title: There are many potential medical therapies for atraumatic osteonecrosis.
abstract: Atraumatic osteonecrosis is a common complication of SLE and is seen in other connective tissue diseases, in patients treated with high doses of CSs, in HIV-infected patients and in alcoholic patients. Standard care is confined to analgesia, core decompression if the condition is early and affects the femoral head and joint replacement. However, consideration of the underlying biological mechanisms leads to the recognition of many potential therapies that might either prevent progression or, even, reverse the process if it is not yet too far advanced. These potential therapies merit detailed consideration. Critical points are that (i) histopathological evidence shows that the initial cellular event is apoptosis of osteocytes; and (ii) another requisite, as homeostasis requires that death and rebirth of osteocytes be balanced, is an accompanying inadequate proliferative capacity of osteoblasts. Thus, a logical approach to treatment includes measures that (i) reduce apoptosis of osteocytes and (ii) enhance proliferation of osteoblasts/pre-osteoblasts. Measures to reduce the ongoing apoptosis of osteocytes require reinforcing the effects of members of the Bcl-2 family (Bcl-2 itself and Mcl-1), the Wnt/catenin pathways (using an available sclerostin antibody) and HSPs (by application of local heat using US, deep wave diathermy or infrared), as well as administration of bisphosphonates and nitrates. Measures to enhance proliferation of osteoblasts/pre-osteoblasts include the use of stem cells, extracorporeal shock wave therapy, aspirin, the proteosome inhibitor bortezomib, melatonin and application of local heat. Use of VEGF would encourage proliferation of blood vessels and osteogenesis. Certain drugs that inhibit osteoblast proliferation should be avoided, including NSAIDs, serotonin reuptake inhibitors and thiazolidinediones.
authors.affiliation: Kaiser Permanente Medical Center, Department of Medicine, 2238 Geary Boulevard, San Francisco, CA 94115, USA. jeffrey.fessel@kp.org
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Fessel
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D010006:Osteoblasts / Q000166:cytology; D010011:Osteocytes / Q000473:pathology; D010020:Osteonecrosis / Q000628:therapy*