Data from a preliminary study suggest that a genetic predisposition for poor bone tissue quality (BTQ) could be a risk factor for hip fracture.

“Many fractures occur in people without osteoporosis based on [bone mineral density (BMD)], indicating that there may be an important role for factors, such as BTQ, that are hard to clinically assess given current [technological limitations],” Thomas F. Lang, PhD, study investigator from the University of California, San Francisco, said in an interview.

The study was presented at the American Society for Bone and Mineral Research (ASBMR) 2016 Annual Meeting.

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The catalyst for the analysis, Dr Lang said, was the results from previous research, including one study titled “A Study of Reduced Bone Quality as a cause of fractures.”

“That study involved analysis of material properties and composition of iliac crest bone tissue from women with and without fracture matched for bone density, and showed that fracturing women had different bone material properties and composition from controls even though they had the same BMD,” Dr Lang said. “Looking for genetic and molecular regulatory factors was an obvious next step.”

The present study included publicly available gene expression data from iliac crest biopsies of 27 female fracture cases and 39 non-fractured control women of similar age. From the data, Dr Lang and colleagues detected 24 candidate BTQ-related transcripts that were differentially expressed between groups independent of age, BMI, and both hip and spine BMD.

Researchers identified significant cis-expression single nucleotide polymorphisms (eSNPs; P≤.05) in 63% of the 24 candidate BTQ genes, and assessed risk scores of women (mean age, 71.8 years) from the Study of Osteoporotic Fractures (SOF).

Mean follow-up was 12.7 years.

According to results, in SOF, higher protective risk score values were associated with a lower risk for fracture (hazard ratio [HR], 0.86; P=.002), whereas higher values in the risk increasing score produced a higher risk (HR, 1.14; P=.007). After adjustment for femoral neck BMD, both associations remained significant (protective risk score, P=.002; risk increasing score, P=.015).

“This BMD independence is evidence that these SNPs and genes are related to fracture through some aspect of bone quality,” Dr Lang said. “It was surprising that we got relatively strong results even though we only had access to [expression quantitative trait loci] data from osteoblasts, and thus missed out on some potentially fracture-related genes.”

However, Dr Lang cautioned that the study is preliminary, and the findings have not yet been validated across multiple large prospective studies. “Nor have we carried out studies in animal models that could give us mechanistic information,” he said. “That may take some time.”

Disclosures: Dr Lang reports no relevant financial disclosures.

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  1. Evans D, Alliston T, Zhang B, et al. Abstract LB-SA0362. Genetic risk of hip fracture due to bone quality deficit. Presented at: ASBMR 2016 Annual Meeting; September 16-19, 2016; Atlanta, Georgia. 

This article originally appeared on Endocrinology Advisor