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Fracture risk not linked to low vitamin D or calcium levels

Bone mineral density is risk factor for fracture risk, suggest study

Adrian O'Dowd

Thursday, 30 August 2018

People who have a genetic predisposition to lower vitamin D levels and calcium intake do not appear to have a higher risk of osteoporotic fracture, according to a study* published today in The BMJ.

The findings add to an ongoing debate over the benefits for the general population of vitamin D supplementation, which is currently recommended by clinical guidelines to prevent fractures.

An international team of researchers set out to assess the role of 15 clinical risk factors considered to be associated with risk of osteoporotic fractures – including vitamin D levels, calcium intake, fasting glucose levels, age of puberty, age at menopause, diabetes and rheumatoid arthritis – using genetics.

Initially, the team – co-led by researchers from McGill University in Montreal, Canada and the Erasmus University Medical Center in Rotterdam, The Netherlands – analysed the results of genome-wide association studies to evaluate the influence of genetic variation on fracture risk.

Using data from 37,857 fracture cases and 227,116 controls, they identified 15 genetic loci (areas on the chromosomes) associated with fracture risk. They then replicated their findings in 147,200 fracture cases and 150,085 controls.

All 15 of these loci were linked to fracture risk as well as bone mineral density.

Then using a technique called Mendelian randomisation, the researchers examined the association of 15 genetic variants (each representing an individual clinical risk factor for osteoporotic fracture) against fracture risk.

Analysing genetic information in this way avoided some problems that impact on traditional observational studies, making the results less prone to confounding factors, and therefore more likely to be reliable.

The Mendelian randomisation showed that only bone mineral density had a clear effect on fracture risk.

None of the other well-accepted risk factors tested – such as rheumatoid arthritis, vitamin D levels, calcium intake from dairy sources, fasting glucose, type 2 diabetes and coronary heart disease – had a major causal effect on fracture risk.

The researchers explained that older individuals at high risk of fractures often have low vitamin D levels, therefore, fracture prevention guidelines have suggested the use of vitamin D supplementation in the general population.

“Our analyses showed that vitamin D levels had no protective linear effect on fracture in community dwelling individuals,’ they said.

Similarly, they found no evidence for a protective effect of sustained intake of dairy derived calcium on fracture risk.

The study had some limitations, said the researchers, but they described their work as the largest and most comprehensive assessment of the genetic determinants of fracture risk so far.

They concluded: “Our findings are a reminder that clinically relevant changes in most of these risk factors are unlikely to result in large differences in fracture risk.

“These findings provide guidance for the design of future clinical trials on interventions that are more likely to be successful in reducing fracture risk.”


*Rivadeneira, F, Richards, J B, et al on behalf of the GEFOS/GENOMOS consortium and the 23andMe research team. Assessment of the genetic and clinical determinants of fracture risk: meta-analysis of genome wide association studies using a mendelian randomisation approach. BMJ 2018;362:k3225. DOI: 10.1136/bmj.k3225

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