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Variable osteoclast appearance in human infantile osteopetrosis
1Department of Orthopaedic Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Insights
Infantile osteopetrosis involves increased osteoclasts with variable abnormalities. Some patients show normal marrow, while others have a hyperosteoclastic state linked to severe disease, impacting prognosis.
Area of Science:
- Pediatric Bone Diseases
- Cellular Biology
- Histopathology
Background:
- Infantile osteopetrosis is a rare genetic disorder characterized by impaired osteoclast function.
- Osteoclasts are crucial for bone resorption and remodeling.
Purpose of the Study:
- To investigate osteoclast abnormalities in infantile osteopetrosis using light and transmission electron microscopy (TEM).
- To correlate osteoclast findings with clinical severity and bone marrow cellularity.
Main Methods:
- Biopsy of iliac crest metaphyseal bone from nine infantile osteopetrosis patients before treatment.
- Light microscopy and TEM for detailed osteoclast morphology and quantification.
- Histomorphometry to assess bone and cartilage surface coverage by osteoclasts.
Main Results:
- All patients exhibited increased osteoclast numbers, with variable size and nucleation.
- Seven of nine patients showed absent or diminished ruffled border-clear zone complexes in osteoclasts.
- A hyperosteoclastic state with reduced hematopoietic cells correlated with more severe clinical presentation.
Conclusions:
- Osteoclast abnormalities in infantile osteopetrosis are diverse, impacting bone remodeling.
- TEM assessment of osteoclast morphology, particularly the ruffled border, is critical.
- Early assessment using light and TEM can provide prognostic information and guide treatment.
Abstract:
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.