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J Bone Miner Res. 2017 Feb 8. doi: 10.1002/jbmr.3094. [Epub ahead of print]

Serum Phosphate Is Associated with Fracture Risk: The Rotterdam Study and MrOS.

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  • 1Department of Internal Medicine, Erasmus MC Rotterdam, The Netherlands.
  • 2Bone and Mineral Unit, Oregon Health & Science University, Portland, OR, USA.
  • 3Department of Epidemiology, Erasmus MC Rotterdam, The Netherlands.
  • 4School of Public Health, Oregon Health & Science University, Portland, OR, USA.


Extreme phosphate levels (P) have been associated with mineralization defects and increased fracture risk. Whether P within normal range is related to bone health in the general population is not well understood. To investigate the association of P with bone mineral density (BMD) and fracture risk, we assessed two population-based cohorts: the Dutch Rotterdam Study (RS-I, RS-II, RS-III; n = 6791) and the US Osteoporotic Fractures in Men (MrOS; n = 5425) study. The relationship of P with lumbar spine (LS) and femoral neck (FN) BMD was tested in all cohorts via linear models; fracture risk was tested in RS-I, RS-II and MrOS through Cox models, after follow-up of 8.6, 6.6 and 10.9 years, respectively. Adjustments were made for age, body mass index, smoking, serum levels of calcium, potassium, 25-hydroxyvitamin D, and estimated glomerular filtration rate, FN-BMD, prevalent diabetes and cardiovascular disease. Additional adjustments were made for phosphate intake, parathyroid hormone, and fibroblast growth factor 23 levels in MrOS. We further stratified by eGFR. Results were pooled through study-level meta-analyses. Hazard ratios (HR) and betas (β) (from meta-analyses) are expressed per 1 mg/dL P increase. P was positively associated with fracture risk in men and women from RS and findings were replicated in MrOS (pooled HR all (95% CI): 1.47 (1.31-1.65)). P was associated with fracture risk in subjects without CKD: all (1.44 (1.26-1.63)) and in men with CKD (1.93 (1.42-2.62)). P was inversely related to LS-BMD in men (β: -0.06 (-0.11 to -0.02)) and not to FN-BMD in either sex. In summary, serum P was positively related to fracture risk independently from BMD and phosphate intake after adjustments for potential confounders. P and LS-BMD were negatively related in men. Our findings suggest that increased P levels even within normal range might be deleterious for bone health in the normal population. This article is protected by copyright. All rights reserved.


25-hydroxyvitamin D; BMD; calcium; fractures; phosphate levels

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