Chapter 72 – Osteopetrosis

Publisher Summary Osteopetrosis results from a reduction in bone resorption relative to bone formation, leading to an accumulation of excessive amounts of bone. The relative decrease in resorption is a consequence of inadequate osteoclastic bone resorption. Classically, osteopetrosis has been divided into a fatal infantile malignant form, Albers–Schonberg disease, and a milder adult form of osteopetrosis with long-term survival. Functionally, the defect causes the absence of the α3-subunit, OC116, of the V-type proton pump that is present along the ruffled border and responsible for acidification next to the bone surface. In the absence of this acidification, calcium cannot be removed from the surface of the bone. Regarding treatment, transplantation has been the mainstay; however, somewhat disappointing results and, at present, the lack of available donors have made it difficult to rely on transplantation as the sole therapy for this disease. Because the mortality associated with failed transplantations is high, other treatment alternatives and stopgap measures remain important despite the inability of these therapies to completely cure the condition in most patients. These therapies may be the sole therapy of the patient or may result in a milder course of the disease while awaiting a definitive cure. Thus, a variety of other therapies have been attempted with some success.