ULTRASTRUCTURAL INVESTIGATIONS OF BONE RESORPTIVE CELLS IN 2 TYPES OFAUTOSOMAL-DOMINANT OSTEOPETROSIS

In order to investigate the ultrastructure of bone resorptive cells in the two types of adult benign human osteopetrosis, iliac crest biopsi es were obtained from 11 patients and 10 normal males, who served as a control group. Six patients had the radiological type 1 (4 women, 2 m en, aged 23-58 years, mean = 36.5 years), and 5 type II disease (5 men , aged 20-48 years, mean = 29.8 years). The normal controls (aged 23-4 8 years, mean 34.1 years) were recruited from the medical staff. The b iopsies were immediately divided. From each patient, half was embedded in paraffin for histochemistry and light microscopy, and half in epon for transmission electron microscopy. The osteoclasts were markedly r educed in number and size in Type I disease (0.2 +/- .7 cells vs. 2.9 +/- 1.0 cells per 2.7 mm2 of bone area, p < 0.01) compared to controls , and stained only weakly for tartrate-resistant acid phosphatase (TRA P). At the ultrastructural level, no signs of active bone resorption w ere identified, whereas numerous mononuclear cells were observed at th e bone surfaces. In type II disease, the osteoclasts were large and hi ghly multi-nucleated, with an increased number (8.3 +/- 2.3 cells vs. 2.9 +/- 1.0. cells per 2.7 mm2 of bone area, p < 0.01) compared to con trols. In all patients with this type but never in type I or in the co ntrols, a smooth, TRAP-positive substance was seen between the osteocl asts and the bone surface. Ultrastructurally, this substance was amorp hous, with a condensation along the cell membrane. Neither ruffled bor ders, nor clear zones were identified. Nuclear inclusions resembling t ubular structures were observed in some osteoclasts in all patients wi th type II disease. It is concluded that characteristic differences ex it between the two types of adult human osteopetrosis at the ultrastru ctural level. Type I is morphologically similar to some murine mutatio ns characterized by defective maturation of bone resorptive cells. In type II, a defect in the resorptive capacity of their giant osteoclast s is proposed. The pathogenetical significance of nuclear inclusions i n type II osteoclasts is unknown.