The Paradoxical Role of Uric Acid in Osteoporosis

Abstract

Because of its high prevalence worldwide, osteoporosis is considered a serious public health concern. Many known risk factors for developing osteoporosis have been identified and are crucial if planning health care needs. Recently, an association between uric acid (UA) and bone fractures had been explored. Extracellular UA exhibits antioxidant properties by effectively scavenging free radicals in human plasma, but this benefit might be disturbed by the hydrophobic lipid layer of the cell membrane. In contrast, intracellular free oxygen radicals are produced during UA degradation, and superoxide is further enhanced by interacting with NADPH oxidase. This intracellular oxidative stress, together with inflammatory cytokines induced by UA, stimulates osteoclast bone resorption and inhibits osteoblast bone formation. UA also inhibits vitamin D production and thereby results in hyper-parathyroidism, which causes less UA excretion in the intestines and renal proximal tubules by inhibiting the urate transporter ATP-binding cassette subfamily G member 2 (ABCG2). At normal or high levels, UA is associated with a reduction in bone mineral density and protects against bone fracture. However, in hyperuricemia or gout arthritis, UA increases bone fracture risk because oxidative stress and inflammatory cytokines can increase bone resorption and decrease bone formation. Vitamin D deficiency, and consequent secondary hyperparathyroidism, can further increase bone resorption and aggravated bone loss in UA-induced osteoporosis.

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.…”

Evaluation Of The Relationship between Serum Uric Acid and Bone Mineral Density In Rheumatoid Arthritis Male Patients

“…The positive correlation between serum UA levels and bone mineral density has frequently been reported in the normal population and in postmenopausal females (2,3,5) . However, there are little data regarding the effect of serum UA levels on bone loss in male patients with rheumatoid arthritis.…”

“…That's why there had been epidemiological evidence that hyperuricemia is a risk factor for conditions associated with oxidative stress, such as cardiovascular diseases, metabolic syndrome, and chronic kidney diseases (1) . Alternatively, there is an increasing clinical evidence that serum UA, while within the normal range, has anti-inflammatory and anti-oxidative effects, and plays a protective role as an antioxidant (2) .…”

Serum Uric Acid Level Is Positively Associated With Higher Bone Mineral Density at Multiple Skeletal Sites Among Healthy Qataris

“…Oxidative stress inhibits osteoblast cell differentiation and function in mineralizing the bone tissue and may even induce cell death with evident reversal of all changes upon treatment with antioxidants such as Trolox or ascorbic acid ( 47 , 48 ). Oxidative stress may also stimulate the development and function of osteoclast cells that exhibit bone resorption via ROS-mediated mechanisms ( 49 , 50 ).…”