul;121(1):15–28. doi: 10.1002/aja.1001210103. [DOI] [PubMed] [Google Scholar]
- Siris E. S., Sherman W. H., Baquiran D. C., Schlatterer J. P., Osserman E. F., Canfield R. E. Effects of dichloromethylene diphosphonate on skeletal mobilization of calcium in multiple myeloma. N Engl J Med. 1980 Feb 7;302(6):310–315. doi: 10.1056/NEJM198002073020602. [DOI] [PubMed] [Google Scholar]





