The effect of uric acid-lowering therapy on bone mineral density in gout patients

Introduction and Aim: Gout is a chronic metabolic disorder characterized by the deposition of monosodium urate (MSU) crystals in joints and surrounding tissues as a result of hyperuricemia, leading to acute inflammatory attacks. It is commonly observed in middle-aged to elderly men and postmenopausal women. Hyperuricemia is the central pathophysiological component of gout, and elevated serum uric acid (SUA) levels play a critical role in both the development and severity of the disease. In the literature, studies examining the relationship between SUA levels and bone mineral density (BMD) have yielded conflicting results. Some suggest that SUA may enhance BMD and reduce the risk of osteoporosis by inhibiting bone resorption and promoting osteoblast activity, whereas others report that elevated SUA levels may adversely affect bone tissue by triggering inflammatory processes and oxidative stress. Urate-lowering therapies (ULTs) are frequently employed to reduce SUA levels in gout patients. However, studies directly investigating the effects of these therapies on BMD are limited. The aim of this study is to evaluate the impact of SUA reduction via ULT on bone mineral density in patients with gout. Materials and Methods: This prospective study was conducted at Yuzuncu Yil University, Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Rheumatology Outpatient Clinic, between May 2024 and May 2025. Sixty patients aged 30 to 85 years, diagnosed with gout according to the 2015 ACR/EULAR criteria, were included. Patients were divided into two groups: those receiving ULT (n=30) and those not receiving ULT (n=30). For both groups, serum uric acid levels and bone mineral density (T scores of L1–L4 lumbar vertebrae and femoral neck) were measured at the beginning of the treatment and at the end of the 12th month. Statistical analyses included tests for normality, independent and paired sample t-tests, Mann-Whitney U test, Wilcoxon test, and correlation analyses. All analyses were conducted using SPSS version 28.0. Results: Although there were some baseline demographic differences between the two groups, such as age and height, no statistically significant differences were observed in terms of sex distribution, body mass index, or initial BMD values. In the ULT group, a significant decrease in serum uric acid levels was observed after treatment (p<0.05), whereas a slight increase was noted in the control group. However, when comparing pre- and post-treatment values, no statistically significant changes were found in the T-scores of L1–L4 and femoral neck in either group (p>0.05). Additionally, no significant correlation was observed between changes in SUA levels and BMD before and after treatment (p>0.05). These findings indicate that changes in uric acid levels do not have a direct effect on bone mineral density. Conclusion: This study demonstrated that urate-lowering therapy significantly reduces serum uric acid levels in patients with gout; however, it does not have a notable impact on bone mineral density in the short term. The existing literature presents conflicting evidence regarding the effects of uric acid on bone metabolism. While some studies suggest a protective role via antioxidant properties, others highlight the potential for bone damage through inflammation and oxidative stress associated with high SUA levels. Despite achieving a significant reduction in SUA through ULT in our study, the absence of a meaningful change in BMD suggests that the relationship may not be direct or short-term. Further advanced studies involving larger sample sizes, long-term follow-up data, and multivariate analyses are needed to more comprehensively evaluate the effects of ULT on bone health. Particularly, future research should incorporate additional factors influencing bone metabolism such as vitamin D levels, parathyroid hormone levels, inflammatory markers, and physical activity to better inform clinical decision-making. Keywords: Gout Disease, Urate-Lowering Therapy, Serum Uric Acid, Bone Mineral Density, Osteoporosis