The genetic contribution to longitudinal changes in knee structure and muscle strength: A sibpair study

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Abstract
Objective To estimate the heritability of longitudinal changes in knee cartilage volume, chondral defects, subchondral bone size, and lower limb muscle strength. Methods A sibpair design was used. Longitudinal changes in lateral and medial tibial cartilage volume and bone size, as well as progression of chondral defects, were determined on serial magnetic resonance images. Radiographs were obtained and scored for individual features of radiographic osteoarthritis (OA) at baseline. Lower limb muscle strength was measured by dynamometry. Heritability was estimated using the SOLAR software package. Results A total of 115 subjects (55 men and 60 women, mean age 45 years) from 48 families representing 95 sibling pairs were successfully followed up for a mean of 2.4 years. The adjusted heritability estimates for changes in cartilage volume were 73% for the medial compartment (P < 0.01) and 40% for the lateral compartment (P = 0.10). The adjusted heritability estimates for changes in bone size were 62% for the lateral compartment (P = 0.03) and 20% for the medial compartment (P = 0.22). The adjusted heritability estimate for changes in muscle strength was 64% (P = 0.01). The adjusted heritability estimates for progression of chondral defects were 80% for the lateral compartment (P = 0.06) and 98% for the medial compartment (P = 0.03). These estimates changed little after adjusting for each other and for the predominantly mild radiographic OA, with the exception of progression of chondral defects in the lateral compartment. Conclusion Early longitudinal changes in knee structures of relevance to later OA, such as changes in medial tibial cartilage volume, lateral tibial bone size, progression of chondral defects, and muscle strength, have high heritability, most likely reflecting a strong genetic component and suggesting their potential to be studied in quantitative trait linkage and association analysis.