Congenital osteopetrosis is a group of disorders resulting in decreased osteoclastic function and hence decreased
bone resorption. Various medical treatments have been attempted to ameliorate the osteopetrotic condition. A
calcium-deficient diet has limited further
sclerosis in some patients.
Prednisone therapy has improved haematological function in some patients, but has not resulted in a reduction in bone mass. Calcitrophic
hormones, such as
parathyroid hormone (PTH) infusions and oral
calcitriol, stimulate osteoclastic activity, and
calcitriol in particular has stimulated osteoclastic
bone resorption in some patients with
osteopetrosis.
Bone marrow transplantation, although curative, is limited by paucity of donors, risk of
graft-versus-host disease and relapse of the disease. The demonstration of defective leucocyte
superoxide production in osteopetrotic patients and the premise that osteoclasts appear to arise from the granulocyte macrophage lineage have led to attempts at treating
osteopetrosis with
immunomodulators. Since treatment with recombinant interferon-γ-1b (interferon γ-1b, IFNγ-1b) has resulted in increased level of
superoxide generation and clinical improvement in
chronic granulomatous disease, a similar strategy has been employed using IFNγ-1b to treat patients with
osteopetrosis. IFNγ-1b has been demonstrated to increase osteoclastic
bone resorption and leucocytic function. Long term
therapy with IFNγ-1b by
subcutaneous injection 3 times weekly resulted in marked clinical improvement, a decreased incidence of
infections, a decreased trabecular bone mass, and an increased marrow space resulting in improved haemopoiesis. The
therapy has been associated with few adverse effects, mainly
fever and diarrhoea which have been managed with a reduction in IFNγ-1b dosage. The low-
calcium diet occasionally results in hypocalcaemic
tetany, which may be corrected by increased
dietary calcium intake. Thus, IFNγ-1b has a distinct place in the therapeutic armamentarium for patients with
osteopetrosis and is a feasible treatment option in such patients.