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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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Serum intact PTH and TNF-α levels (median and interquartile range) in patients with and without incident fractures.
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Figure 2: Serum intact PTH and TNF-α levels (median and interquartile range) in patients with and without incident fractures.

Mentions: C-Reactive Protein, IL-6 a and TNF-α levels above the upper limit of the normal range were observed in 65%, 77% and 78% of patients, respectively (Figure 1). During the follow-up period (median 74 months; range: 0.5-84.0 months) 18 patients had incident fractures (vertebral = 10 ; pelvic = 4; femoral neck = 1; humerus = 1; costal = 1; clavicle = 1). Patients with incident fractures had higher levels of serum intact PTH, and TNF-α when compared to those without these complications (Table 1, Figure 2) while CRP and IL-6 levels were similar in the two groups. The proportion of patients with PTH in the range denoting low bone turn-over (<100 pg/ml) according to current guidelines [18] did not differ, while the proportion of those with high turn-over (>800 pg/ml) was higher among patients with incident fractures (Table 1). The proportion of patients who had suffered from a previous fracture was markedly higher in patients who had incident fractures (Table 1).


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)

Serum intact PTH and TNF-α levels (median and interquartile range) in patients with and without incident fractures.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Serum intact PTH and TNF-α levels (median and interquartile range) in patients with and without incident fractures.
Mentions: C-Reactive Protein, IL-6 a and TNF-α levels above the upper limit of the normal range were observed in 65%, 77% and 78% of patients, respectively (Figure 1). During the follow-up period (median 74 months; range: 0.5-84.0 months) 18 patients had incident fractures (vertebral = 10 ; pelvic = 4; femoral neck = 1; humerus = 1; costal = 1; clavicle = 1). Patients with incident fractures had higher levels of serum intact PTH, and TNF-α when compared to those without these complications (Table 1, Figure 2) while CRP and IL-6 levels were similar in the two groups. The proportion of patients with PTH in the range denoting low bone turn-over (<100 pg/ml) according to current guidelines [18] did not differ, while the proportion of those with high turn-over (>800 pg/ml) was higher among patients with incident fractures (Table 1). The proportion of patients who had suffered from a previous fracture was markedly higher in patients who had incident fractures (Table 1).

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