Genetics Study Finds Bone Mineral Density, Not Vitamin D, Significantly Affects Fracture Risk

A study investigating the genetic determinants of fracture risk identified 15 genetic determinants of fracture, which also influenced bone mineral density. Among the clinical risk factors considered, only bone mineral density demonstrated a major causal effect on fracture, while genetic predisposition to lower levels of vitamin D and estimated calcium intake from dairy were not associated with fracture risk, according to the results.

The research involved a discovery set of 37,857 fracture cases and 227,116 controls, with a replication in up to 147,200 fracture cases and 150,085 controls. The fracture cases were defined as individuals who had fractures at any skeletal site that is confirmed by medical, radiological, or questionnaire reports. Additionally, instrumental variable analyses were conducted to estimate the effects of 15 selected clinical risk factors for fracture.

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The results revealed that of the 15 fracture associated loci identified, all were associated with bone mineral density and mapped to genes clustering in pathways known to be critical to bone biology. Also, the mendelian randomization analyses demonstrated a clear effect of bone mineral density on fracture risk.

In addition, the researchers found that hand grip strength was inversely associated with fracture risk, however, the result was not significant after multiple testing correction. The remaining clinical factors, including vitamin D levels, did not show any evidence for an effect on fracture, according to the study.

“These findings suggest that interventions aimed at increasing bone strength are more likely to prevent fractures than widespread supplementation with vitamin D,” Brent Richards, MD, MSc, a genetic epidemiologist at the Lady Davis Institute at the Jewish General Hospital and professor of medicine at McGill University, said in a statement. “Our study, the first genome-wide association study for fracture risk, has provided important insight on the biologic mechanisms leading to fracture and how to prevent it.”

The authors emphasized that since the study confirms bone mineral density as a cause of osteoporotic fracture, interventions that are aimed at increasing bone mineral density and necessary and are likely to be clinically effective at fracture risk reduction.

“Our research confirms that BMD is the most important determinant of fracture risk and that prevention strategies aimed at increasing or maintaining bone density are the most likely to be successful,” Richards concluded. “One of the most important aspects of this research is the robust evidence showing that vitamin D supplementation in the general population is unlikely to be effective for the prevention of fracture. This will encourage clinicians to focus patients on building bone density as a more effective preventive measure against fracture.”

Reference

Trajanoska K, Morris JA, Oei L, et al. Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study. [published online August 29, 2018] BMJ. doi: 10.1136/bmj.k3225.