The osteoporosis of heparinotherapy and systemic mastocytosis.

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.