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

Panuccio V, Enia G, Tripepi R, Aliotta R, Mallamaci F, Tripepi G, Zoccali C - BMC Nephrol (2012)

Bottom Line: Pro-inflammatory cytokines play a key role in bone remodeling.We studied the relationship between inflammatory cytokines and incident bone fractures in a cohort of CKD-5D patients.Patients were followed-up until the first non traumatic fracture.

View Article: PubMed Central - HTML - PubMed

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

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.

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Fracture-free survival according to PTH tertiles. Kaplan-Meyer curves and log-rank test.
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Figure 4: Fracture-free survival according to PTH tertiles. Kaplan-Meyer curves and log-rank test.

Mentions: On Kaplan-Meyer analysis fracture-free survival was longer in patients with TNF-α in the lower tertile as compared to those with levels in the upper tertile (Figure 3). Similarly PTH levels in the lower tertile were associated to a longer fracture-free survival (Figure 4). On univariate Cox analysis the association between TNF-α with incident fractures was significant (HR for 5 pg/ml increase in TNF-α: 1.62 95% CI: 1.05-2.50; p = 0.03) as it was the association between fractures and PTH (HR for 100 pg/ml increase in PTH: 1.15 95% CI: 1.04-1.27; p = 0.005). History of previous fractures increased by four-fold the risk of incident fractures (HR 4.47 95% CI: 1.46-13.7; p = 0.009). CRP and IL-6, total and bone alkaline phosphatase, serum calcium and phosphate largely failed to predict fractures.


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

Panuccio V, Enia G, Tripepi R, Aliotta R, Mallamaci F, Tripepi G, Zoccali C - BMC Nephrol (2012)

Fracture-free survival according to PTH tertiles. Kaplan-Meyer curves and log-rank test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472278&req=5

Figure 4: Fracture-free survival according to PTH tertiles. Kaplan-Meyer curves and log-rank test.
Mentions: On Kaplan-Meyer analysis fracture-free survival was longer in patients with TNF-α in the lower tertile as compared to those with levels in the upper tertile (Figure 3). Similarly PTH levels in the lower tertile were associated to a longer fracture-free survival (Figure 4). On univariate Cox analysis the association between TNF-α with incident fractures was significant (HR for 5 pg/ml increase in TNF-α: 1.62 95% CI: 1.05-2.50; p = 0.03) as it was the association between fractures and PTH (HR for 100 pg/ml increase in PTH: 1.15 95% CI: 1.04-1.27; p = 0.005). History of previous fractures increased by four-fold the risk of incident fractures (HR 4.47 95% CI: 1.46-13.7; p = 0.009). CRP and IL-6, total and bone alkaline phosphatase, serum calcium and phosphate largely failed to predict fractures.

Bottom Line: Pro-inflammatory cytokines play a key role in bone remodeling.We studied the relationship between inflammatory cytokines and incident bone fractures in a cohort of CKD-5D patients.Patients were followed-up until the first non traumatic fracture.

View Article: PubMed Central - HTML - PubMed

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

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.

Show MeSH
Related in: MedlinePlus