Journal
JOURNAL OF BONE AND MINERAL RESEARCH
Volume 32, Issue 6, Pages 1182-1193Publisher
WILEY
DOI: 10.1002/jbmr.3094
Keywords
PHOSPHATE LEVELS; FRACTURES; BMD; CALCIUM; 25-HYDROXYVITAMIN D
Categories
Funding
- Erasmus Medical Center, Rotterdam
- Netherlands Organization for the Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly (RIDE)
- Ministry of Education, Culture, and Science
- Ministry for Health, Welfare, and Sports
- European Commission (DG XII)
- Municipality of Rotterdam
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- National Institute on Aging
- National Center for Research Resources
- NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01 AG027810, UL1 TR000128]
- NIAMS [K01 AR062655]
- Erasmus University, Rotterdam
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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 metaanalyses. Hazard ratios (HR) and betas (b) (from meta-analyses) are expressed per 1mg/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 (b: -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 werenegatively related in men. Our findings suggest that increased P levels even within normal range might be deleterious for bone health in the normal population. (C) 2017 American Society for Bone and Mineral Research.
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