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
- 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
Fragility Fracture Risk Prediction: Beyond BMD
This basic science tip 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.
Bone mineral density (BMD)—a measure of both cortical and trabecular bone—has been widely used as an index of bone fragility. The femoral neck and lumbar vertebrae are the areas most commonly measured with BMD, but hip osteoarthritis and lumbar spondylosis can mask systemic osteoporosis. In addition, the most common fragility fractures occur at the distal radius.
Investigators conducted a prospective study using high-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal radius and tibia to determine whether baseline skeletal parameters could predict fragility fractures in women. A second goal was to establish whether women who have fragility fractures experience bone loss at a faster rate than those who do not have fractures.
Among 149 women older than 60 years who had baseline and 5-year follow-up HR-pQCT, 22 had a fragility fracture during the study period and 127 did not. HR-pQCT is able to record total bone mineral density (Tt.BMD), trabecular bone mineral density (Tb.BMD), trabecular number (Tb.N), and trabecular separation (Tb.Sp).
The analysis showed that women with fragility fractures had lower baseline Tt.BMD (19%), Tb.BMD (25%), and Tb.N (14%), along with higher Tb.Sp (19%) than women who did not experience a fracture. Analysis of the tibia measures yielded similar results, showing that women with incident fracture had lower Tt.BMD (15%), Tb.BMD (12%), cortical thickness (14%), and cortical area (12%). Also, women with fractures had lower failure load (10%) with higher total area and trabecular area than women without fractures.
For each standard deviation decrease of a measure at the distal radius, the odds ratio for fragility fracture was 2.1 for Tt.BMD. 2.0 for Tb.BMD, and 1.7 for Tb.N. ORs for those measures at the tibia were similar.
In contrast to these findings, the annualized percent rate of bone loss was not different between groups with and without fractures. These results suggest that future fragility-fracture risk prediction should rely at least as much on bone architecture and strength as on simple BMD measurements.
Reference
Burt LA, Manske SL, Hanley DA, Boyd SK. Lower Bone Density, Impaired Microarchitecture, and Strength Predict Future Fragility Fracture in Postmenopausal Women: 5-Year Follow-up of the Calgary CaMos Cohort. J Bone Miner Res. 2018 Jan 24. doi: 10.1002/jbmr.3347 PMID: 29363165
Fracture Liaison Service Boosts Patient Engagement with Secondary Prevention
OrthoBuzz has published several posts about osteoporosis, fragility fractures, and secondary fracture prevention. In the May 17, 2017 edition of JBJS, Bogoch et al. add to evidence suggesting that a coordinator-based fracture liaison service (FLS) improves engagement with secondary-prevention practices among inpatients and outpatients with a fragility fracture.
The Division of Orthopaedic Surgery at the University of Toronto initiated a coordinator-based FLS in 2002 to educate patients with a fragility fracture and refer them for BMD testing and management, including pharmacotherapy if appropriate. Bogoch et al. analyzed key clinical outcomes from 2002 to 2013 among a cohort of 2,191 patients who were not undergoing pharmacotherapy when they initially presented with a fragility fracture.
- Eighty-four percent of inpatients and 85% of outpatients completed BMD tests as recommended.
- Eighty-five percent of inpatients and 79% of outpatients who were referred to follow-up bone health management were assessed by a specialist or primary care physician.
- Among those who attended the referral appointment, 73% of inpatients and 52% of outpatients received a prescription for anti-osteoporosis medication.
The authors conclude that “a coordinator-based fracture liaison service, with an engaged group of orthopaedic surgeons and consultants…achieved a relatively high rate of patient investigation and pharmacotherapy for patients with a fragility fracture.”
Increased Calcium Intake Neither Boosts BMD nor Reduces Fracture Risk
In two separate studies published recently in the BMJ, New Zealand researchers concluded that increased calcium intake, through diet or supplements, is unlikely to have clinically meaningful effects on bone density or fracture prevention. The findings call into question recommendations from most health care professionals for daily calcium intake of at least 1,000 to 1,200 mg in older adults.
The first study reviewed 59 randomized controlled trials (nearly 14,000 patients total) that examined the association between bone mineral density (BMD) and either dietary or supplemental sources of calcium. Increases in BMD ranged from only 0.6% to 1.8% with increased calcium intake, regardless of the source and whether calcium was taken with vitamin D. The authors concluded that these small BMD effects were “unlikely to translate into clinically meaningful reductions in fractures.”
The second study reviewed 28 randomized trials and 44 observational studies (more than 58.000 patients total) that examined the relationship between increased calcium intake and fracture prevention among people older than 50 years. The analysis found that calcium supplements have “small inconsistent benefits on fracture prevention” but that overall “there is currently no evidence that increasing calcium intake prevents fractures.”
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