Risk Factors for Fracture in Patients with Coexisting Chronic Kidney Disease and Type 2 Diabetes: An Observational Analysis from the CREDENCE Trial.

Background

The fracture pathophysiology associated with type 2 diabetes and chronic kidney disease (CKD) is incompletely understood. We examined individual fracture predictors and prediction sets based on different pathophysiological hypotheses, testing whether any of the sets improved prediction beyond that based on traditional osteoporotic risk factors.

Methods

Within the CREDENCE cohort with adjudicated fracture outcomes, we assessed the association of individual factors with fracture using Cox regression models. We used the Akaike information criteria (AIC) and Schwartz Bayes Criterion (SBC) to assess six separate variable sets based on hypothesized associations with fracture, namely, traditional osteoporosis, exploratory general population findings, cardiovascular risk, CKD-mineral and bone disorder, diabetic osteodystrophy, and an all-inclusive set containing all variables.

Results

Fracture occurred in 135 (3.1%) participants over a median 2.35 [1.88-2.93] years. Independent fracture predictors were older age (hazard ratio [HR] 1.04, confidence interval [CI] 1.01-1.06), female sex (HR 2.49, CI 1.70-3.65), previous fracture (HR 2.30, CI 1.58-3.34), Asian race (HR 1.74, CI 1.09-2.78), vitamin D therapy requirement (HR 2.05, CI 1.31-3.21), HbA1c (HR 1.14, CI 1.00-1.32), prior cardiovascular event (HR 1.60, CI 1.10-2.33), and serum albumin (HR 0.41, CI 0.23-0.74) (lower albumin associated with greater risk). The goodness of fit of the various hypothesis sets was similar (AIC range 1870.92-1849.51, SBC range 1875.60-1948.04).

Conclusion

Independent predictors of fracture were identified in the CREDENCE participants with type 2 diabetes and CKD. Fracture prediction was not improved by models built on alternative pathophysiology hypotheses compared with traditional osteoporosis predictors.

Informations de copyright

Copyright © 2022 Tamara K. Young et al.

Déclaration de conflit d'intérêts

TY is supported by a UPA scholarship at The George Institute for Global Health. NT has received honoraria, travel support, and research funding from Amgen, Shire, Takeda, and Sanofi. CA is supported by an MRFF Priority Investigator Grant and a NSW Health EMCR Grant. AES has received speaker honoraria from Omron, Novartis, Sanofi, Takeda, and Servier and served as consultant for Abbott. DCW has an ongoing consultancy contract with AstraZeneca. He has received honoraria and/or speaker fees from AstraZeneca, Astellas, Amgen, Bayer, Boehringer Ingelheim, Gilead, GlaxoSmithKline, Janssen, Mundipharma, Napp, Merck Sharp and Dohme, Vifor Fresenius, and Zydus. VP has received fees for advisory boards, steering committee roles, or scientific presentations from AbbVie, Astellas, AstraZeneca, Bayer, Baxter, BMS, Boehringer Ingelheim, Dimerix, Durect, Eli Lilly, Gilead, GSK, Janssen, Merck, Mitsubishi Tanabe, Mundipharma, Novartis, Novo Nordisk, Pfizer, Pharmalink, Relypsa, Retrophin, Sanofi, Servier, Vifor, and Tricida. K.W. Mahaffey's financial disclosures can be viewed at: http://med.stanford.edu/profiles/kenneth-mahaffey. RA has received research funding from GlaxoSmithKline; has received personal fees from Akebia, Bayer, Johnson & Johnson, Boehringer Ingelheim, Takeda, Daiichi Sankyo, Amgen, AstraZeneca, Sanofi, Celgene, Reata, Relypsa, GlaxoSmithKline, Gilead, ER Squibb and Sons, Fresenius, Ironwood Pharmaceuticals, Otsuka, OPKO, and Eli Lilly; and has served as associate editor of the American Journal of Nephrology and Nephrology, Dialysis, and Transplantation and as an author on UpToDate. G B has received research funding paid to the University of Chicago for serving as principal investigator on national clinical trials for Bayer, Janssen, and Novo Nordisk; has served as a consultant for Merck, Relypsa, Novo Nordisk, and AstraZeneca; has served on a steering committee for Vascular Dynamics; has served as Editor of the American Journal of Nephrology and Nephrology, Editor-in-Chief of UpToDate, and Nephrology and Hypertension Section Editor of UpToDate; and has served as Associate Editor of Diabetes Care, Hypertension Research, and Nephrology, Dialysis, and Transplantation. DMC has received fees paid by Janssen Pharmaceuticals to the Baim Institute for work on the CREDENCE trial Steering Committee and as scientific lead; and received salary support from the Baim Institute for this work through October 2018. After that time, he received consulting fees from Baim. He has consulted for Amgen, AstraZeneca, Medtronic/Covidien, ZOLL, Fresenius, Daiichi Sankyo, Douglas and London, Eli Lilly, Merck, Gilead, GlaxoSmithKline, and Novo Nordisk; has served on data safety and monitoring boards for AstraZeneca; has served on a CEC for Merck and PLC Medical; and has received research support from Amgen, Bioporto, and Medtronic. HJLH has served as a consultant for AbbVie, Astellas, AstraZeneca, Boehringer Ingelheim, Chinook, Fresenius, Gilead, Janssen, Merck, Mundipharma, Mitsubishi-Tanabe, CSL Pharma, and Retrophin and has received grant support from AbbVie, AstraZeneca, Boehringer Ingelheim, and Janssen. AL serves as a scientific advisor to Boehringer Ingelheim, AstraZeneca, and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and is on the data safety and monitoring committee for NIDDK, Kidney Precision Medicine, and University of Washington Kidney Research Institute Scientific Advisory Committee. She has been funded by Canadian Institute of Health Research and Kidney Foundation of Canada. She has received fees for time as CREDENCE National Coordinator from Janssen, which were directed to her academic team. C. P has received honoraria for serving on advisory boards and as a speaker for Merck Sharpe & Dohme, AstraZeneca, and Boehringer Ingelheim/Eli Lilly. HZ has received consulting and travel fees from Janssen for the role as a member of the CREDENCE Steering Committee. MJJ is supported by a Medical Research Future Fund Next Generation Clinical Researchers Program Career Development Fellowship; is responsible for research projects that have received unrestricted funding from Baxter, Amgen, Eli Lilly, and Merck Sharpe Dohme; serves on a Steering Committee sponsored by CSL; has served on advisory boards sponsored by Akebia, Baxter, Boehringer Ingelheim, and Vifor; and has spoken at scientific meetings sponsored by Janssen and Amgen, with any consultancy, honoraria, or travel support paid to her institution.