Ultrastructural investigations of bone resorptive cells in two types of autosomal dominant osteopetrosis

In order to investigate the ultrastructure of bone resorptive cells in the two types of adult benign human osteopetrosis, iliac crest biopsies were obtained from 11 patients and 10 normal males, who served as a control group. Six patients had the radiological type I (4 women, 2 men, 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 23–48 years, mean 34.1 years) were recruited from the medical staff. The biopsies 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 reduced in number and size hi Type I disease (0.2 ± .7 cells vs. 2.9 ± 1.0 cells per 2.7 mm 2 of bone area, p < 0.01) compared to controls, and stained only weakly for tartrate-resistant acid phosphatase (TRAP). At the ultrastructural level, no signs of active bone resorption were identified, whereas numerous mononuclear cells were observed at the bone surfaces. In type II disease, the osteoclasts were large and highly multi-nucleated, with an increased number (8.3 ± 2.3 cells vs. 2.9 ± 1.0. cells per 2.7 mm 2 of bone area, p < 0.01) compared to controls. In all patients with this type, but never in type I or in the controls, a smooth, TRAP-positive substance was seen between the osteoclasts and the bone surface. Ultrastructurally, this substance was amorphous, with a condensation along the cell membrane. Neither ruffled borders nor clear zones were identified. Nuclear inclusions resembling tubular structures were observed in some osteoclasts in all patients with type II disease. It is concluded that characteristic differences exist between the two types of adult human osteopetrosis at the ultrastructural level. Type I is morphologically similar to some murine mutations characterized by defective maturation of bone resorptive cells. In type II, a defect in the resorptive capacity of their giant osteoclasts is proposed. The pathogenetical significance of nuclear inclusions in type II osteoclasts is unknown.