Vitamin D receptor gene polymorphisms modulate the clinico-radiological response to vitamin D supplementation in knee osteoarthritis

Abstract

Purpose: Osteoarthritis (OA) is one of the most frequent causes of pain, loss of function and disability in the elderly. Knee OA is particularly common in Indian patients and there is currently no therapy that can slow its progression. A beneficial effect of vitamin D supplementation on symptomatic improvement in OA knee patients has recently been reported. Vitamin D receptor (VDR) gene plays an important role in regulation of bone mass and in human articular chondrocytes of cartilage. In view of the importance of the vitamin D in bone development the abnormalities in the VDR gene are viewed as potential contributors to OA. Therefore, this study was planned as a pilot study to find out to whether the clinico‐radiological response to vitamin D was modulated by VDR gene polymorphisms. Methods: This randomized placebo‐controlled trial recruited 103 KOA cases as per American College of Rheumatology (ACR) guideline having vitamin D insufficiency (25(OH)D ≤ 50 nmol/L). Enrolled cases were randomly allocated in two groups to receive placebo (51) and vitamin D (52). Primary outcome measures: pain and functional disability which were recorded by knee specific WOMAC index and secondary outcome measure were radiological features (joint space width and osteophytes). The serum levels of vitamin D were assessed by a method Enzyme Linked Immunosorbent Assay using IDS, UK kit. Detection of VDR polymorphisms (Taq1 & Apa I) were done by PCR‐RFLP technique. 25(OH)D levels, clinical and radiological features were recorded at baseline and at one year follow up. Results: At one year, in vitamin D supplemented group, TT genotype of TaqI polymorphism showed the maximum increment in the level of 25(OH)D in comparison to Tt and tt genotype whereas in placebo group it remained same. No such association was observed for ApaI polymorphism. In clinical features, pain and functional disability improved in each genotype although least in tt genotype in vitamin D supplemented group whereas in placebo group it significantly worsened in Tt and tt genotype. Total WOMAC scores improved in each genotype of vitamin D supplemented group and was significant in case of Tt and TT genotype (p < 0.05). In radiological features, no changes was observed in vitamin D group whereas in placebo group decreased Medial‐JSW and increased Osteophyte was observed in Tt and tt genotype in comparion to TT genotype of TaqI polymorphism. These changes were of borderline significance. No similar effect was observed for ApaI polymorphism. Conclusions: VDR gene polymorphism (TaqI) influences the clinicoradiological response to vitamin D supplementation in Osteoarthritis knee with insufficient 25‐OHD levels. If these results are confirmed by the larger studies, this would justify tailoring vitamin D supplementation using VDR genotyping in vitamin D insufficient KOA patients.