Serum Phosphate Is Associated With Fracture Risk

The Rotterdam Study and MrOS

Natalia Campos-Obando, W. Nadia H. Koek, Elizabeth R. Hooker, Bram C.J. van der Eerden, Huibert A. Pols, Albert Hofman, Johannes P.T.M. van Leeuwen, Andre G. Uitterlinden, Carrie Nielson, M. Carola Zillikens

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1182-1193
Number of pages12
JournalJournal of Bone and Mineral Research
Volume32
Issue number6
DOIs
StatePublished - Jun 1 2017

Fingerprint

Bone Density
Phosphates
Serum
Femur Neck
Social Adjustment
Spine
Glomerular Filtration Rate
Chronic Renal Insufficiency
Meta-Analysis
Reference Values
Population
Bone and Bones
Osteoporotic Fractures
Bone Fractures
Health
Parathyroid Hormone
Proportional Hazards Models
Linear Models
Potassium
Body Mass Index

Keywords

  • 25-HYDROXYVITAMIN D
  • BMD
  • CALCIUM
  • FRACTURES
  • PHOSPHATE LEVELS

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Campos-Obando, N., Koek, W. N. H., Hooker, E. R., van der Eerden, B. C. J., Pols, H. A., Hofman, A., ... Zillikens, M. C. (2017). Serum Phosphate Is Associated With Fracture Risk: The Rotterdam Study and MrOS. Journal of Bone and Mineral Research, 32(6), 1182-1193. https://doi.org/10.1002/jbmr.3094

Serum Phosphate Is Associated With Fracture Risk : The Rotterdam Study and MrOS. / Campos-Obando, Natalia; Koek, W. Nadia H.; Hooker, Elizabeth R.; van der Eerden, Bram C.J.; Pols, Huibert A.; Hofman, Albert; van Leeuwen, Johannes P.T.M.; Uitterlinden, Andre G.; Nielson, Carrie; Zillikens, M. Carola.

In: Journal of Bone and Mineral Research, Vol. 32, No. 6, 01.06.2017, p. 1182-1193.

Research output: Contribution to journalArticle

Campos-Obando, N, Koek, WNH, Hooker, ER, van der Eerden, BCJ, Pols, HA, Hofman, A, van Leeuwen, JPTM, Uitterlinden, AG, Nielson, C & Zillikens, MC 2017, 'Serum Phosphate Is Associated With Fracture Risk: The Rotterdam Study and MrOS', Journal of Bone and Mineral Research, vol. 32, no. 6, pp. 1182-1193. https://doi.org/10.1002/jbmr.3094
Campos-Obando N, Koek WNH, Hooker ER, van der Eerden BCJ, Pols HA, Hofman A et al. Serum Phosphate Is Associated With Fracture Risk: The Rotterdam Study and MrOS. Journal of Bone and Mineral Research. 2017 Jun 1;32(6):1182-1193. https://doi.org/10.1002/jbmr.3094
Campos-Obando, Natalia ; Koek, W. Nadia H. ; Hooker, Elizabeth R. ; van der Eerden, Bram C.J. ; Pols, Huibert A. ; Hofman, Albert ; van Leeuwen, Johannes P.T.M. ; Uitterlinden, Andre G. ; Nielson, Carrie ; Zillikens, M. Carola. / Serum Phosphate Is Associated With Fracture Risk : The Rotterdam Study and MrOS. In: Journal of Bone and Mineral Research. 2017 ; Vol. 32, No. 6. pp. 1182-1193.
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