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Review
. 2019 Sep 5;11(9):2111.
doi: 10.3390/nu11092111.

The Paradoxical Role of Uric Acid in Osteoporosis

Kun-Mo Lin  1 , Chien-Lin Lu  2 , Kuo-Chin Hung  3 , Pei-Chen Wu  4 , Chi-Feng Pan  5 , Chih-Jen Wu  6 , Ren-Si Syu  7 , Jin-Shuen Chen  8 , Po-Jen Hsiao  9   10   11 , Kuo-Cheng Lu  12
Affiliations
Review

The Paradoxical Role of Uric Acid in Osteoporosis

Kun-Mo Lin et al. Nutrients. .

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.

Keywords: inflammatory cytokines; osteoporosis; oxidative stress; secondary hyperparathyroidism; uric acid; vitamin D deficiency.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Uric acid (UA) acts as a hydrophobic pro-oxidant within the cell and a hydrophilic antioxidant outside the cell. Urate enters the cell via UA transporter 1 (URAT1) on the cell membrane. UA is produced from xanthine via xanthine oxidase (XO) in the cell and also generates superoxide ions (O2-), which also promotes oxidative stress by superoxide free radicals produced via NADPH oxidase (NOX4). UA intracellularly induces endothelial nitric oxide synthase (eNOs) with a decrease in nitric oxide (NO) generation. It also directly increases inflammation, which leads to cell injury.
Figure 2
Figure 2
Hyperuricemia-/gout-induced inflammatory cytokines and related reactive oxygen species (ROS) activate osteoclast (OC) activity and inhabit osteoblast cell (OB) viability. Cytokines induce oxidative stress via xanthine oxidase (XO), then leads to enhanced bone loss.
Figure 3
Figure 3
Conceivable mechanisms of hyperuricemia-/gout-induced bone loss.
See this image and copyright information in PMC

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