The Genetic Contribution and Relevance of Knee Cartilage Defects: Case-Control and Sib-Pair Studies

CHANGHAI DING, FLAVIA CICUTTINI, FIONA SCOTT, JAMES STANKOVICH, HELEN COOLEY, and GRAEME JONES

ABSTRACT.

Objective. To describe the differences in knee cartilage defects between offspring of subjects with at least one parent with a total knee replacement for severe primary knee osteoarthritis (OA) and controls; and to estimate the heritability of knee cartilage defects in sib-pairs.

Methods. Population based, case-control study of 186 matched pairs (mean age 45 yrs, range 26–61) and sib-pair study of 128 subjects from 51 families (115 sib-pairs) within the case-control study. Knee cartilage defect scores (0–4) and prevalence (a cartilage defect score ≥ 2) were assessed at the patellar, tibial, and femoral sites by processing images acquired using T1 weighted fat-saturated magnetic resonance imaging. Heritability was estimated using the SOLAR genetic analysis program.

Results. The prevalence of knee cartilage defects was surprisingly high (50% scored ≥ 2 in any site). Compared to controls, offspring had higher knee cartilage defect scores and prevalence in tibiofemoral (4.39 vs 4.01, p = 0.003; 41% vs 28%, p = 0.009), patellar (1.32 vs 1.10, p = 0.031; 35% vs 26%, p = 0.075), and whole (5.71 vs 5.10, p = 0.002; 57% vs 42%, p = 0.007) compartments. These all became nonsignificant after adjustment for knee pain and radiographic OA. In the sib-pair component, knee cartilage defects had heritability for scores and prevalence, respectively, of 38% (p = 0.072) and 47% (p = 0.082) for tibiofemoral, 52% (p = 0.009) and 78% (p = 0.025) for patellar, and 43% (p = 0.038) and 68% (p = 0.072) for the whole compartments. These estimates became weaker at tibiofemoral and whole compartments after adjustment for bone size, knee pain, and radiographic OA.

Conclusion. Knee cartilage defects are common, have a genetic component that is linked to the genetic contribution to knee pain and bone size, and may have a role in the genetic pathogenesis of knee OA. (J Rheumatol 2005;32:1937-42)

Key Indexing Terms:

KNEE
CARTILAGE DEFECTS
OSTEOARTHRITIS
GENETICS
HERITABILITY

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From Menzies Research Institute, University of Tasmania, Hobart; Department of Epidemiology and Preventive Medicine, Monash University Medical School, Melbourne; and The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.

Supported by the National Health and Medical Research Council of Australia, Masonic Centenary Medical Research Foundation.

C.H. Ding, MD, Research Fellow; F. Scott, MBBS, Research Associate; H. Cooley, MD, Senior Research Fellow; G. Jones, MD, Professor, University of Tasmania; F. Cicuttini, PhD, Associate Professor, Monash University; J. Stankovich, PhD, Biostatistician, The Walter and Eliza Hall Institute of Medical Research.

Address reprint requests to Prof. G. Jones, Menzies Research Institute, Private Bag 23, Hobart, Tasmania 7000, Australia. E-mail: g.jones@utas.edu.au

Accepted for publication May 30, 2005.

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