Familial Clustering of Erosive Hand Osteoarthritis in a Large Statewide Cohort

Abstract

Objective: Erosive hand osteoarthritis (OA) is a severe and rapidly progressing subset of hand OA. Its etiology remains largely unknown, which has hindered development of successful treatments. This study was undertaken to test the hypothesis that erosive hand OA demonstrates familial clustering in a large statewide population linked to genealogical records, and to determine the association of potential risk factors with erosive hand OA.

Methods: Patients diagnosed as having erosive hand OA were identified by searching 4,741,840 unique medical records from a comprehensive statewide database, the Utah Population Database (UPDB). Affected individuals were mapped to pedigrees to identify high-risk families with excess clustering of erosive hand OA as defined by a familial standardized incidence ratio (FSIR) of ≥2.0. The magnitude of familial risk of erosive hand OA in related individuals was calculated using Cox regression models. Association of potential erosive hand OA risk factors was analyzed using multivariate conditional logistic regression and logistic regression models.

Results: We identified 703 affected individuals linked to 240 unrelated high-risk pedigrees with excess clustering of erosive hand OA (FSIR ≥2.0, P < 0.05). The relative risk of developing erosive hand OA was significantly elevated in first-degree relatives (P < 0.001). There were significant associations between a diagnosis of erosive hand OA and age, sex, diabetes, and obesity (all P < 0.05).

Conclusion: Familial clustering of erosive hand OA observed in a statewide database indicates a potential genetic contribution to the etiology of the disease. Age, sex, diabetes, and obesity are risk factors for erosive hand OA. Identification of causal gene variants in these high-risk families may provide insight into the genes and pathways that contribute to erosive hand OA onset and progression.

Figure 1 – A

, Example of a high-risk erosive hand osteoarthritis pedigree identified in the Utah Population Database. Circles = females, squares = males, arrow = family founder, slashes = deceased. White circles/squares = affection status unknown. Black circles/squares = individuals affected with erosive hand osteoarthritis. B, C, D indicate individuals with hand radiographs. B-D, Hand radiographs of individuals (B-D) in the high-risk EOA pedigree (A). Asterisks indicate central subchondral erosions and arrowheads indicate a ‘gull-wing’ appearance of the joint.