FC 079HIGH SERUM PHOSPHATE, A NOVEL POTENTIAL RISK FACTOR FOR BONE FRAGILITY FRACTURES IN THE COSMOS STUDY
Authors: Barrera Baena Pedro , Rodríguez García Minerva , Rodríguez Rubio Enrique , González Llorente Lucía , Locatelli Francesco , Floege Jurgen , Ketteler Markus , London Gerard Michel , Gorriz Teruel Jose Luis , Ferreira Manuel Anibal A , Zoccali Carmine , Ortiz Alberto , Cohen-Solal Martine , Suárez Hevia Miguel Ángel , Fernández Gómez Jesús María , Martín-Carro Beatriz , Gómez-Alonso Carlos , Alonso-Montes Cristina , Cannata-Andia Jorge B , Fernandez-Martin José Luis 
Published: May 2021

Abstract

Background and Aims
Bone fragility fractures (bone fractures) are extremely frequent in haemodialysis (HD) patients. Serum phosphate (P) has been suggested as a risk factor for bone fracture, nonetheless, evidence is poor. The aim of this study was to assess the association between incidence of bone fractures and serum phosphate (P), calcium (Ca) and parathyroid hormone (PTH) in patients from the COSMOS study.

Method
COSMOS is an observational, prospective, open cohort study with 3 years of follow-up including 6797 haemodialysis patients from 227 centres randomly selected from 20 European countries.
At baseline, demographics, comorbidities, treatments, serum biochemical parameters of the previous six months and bone fractures of the previous 12 months were collected. Every 6 months, all these variables, outcomes, and incident bone fractures, were collected. Patients who had at least one bone fracture during follow-up were compared with those who had not.
Multivariate binary logistic regression and Poisson regression were used to assess the association between incidence of bone fractures and serum P, Ca and PTH. Time to fracture (and possible re-fracture) was also evaluated using Cox regression and Cox regression for recurrent events. All the results were adjusted by 23 variables including Ca, P, PTH, albumin and haemoglobin (full adjusted model).

Results
Analysis included 6274 patients who had follow-up data and non-missing information regarding bone fractures at baseline and during follow-up; 252 patients (4.0%), suffered at least one incident bone fracture. The fractured patients were older (68.1±12.9 vs. 63.8±14.5 years, p&lt;0.001), with a higher percentage of women (56.3% vs. 38.6%, p&lt;0.001) and history of cardiovascular disease (79.4% vs. 71.7%, p=0.010), longer haemodialysis vintage (55.9±64.0 vs. 38.3±48.8 months, p&lt;0.001), and higher serum calcium (9.2±0.8 vs. 9.1±0.7 mg/dL, p=0.025) and lower serum albumin (3.7±0.5 vs. 3.8±0.5 g/dL, p=0.004) levels.
Multivariate binary logistic regression showed that “well known risk factors for bone fracture”, such as a previous bone fracture (OR: 7.78[95%CI:4.83-12.55], p&lt;0.001), older age (OR: 1.03[95%CI:1.01-1.04], p&lt;0.001, per 1 year), sex female (OR: 1.71[95%CI:1.28-2.30], p&lt;0.001), haemodialysis vintage (OR: 1.00[95%CI: 1.00-1.01], p=0.002, per 1 month), and serum PTH &gt; 800 pg/mL (OR: 1.60[95%CI: 1.01-2.55], p=0.047), were associated with a higher incidence of follow-up bone fractures. In addition to the “well known bone risk factors for fracture”, serum P &gt; 6.1 mg/dL (OR: 1.50[95% CI: 1.07-2.11], p=0.02) and serum Ca &gt; 9.7 mg/dL (OR: 1.42[95%CI: 1.01-2.03], p=0.043), were also associated with a higher incidence of bone fractures in the full-adjusted model.
These findings were partly consistent with Poisson regression for serum P &gt;6.1 mg/dL (IRR: 1.46[95% CI: 1.00-2.13], p=0.0085) and serum Ca &gt; 9.7 mg/dL (IRR: 1.49[95%CI: 1.06-2.08], p=0.0047), but not for PTH.
In addition, Cox regression analysis showed association between bone fractures and serum P &gt;6.1 mg/dl (HR: 1.61 [95%CI: 1.16-2.24], p=0.0049) and 1.60 [95%CI: 1.14-2.24] (p=0.0066) for simple and recurrent events respectively, but no association was found with serum Ca and PTH in the 2 full-adjusted models for the Cox regression analyses.

Conclusion
In COSMOS, a large haemodialysis patient’s cohort with 3 years follow up, serum P was the only biochemical parameter that remained as a significant risk factor for bone fractures after 4 statistic approaches. Thus, for the first time, in a large scale well controlled study, high serum P has been identified as a new independent potential risk factor for incident bone fractures in haemodialysis patients.