Osteonecrosis in Antiphospholipid Syndrome: An Evidence Map and Diagnostic Attribution Framework for a Noncriteria...

Osteonecrosis has been reported in antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPL) positivity, but because it also follows glucocorticoid exposure, systemic lupus erythematosus (SLE), alcohol use, trauma, pregnancy, transplantation, and thrombophilia, its status as an APS-related manifestation is uncertain, and clinicians lack a structured way to decide whether it is APS-attributable or coincidental. We conducted a structured narrative review with evidence mapping, searching PubMed/MEDLINE, Embase, and Scopus from inception to May 2026 with citation chasing; eligible reports described osteonecrosis, avascular necrosis, aseptic necrosis, or bone infarction in confirmed APS or documented aPL positivity. Twenty-two publications were charted for design, phenotype, osteonecrosis site, diagnostic modality, competing etiologies, and attribution, and synthesized narratively. Reported frequencies ranged from 3.75% and 4.5% for clinically ascertained disease to 20% for asymptomatic magnetic resonance imaging screen-detected disease in steroid-naïve primary APS-estimates that are not directly comparable. Femoral-head disease predominated, but multifocal, bilateral, and atypical-site lesions were repeatedly described. Attribution was strongest in young patients with persistent high-risk aPL, minimal traditional risk factors, and concurrent thrombotic, obstetric, or microvascular features, yet competing causes, especially glucocorticoids and SLE-frequently coexisted. We propose the APSO framework, stratifying attribution into four tiers (high-confidence, probable, uncertain/mixed, and aPL-positive osteonecrosis without classifiable APS) by APS certainty, aPL risk, osteonecrosis phenotype, and competing-cause burden. Osteonecrosis is a candidate noncriteria skeletal manifestation of APS, but aPL positivity alone is insufficient for causal attribution; prospective validation is required.