The pathogenesis, diagnosis and clinical manifestations of steroid-induced osteonecrosis

Highlights

• The most common etiology of non-traumatic osteonecrosis is corticosteroid use.

• The dose of corticosteroids required to cause osteonecrosis is not known, but it is clear that risk increases with higher dose and duration, and certain co-morbid conditions.

• The most common presentation of osteonecrosis of the femoral head is pain, which in the later stages can progress to reduced mobility.

• Pathologic mechanisms for osteonecrosis include defects in apoptosis, coagulation, lipid metabolism, immune dysregulation, oxidative stress, endothelial cell damage.

• Magnetic resonance imaging (MRI) is the best radiologic modality for diagnosing osteonecrosis.

Abstract

Corticosteroid associated osteonecrosis is bone death resulting from the use of chronic glucocorticoids and most commonly affects the femoral head, although the bones such as around knee joint, wrist joint and ankle joint can be affected. The pathogenesis is likely multifactorial, with genetic and environmental factors playing a role. Epigenetics may be the mechanism by which environment exerts it effects. In spite of recent discoveries, the exact pathogenesis of corticosteroid associated osteonecrosis is unknown. Over the past few years, more miRNA's have been found to be associated with osteonecrosis. The older mechanisms such as a coagulopathy, abnormalities in apoptosis and lipid metabolism dysfunction are still believed to play a role. The role of inflammatory pathways including the PDK1/AKT/mTOR signaling pathway, the PERK and Parkin pathways have been increasingly recognized as playing a mechanistic role. Histological damage to the joint can occur before the presence of symptoms. The most common symptoms are pain and an inability to bear weight. Differential diagnosis includes infection, bone marrow edema syndrome or subchondral fracture. Early detection is important for successful management of the condition. MRI is the best radiologic technique to diagnosis femoral head osteonecrosis. Multiple staging systems for osteonecrosis have been used over the years, including the Ficat and Arlet system and the Steinberg criteria. The later stages of these staging systems are irreversible. Both non-surgical (conservative) and surgical modes of therapy are used in the treatment of osteonecrosis.

Introduction

Osteonecrosis is also known as avascular necrosis, ischemic necrosis, osteochondritis dissecans and aseptic necrosis. Non-traumatic osteonecrosis is a serious condition which has been associated with a variety of natural and iatrogenic conditions, ranging from congenital defects such as Legg-Perthes-Calve syndrome to the use of chronic medications such as corticosteroids. The femoral head is the most common affected site, but other bones can be involved. The pathogenesis of many of these etiologies is unclear, but eventually the changes that occur result in failure to deliver nutrients to affected bone. The events in the early stages may include vascular damage, mechanical stresses, increased intraosseous pressure, adipocyte dysfunction, defects in apoptosis and coagulation dysfunction. But in the end, the final common pathway is an inability to deliver nutrients to the watershed areas of the femoral head, leading to bone death.

The average age of patients with osteonecrosis is younger than that of osteoarthritis, meaning that if surgery is needed, osteonecrosis patients will most likely outlive their artificial joint, thus requiring repeat surgeries. In addition to total hip replacements, a variety of other treatments, both surgical and non-surgical have been introduced. However, the outcomes of these measures are typically unsatisfactory. The treatment of osteonecrosis is not within the scope of this paper, in which we will focus primarily on the clinical presentation, diagnosis and pathogenesis of corticosteroid associated osteonecrosis.