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Open Access Research article

Pro-inflammatory cytokines and bone fractures in CKD patients. An exploratory single centre study

Vincenzo Panuccio12, Giuseppe Enia12*, Rocco Tripepi2, Roberta Aliotta12, Francesca Mallamaci12, Giovanni Tripepi2 and Carmine Zoccali12

Author Affiliations

1 Nephrology, Dialysis, Hypertension and Renal Transplantation Unit Azienda Ospedaliera, Via vallone Petrara, 89124, Reggio Calabria, Italy

2 CNR-IBIM Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Via vallone Petrara, 89124, Reggio Calabria, Italy

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BMC Nephrology 2012, 13:134  doi:10.1186/1471-2369-13-134

Published: 9 October 2012

Abstract

Background

Pro-inflammatory cytokines play a key role in bone remodeling. Inflammation is highly prevalent in CKD-5D patients, but the relationship between pro-inflammatory cytokines and fractures in CKD-5D patients is unclear. We studied the relationship between inflammatory cytokines and incident bone fractures in a cohort of CKD-5D patients.

Methods

In 100 CKD-5D patients (66 on HD, 34 on CAPD; males:63, females:37; mean age: 61 ± 15; median dialysis vintage: 43 months) belonging to a single renal Unit, we measured at enrolment bone metabolic parameters (intact PTH, bone and total alkaline phosphatase, calcium, phosphate) and inflammatory cytokines (TNF-α, IL-6, CRP). Patients were followed-up until the first non traumatic fracture.

Results

During follow-up (median: 74 months; range 0.5 -84.0) 18 patients experienced fractures. On categorical analysis these patients compared to those without fractures had significantly higher intact PTH (median: 319 pg/ml IQ range: 95–741 vs 135 pg/ml IQ: 53–346; p = 0.04) and TNF-α levels (median: 12 pg/ml IQ: 6.4-13.4 vs 7.8 pg/ml IQ: 4.6-11; p = 0.02). Both TNF-α (HR for 5 pg/ml increase in TNF-α: 1.62 95% CI: 1.05-2.50; p = 0.03) and intact PTH (HR for 100 pg/ml increase in PTH: 1.15 95% CI: 1.04-1.27; p = 0.005) predicted bone fractures on univariate Cox’s regression analysis. In restricted (bivariate) models adjusting for previous fractures, age, sex and other risk factors both PTH and TNF-α maintained an independent association with incident fractures.

Conclusions

In our bivariate analyses TNF-α was significantly associated with incident fractures. Analyses in larger cohorts and with adequate number of events are needed to firmly establish the TNF α -fracture link emerged in the present study.

Keywords:
Bone fractures; CKD; Dialysis; Hyperparathyroidism; TNF-alpha; Inflammation