Osteonecrosis of the femoral head (ONFH) involves necrosis of bone and bone marrow of the femoral head caused by ischemia with unknown etiology. Previous genetic studies on ONFH failed to produce consistent results, presumably because ONFH has various causes with different genetic backgrounds and the underlying diseases confounded the associations. Steroid-associated ONFH (S-ONFH) accounts for one-half of all ONFH, and systemic lupus erythematosus (SLE) is a representative disease underlying S-ONFH. We performed a genome-wide association study (GWAS) to identify genetic risk factors for S-ONFH in patients with SLE. We conducted a two-staged GWAS on 636 SLE patients with S-ONFH and 95 588 non-SLE controls. Among the novel loci identified, we determined S-ONFH-specific loci by comparing allele frequencies between SLE patients without S-ONFH and non-SLE controls. We also used Korean datasets comprising 148 S-ONFH cases and 37 015 controls to assess overall significance. We evaluated the functional annotations of significant variants by in silico analyses. The Japanese GWAS identified 4 significant loci together with 12 known SLE susceptibility loci. The four significant variants showed comparable effect sizes on S-ONFH compared with SLE controls and non-SLE controls. Three of the four loci, MIR4293/MIR1265 [odds ratio (OR) = 1.99, P-value = 1.1 × 10⁻⁹)], TRIM49/NAALAD2 (OR = 1.65, P-value = 4.8 × 10⁻⁸) and MYO16 (OR = 3.91, P-value = 4.9 × 10⁻¹⁰), showed significant associations in the meta-analysis with Korean datasets. Bioinformatics analyses identified MIR4293, NAALAD2 and MYO16 as candidate causal genes. MIR4293 regulates a PPARG-related adipogenesis pathway relevant to S-ONFH. We identified three novel susceptibility loci for S-ONFH in SLE.

We investigated the repair of femoral head necrosis with extensive necrotic lesions treated by high-degree posterior rotational osteotomy (HDPRO) in young adults and adolescents (mean age; 30.8 years) using magnetic resonance imaging (MRI). HDPRO was performed on 72 hips from 66 cases, and of those, 60 hips from 60 cases were included in this study for data analysis. All cases had extensive collapsed lesion preoperative anteroposterior radiographs. In total, 34 hips were male and 26 were females. In total, 19 had a history of steroid administration, 11 had a previous femoral neck fracture, 7 had no particular etiologic factor, and 4 had a followed slipped capital femoral epiphysis. Antero-inferior viable areas were transferred to the loaded portion below the acetabular roof by this operation. The mean posterior rotational angle was 118.5°. MRI was taken after 1 month, 6 months and 1-year post-operatively. Post-operative necrotic lesion volume compared with the preoperative necrotic lesion volume was defined as lesion volume ratio (%). The reduction of necrotic volume was observed over time, and at 1 year post-operatively, it was 19.4% for patients in their teens, 35.3% for those in twenties, 42.8% for those in their thirties and 59.5% for those in their forties. From this study, we concluded that the extensive necrotic lesions decreased in size within a short period after HDPRO in young patients.

Aims: The localization of necrotic areas has been reported to impact the prognosis and treatment strategy for osteonecrosis of the femoral head (ONFH). Anteroposterior localization of the necrotic area after a femoral neck fracture (FNF) has not been properly investigated. We hypothesize that the change of the weight loading direction on the femoral head due to residual posterior tilt caused by malunited FNF may affect the location of ONFH. We investigate the relationship between the posterior tilt angle (PTA) and anteroposterior localization of osteonecrosis using lateral hip radiographs.Methods: Patients aged younger than 55 years diagnosed with ONFH after FNF were retrospectively reviewed. Overall, 65 hips (38 males and 27 females; mean age 32.6 years (SD 12.2)) met the inclusion criteria. Patients with stage 1 or 4 ONFH, as per the Association Research Circulation Osseous classification, were excluded. The ratios of anterior and posterior viable areas and necrotic areas of the femoral head to the articular surface were calculated by setting the femoral head centre as the reference point. The PTA was measured using Palm’s method. The association between the PTA and viable or necrotic areas of the femoral head was assessed using Spearman’s rank correlation analysis (median PTA 6.0° (interquartile range 3 to 11.5)).Results: We identified a negative correlation between PTA and anterior viable areas (rho −0.477; p = 0.001), and no correlation between PTA and necrotic (rho 0.229; p = 0.067) or posterior viable areas (rho 0.204; p = 0.132).Conclusion: Our results suggest that residual posterior tilt after FNF could affect the anteroposterior localization of necrosis.Cite this article: Bone Jt Open 2024;5(5):394–400.