Osteonecrosis of the femoral head (ONFH) is a disease of the young patient with up to 25% of affected patients being less than 25 years in some institutions (1). Most patients will ultimately need total hip arthroplasty (THA) and it is estimated that ONFH constitutes about 10% of indications of THA procedures performed in the United States (1,2,3). Consequently, it represents a very large economic burden on healthcare systems, but more importantly, it is a large burden on the young patient population it affects, since THA in this population has been shown to yield relatively poor outcomes with increased risk of mechanical complications and the large majority of patients will need at least one revision procedure during their lifetime (1,4,5). Alternatives to THA have been sought and core decompression is one of the most commonly performed procedures nowadays with successful results in the early stages of the disease, as well as low morbidity and low rate of complications (<1% in most reported series) (1). However, many efforts have been spent during the past years to find still less invasive means to address the disease, especially at the very early stages or even as prophylaxis in high-risk patients. The largest difficulty in identifying the most suitable agents for such a task stems from all the unknowns in the pathogenesis of the disease and the controversies about its natural history. Many modalities have succeeded in slowing the progress of the disease process or even halt it and prevent the collapse of the femoral head and their use could be promising at the early stages of the disease. These nonoperative means of treatment currently include pharmacologic agents such as statins, anticoagulants, vasodilators, and bisphosphonates, as well as biophysical therapies like electromagnetic fields, extracorporeal shock waves (ESWs), and hyperbaric oxygen (HBO) therapy.

Observation or reduced weight bearing (no or partial weight bearing with the use of walking aids) has been a subject of controversy for a long time in the treatment of asymptomatic or very early stage ONFH. The main reason is that reports about the natural history of the disease are controversial and present wide variations between different authors.

Mont et al. (6) in 1996 after reviewing available studies at that time identified satisfactory clinical outcomes in around 23% of cases treated conservatively, with almost 80% of patients ultimately requiring THA or other surgical interventions. This meta-analysis included 819 hips treated with nonoperative management (observation with full weight bearing, partial weight bearing, or no weight bearing) with a mean follow-up of 34 months. The observed results led the authors to discard any possible role of such conservative measures in the treatment of ONFH.

In an attempt to shed more light into the natural history of ONFH, Nishii et al. (7) followed patients with precollapse stage ONFH for at least 5 years. Almost half of the hips ended up collapsing, including the ones that had small lesions (involving less than the medial 2/3 of the weight-bearing area). However, in 54% of these lesions, collapse stopped progressing and 64% of patients with cessation of collapse (9/14) eventually became asymptomatic. Cessation of collapse was found to be significantly correlated with the extent of the necrotic lesion (89% cessation in hips that initially had necrosis of less than 2/3 of the weight-bearing area) and with the amount of collapse at final examination (0% progression in 11 hips with less than 2 mm collapse at final examination). The authors concluded that collapse of the femoral head does not necessarily indicate a relentless progression of the underlying disease. Cessation of collapse can happen, especially in small lesions, and clinical improvement can follow without the need for any invasive intervention. Limited progression of the disease in cases with small lesions has also been observed by many other authors (8,9,10,11).

Hernigou et al. conducted a prospective study with a minimum of 10-year follow-up in 40 patients with small lesions (stage I according to Steinberg et al. (12)) identified on MRI in contralateral hips of patients presenting with symptomatic ONFH (13). At latest follow-up (average follow-up was 11 years), 88% of hips had become symptomatic and 73% had evidence of collapse, all of which eventually required surgical intervention. However, the fate of bilateral disease
could be different from unilateral disease and should not be extrapolated to all cases. Indeed, Cheng et al. (14) have identified spontaneous resolution in 3/13 hips with asymptomatic unilateral ONFH detected through prospective screening in solid organ transplant patients. In this study 9/17 (53%) hips with asymptomatic ONFH in patients who had presented with contralateral symptomatic ONFH ultimately became symptomatic and were treated with core decompression, versus only 2/13 hips (15%) in posttransplant cohort.

Min et al. (15) looked at MRI-identified asymptomatic ONFH in 81 patients who presented with symptomatic ONFH on the contralateral side. Included patients had a minimum follow-up of 5 years (average follow-up was 8.3 years). Thirty-eight percent of the hips were symptomatic at the latest follow-up visit and hip survival rates (as defined by absence of collapse) were 91.4% at 5 years and 70% at 10 years. Although patient age, gender, weight, and presumed etiology of ONFH were poor predictors of collapse, extent and location of necrosis was a strong predicting factor. Type C2 lesions according to Sugano et al. (16) had the worst outcome (lesions occupying more than the medial two-thirds and extending laterally to the acetabular edge). The occurrence of pain was deemed a strong sign of impending collapse and all collapse cases were preceded by the occurrence of pain of an average of 8-month duration.

In conclusion, the natural history of ONFH is still poorly understood to help in identifying a role for conservative management. Even though small asymptomatic lesions have shown a low rate of progression in some studies, many authors argue that with extended follow-up progression eventually occurs and observation or reduced weight bearing have no place in the management of ONFH.

Diverse pharmacologic agents have been shown to have a role in management of patients with early stage ONFH. These agents target hypothesized pathophysiologic mechanisms for osteonecrosis such as increased bone marrow pressure, adipogenesis, and thrombogenesis.