Introduction

Avascular necrosis (AVN), or osteonecrosis, is a frequent yet often unsettling diagnosis for the practicing rheumatologist. Beyond the radiographic labels of Ficat or ARCO stages lies a daily clinical dilemma: why has this patient developed AVN, how aggressively will it behave, and what does it signify about the underlying systemic disease or its treatment? In routine practice, AVN is often approached as a structural orthopedic problem, but for the rheumatologist it represents a biological footprint of vascular injury, inflammation, thrombosis, or metabolic stress. A phenotypic approach which is integrating the etiology, histopathology, clinical presentation, age of onset, and distribution (unifocal or multifocal) offers a more meaningful framework to interpret AVN in day-to-day rheumatology practice. The prevalence of AVN in India in systemic rheumatic diseases is 0.8%. It occurs more frequently in men than women, the male: female ratio being 8: 1.

Etiological Phenotypes: Asking the First Question

When confronted with AVN, the rheumatologist’s first instinct is not staging but causation. Traumatic AVN, following femoral neck fractures or hip dislocation, is usually straightforward and localized. In contrast, non-traumatic AVN raises immediate concern for systemic causes like corticosteroid exposure, alcohol use, active systemic lupus erythematosus (SLE), antiphospholipid antibody syndrome (APLA), vasculitis, or hematological disorders such as sickle cell disease. In daily practice, it becomes evident that corticosteroids alone rarely explain the disease and AVN often reflects the combined effect of active inflammation, hypercoagulability, and metabolic factors like obesity and other comorbidities. Recognizing this helps shift the clinical focus from merely attributing blame to steroids toward reassessing disease control and systemic risk factors.

Pediatric Vs adult AVN

Children can have either the regular causes of avascular necrosis or they may have certain unique causes like Legg–Calvé–Perthes disease,  sickle cell-related AVN therapy-related (leukemia/lymphoma, HSCT)

In children, the outcomes depend strongly on age at onset and extent of involvement. Younger children often do better. There is greater potential for remodeling and restoration of femoral head shape. However in adults in view of limited regenerative capacity, lesions are more likely to progress to femoral head collapse and symptomatic osteoarthritis, particularly with larger lesions or lateral-location lesions.

Although young adults appear particularly susceptible to steroid-associated AVN during intensive regimens, pediatric SLE cohorts show lower reported AVN rates compared with adults with SLE in some series, but this varies by steroid dosing, cumulative exposure, and concurrent therapies.

Histopathological Phenotypes: Mechanism Matters

Although histology is not routinely obtained, understanding the dominant pathological process helps the clinician to understand the disease. Steroid- and alcohol-associated AVN are typically driven by marrow fat hypertrophy and lipid accumulation, leading to raised intraosseous pressure and microcirculatory compromise. Thrombotic or vasculitic AVN, often encountered in APLA syndrome or systemic vasculitis, reflects primary vascular occlusion or inflammatory vessel damage. In hemoglobinopathies, repetitive ischemia–reperfusion injury dominates. Appreciating these mechanisms explains why some lesions remain indolent while others progress rapidly despite similar radiographic appearances.

Multifocal AVN

Multifocal osteonecrosis (MFON) is defined as osteonecrosis affecting three or more anatomic sites, occurring either simultaneously or sequentially. It is uncommon, with prevalence ranging from 3% to 10 %. Corticosteroid use is the most common risk factor. Other associated conditions include systemic lupus erythematosus, HIV infection, coagulation disorders, renal failure, inflammatory bowel disease, multiple sclerosis, Sjögren’s syndrome, sickle cell disease, hematological malignancies, and COVID-19.

The femoral head is most frequently involved, followed by the knee, shoulder, and ankle. MFON is often underdiagnosed due to asymptomatic early disease and limited imaging beyond the index joint. To reduce missed diagnoses, MRI whole body can be considered in high risk patients to screen for multifocal osteonecrosis.

As rheumatologists, we approach avascular necrosis (AVN) with a focus on early recognition, risk stratification, and prevention of progression, rather than viewing it solely as a structural complication. In systemic lupus erythematosus, the emphasis is on achieving rapid disease control to enable early and sustained steroid tapering; in selected patients, the use of steroid-sparing agents such as rituximab may facilitate this strategy. In patients with antiphospholipid antibody positivity, although the debate between antiplatelet therapy and anticoagulation remains unresolved, we often favor anticoagulation, guided by the underlying thrombotic pathomechanism and overall clinical context.

Magnetic resonance imaging is our preferred modality for early diagnosis and for screening additional joints once AVN is identified, particularly in high-risk systemic diseases. Equally important is optimization of the underlying inflammatory disorder and correction of contributory metabolic factors such as obesity. Close collaboration with orthopedic surgeons and radiologists is essential—not only to refine staging, but also to identify joint-preserving strategies and to plan timely surgical intervention when indicated.

References:

• Mont, Michael A. MD; Salem, Hytham S. MD; Piuzzi, Nicolas S. MD; Goodman, Stuart B. MD, PhD; Jones, Lynne C. PhD. Nontraumatic Osteonecrosis of the Femoral Head: Where Do We Stand Today?: A 5-Year Update. The Journal of Bone and Joint Surgery 102(12):p 1084-1099, June 17, 2020.
• Konarski W, Poboży T, Konarska K, et al. Osteonecrosis Related to Steroid and Alcohol Use-An Update on Pathogenesis. Healthcare (Basel). 2023;11(13):1846.
• Goncharov EN, Koval OA, Nikolaevich Bezuglov E, Aleksandrovich Vetoshkin A, Gavriilovich Goncharov N, Encarnación Ramirez MJ, Montemurro N. Conservative Treatment in Avascular Necrosis of the Femoral Head: A Systematic Review. Med Sci (Basel). 2024 Jul 2;12(3):32. doi: 10.3390/medsci12030032. PMID: 39051378; PMCID: PMC11270198.