Osteonecrosis of the femoral head usually affects young individuals and is responsible for up to 12% of total hip arthroplasties. The underlying pathophysiology of the death of the bone cells remains uncertain. We have investigated nitric oxide mediated apoptosis as a potential mechanism and found that steroid- and alcohol-induced osteonecrosis is accompanied by widespread apoptosis of osteoblasts and osteocytes. Certain drugs or their metabolites may have a direct cytotoxic effect on cancellous bone of the femoral head leading to apoptosis rather than purely necrosis.

To investigate the underlying mechanism of osteocyte death in osteonecrosis of the femoral head (ONFH).

Although there are a plethora of conditions that predispose to ONFH the underlying mechanism that results in the death of osteocytes is poorly understood. Consequently, treatment for early disease has a variable outcome. Recent investigation has focussed on the role of nitric oxide (NO) in the local control of bone turnover. NO is central to bone cell metabolism and has been implicated in the development of apoptosis.

Bone samples were harvested from the femoral heads of 40 patients undergoing total hip arthroplasty – 20 for advanced ONFH and 20 for osteoarthritis (control group). Immunocytochemical techniques were used to demonstrate evidence of NO synthase (iNOS and eNOS) as a marker of NO production and for evidence of apoptosis.

There was a marked increase in the expression of both eNOS and iNOS in the bone marrow and osteocytes from patients with ONFH secondary to steroids and alcohol with a correspondingly high proportion of apoptotic cells. Very little evidence of either eNOS or iNOS could be demonstrated in the control group and no significant apoptosis could be demonstrated. Samples from patients with ONFH secondary to sickle cell disease likewise had little evidence of apoptosis and a less marked increase iNOS production.

Our findings suggest that sickle cell disease may cause infarction of bone which subsequently leads to osteonecrosis. However, steroids and alcohol, or their metabolites, may have a direct cytotoxic effect upon bone leading to an increased NO production and NO-mediated apoptosis rather than necrosis. Our findings may provide important clues as to the underlying pathway leading osteocyte death. Therapeutic measures aimed at preventing production of toxic levels of NO or by blocking specific pathways in apoptosis may provide effective an treatment during the early stages of ONFH by halting disease progression.