Abstract
Summary
Bone disorder is a common complication of chronic kidney disease (CKD). The clinical usefulness of bone mineral density (BMD) in CKD is not well known. Our study shows that low BMD is associated with physical activity and dietary Na/K intake ratio and can predict poor renal outcome in non-dialysis CKD.
Purpose
Despite evidence of a link between bone mineral disorders and chronic kidney disease (CKD), the clinical implications of bone mineral density (BMD) in CKD are not well established. We investigated risk factors and renal outcomes of low BMD in CKD.
Methods
We analyzed data from the KNOW-CKD. BMD measured by dual-energy x-ray absorptiometry was classified by T score: normal (T score ≥ − 1.0), osteopenia (− 1.0 > T score > − 2.5), and osteoporosis (T score ≤ − 2.5) of the lumbar spine, hip, or femoral neck. Logistic regression analysis to assess risk factors of low BMD (T score < − 1.0) and Cox proportional hazards models to estimate risk of incident end-stage renal disease (ESRD).
Results
Low BMD was prevalent (osteopenia 33%; osteoporosis 8%) in 2128 adults with CKD (age 54 ± 12 years; male 61%). Over a median follow-up of 4.3 years, there were 521 cases of incident ESRD. Lower BMD was associated with female sex, older age, low eGFR, low BMI, and lifestyle factors of physical activity (odds ratio (OR) = 0.62, 95% confidence interval (0.49–0.77)) and spot urine Na/K ratio (1.07 (1.00–1.15)). In adjusted Cox models, low BMD was associated with increased incident ESRD (hazard ratio (HR) = 1.14 (0.92–1.41) for osteopenia; 1.43 (1.01–2.04) for osteoporosis, P for trend < 0.05) compared with the reference of normal BMD. The association between low BMD and ESRD was similar according to T score discordance classification.
Conclusions
Low BMD was associated with modifiable lifestyle factors including low physical activity and high dietary Na/K intake ratio. The presence of low BMD is associated with poor renal outcomes in non-dialysis CKD.
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References
Ketteler M, Block GA, Evenepoel P, Fukagawa M, Herzog CA, McCann L, Moe SM, Shroff R, Tonelli MA, Toussaint ND, Vervloet MG, Leonard MB (2017) Executive summary of the 2017 KDIGO chronic kidney disease-mineral and bone disorder (CKD-MBD) guideline update: what’s changed and why it matters. Kidney Int 92(1):26–36. https://doi.org/10.1016/j.kint.2017.04.006
Mazzaferro S, Massy ZA, Vervloet M, Cozzolino M (2017) Bone in CKD: why the ERA EDTA CKD-MBD working group organized a dedicated meeting? J Nephrol 30(5):621–622. https://doi.org/10.1007/s40620-017-0436-4
Vervloet MG, Massy ZA, Brandenburg VM, Mazzaferro S, Cozzolino M, Urena-Torres P, Bover J, Goldsmith D, C-MWGo ERA-EDTA (2014) Bone: a new endocrine organ at the heart of chronic kidney disease and mineral and bone disorders. Lancet Diabetes Endocrinol 2(5):427–436. https://doi.org/10.1016/S2213-8587(14)70059-2
Compston JE, McClung MR, Leslie WD (2019) Osteoporosis. Lancet 393(10169):364–376. https://doi.org/10.1016/S0140-6736(18)32112-3
Qu X, Huang X, Jin F, Wang H, Hao Y, Tang T, Dai K (2013) Bone mineral density and all-cause, cardiovascular and stroke mortality: a meta-analysis of prospective cohort studies. Int J Cardiol 166(2):385–393. https://doi.org/10.1016/j.ijcard.2011.10.114
Cortet B (2016) Does low bone mineral density predict mortality? Joint Bone Spine 83(6):623–624. https://doi.org/10.1016/j.jbspin.2016.05.005
Bucur RC, Panjwani DD, Turner L, Rader T, West SL, Jamal SA (2015) Low bone mineral density and fractures in stages 3-5 CKD: an updated systematic review and meta-analysis. Osteoporos Int 26(2):449–458. https://doi.org/10.1007/s00198-014-2813-3
Chen Z, Qureshi AR, Ripsweden J, Wennberg L, Heimburger O, Lindholm B, Barany P, Haarhaus M, Brismar TB, Stenvinkel P (2016) Vertebral bone density associates with coronary artery calcification and is an independent predictor of poor outcome in end-stage renal disease patients. Bone 92:50–57. https://doi.org/10.1016/j.bone.2016.08.007
Veronese N, Stubbs B, Crepaldi G, Solmi M, Cooper C, Harvey NCW, Reginster JY, Rizzoli R, Civitelli R, Schofield P, Maggi S, Lamb SE (2017) Relationship between low bone mineral density and fractures with incident cardiovascular disease: a systematic review and meta-analysis. J Bone Miner Res 32(5):1126–1135. https://doi.org/10.1002/jbmr.3089
Moe S, Drueke T, Cunningham J et al (2006) Definition, evaluation, and classification of renal osteodystrophy: a position statement from kidney disease: improving global outcomes (KDIGO). Kidney Int 69(11):1945–1953. https://doi.org/10.1038/sj.ki.5000414
Jamal SA, Nickolas TL (2015) Bone imaging and fracture risk assessment in kidney disease. Curr Osteoporos Rep 13(3):166–172. https://doi.org/10.1007/s11914-015-0262-3
El Maghraoui A, Roux C (2008) DXA scanning in clinical practice. QJM 101(8):605–617. https://doi.org/10.1093/qjmed/hcn022
Kim CS, Bae EH, Ma SK, Han SH, Lee KB, Lee J, Oh KH, Chae DW, Kim SW, Group K-CS (2017) Chronic kidney disease-mineral bone disorder in Korean patients: a report from the KoreaN cohort study for outcomes in patients with chronic kidney disease (KNOW-CKD). J Korean Med Sci 32(2):240–248. https://doi.org/10.3346/jkms.2017.32.2.240
Levin A, Stevens PE (2014) Summary of KDIGO 2012 CKD guideline: behind the scenes, need for guidance, and a framework for moving forward. Kidney Int 85(1):49–61. https://doi.org/10.1038/ki.2013.444
Zhu K, Prince RL (2015) Lifestyle and osteoporosis. Curr Osteoporos Rep 13(1):52–59. https://doi.org/10.1007/s11914-014-0248-6
Sjöström M, Oja P, Hagströmer M, Smith BJ, Bauman A (2006) Health-enhancing physical activity across European Union countries: the Eurobarometer study. J Public Health (Oxf) 14(5):291–300. https://doi.org/10.1007/s10389-006-0031-y
Cao WT, He J, Chen GD, Wang C, Qiu R, Chen YM (2017) The association between urinary sodium to potassium ratio and bone density in middle-aged Chinese adults. Osteoporos Int 28(3):1077–1086. https://doi.org/10.1007/s00198-016-3835-9
Masud T, Manatunga A, Cotsonis G, Mitch WE (2002) The precision of estimating protein intake of patients with chronic renal failure. Kidney Int 62(5):1750–1756. https://doi.org/10.1046/j.1523-1755.2002.00606.x
Tangri N, Stevens LA, Griffith J, Tighiouart H, Djurdjev O, Naimark D, Levin A, Levey AS (2011) A predictive model for progression of chronic kidney disease to kidney failure. JAMA 305(15):1553–1559. https://doi.org/10.1001/jama.2011.451
Papaioannou A, Kennedy CC, Cranney A, Hawker G, Brown JP, Kaiser SM, Leslie WD, O’Brien CJM, Sawka AM, Khan A, Siminoski K, Tarulli G, Webster D, McGowan J, Adachi JD (2009) Risk factors for low BMD in healthy men age 50 years or older: a systematic review. Osteoporos Int 20(4):507–518. https://doi.org/10.1007/s00198-008-0720-1
Waugh EJ, Lam MA, Hawker GA, McGowan J, Papaioannou A, Cheung AM, Hodsman AB, Leslie WD, Siminoski K, Jamal SA, Perimenopause BMD Guidelines Subcommittee of Osteoporosis Canada (2009) Risk factors for low bone mass in healthy 40-60 year old women: a systematic review of the literature. Osteoporos Int 20(1):1–21. https://doi.org/10.1007/s00198-008-0643-x
Shams-White MM, Chung M, Du M et al (2017) Dietary protein and bone health: a systematic review and meta-analysis from the National Osteoporosis Foundation. Am J Clin Nutr 105(6):1528–1543. https://doi.org/10.3945/ajcn.116.145110
Fatahi S, Namazi N, Larijani B, Azadbakht L (2018) 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 37(6):522–532. https://doi.org/10.1080/07315724.2018.1431161
Hu D, Cheng L, Jiang W (2018) Fruit and vegetable consumption and the risk of postmenopausal osteoporosis: a meta-analysis of observational studies. Food Funct 9(5):2607–2616. https://doi.org/10.1039/c8fo00205c
Fern EB, Watzke H, Barclay DV, Roulin A, Drewnowski A (2015) The nutrient balance concept: a new quality metric for composite meals and diets. PLoS One 10(7):e0130491. https://doi.org/10.1371/journal.pone.0130491
Rutishauser IH (2005) Dietary intake measurements. Public Health Nutr 8(7A):1100–1107. https://doi.org/10.1079/phn2005798
Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF (2008) Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 93(1):40–46. https://doi.org/10.1210/jc.2007-1217
Jean G, Souberbielle JC, Chazot C (2017) Vitamin D in chronic kidney disease and dialysis patients. Nutrients 9(4):328. https://doi.org/10.3390/nu9040328
Moe SM (2017) Renal osteodystrophy or kidney-induced osteoporosis? Curr Osteoporos Rep 15(3):194–197. https://doi.org/10.1007/s11914-017-0364-1
Khairallah P, Nickolas TL (2018) Updates in CKD-associated osteoporosis. Curr Osteoporos Rep 16(6):712–723. https://doi.org/10.1007/s11914-018-0491-3
Woodson G (2000) Dual X-ray absorptiometry T-score concordance and discordance between the hip and spine measurement sites. J Clin Densitom 3(4):319–324. https://doi.org/10.1385/jcd:3:4:319
Akchurin OM, Kaskel F (2015) Update on inflammation in chronic kidney disease. Blood Purif 39(1–3):84–92. https://doi.org/10.1159/000368940
Mundy GR (2007) Osteoporosis and inflammation. Nutr Rev 65(12 Pt 2):S147–S151. https://doi.org/10.1111/j.1753-4887.2007.tb00353.x
Richter B, Faul C (2018) FGF23 actions on target tissues-with and without klotho. Front Endocrinol (Lausanne) 9:189. https://doi.org/10.3389/fendo.2018.00189
Shim JS, Oh K, Kim HC (2014) Dietary assessment methods in epidemiologic studies. Epidemiol Health 36:e2014009. https://doi.org/10.4178/epih/e2014009
Orlandi PF, Huang J, Fukagawa M, Hoy W, Jha V, Oh KH, Sola L, Cockwell P, Levin A, Feldman HI (2019) A collaborative, individual-level analysis compared longitudinal outcomes across the international network of chronic kidney disease (iNETCKD) cohorts. Kidney Int 96(5):1217–1233. https://doi.org/10.1016/j.kint.2019.07.024
Funding
The KNOW-CKD was funded by grants 2011E3300300, 2012E3301100, and 2013E3301600 from Research of the Korea Centers for Disease Control and Prevention.
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Hyun, Y.Y., Lee, KB., Han, S.H. et al. Risk factors and renal outcomes of low bone mineral density in patients with non-dialysis chronic kidney disease. Osteoporos Int 31, 2373–2382 (2020). https://doi.org/10.1007/s00198-020-05531-9
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DOI: https://doi.org/10.1007/s00198-020-05531-9