Background
Osteopetrosis is a clinical syndrome characterized by the failure of osteoclasts to resorb bone. As a consequence, bone modeling and remodeling are impaired. The defect in bone turnover characteristically results in skeletal fragility despite increased bone mass, and it may also cause hematopoietic insufficiency, disturbed tooth eruption, nerve entrapment syndromes, and growth impairment. (See Etiology and Presentation.)
Although human osteopetrosis is a heterogeneous disorder encompassing different molecular lesions and a range of clinical features, all forms share a single pathogenic nexus in the osteoclast.
Osteopetrosis was first described in 1904, by German radiologist Albers-Schönberg. (See Etiology.)
Classification
In humans, 3 distinct clinical forms of the disease—infantile, intermediate, and adult onset—are identified based on age and clinical features. These variants, which are diagnosed in infancy, childhood, or adulthood, respectively, account for most cases. (See Table 1, below.)
Table 1. Clinical Classification of Human Osteopetrosis (Open Table in a new window)
Characteristic |
Adult onset |
Infantile |
Intermediate |
Inheritance |
Autosomal dominant |
Autosomal recessive |
Autosomal recessive |
Bone marrow failure |
None |
Severe |
None |
Prognosis |
Good |
Poor |
Poor |
Diagnosis |
Often diagnosed incidentally |
Usually diagnosed before age 1y |
Not applicable |
The classification of osteopetrosis shown above is purely clinical and must be supplemented by the molecular insights gained from animal models (see Table 2, in Etiology).
Other, rare forms of osteopetrosis have been described (eg, lethal, transient, postinfectious, acquired). A distinct form of osteopetrosis occurs in association with renal tubular acidosis and cerebral calcification due to carbonic anhydrase isoenzyme II deficiency. (See Etiology.)
Epidemiology
Overall incidence of osteopetrosis is estimated to be 1 case per 100,000-500,000 population.
However, the actual incidence is unknown, because epidemiologic studies have not been conducted.
Prognosis
In infantile osteopetrosis, bone marrow failure may occur. If untreated, infantile osteopetrosis usually results in death by the first decade of life due to severe anemia, bleeding, or infections. Patients with this condition fail to thrive, have growth retardation, and suffer increased morbidity. The prognosis of some patients with infantile osteopetrosis can markedly change after bone marrow transplantation (BMT). Patients with adult osteopetrosis have good long-term survival rates. (See Treatment and Medication.)
Patient education
Counsel patients with osteopetrosis on appropriate lifestyle modifications to prevent fractures. Provide genetic counseling to patients to allow appropriate family planning. (See Treatment.)