BOG Fracture-Risk Score Combines DNA Info with Physiological Factors

This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson. 

During childhood and adulthood, we often put ourselves at risk for future fractures based on our activity, diet, and social habits. Many factors affect the risk of both stress fractures in younger people and fragility fractures later in life. Everyone—but especially athletes and active-duty military personnel—could benefit from an early heads-up regarding their genetic and phenotypic predisposition to stress fractures. Later in life, the FRAX index is a very useful multifactor risk score, but it is usually calculated only after a sentinel event, such as a fragility fracture.

Ultrasound is a readily available and inexpensive way to obtain an estimated heel bone mineral density (eBMD). Many common genetic variants contribute to the genetic basis for the eBMD phenotype. These variants are most commonly characterized by single nucleotide polymorphisms (SNPs, pronounced “snips”). Stanford researcher Stuart Kim developed the BMD Osteoporosis Genetic (BOG) risk score by combining 22,886 SNPs with data on height, weight, sex, and age.¹ The correlation between actual eBMD and the BOG algorithm was 0.496, which was higher than the correlations achieved using the 22,886 genetic predictors or the four covariates alone.

Individuals with low BOG scores had a 17.4-fold increased risk for osteoporosis compared to those with the median BOG score. Low BOG scores were also associated with a 1.9-fold higher risk for bone fractures compared to median BOG values. However, the algorithm’s ability to discriminate cases from controls in the overall population was modest. The receiver operator area under the curve for predicting osteoporosis or fracture by the BOG algorithm was 0.78 and 0.57, respectively.

Although the effect of an individual SNP may be inconsequential, the cumulative effect from many SNPs can be large. The author stated that “an algorithm such as the BOG risk score might be useful to screen the general population…to identify individuals that warrant closer examination, such as BMD measurement via DXA [dual-energy X-ray absorptiometry].”

Reference

1. Kim SK. Identification of 613 new loci associated with heel bone mineral density and a polygenic risk score for bone mineral density, osteoporosis and fracture. PLoS One. 2018 Jul 26;13(7):e0200785. doi: 10.1371/journal.pone.0200785. eCollection 2018. PMID: 30048462