Year: 2017
Type: article
Study design: Observational Study
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. © 2017 American Society for Bone and Mineral Research.
DOI: 10.1002/jbmr.3094
Institutions: Erasmus MC, Oregon Health & Science University
Language: English
Subfield: Orthopedics and Sports Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: European Commission, ZonMw, Erasmus Medisch Centrum, Ministerie van Onderwijs, Cultuur en Wetenschap, National Institutes of Health, National Institute on Aging, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: Osteoporotic Fractures in Men (MrOS) - Minneapolis, Osteoporotic Fractures in Men, Oregon Clinical and Translational Research Institute, G2297452346, Osteoporotic Fractures in Men - MrOS Renewal, Osteoporotic Fractures in Men, Osteoporotic Fractures in Men - MrOS Renewal - Birmingham, Osteoporotic Fractures in Men - MrOS Renewal - Pittsburgh, Osteoporotic Fractures in Men (MrOS) - Administrative Center, Osteoporosis in Men, G5524581141, Osteoporotic Fractures in Men (MrOS) Renewal - Portland, Osteoporotic Fractures in Men (MrOS) - San Francisco Coordinating Center, G7058527481, Mineralization Gene Variants: Biochemical Implications and Associations with BMD, G9000125773
OpenAlex ID: W2593791892