Variable osteoclast appearance in human infantile osteopetrosis.

A light and transmission electron microscopic (TEM) study of iliac crest metaphyseal bone from nine patients with infantile osteopetrosis demonstrates a variable spectrum of osteoclast abnormalities. All bone was obtained at biopsy before treatment. The average age at biopsy was 6 months with a range from 1 to 12 months. Osteoclast number was always increased and the cells were always appropriately positioned in relation to bone and cartilage. Osteoclast number, size, and nucleation varied from midly to markedly increased. In those with only a mild-to-moderate osteoclast increase, the marrow had an otherwise near-normal appearance with a good complement of hematopoietic cells. In those with markedly increased osteoclasts (hyperosteoclastic state) there were only scanty collections of hematopoietic cells. Light microscopic histomorphometry documented the percentage of bone and cartilage surfaces covered by osteoclasts. Controls from areas of greatest osteoclast presence documented a 5% coverage. One osteopetrotic patient registered a 4.8% value with all others elevated from 7.6 to 27.9%. Quantitative electron microscopy showed the ruffled border-clear zone complex to be absent or markedly diminished in seven of the nine patients. In two, however, osteoclast profiles had abundant ruffled border-clear zone complexes. Patients with the hyperosteoclastic bone marrow were more severely affected clinically. Light and TEM studies of marrow biopsies in initial assessment of osteopetrosis establish a baseline profile, may provide prognostic information, and allow for more meaningful treatment follow-up.