Predicting the risk of fractures in kidney transplant recipients

BACKGROUND. Chronic kidney disease leads to a significant increase in the risk of fractures, which increases even more after kidney transplantation.
THE AIM. The goal of this study was to develop simple, accessible criteria for predicting the risk of fracture in patients with a functioning kidney transplant.
PATIENTS AND METHODS. The prospective study included 131 kidney transplant recipients (men-55, women-76) (average age 39.7±11.7 years). The duration of follow-up was 40.7±21.2 months. Bone mineral density was assessed using dual-energy x-ray absorptiometry. To determine the prognostic significance of variables, we used stepwise regression (Cox model) analysis. p < 0.05 was considered statistically significant.
RESULTS. During the follow-up period, fractures were registered in 47 patients (35.9 %). Fractures were detected more often in women (42 %) than in men (27.3 %). All patients with fractures had lower bone mineral density and longer-term renal replacement therapy. Stepwise multivariate regression analysis showed that the combination of bone mineral density scores of lumbar vertebra and duration of renal replacement therapy best predicts the overall fracture risk. Adding the other variables to the analysis did not increase significantly their predictive value. A comparative analysis of the cumulative proportion of males and females with fractures confirmed a greater susceptibility of female transplant recipients to fractures.
CONCLUSIONS. The combination of bone mineral density scores of the lumbar vertebra with the duration of renal replacement therapy best predict the risk of fracture in patients with kidney transplants and can be used in the choice of prevention measures.

1. Maravic M, Ostertag A, Torres PU, Cohen-Solal M. Incidence and risk factors for hip fractures in dialysis patients. Osteoporos Int 2014;25(1):159–165. doi: 10.1007/s00198-013-2435-1

2. Chen YJ, Kung PT, Wang YH et al. Greater risk of hip fracture in hemodialysis than in peritoneal dialysis. Osteoporos Int 2014;25(5):1513–1518. doi: 10.1007/s00198-014-2632-6

3. Czyżewski L, Sańko-Resmer J, Wyzgał J, Kurowski A. Assessment of health-related quality of life of patients after kidney transplantation in comparison with hemodialysis and peritoneal dialysis. Ann Transplant 2014;19:576. doi:585. Published 2014 Nov 9. doi: 10.12659/AOT.891265

4. Bouquegneau A, Salam S, Delanaye P, Eastell R, Khwaja A. Bone Disease after Kidney Transplantation. Clin J Am Soc Nephrol 2016;11(7):1282–1296. doi: 10.2215/CJN.11371015

5. Мазуренко СО, Шишкин АН, Мазуренко ОГ. Ремоделирование костной ткани и патологическая физиология почечных остеодистрофий. Нефрология. 2002;6(2):15–27 Mazurenko SO, Shishkin AN, Mazurenko OG. Bone remodeling and pathophysiology of renal osteodystrophies. Nephrology (Saint-Petersburg) 2002;6(2):15–27 (In Russ.). doi: 10.24884/1561-6274-2002-6-2-15-27

6. Genant HK, Lang, TF, Engelke K et al. Advances in the noninvasive assessment of bone density, quality, and structure. Calcif Tissue Int 59, S10–S15 (1996). doi: 10.1007/s002239900169

7. Cosman F, de Beur SJ, LeBoff MS et al. Clinician's Guide to Prevention and Treatment of Osteoporosis [published correction appears in Osteoporos Int. 2015 Jul;26(7):2045-7]. Osteoporos Int 2014;25(10):2359–2381. doi: 10.1007/s00198-014-2794-2

8. Malluche HH, Davenport DL, Cantor T, Monier-Faugere MC. Bone mineral density and serum biochemical predictors of bone loss in patients with CKD on dialysis. Clin J Am Soc Nephrol 2014;9(7):1254–1262. doi: 10.2215/CJN.09470913

9. Blomquist GA, Davenport DL, Mawad HW, Monier-Faugere MC, Malluche HH. Diagnosis of low bone mass in CKD-5D patients. Clin Nephrol. 2016;85(2):77–83. doi: 10.5414/CN108708

10. Iseri K, Qureshi AR, Dai L, Ripsweden J, Heimbürger O, Barany P et al. Bone mineral density at different sites and 5 years mortality in end-stage renal disease patients: A cohort study. Bone 2020;130:115075. doi: 10.1016/j.bone.2019.115075

11. Mazurenko SO, Staroselsky KG, Enkin AA, Mazurenko OG, Ermolaeva LG. Multivariate analysis of bone mineral density and fracture risk assessment in hemodialysis patients. Osteoporosis International 2015; 26(1): 138–139. doi: 10.1007/s00198-015-3068-3

12. Kanis JA, Johansson H, Harvey NC, McCloskey EV. A brief history of FRAX. Arch Osteoporos 2018 Oct 31;13(1):118. doi: 10.1007/s11657-018-0510-0. PMID: 30382424; PMCID: PMC6290984

13. Silverman SL, Calderon AD. The utility and limitations of FRAX: A US perspective. Curr Osteoporos Rep 2010;8(4):192–197. doi: 10.1007/s11914-010-0032-1

14. Silverman SL, Calderon AD. The utility and limitations of FRAX: A US perspective. Curr Osteoporos Rep 2010;8(4):192–197. doi: 10.1007/s11914-010-0032-1

15. Crandall CJ, Schousboe JT, Morin SN, Lix LM, Leslie W. Performance of FRAX and FRAX-Based Treatment Thresholds in Women Aged 40 Years and Older: The Manitoba BMD Registry. J Bone Miner Res 2019;34(8):1419–1427. doi: 10.1002/jbmr.3717

16. Jamal SA, West SL & Nickolas TL. The clinical utility of FRAX to discriminate fracture status in men and women with chronic kidney disease. Osteoporos Int 25, 71–76 (2014). doi: 10.1007/s00198-013-2524