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Chronic kidney disease–related osteoporosis is associated with incident frailty among patients with diabetic kidney disease: a propensity score–matched cohort study

Osteoporosis International volume 31, pages 699–708 (2020)Cite this article

Abstract

Summary

Chronic kidney disease (CKD)-related osteoporosis is a major complication in patients with CKD, conferring a higher risk of adverse outcomes. We found that among those with diabetic kidney disease, this complication increased the risk of incident frailty, an important mediator of adverse outcomes.

Introduction

Renal osteodystrophy and chronic kidney disease (CKD)-related osteoporosis increases complications for patients with diabetic kidney disease (DKD). Since musculoskeletal degeneration is central to frailty development, we investigated the relationship between baseline osteoporosis and the subsequent frailty risk in patients with DKD.

Methods

From the Longitudinal Cohort of Diabetes Patients in Taiwan (n = 840,000), we identified 12,027 patients having DKD with osteoporosis and 24,054 propensity score-matched controls having DKD but without osteoporosis. The primary endpoint was incident frailty on the basis of a modified FRAIL scale. Patients were prospectively followed-up until the development of endpoints or the end of this study. The Kaplan-Meier technique and Cox proportional hazard regression were used to analyze the association between osteoporosis at baseline and incident frailty in these patients.

Results

The mean age of the DKD patients was 67.2 years, with 55.4% female and a 12.6% prevalence of osteoporosis at baseline. After 3.5 ± 2.2 years of follow up, the incidence rate of frailty in patients having DKD with osteoporosis was higher than that in DKD patients without (6.6 vs. 5.7 per 1000 patient-year, p = 0.04). A Cox proportional hazard regression showed that after accounting for age, gender, obesity, comorbidities, and medications, patients having DKD with osteoporosis had a significantly higher risk of developing frailty (hazard ratio, 1.19; 95% confidence interval, 1.02–1.38) than those without osteoporosis.

Conclusions

CKD-related osteoporosis is associated with a higher risk of incident frailty in patients with DKD.

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Data availability

The dataset generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

References

  1. KDIGO (2009) Clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease–mineral and bone disorder (CKD–MBD). Chapter 1: introduction and definition of CKD–MBD and the development of the guideline statements. Kidney Int 76:S3–S8

    Google Scholar 

  2. Bellasi A, Mandreoli M, Baldrati L, Corradini M, Di Nicolo P, Malmusi G, Santoro A (2011) Chronic kidney disease progression and outcome according to serum phosphorus in mild-to-moderate kidney dysfunction. Clin J Am Soc Nephrol 6:883–891

    CAS  PubMed  PubMed Central  Google Scholar 

  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

    PubMed  Google Scholar 

  4. Chao CT, Yuan TH, Yeh HY, Chen HY, Huang JW, Chen HW (2019) Risk factors associated with altered circulating microRNA-125b and their influences on uremic vascular calcification among patients with end-stage renal disease. J Am Heart Assoc 8:e010805

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Block GA, Kilpatrick RD, Lowe KA, Wang W, Danese MD (2013) CKD–mineral and bone disorder and risk of death and cardiovascular hospitalization in patients on hemodialysis. Clin J Am Soc Nephrol 8:2132–2140

    PubMed  PubMed Central  Google Scholar 

  6. Naylor KL, Garg AX, Zou G, Langsetmo L, Leslie WD, Fraser LA, Adachi JD, Morin S, Goltzman D, Lentle B, Jackson SA, Josse RG, Jamal SA (2015) Comparison of fracture risk prediction among individuals with reduced and normal kidney function. Clin J Am Soc Nephrol 10:646–653

    PubMed  PubMed Central  Google Scholar 

  7. Schwartz A, Sellmeyer D (2007) Diabetes, fracture, and bone fragility. Curr Osteoporos Rep 5:105–111

    PubMed  Google Scholar 

  8. Moseley KF (2012) Type 2 diabetes and bone fractures. Curr Opin Endocrinol Diabetes Obes 19:128–135

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Arévalo-Lorido JC, Carretero-Gómez J, García-Sánchez F, Macia-Botejara E, Ramiro-Lozano JM, Masero-Carretero A, Robles NR, Bureo-Dacal JC (2016) Secondary hyperparathyroidism prevalence and profile, between diabetic and non-diabetic patients with stage 3 to 4 chronic kidney disease attended in internal medicine wards. MiPTH study. Diabetes Metab Syndr 10:S16–S21

    PubMed  Google Scholar 

  10. Winocour PH (2018) Diabetes and chronic kidney disease: an increasingly common multi-morbid disease in need of a paradigm shift in care. Diabet Med 35:300–305

    CAS  PubMed  Google Scholar 

  11. Chao C-T, Hsu Y-H, Chang P-Y, He Y-T, Ueng R-S, Lai C-F, Chiang C-K, Huang J-W, Huang S-J (2015) Simple self-report FRAIL scale might be more closely associated with dialysis complications than other frailty screening instruments in rural chronic dialysis patients. Nephrology 20:321–328

    PubMed  Google Scholar 

  12. Vermeiren S, Vella-Azzopardi R, Beckwée D, Habbig AK, Scafoglieri A, Jansen B, Bautmans I (2016) Frailty and the prediction of negative health outcomes: a meta-analysis. J Am Med Dir Assoc 17:1163.e1–1163.e17

    Google Scholar 

  13. Chao C-T, Chiang C-K, Huang J-W, Chan D-C, COGENT study group (2016) Effect of frail phenotype on bone mass and vertebral compression fracture in individuals undergoing dialysis. J Am Geriatr Soc 64:e19–e21

    PubMed  Google Scholar 

  14. Kakio Y, Uchida HA, Takeuchi H, Okuyama Y, Okuyama M, Umebayashi R, Wada K, Sugiyama H, Sugimoto K, Rakugi H, Kasahara S, Wada J (2018) Diabetic nephropathy is associated with frailty in patients with chronic hemodialysis. Geriatr Gerontol Int 18:1597–1602

    PubMed  Google Scholar 

  15. Chao C-T, Wang J, Chien K-L, COGENT study group (2018) Both pre-frailty and frailty increase healthcare utilization and adverse health outcomes in patients with type 2 diabetes mellitus. Cardiovasc Diabetol 17:130

    PubMed  PubMed Central  Google Scholar 

  16. Chao C-T, Wang J, Wu H-Y, Huang J-W, Chien K-L (2018) Age modifies the risk factor profiles for acute kidney injury among recently diagnosed type 2 diabetic patients: a population-based study. GeroScience 40:201–217

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Chao C-T, Wang J, Huang J-W, Chien K-L (2018) Acarbose use and liver injury in diabetic patients with severe renal insufficiency and hepatic diseases: a propensity score-matched cohort study. Front Pharmacol 9:860

    PubMed  PubMed Central  Google Scholar 

  18. Chang H, Weiner J, Richards T, Bleich S, Segal J (2012) Predicting costs with diabetes complications severity index in claims data. Am J Manag Care 18:213–219

    PubMed  Google Scholar 

  19. Ott SM (2017) Renal osteodystrophy—time for common nomenclature. Curr Osteoporos Rep 15:187–193

    PubMed  Google Scholar 

  20. 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 92:26–36

    PubMed  Google Scholar 

  21. West SL, Lok CE, Langsetmo L, Cheung AM, Szabo E, Pearce D, Fusaro M, Wald R, Weinstein J, Jamal SA (2015) Bone mineral density predicts fractures in chronic kidney disease. J Bone Miner Res 30:913–919

    PubMed  Google Scholar 

  22. Moe SM (2017) Renal osteodystrophy or kidney-induced osteoporosis? Curr Osteoporos Rep 15:194–197

    PubMed  PubMed Central  Google Scholar 

  23. Damasiewicz MJ, Nickolas TL (2018) Rethinking bone disease in kidney disease. JBMR Plus 2:309–322

    PubMed  PubMed Central  Google Scholar 

  24. Cancienne JM, Brockmeier SF, Kew ME, Deasey MJ, Werner BC (2019) The association of osteoporosis and bisphosphate use with revision shoulder surgery after rotator cuff repair. Arthroscopy 35:2314–2320

    PubMed  Google Scholar 

  25. Rice JB, White AG, Johnson M, Wagh A, Qin Y, Bartels-Peculis L, Ciepielewska G, Nelson WW (2018) Quantitative characterization of the relationship between levels of extended corticosteroid use and related adverse events in a US population. Curr Med Res Opin 34:1519–1527

    CAS  PubMed  Google Scholar 

  26. Khairallah P, Nickolas TL (2018) Updates in CKD-associated osteoporosis. Curr Osteoporos Rep 16:712–723

    PubMed  PubMed Central  Google Scholar 

  27. Wang W-J, Chao C-T, Huang Y-C, Wang C-Y, Chang C-H, Huang T-M, Lai C-F, Huang H-Y, Shiao C-C, Chu T-S, Chen Y-M, Wu V-C, Ko W-J, Wu K-D (2014) The impact of acute kidney injury with temporary dialysis on the risk of fracture. J Bone Miner Res 29:676–684

    PubMed  Google Scholar 

  28. Ray S, Beatrice AM, Ghosh A, Pramanik S, Bhattacharjee R, Ghosh S, Raychaudhury A, Mukhopadhyay S, Chowdhury S (2017) Profile of chronic kidney disease related-mineral bone disorders in newly diagnosed advanced predialysis diabetic kidney disease patients: a hospital based cross-sectional study. Diabetes Metab Syndr 11:S931–S937

    PubMed  Google Scholar 

  29. Huang J-H, Cheng F-C, Wu H-C (2015) Low magnesium exacerbates osteoporosis in chronic kidney disease patients with diabetes. Int J Endocrinol 2015:380247

    PubMed  PubMed Central  Google Scholar 

  30. Rigalleau V, Lasseur C, Raffaitin C, Perlemoine C, Barthe N, Chauveau P, Aparicio M, Combe C, Gin H (2007) Bone loss in diabetic patients with chronic kidney disease. Diabet Med 24:91–93

    CAS  PubMed  Google Scholar 

  31. Feng Z, Lugtenberg M, Franse C, Fang X, Hu S, Jin C, Raat H (2017) Risk factors and protective factors associated with incident or increase of frailty among community-dwelling older adults: a systematic review of longitudinal studies. PLoS One 12:e0178383

    PubMed  PubMed Central  Google Scholar 

  32. Johansen KL, Dalrymple LS, Delgado C, Chertow GM, Segal MR, Chiang J, Grimes B, Kaysen GA (2017) Factors associated with frailty and its trajectory among patients on hemodialysis. Clin J Am Soc Nephrol 12:1100–1108

    PubMed  PubMed Central  Google Scholar 

  33. Noori N, Sharma Parpia A, Lakhani R, Janes S, Goldstein MB (2018) Frailty and the quality of life in hemodialysis patients: the importance of waist circumference. J Ren Nutr 28:101–109

    PubMed  Google Scholar 

  34. Yoneki K, Kitagawa J, Hoshi K, Harada M, Watanabe T, Shimoda T, Matsuzawa R, Yoshida A, Matsunaga Y, Takeuchi Y, Kamiya K, Matsunaga A (2019) Association between frailty and bone loss in patients undergoing maintenance hemodialysis. J Bone Miner Metab 37:81–89

    PubMed  Google Scholar 

  35. Milte R, Crotty M (2014) Musculoskeletal health, frailty and functional decline. Best Pract Res Clin Rheumatol 28:395–410

    CAS  PubMed  Google Scholar 

  36. McNerny EMB, Nickolas TL (2017) Bone quality in chronic kidney disease: definitions and diagnostics. Curr Osteoporos Rep 15:207–213

    PubMed  PubMed Central  Google Scholar 

  37. Rodríguez-Sánchez I, García-Esquinas E, Rodríguez-Artalejo F, Mesas AE, Martín-Moreno JM, Rodríguez-Mañas L (2019) Frequency, intensity and localization of pain as risk factors for frailty in older adults. Age Ageing 48:74–80

    PubMed  Google Scholar 

  38. Malafarina V, Úriz-Otano F, Iniesta R, Gil-Guerrero L (2012) Sarcopenia in the elderly: diagnosis, physiopathology and treatment. Maturitas 71:109–114

    PubMed  Google Scholar 

  39. Chao C-T, Yang R-S, Huang W-J, Tsai K-S, Chan D-C (2019) Risk factors for poor functional recovery, mortality, recurrent fractures, and falls among patients participating in a fracture liaison service program. J Am Med Dir Assoc 20:1129–1136

    PubMed  Google Scholar 

  40. Beben T, Ix JH, Shlipak MG, Sarnak MJ, Fried LF, Hoofnagle AN, Chonchol M, Kestenbaum BR, de Boer IH, Rifkin DE (2016) Fibroblast growth Factor-23 and frailty in elderly community-dwelling individuals: the cardiovascular health study. J Am Geriatr Soc 64:270–276

    PubMed  PubMed Central  Google Scholar 

  41. Tartaglione L, Mazzaferro S, Guglielmo C, Urena Torres PA, Bover J, Tartaglione L, Pasquali M, La Manna G (2018) Bone, inflammation and the bone marrow niche in chronic kidney disease: what do we know? Nephrol Dial Transplant 33:2092–2100

    PubMed  Google Scholar 

  42. Mac Way F, Lessard M, Lafage-Proust M-H (2012) Pathophysiology of chronic kidney disease-mineral and bone disorder. Joint Bone Spine 79:544–549

    CAS  PubMed  Google Scholar 

  43. Bruyère O, Cavalier E, Buckinx F, Reginster J-Y (2017) Relevance of vitamin D in the pathogenesis and therapy of frailty. Curr Opin Clin Nutr Metab Care 20:26–29

    PubMed  Google Scholar 

  44. Lang CC, Muo CH, Wang IK, Chang CT, Chou CY, Liu JH, Yen TH, Huang CC, Chung CJ (2014) Peptic ulcer disease risk in chronic kidney disease: ten-year incidence, ulcer location, and ulcerogenic effect of medications. PLoS One 9:e87952

    Google Scholar 

  45. Chen DY, Wang SH, Mao CT, Tsai ML, Lin YS, Chou CC, Wen MS, Wang CC, Hsieh IC, Hung KC, Chen TH (2015) Sitagliptin and cardiovascular outcomes in diabetic patients with chronic kidney disease and acute myocardial infarction: a nationwide cohort study. Int J Cardiol 181:200–206

    PubMed  Google Scholar 

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Acknowledgments

We are grateful for the assistance of the Second Core Laboratory, Department of Medical Research of National Taiwan University Hospital and the Genomic Center of National Taiwan University College of Medicine, Taipei, Taiwan.

Funding

The study is financially sponsored by Ministry of Science and Technology, Taiwan (MOST-108-2314-B-002-055-).

Author information

Authors and Affiliations

  1. Department of Internal Medicine, National Taiwan University Hospital BeiHu Branch, Taipei, Taiwan

    C.-T. Chao

  2. Geriatric and Community Medicine Research Center, National Taiwan University Hospital BeiHu Branch, Taipei, Taiwan

    C.-T. Chao

  3. Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei, Taiwan

    C.-T. Chao

  4. Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan

    J. Wang & K.-L. Chien

  5. Nephrology division, Department of Internal Medicine, National Taiwan University Hospital YunLin branch, Douliou, YunLin County, Taiwan

    J.-W. Huang

  6. Department of Internal Medicine, National Taiwan University Hospital ChuTung branch, Zhudong, HsinChu County, Taiwan

    D.-C. Chan

  7. Department of Internal Medicine, National Taiwan University Hospital HsinChu branch, HsinChu City, Taiwan

    K.-Y. Hung

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  1. C.-T. Chao
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Consortia

on behalf of the COhort of GEriatric Nephrology in NTUH (COGENT) study group

Corresponding author

Correspondence to J.-W. Huang.

Ethics declarations

This study has been approved by the institutional review board of National Taiwan University Hospital (NO. 201802063W). Its protocol adhered to the Declaration of Helsinki. Informed consent was waived due to data anonymity based on the recommendation of the institutional review board.

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Chao, CT., Wang, J., Huang, JW. et al. Chronic kidney disease–related osteoporosis is associated with incident frailty among patients with diabetic kidney disease: a propensity score–matched cohort study. Osteoporos Int 31, 699–708 (2020). https://doi.org/10.1007/s00198-020-05353-9

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  • DOI: https://doi.org/10.1007/s00198-020-05353-9

Keywords

  • Chronic kidney disease
  • Chronic kidney disease-mineral bone disorder
  • Fracture
  • Frailty
  • Frail phenotype
  • Osteoporosis
  • Renal osteodystrophy