Evidence for a differential association of the Arg200Trp single-nucleotide polymorphism in FRZB with hip osteoarthritis and osteoporosis

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Abstract
Sir, Osteoarthritis and osteoporosis are disabling diseases in the elderly. Clinical observations suggest an inverse relationship between these disorders (for review see [1]). This hypothesis is still controversial and no molecular basis for this observation has been demonstrated. Genome-wide linkage analysis and subsequent association study identified a single-nucleotide polymorphism (SNP) (Arg324Gly) in the frizzled-related protein (FRZB) gene associated with hip osteoarthritis in Caucasian females [2] and with generalized osteoarthritis at multiple sites in Caucasians [3]. The haplotype coding for substitutions of two arginines (Arg200Trp and Arg324Gly) in FRZB appears to be a strong risk factor for primary hip osteoarthritis in Caucasian females. FRZB is a secreted antagonist of Wnt signalling molecules [4]. The Wnt pathway is of critical importance in development, homeostasis and pathology [5]. Wnt signalling, in particular Wnt co-receptor LRP-5 and Wnt antagonist sFRP1, has also been associated with osteoporosis [6–8].