Approved Research

External Validation of Genetic Polymorphisms and Pharmacologic Exposure Linked to Increased Risk of Femoral Head Osteonecrosis

Lay summary

Osteonecrosis of the femoral head is a disease afflicting the hip joint in a typically young patient cohort. These patients develop severe pain from their collapsed bone and often require hip replacement to alleviate the problem. Osteonecrosis accounts for 10% of all hip replacements worldwide and over 1/3 of hip replacements in patients under age 50. There are many described risk factors for osteonecrosis, nevertheless, upwards of 40% of cases are never shown to be linked with these risk factors.

Our group has recently linked disruption in the gene PPARG with increased osteonecrosis risk. This was shown both with a series of changes in the PPARG gene, as well as in patients taking a class of drugs call thiazolidinediones, which upregulate PPARG in the body. These corroborating lines of evidence are further strengthened by the intuitive biologic implications of PPARG, as changes in expression of this gene provide a logical explanation for development of osteonecrosis. We aim to further validate the results through assessment of patients with osteonecrosis in the UK Biobank against unaffected patients. Access to patient genetic profiles, demographic information, and pharmacologic exposure history will enable our team to perform bioinformatic and statistical analysis to identify whether our results remain valid in an external cohort. If validated, these results would hold tremendous importance for patients across the globe affected by osteonecrosis, and pave the way for novel diagnostics, risk stratification tests, and therapeutics.

Once we obtain the data, it is anticipated the project can be completed within 1 year.