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].”
- 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
As new advances in medical technology lead to treatments for injuries and diseases, one concept that has emerged is the importance of genetic predisposition to health, sickness, and functional recovery after trauma. Indeed, as the future of medicine will most likely concentrate on health as opposed to health care, understanding the genetic predisposition to medical conditions will become paramount. In the February 2016 issue of JBJS Reviews, Prodromidis and Charalambous focus on the role of genetics in the development and treatment of frozen shoulder. This article represents a careful analysis of the relationship between genetics and disease.
Frozen shoulder, or adhesive capsulitis, is a common condition that leads to functional loss and impairment of activities of daily living. However, despite the prevalence of this condition, its pathogenesis is not fully understood. Prodromidis and Charalambous performed a systematic review and meta-analysis in order to assess the evidence that suggests a genetic link to frozen shoulder.
The investigators performed a literature search of MEDLINE, EMBASE, and CINAHL using relevant keywords and found an initial 5506 studies. After further screening, seven studies were analyzed. The results were fascinating. One study, involving 1828 twin pairs, showed an 11.6% prevalence and demonstrated a heritability of 42% for frozen shoulder after adjusting for age. In a second study, involving 273 patients, 20% of patients with frozen shoulder had a positive family history involving a first-degree relative. A third study, involving 87 patients, showed that 29% of patients with frozen shoulder had a first-degree relative with this condition.
Two further studies evaluated racial predilection. One of these studies (50 patients) showed a substantially higher number of white patients with frozen shoulder than black patients with the condition. The other study (87 patients) showed that being born or having parents or grandparents who were born in the British Isles were risk factors for this condition.
Finally, four immunological studies investigated HLA-B27 as a risk factor for frozen shoulder. A meta-analysis of two of these studies with clearly defined controls showed higher rates of HLA-B27 positivity in patients with this condition as compared with controls (p < 0.001).
Thomas Einhorn, Editor