A large study that looked at long-term records for patients in Denmark does not support a role for vitamin D supplements in improving bone health and preventing osteoporotic fractures, researchers reported online April 7 in the journal Clinical Chemistry.
The researchers had extensive records at their disposal for analyzing the relation between the levels of 25-hydroxyvitamin D and outcomes over time. The study involved the analysis of records for a total of close to 36,000 people who had taken part in two large, prospective, population-based research projects in Denmark -- the Copenhagen City Heart Study and the Copenhagen General Population Study. Available data included blood tests showing levels of serum vitamin D, with 50 nmol/L used as the threshold for higher concentrations, and profiling of genes that are known to affect vitamin D levels.
The study spanned records for people who were tracked for up to 36 years. Vitamin D was measured using the DiaSorin Liaison 25(OH) vitamin D Total Assay and single nucleotide polymorphism (SNP) genotyping was performed using ThermoFisher Scientific's TaqMan tests.
Writing in Clinical Chemistry, the authors noted that they chose to look at variants around CYP2R1 (rs12794714 and rs10741657) and DHCR7 (rs7944926 and rs11234027), because these are expected to influence biologically active plasma 25-hydroxyvitamin D concentrations through either synthesis of pre-vitamin D from 7-dehydrocholesterol in the skin or conversion of vitamin D to 25-hydroxyvitamin D in the liver.
For the study, the researchers conducted a Mendelian randomization analysis to assess the association of vitamin D levels with rates of fractures. Results were reported by Dr. Børge Nordestgaard of Copenhagen University Hospital in Denmark and colleagues.
Records from the population studies indicated the following number of fractures during up to 36 years of follow-up:
- Total: 17,820
- Osteoporotic: 10,861
- Hip or femur: 3,472
The rates of fractures were higher for those with vitamin D levels between 25 nmol/L and 49.9 nmol/L, compared with those over 50 nmol/L, the researchers reported. This includes the rates of total fractures, osteoporotic fractures, and fractures of hip or femur. However, there was no evidence for a causal role for vitamin D and fracture risk in the Mendelian randomization analysis, Nordestgaard and colleagues reported.
"Thus, low 25-hydroxyvitamin D per se may not be a cause of osteoporotic fractures. Interestingly, we observed that low plasma 25-hydroxyvitamin D concentrations could be associated with reduced risk of fractures in Mendelian randomization analysis, indicating that high vitamin D could increase risk of fractures," the authors wrote.
The Clinical Chemistry report adds to a body of evidence against supplementation with vitamin D to improve health. One randomized trial actually found that when vitamin D is given at high doses alone it is associated with lower bone mineral density, they noted.
"This could explain our finding that low plasma 25-hydroxyvitamin D concentrations were associated with reduced risk of total fractures in genetic analyses, meaning that high vitamin D could increase risk of fractures," the authors wrote.
The U.S. Preventive Services Task Force recommends against supplementation in older adults to prevent fractures, but the Endocrine Society and American Geriatric Society advocate for it, the group noted.
