Effect of Salt Substitution on Fracture-a Secondary Analysis of the Salt Substitute and Stroke Study (SSaSS)

Overview

Journal BMC Med

Publisher Biomed Central

Specialty General Medicine

Date 2024 Sep 5

PMID 39232779

Authors

Faxuan Wang

Yangyang Pi

Yi Zhao

YuHong Zhang

Bo Zhou

Zhifang Li

Jixin Sun

Yan Yu

Maoyi Tian

Minghui Yang

Liping Huang

Hongyi Song

Bruce Neal

Katrina R Kissock

Affiliations

Soon will be listed here.

Abstract

Background: Associations of dietary sodium and potassium intake with fracture risk are inconsistent and the effects of salt substitute on fracture incidence are unknown. We assessed the effect of salt substitute compared to regular salt intake on fracture incidence using data from the Salt Substitute and Stroke Study (SSaSS).

Methods: SSaSS was a cluster-randomized controlled trial conducted in 600 villages in northern China. Villages were randomly allocated into intervention and control groups in a 1:1 ratio. Salt substitute was provided to intervention villages and control villages continued regular salt use for 5 years. The primary outcome for this secondary analysis was the incidence of all fractures. Secondary outcomes included incidence of vertebral fracture, non-vertebral fracture, and fracture of unknown or non-specific location.

Results: 20,995 participants were included in this study, and 821 fractures occurred during follow-up. Intention-to-treat analyses showed no differences between the salt substitute and regular salt groups in the incidence of all fractures (rate ratio (RR) 0.96; 95% CI 0.81 to 1.14), vertebral fracture (RR 0.82; 95% CI 0.53 to 1.26), non-vertebral fracture (RR 1.05; 95% CI 0.86 to 1.29), or fracture of unknown or non-specific location (RR 0.80; 95% CI 0.54 to 1.18).

Conclusions: Use of salt substitute compared to regular salt had no detectable effect on the incidence of fracture in a population at high risk of cardiovascular disease and fracture.

Trial Registration: ClinicalTrials.gov, NCT02092090. Registered on March 12, 2014.

References

Hong S, Choi J, Park J, Lee C . The association between dietary sodium intake and osteoporosis. Sci Rep. 2022; 12(1):14594. PMC: 9418184. DOI: 10.1038/s41598-022-18830-4. View

Watts N, Manson J . Osteoporosis and Fracture Risk Evaluation and Management: Shared Decision Making in Clinical Practice. JAMA. 2016; 317(3):253-254. DOI: 10.1001/jama.2016.19087. View

Neal B, Tian M, Li N, Elliott P, Yan L, Labarthe D . Rationale, design, and baseline characteristics of the Salt Substitute and Stroke Study (SSaSS)-A large-scale cluster randomized controlled trial. Am Heart J. 2017; 188:109-117. DOI: 10.1016/j.ahj.2017.02.033. View

Borgstrom F, Karlsson L, Ortsater G, Norton N, Halbout P, Cooper C . Fragility fractures in Europe: burden, management and opportunities. Arch Osteoporos. 2020; 15(1):59. PMC: 7166207. DOI: 10.1007/s11657-020-0706-y. View

Cohen A, Roe F . Review of risk factors for osteoporosis with particular reference to a possible aetiological role of dietary salt. Food Chem Toxicol. 2000; 38(2-3):237-53. DOI: 10.1016/s0278-6915(99)00145-3. View

Verbalis J, Barsony J, Sugimura Y, Tian Y, Adams D, Carter E . Hyponatremia-induced osteoporosis. J Bone Miner Res. 2009; 25(3):554-63. PMC: 3153395. DOI: 10.1359/jbmr.090827. View

Harrington M, Cashman K . High salt intake appears to increase bone resorption in postmenopausal women but high potassium intake ameliorates this adverse effect. Nutr Rev. 2003; 61(5 Pt 1):179-83. DOI: 10.1301/nr.2003.may.179-183. View

Park Y, Kwon S, Ha Y . Association between Urinary Sodium Excretion and Bone Health in Male and Female Adults. Ann Nutr Metab. 2016; 68(3):189-96. DOI: 10.1159/000444536. View

Nieves J, Melsop K, Curtis M, Kelsey J, Bachrach L, Greendale G . Nutritional factors that influence change in bone density and stress fracture risk among young female cross-country runners. PM R. 2010; 2(8):740-50. DOI: 10.1016/j.pmrj.2010.04.020. View

10.

Ha J, Kim S, Lim K, Shin S . The association of potassium intake with bone mineral density and the prevalence of osteoporosis among older Korean adults. Nutr Res Pract. 2020; 14(1):55-61. PMC: 6997142. DOI: 10.4162/nrp.2020.14.1.55. View

11.

Bergh C, Wennergren D, Moller M, Brisby H . Fracture incidence in adults in relation to age and gender: A study of 27,169 fractures in the Swedish Fracture Register in a well-defined catchment area. PLoS One. 2020; 15(12):e0244291. PMC: 7751975. DOI: 10.1371/journal.pone.0244291. View

12.

Yin X, Rodgers A, Perkovic A, Huang L, Li K, Yu J . Effects of salt substitutes on clinical outcomes: a systematic review and meta-analysis. Heart. 2022; 108(20):1608-1615. DOI: 10.1136/heartjnl-2022-321332. View

13.

Jones G, Beard T, Parameswaran V, Greenaway T, von Witt R . A population-based study of the relationship between salt intake, bone resorption and bone mass. Eur J Clin Nutr. 1997; 51(8):561-5. DOI: 10.1038/sj.ejcn.1600452. View

14.

Kupisz-Urbanska M, Marcinowska-Suchowierska E . Malnutrition in Older Adults-Effect on Falls and Fractures: A Narrative Review. Nutrients. 2022; 14(15). PMC: 9370498. DOI: 10.3390/nu14153123. View

15.

Dar H, Singh A, Shukla P, Anupam R, Mondal R, Mishra P . High dietary salt intake correlates with modulated Th17-Treg cell balance resulting in enhanced bone loss and impaired bone-microarchitecture in male mice. Sci Rep. 2018; 8(1):2503. PMC: 5802842. DOI: 10.1038/s41598-018-20896-y. View

16.

Hannon M, Verbalis J . Sodium homeostasis and bone. Curr Opin Nephrol Hypertens. 2014; 23(4):370-6. DOI: 10.1097/01.mnh.0000447022.51722.f4. View

17.

Polinder S, Haagsma J, Panneman M, Scholten A, Brugmans M, van Beeck E . The economic burden of injury: Health care and productivity costs of injuries in the Netherlands. Accid Anal Prev. 2016; 93:92-100. DOI: 10.1016/j.aap.2016.04.003. View

18.

BERGSTROM W, WALLACE W . Bone as a sodium and potassium reservoir. J Clin Invest. 1954; 33(6):867-73. PMC: 438522. DOI: 10.1172/JCI102959. View

19.

Fatahi S, Namazi N, Larijani B, Azadbakht L . The Association of Dietary and Urinary Sodium With Bone Mineral Density and Risk of Osteoporosis: A Systematic Review and Meta-Analysis. J Am Coll Nutr. 2018; 37(6):522-532. DOI: 10.1080/07315724.2018.1431161. View

20.

Veronese N, Stubbs B, Crepaldi G, Solmi M, Cooper C, Harvey N . Relationship Between Low Bone Mineral Density and Fractures With Incident Cardiovascular Disease: A Systematic Review and Meta-Analysis. J Bone Miner Res. 2017; 32(5):1126-1135. PMC: 5417361. DOI: 10.1002/jbmr.3089. View