Review of the Literature Examining the Association of Serum Uric Acid with Osteoporosis and Mechanistic Insights into Its Effect on Bone Metabolism

Abstract

Background And Objective: Osteoporosis is a common bone disorder that increases susceptibility to fragility bone fractures. The clinical and public health repercussions of osteoporosis are huge due to the morbidity, mortality, and cost of medical care linked with fragility fractures. Clinical assessment of osteoporotic risk factors can help to identify candidates at an early stage that will benefit from medical intervention and potentially lowering the morbidity and mortality seen with fractures and complications. Given this, research is ongoing to evaluate the association of osteoporosis with some novel or less well-studied risk factors/bio-markers such as uric acid (UA). Discussion: Uric acid’s antioxidant activity has been proposed to be one of the factors responsible for increasing longevity and lowering rates of age-related cancers during primate evolution, the level of which increased markedly due to loss of uricase enzyme activity (mutational silencing). Accumulated evidence shows that oxidative stress is the fundamental mechanism of age-related bone loss and acts via enhancing osteoclastic activity and increasing bone resorption. Antioxidant substances such as ascorbic acid scavenge free radicals are positively related to bone health. Thus, it is hypothesized that uric acid holds bone-protective potential owing to its potent antioxidative property. Several correlation studies have been conducted globally to investigate the relationship between serum uric acid with bone mineral density and osteoporosis. Few pre-clinical studies have tried to investigate the interaction between uric acid and bone mineral density and reported important role played via Runt-related transcription factor 2 (RUNX2)/core-binding factor subunit alpha-1 (CBF-alpha-1), Wingless-related integration site (Wnt)-3a/β-catenin signaling pathway and 11β Hydroxysteroid Dehydrogenase type 1. Conclusion: In this review, the authors provided a comprehensive summary of the literature related to association studies reported in humans as well work done until date to understand the potential cellular and molecular mechanisms that interplay between uric acid and bone metabolism.

The Association between Serum Uric Acid and Bone Mineral Density in Older Adults

“…Hyperuricemia is a key causal factor of gout, as well as associated with a wide range of conditions, such as chronic kidney disease, obesity, and hypertension [ 17 , 18 ]. On the other hand, higher sUA might play a beneficial role in some conditions, including osteoporosis [ 10 ]. Among our representative US population, a higher sUA was associated with a greater lumbar BMD in most old adults.…”

“…However, there is growing evidence that UA, as an antioxidant, might play protective roles in cancer [ 4 ] and nervous system diseases, such as dementia [ 5 ], Parkinson's disease [ 6 ], Alzheimer's disease [ 7 ], multiple sclerosis [ 8 ], and amyotrophic lateral sclerosis [ 9 ]. Moreover, due to its antioxidant properties, UA is also considered to contribute to greater BMD by inhibiting osteoclastic bone resorption and promoting osteoblastic differentiation [ 10 ].…”

“…Recently, studies are being focused on the relationship between sUA and BMD, but with controversial findings having been reported in this limited body of evidence. Specifically, while a higher sUA level was associated with greater BMD [ 10 ], other studies did not identify a protective effect of higher sUA on BMD [ 11 – 13 ]. Accordingly, our aim in this study was to evaluate the relationship between sUA and BMD using a representative sample of older adults from the National Health and Nutrition Examination Survey (NHANES).…”

High-Throughput Metabolomics Discovers Metabolic Biomarkers and Pathways to Evaluating the Efficacy and Exploring Potential Mechanisms of Osthole Against Osteoporosis Based on UPLC/Q-TOF-MS Coupled With Multivariate Data Analysis

“…Blood uric acid is a lowering material in the human body, it has a strong antioxidant capacity in the redox reaction in the human body, which could scavenge free radicals to resist DNA damage ( Wang et al, 2013 ). It has reported the physiological concentrations of uric acid in the blood possess anti-osteoporotic effects ( Gormally et al, 2019 ; Lin et al, 2019 ; Kaushal et al, 2019 ). On the one hand, uric acid possess a certain protective effect on bone metabolism and is thought to be related to its antioxidant function.…”

Boric Acid (H3(BO3): Recognize The Molecular Interactions in Solutions

“…Sintesis (40) asam borat, dapat dilakukan dengan cara mereaksikan (41)(42)(43)(44)(45) sodium tetraborat dekahidrat dengan asam mineral, (46)(47)(48)(49)(50) (51) sebagai antiseptik (52)(53)(54) terkadang digunakan dalam salep atau pembalut.…”