DNA hypermethylation of GDF5 in developmental dysplasia of the hip (DDH).

INTRODUCTION & OBJECTIVE: Developmental Dysplasia of the Hip (DDH) is one of the most common congenital skeletal anomalies. Body of evidence suggests that genetic variations in GDF5 are associated with susceptibility to DDH. DDH is a multifactorial disease and its etiology has not been entirely determined. Epigenetic changes such as DNA methylation could be linked to DDH. In this scheme, we hypothesized that changes in GDF5 DNA methylation could predispose a susceptible individual to DDH. METHODS: This study consisted of 45 DDH patients and 45 controls with healthy femoral neck cartilage, who underwent hemi-, or total arthroplasty for the femoral neck fracture. A cartilage sample of 1 cm in diameter and 1 mm in the thickness was obtained for DNA extraction. DNA was extracted and DNA methylation of GDF5 was evaluated by metabisulfite method. RESULTS: Methylation analysis showed that the promoter of GDF5 in cartilage samples from DDH patients was hypermethylated in comparison to healthy controls (p = .001). CONCLUSION: Our study showed that the methylation status of the GDF5 in patients with DDH is dysregulated. This dysregulation indicates that adjustment in the methylation might modify the expression of this gene. Since this gene plays an essential role in cartilage and bone development, thus reducing its expression can contribute to the pathogenesis of DDH. Further studies are needed to elucidate the role of GDF5 in this disease.

Cost-effective prophylaxis against venous thromboembolism after total joint arthroplasty: warfarin versus aspirin.

Although recent guidelines suggest aspirin for venous thromboembolism (VTE) prophylaxis in low risk patients following total hip arthroplasty (THA) and total knee arthroplasty (TKA), there are no cost-effectiveness studies comparing aspirin and warfarin. In a Markov cohort cost-effectiveness analysis, we found that aspirin cost less and saved more quality-adjusted life-years (QALYs) than warfarin in all age groups. Cost per QALY gained by aspirin was $24,506.20 at age of 55 and $47,148.10 at the age of 85 following THA and $15,117.20 and $24,458.10 after TKA, which were greater than warfarin. In patients undergoing THA/TKA without prior VTE, aspirin is more cost-effective prophylactic agent than warfarin. Warfarin might be a better prophylaxis in TKA patients with high probability of VTE and very low probability of bleeding.