Pathologically high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels in patients with acromegaly are associated with arthropathy. Several studies highlight the potential role of the GH/IGF-1 axis in primary osteoarthritis (OA). We aimed to disentangle the role of IGF-1 levels in primary OA pathogenesis.
Patients from the Genetics osteoARthritis and Progression (GARP) Study with familial, generalized, symptomatic OA (N=337, mean age 59.8±7.4 years, 82% female) were compared to Leiden Longevity Study (LLS) controls (N=456, mean age 59.8±6.8 years, 51% female). Subjects were clinically and radiographically assessed, serum IGF-1 levels were measured, and 10 quantitative trait loci (QTL) in the FOXO3, IGBP3/TNS3, RPA3, SPOCK2 genes, previously related to serum IGF-1 levels, were genotyped. Linear or binary logistic generalized estimating equation models were performed.
Serum IGF-1 levels were increased in OA patients, with male patients exhibiting the strongest effect (males OR=1.10 (1.04-1.17), P=0.002 vs. females OR=1.04 (1.01-1.07), P=0.02). Independent of the increased IGF-1 levels, male carriers of the minor allele of FOXO3 QTL rs4946936 had lower risk to develop hip OA (OR=0.41 (0.18-0.90), P=0.026). Additionally, independent of IGF-1 levels, female carriers of the minor alleles of RPA3 QTL rs11769597 had higher risk to develop knee OA (OR=1.90 (1.20-2.99), P=0.006).
Patients with primary OA had significantly higher IGF-1 levels compared to controls. Moreover, SNPs in the FOXO3 and RPA3 genes were associated with an altered risk of OA. Therefore, altered IGF-1 levels affect the development of OA, and are potentially the result of the pathophysiological OA process.