Background/Purpose: Much of osteoarthritis (OA) research has focused on identifying treatments for late stage disease. However, interventions in early disease may be most effective. Capitalizing on the heritability of knee OA, we assessed the feasibility of using the phenotype of a proband to study risk factors in their offspring. The objectives of this study were: 1) to establish feasibility of deploying such an offspring study within the Osteoarthritis Initiative (OAI) where the proband phenotype is well-characterized, 2) to assess whether this offspring design can detect known risk factors of medial compartment knee OA, and 3) to evaluate exploratory risk factors.

Methods: We selected two groups of proband OAI participants from the University of Pittsburgh site: medial tibiofemoral OA group and no OA group. To preferentially include those more likely to have a heritable etiology of their phenotype, we recruited probands with the same OA phenotype in both knees.  The case probands had bilateral medial tibiofemoral OA; control probands had no radiographic evidence of OA in either knee.  We only included biological offspring who were ≥18 years old.  We approached current OAI participants from the Pittsburgh site who met our eligibility criteria.  We developed a privacy-sensitive method of contacting the proband’s offspring to invite them to participate. Willing offspring completed an online survey that assessed OA symptoms and diagnoses as well as known and exploratory risk factors.  We calculated the percentage of probands with OA in each strata of the risk factors.  To see if OA risk factors in offspring are associated with proband OA status, we used logistic regression models conducted with generalized estimating equations to account for the correlation among offspring related to a given proband. 

Results: We established contact with 269/413 (65.1%) potential probands. Most (227/269,84.4%) had ≥1 eligible biological offspring, with 213/227 (93.8%) willing to share information about the study with their offspring.  Our online survey was completed by 185 offspring from 109 probands. Offspring age ranged from 21 – 67 years old (mean=42.9), with 64.9% female, 84.3% White/Caucasian, and mean BMI=23.7 kg/m². Median time to complete survey =14.1 minutes.

Conclusion: Our pilot study establishes feasibility of deploying an offspring study within the OAI using an online survey.  Using this design, we detected significant associations between offspring presence of Heberden’s nodes and hypertension, and presence of parental OA.  Our findings show good proof of concept for performing an offspring study based out of the OAI.