Serum Phosphate Is Associated With Fracture Risk: The Rotterdam Study and MrOS.
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, estimated glomerular filtration rate (eGFR), 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 chronic kidney disease (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. © 2017 American Society for Bone and Mineral Research.
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Natalia
N
Campos-Obando
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
W Nadia H
WNH
Koek
Bone and Mineral Unit, Oregon Health & Science University, Portland, OR, USA.
Elizabeth R
ER
Hooker
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Bram Cj
BC
van der Eerden
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
Huibert A
HA
Pols
Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
Albert
A
Hofman
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Johannes Ptm
JP
van Leeuwen
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
Andre G
AG
Uitterlinden
Bone and Mineral Unit, Oregon Health & Science University, Portland, OR, USA.|School of Public Health, Oregon Health & Science University, Portland, OR, USA.
Carrie M
CM
Nielson
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
M Carola
MC
Zillikens
D000368:Aged; D015519:Bone Density; D005215:Fasting / Q000097:blood; D005260:Female; D005272:Femur Neck / Q000503:physiopathology; D050723:Fractures, Bone / Q000097:blood* / Q000453:epidemiology* / Q000503:physiopathology; D006801:Humans; D015994:Incidence; D008297:Male; D009426:Netherlands; D058866:Osteoporotic Fractures / Q000097:blood* / Q000453:epidemiology* / Q000503:physiopathology; D010710:Phosphates / Q000097:blood*; D012307:Risk Factors
D010710:Phosphates
25-HYDROXYVITAMIN D; BMD; CALCIUM; FRACTURES; PHOSPHATE LEVELS