Hereditary Musculoskeletal Disorders: Osteopetroses

Osteopetrosis is part of a spectrum of diseases characterised by generalised increase in skeletal density. Several forms of osteopetrosis have been described with overlapping clinical and radiographic features.
Two of the main forms of osteopetrosis are the following:

1. Early-onset or precocious form of osteopetrosis is most frequently discovered during the first months of life; it may appear as failure to thrive, malignant hypocalcemia , anaemia with thrombocytopenia, or severe, perhaps overwhelming infection. It generally follows a progressive course leading to death at an early age.

Inheritance is generally autosomal recessive. Rarely, fractures lead to medical attention. Hyperostosis may crowd the marrow cavity, with anaemia and extramedullary hematopoiesis, hepatosplenomegaly, and thrombocytopenia. Anaemia appears to result not from inadequate erythropoiesis but from excessive hemolysis. A defect in macrophage killing of bacteria may account for recurrent infection. Bony encroachment on the optic foramina may lead to optic atrophy and blindness. Hypocalcemia is not uncommon, and serum phosphorus may be low. Serum alkaline phosphatase activity is elevated. Radiographically, the diagnostic findings are a generalised increase in bone density, with defective metaphyseal modelling, and a "bone in bone" appearance most marked in vertebral bodies. Irregular condensation of bone at the metaphyses may produce the appearance of parallel plates of dense bone at the ends of the long bones.

Treatment is aimed at decreasing or arresting progressive hyperostosis, correcting anaemia and thrombocytopenia, and treating infections. A regimen of oral cellulose phosphate, prednisone, and low calcium diet has been reported to be effective in some but not all patients. The prednisone arrests the progression of anaemia Bone marrow transplantation has been reported to be curative in several patients. Generally, the prognosis for survival is poor, and death in the first few months or year from anaemia, bleeding, or overwhelming infection is not uncommon.

2. Osteopetrosis tarda is usually a milder disorder with delayed manifestations and often referred to as Albers-Schonberg disease . This form of osteopetrosis is found in childhood, adolescence, or young adult life because of fractures (about 10% of patients), mild craniofacial disproportion, mild anaemia, complications arising from neurological involvement, or osteitis with osteonecrosis (usually of the mandible). Increased bone density may be discovered incidentally on x- rays.
Most cases appear to represent autosomal dominant inheritance.

Skeletal x- rays show generalised increase in density of cortical bone, with a club-shaped appearance of the long bones due to defective metaphyseal modelling. Over 50% of patients have longitudinal or transverse dense striations at the ends of the long bones. The vertebrae show alternating lucent and dense bands.

Management should be directed at recognition and treatment of complications, with frequent testing of visual fields and acuity and periodic x- rays of the optic foramina. Transfusion and splenectomy may be useful in some patients.

The information in this page is presented in summarised form and has been taken from the following source(s):
1. Vanderbilt University Medical Center, Pediatric Interactive Digital Library: http://www.vanderbiltchildrens.com/