Summary
Heparinotherapy and systemic mastocytosis are two unusual aetiologies of diffuse osteopenia, possibly linked by common pathophysiological factors. Osteoporosis related to heparinotherapy has only been observed in patients treated with doses higher than 10 000 units per day and for more than 4 months. Even in these, it is a rare disorder which has only been reported approximately 15 times in the world literature. Bone histomorphometry has demonstrated the occurrence of marked hyperresorption. In vitro, heparin appears to have resorptive and collagenolytic effects which could play a pathophysiological part in the disorder. Diagnosis of the osteopenic form of systemic mastocytosis may be difficult. Urticaria pigmentosa is a very important clue but may be misdiagnosed or even missing. Hepato or splenomegaly are inconstant. X-rays may show the coexistence of osteosclerotic lesions. Standard biochemical tests are of little help. The urinary excretions of the histamine metabolites methyl histamine and methyl imidazolacetic acid have been found increased when measured. Finally, the diagnosis is made by bone histology which must be performed without decalcification and read by a pathologist informed of the potential diagnosis. Toluidine blue stain shows that mastocytes are numerous in the bone marrow where they are grouped in foci. Histomorphometry demonstrates a high bone turnover with excessive resorption, which could be mediated by heparin or PG E 2 contained in mastocyte granules. Treatment is difficult and may involve cytostatic drugs and/or inhibitors of bone resorption: Clodronate has recently been reported to be at least transiently effective.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Griffith, G.C., Nichols, G., Asher, J.D., Flanagan, B. Heparin osteoporosis. JAMA, 1965, 193, 91–95.
Jaffe, M.D., Willis, P.W. Multiple fractures associated with long-term heparin therapy. JAMA, 1965, 193, 152–154.
Sackler, J.P., Liu, L. Heparin-induced osteoporosis. Br J Radiol 1973, 46, 548–550.
Aarskog, D., Aksnes, L., Lehmann, V. Low 1,25dihydroxyvitamin D in heparin-induced osteopenia. Lancet, 1980, 2, 650–651.
Wise, P.H., Hall, A.J. Heparin-induced osteopenia in pregnancy. Br Med J 1980, 281, 110–111.
Squires, J.W., Pinch, L.W. Heparin-induced spinal fractures. J Am Med Assoc., 1979, 241, 2417–2418.
Megard, M., Cuche, M., Grapeloux, A., Bojoly, C., Meunier, P.J. Ostéoporose de l'héparinothérapie. Analyse histomorphométrique de la biopsie osseuse. Une observation. Nouv Presse Med 1982, 11, 261–264.
Lequesne, M., Lamotte, J., Fourès, N. Ostéoporose de l'héparinothérapie, ostéoporose de la mastocytose. In: L'actualité rhumatologique 1982, Eds: Sèze S. de, Ryckewaert, A., Kahn, M.F., Guérin, C. Expansion Scientifique Française, Paris 1982, 105–115.
De Swiet, M., Dorrington Ward, P., Fidler, J., Horsman, A., Katz, D., Letsky, E., Peacock, M., Wise, P.H. Prolonged heparin therapy in pregnancy causes bone demineralisation. Br J Obstet Gynaecol 1983, 90, 1129–1134.
Avioli, L.V. Heparin-induced osteopenia: an appraisal. Adv Exp Med Biol 1975, 52, 375–387.
Stinchfeis, F.E., Sankaran, B., Samilson, R. Effect of anticoagulant therapy on bone repair. J Bone Joint Surg 1956, 38A, 270–282.
Grillot, G., Petrovic, A. Effects de l'héparine et du fluorure de sodium sur l'os alvéolaire du rat. Sc Rech Odontomatol 1972, 2, 25–26.
Beljan, J.R., Hellewell, A.B. The effect of chronic heparin administration on the mineralization of an experimental osseous defect. Clin Orthop 1977, 125, 205–207.
Sagher, F., Cohen, C., Schorr, S. Concomitant bone changes in urticaria pigmentosa. J Invest Dermatol 1952, 18, 425–432.
Sèze, S. de, Hioco, D., Matraji, H., Tunchot, S., Hubault, A., Dreyfus, P. Ostéoporose et mastocytose. Apropos de deux cas. Semin Hôp Paris 1968, 44, 1609–1615.
Prost, A., Cottin, S., Malkani, K., Bureau, B., Le Bodic, L., Rebel, A. Etude d'une ostéoporose diffuse dans un cas de mastocytose cutanée et osseuses. Rev Rhum 1974, 41, 277–284.
Camus, J.P., Prier, A., Lièvre, J.A., Stephan, J.C., Laveant, C. L'ostéoporose mastocytaire. Rev Rhum 1979, 46, 29–35.
Lucaya, J., Perez-Candela, V., Aso, C., Calvo, J. Mastocytosis with skeletal and gastrointestinal involvement in infancy. Two case reports and a review of the literature. Radiology, 1979, 131, 363–366.
Fallon, M.D., Whyte, M.P., Teitelbaum, S.L. Systemic mastocytosis associated with generalized osteopenia. Histopathological characterisation of the skeletal lesion using undecalcified bone from two patients. Human Pathol 1981, 12, 813–820.
Cyndy, T., Beneton, M.N.C., Darby, A.J., Marshall, W.J., Kanis, J.A. Osteopenia in systemic mastocytosis: natural history and responses to inhibitors of bone resorption. Bone, 1987, 8, 149–155.
Schoenaers, P., De Clerck, L.S., Timmermans, U., Stevens, W.J. Systemic mastocytosis, an unusual cause of osteoporosis. Clin Rheumatol 1987, 6, 458–462.
Gennes, C. de. Mastocytoses osseuses: à propos de sept observations avec étude histomorphométrique. Thesis, Paris, 1987.
Colver, G.B., Ryan, T.J., Dawber, R.P.R., Wojnarowsdka, F., Smith, R. Osteoporosis and mastocytosis with late appearence of urticaria pigmentosa. J Roy Soc Med 1985, 78, 866–867.
Korenblat, P.E., Wedner, J.W., Whyte, M.P., Frankel, S., Avioli, L.V. Systemic mastocytosis. Arch Intern Med 1984, 144, 2249–2253.
Ensslen, R.D., Jakson, F.I., Reid, A.M. Bone and Gallium scans in mastocytosis: Correlation with count rates, radiography and microscopy. J Nucl Med, 1983, 24, 586.
Campbell, E.W., Hector, D., Gossain, V. Heparin activity in systemic mastocytosis. Ann Intern Med, 1979, 90, 240.
Frame, B., Nixon, R.K. Bone marrow mast cells in osteoporosis of aging. N Engl J Med, 1968, 279, 629–630.
Mc Kenna, M.J., Frame, B. The mast cell and bone. Clin Orthop 1985, 200, 226–233.
Bojoly, C., Bouvier, M., Bonversin, B., Lejeune, M. Le mastocyte dans la pathologie osseuse. Nouv Presse Med, 1982, 2703–2706.
Fallon, M.D., Whyte, M.P., Craig, B., Teitelbaum, S.L. Mast cell proliferation in post-menopausal osteoporosis. Calcif Tissue Int, 1983, 35, 29–31.
Hirson, C. Urticaria pigmentosa with disseminated mastocytosis controlled by chlorambucil. Proc Roy Soc Med, 1963, 58, 697.
Conrad, M.E., Carpenter, J.T., Todd, J.N., Murat, T.M. Mithramycin in the treatment of systemic mastocytosis. Ann Intern Med, 1975, 83, 659–660.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bardin, T., Lequesne, M. The osteoporosis of heparinotherapy and systemic mastocytosis. Clin Rheumatol 8 (Suppl 2), 119–123 (1989). https://doi.org/10.1007/BF02207246
Issue Date:
DOI: https://doi.org/10.1007/BF02207246