Objective. To estimate the heritability of muscle strength, knee pain, cartilage volume, bone size, and radiographic osteoarthritis (ROA), and to assess whether heritability of the knee structural components is independent of ROA.Methods. A sibpair design was utilized. Sagittal T1-weighted fat-suppressed magnetic resonance imaging (MRI) of the right knee was performed to determine cartilage volume and bone size. Standing semiflexed radiographs of the same knee were obtained to assess the presence of ROA. Knee pain was assessed by questionnaire and muscle strength by dynamometry. Heritability was estimated using the genetic analysis program SOLAR.Results. A total of 128 subjects (61 men, 67 women; mean age 45 years) from 51 families representing 115 sibpairs were studied. Lower limb muscle strength had high heritability (42%; P ؍ 0.02), as did knee pain (44%; P ؍ 0.07). Heritability estimates for cartilage volume were 65% for medial tibial cartilage, 77% for lateral tibial cartilage, and 84% for patellar cartilage, and heritability estimates for bone size were 85% for medial tibial bone area, 57% for lateral tibial bone area, and 70% for patella bone volume (all P < 0.004). For ROA, heritability was 61% for presence (with a large standard error) (P ؍ 0.16) and 61% for severity (P ؍ 0.02). The estimates for tibial bone areas were the only ones markedly reduced after adjustment for body size, while all estimates with the exception of knee pain were independent of ROA. Cartilage and, to a lesser extent, bone sites investigated by MRI were largely under independent genetic control, with a lesser shared genetic component.Conclusion. With the exception of prevalent ROA, all knee modalities assessed had high heritability, most likely reflecting a strong genetic component. Cartilage volume, bone size, and muscle strength all have the potential to be studied in quantitative trait linkage analyses, but their exact relevance with regard to OA remains uncertain at this time.Osteoarthritis (OA) is the most common form of arthritis and a leading cause of musculoskeletal disability in most developed countries (1). The knee is one of the most frequently affected joints, with a knee OA prevalence of 30% in people older than age 65 years (2) and high resultant disability (3). While its etiology and pathogenesis remain poorly understood, knee OA has been strongly associated with several environmental factors, including obesity (4-9), previous injury (10,11), vitamin D intake (12), and meniscectomy (13-15). In addition, a modest but significant genetic effect in radiographic OA (ROA) of the knee has been demonstrated in most studies (16)(17)(18)(19)(20). However, radiographs provide only a broad-brush view of joint pathology due to their semiquantitative grading scales. Magnetic resonance imaging (MRI) can allow direct visualization of joint structures and provide accurate and reproducible quantitative estimates of cartilage volume and bone area/volume (21-24), and the MRI result thus has the