Serum Uric Acid and Bone Health in Middle-Aged and Elderly Hypertensive Patients: A Potential U-Shaped Association and Implications for Future Fracture Risk

Overview

Journal Metabolites

Publisher MDPI

Date 2025 Jan 24

PMID 39852358

Authors

Shuaiwei Song

Xintian Cai

Junli Hu

Qing Zhu

Di Shen

Huimin Ma

Yingying Zhang

Rui Ma

Pan Zhou

Wenbo Yang

Jing Hong

Nanfang Li

Affiliations

Soon will be listed here.

Abstract

Background: The influence of serum uric acid (SUA) on bone metabolism, as suggested by previous studies, remains a contentious issue. SUA plays a complex role in bone health and hypertension, making it challenging to discern its impact on the skeletal status of middle-aged and elderly hypertensive patients. This study aims to elucidate the effects of SUA on bone health, with a particular focus on its association with osteoporosis and the risk of fractures.

Methods: Multiple linear regression analyzed SUA levels against bone mineral density (BMD) and future fracture risk. Additionally, multivariate logistic regression was used to examine the association between SUA and osteoporosis. Dose-response relationship analysis was conducted using generalized smooth curve fitting (GSCF) and restricted cubic spline (RCS) methods.

Results: With the exception of the total femur region, SUA and BMD showed a positive connection. GSCF analysis revealed an inverted U-shaped relationship between SUA and BMD, alongside a U-shaped trend with FRAX scores. Moreover, RCS analysis indicated a U-shaped relationship between osteoporosis risk and SUA levels, with higher risks identified in the first and third tertiles compared to the second tertile.

Conclusions: In individuals with middle-aged and older hypertension, SUA is substantially linked to bone health. The identification of an inverted U-shaped relationship with BMD and U-shaped relationships with FRAX scores and osteoporosis risk highlights the nuanced influence of SUA. These findings suggest that both low and high SUA levels may adversely affect bone health, emphasizing the need for further research.

Citing Articles

Association of triglyceride-glucose index with bone mineral density and fracture: a systematic review.

Yousefiasl M, Soltanattar A, Ezzatollahi Tanha A, Azami P, Alaei M, Alamdari A Diabetol Metab Syndr. 2025; 17(1):77.

PMID: 40038837 PMC: 11877733. DOI: 10.1186/s13098-025-01642-7.

References

Song S, Cai X, Hu J, Zhu Q, Shen D, Ma H . Plasma aldosterone concentrations elevation in hypertensive patients: the dual impact on hyperuricemia and gout. Front Endocrinol (Lausanne). 2024; 15:1424207. PMC: 11319118. DOI: 10.3389/fendo.2024.1424207. View

Xiao Z, Liu H . The estrogen receptor and metabolism. Womens Health (Lond). 2024; 20:17455057241227362. PMC: 10903191. DOI: 10.1177/17455057241227362. View

Adomako E, Moe O . Uric Acid and Urate in Urolithiasis: The Innocent Bystander, Instigator, and Perpetrator. Semin Nephrol. 2021; 40(6):564-573. PMC: 8127876. DOI: 10.1016/j.semnephrol.2020.12.003. View

Wen Z, Li Y, Xu L, Yue C, Wang Q, Chen R . Triglyceride Glucose-Body Mass Index Is a Reliable Indicator of Bone Mineral Density and Risk of Osteoporotic Fracture in Middle-Aged and Elderly Nondiabetic Chinese Individuals. J Clin Med. 2022; 11(19). PMC: 9572437. DOI: 10.3390/jcm11195694. View

Sanchez-Riera L, Carnahan E, Vos T, Veerman L, Norman R, Lim S . The global burden attributable to low bone mineral density. Ann Rheum Dis. 2014; 73(9):1635-45. DOI: 10.1136/annrheumdis-2013-204320. View

Wang X, Yu J, Wang X, Jing Y, Sun L, Tao B . THE ASSOCIATIONS BETWEEN HYPOVITAMINOSIS D, HIGHER PTH LEVELS WITH BONE MINERAL DENSITIES, AND RISK OF THE 10-YEAR PROBABILITY OF MAJOR OSTEOPOROTIC FRACTURES IN CHINESE PATIENTS WITH T2DM. Endocr Pract. 2018; 24(4):334-341. DOI: 10.4158/EP-2017-0164. View

Orriss I, Arnett T, George J, Witham M . Allopurinol and oxypurinol promote osteoblast differentiation and increase bone formation. Exp Cell Res. 2016; 342(2):166-74. PMC: 4829071. DOI: 10.1016/j.yexcr.2016.03.004. View

Borghi C, Agabiti-Rosei E, Johnson R, Kielstein J, Lurbe E, Mancia G . Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease. Eur J Intern Med. 2020; 80:1-11. DOI: 10.1016/j.ejim.2020.07.006. View

Domazetovic V, Marcucci G, Iantomasi T, Brandi M, Vincenzini M . Oxidative stress in bone remodeling: role of antioxidants. Clin Cases Miner Bone Metab. 2017; 14(2):209-216. PMC: 5726212. DOI: 10.11138/ccmbm/2017.14.1.209. View

10.

Yuan Q, Karmacharya U, Liu F, Chen B, Ma X, Ma Y . Uric acid and its correlation with hypertension in postmenopausal women: A multi-ethnic study (Observational study). Clin Exp Hypertens. 2020; 42(6):559-564. DOI: 10.1080/10641963.2020.1739697. View

11.

Lv Q, Meng X, He F, Chen S, Su H, Xiong J . High serum uric acid and increased risk of type 2 diabetes: a systemic review and meta-analysis of prospective cohort studies. PLoS One. 2013; 8(2):e56864. PMC: 3577701. DOI: 10.1371/journal.pone.0056864. View

12.

Li H, Chen Z, Hou C, Tang Y, Wang F, Fu Q . Uric Acid Promotes Osteogenic Differentiation and Inhibits Adipogenic Differentiation of Human Bone Mesenchymal Stem Cells. J Biochem Mol Toxicol. 2015; 29(8):382-7. DOI: 10.1002/jbt.21707. View

13.

Ensrud K, Crandall C . Osteoporosis. Ann Intern Med. 2017; 167(3):ITC17-ITC32. DOI: 10.7326/AITC201708010. View

14.

Ma H, Cai X, Hu J, Song S, Zhu Q, Zhang Y . Association of systemic inflammatory response index with bone mineral density, osteoporosis, and future fracture risk in elderly hypertensive patients. Postgrad Med. 2024; 136(4):406-416. DOI: 10.1080/00325481.2024.2354158. View

15.

El-Eshmawy M, Ibrahim A, Bahriz R, Shams-Eldin N, Mahsoub N . Serum uric acid/creatinine ratio and free androgen index are synergistically associated with increased risk of polycystic ovary syndrome in obese women. BMC Endocr Disord. 2022; 22(1):315. PMC: 9746110. DOI: 10.1186/s12902-022-01240-y. View

16.

Johnson R, Tolan D, Bredesen D, Nagel M, Sanchez-Lozada L, Fini M . Could Alzheimer's disease be a maladaptation of an evolutionary survival pathway mediated by intracerebral fructose and uric acid metabolism?. Am J Clin Nutr. 2023; 117(3):455-466. PMC: 10196606. DOI: 10.1016/j.ajcnut.2023.01.002. View

17.

Lee H, Hwang J . Impact of Type 2 Diabetes Mellitus and Antidiabetic Medications on Bone Metabolism. Curr Diab Rep. 2020; 20(12):78. DOI: 10.1007/s11892-020-01361-5. View

18.

Chin K, Nirwana S, Wan Ngah W . Significant association between parathyroid hormone and uric acid level in men. Clin Interv Aging. 2015; 10:1377-80. PMC: 4552259. DOI: 10.2147/CIA.S90233. View

19.

Lin K, Lu C, Hung K, Wu P, Pan C, Wu C . The Paradoxical Role of Uric Acid in Osteoporosis. Nutrients. 2019; 11(9). PMC: 6769742. DOI: 10.3390/nu11092111. View

20.

Yan D, Wang J, Hou X, Bao Y, Zhang Z, Hu C . Association of serum uric acid levels with osteoporosis and bone turnover markers in a Chinese population. Acta Pharmacol Sin. 2017; 39(4):626-632. PMC: 5888689. DOI: 10.1038/aps.2017.165. View