Analysis Suggests Back Disease May Run in Families

From Medscape Medical News

Norra MacReady

February 4, 2011 — In an analysis of a database of more than 2 million people, first-degree and third-degree relatives of people with lumbar disc disease had a significantly increased relative risk of developing the back condition themselves compared with expected rates for the general population. "The results of this study support a heritable predisposition to lumbar disc disease," lead author Alpesh A. Patel, MD, and colleagues from the departments of Orthopaedics and Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, report in the February 2 issue of the Journal of Bone and Joint Surgery.

Low back pain is common and costly — its estimated lifetime risk in the United States is 84%, with an annual cost that exceeds $100 billion — yet its etiology remains incompletely understood, the authors write. Several earlier studies have hinted at a familial predisposition, but "we are aware of no study that has evaluated the familial clustering of lumbar disc disease on a population-based, multigenerational level."

To test the hypothesis that lumbar disc disease may be inherited, the authors analyzed data from both the Utah Population Database, which permits the tracking of medical information on the founding pioneers of Utah and their descendents, and the University of Utah Health Sciences Center data warehouse, which has diagnosis and procedure data on all patients treated at the University Hospital. Together, the databases contain information on more than 2.4 million patients. Only patients and control participants with at least 3 generations of genealogical data were included in the study.

Of those individuals, 1254 people had at least 1 diagnosis of lumbar disc disease or lumbar disc herniation, along with the requisite genealogical data. The authors tested for heritability in 2 ways: by estimating the relative risk for lumbar disease in relatives and by determining a genealogical index of familiality (GIF). They compared their findings in affected families with the expected results for the general population of Utah.

First-degree relatives of people with lumbar disc disease had a relative risk of 4.15 of having the disease themselves (95% confidence interval [CI], 2.82 - 6.10; P < .001). In third-degree relatives, the relative risk was 1.46 (95% CI, 1.06 - 2.01; P = .027). Relative risk was slightly elevated in second-degree relatives, at 1.15, but this was not significant (95% CI, .71 - 1.87; P = .60), perhaps because of limitations in the data.

The GIF tests the hypothesis that there is no excess familial clustering, or relatedness, of the phenotype of interest by measuring excess relationships between pairs of patients compared with pairs of control participants. "It is not the absolute value of the GIF statistic that reveals excess relatedness of disease, but the relative value of the case-GIF to the control-GIF," the authors explain. In this analysis, the case overall GIF was 3.05 compared with a mean control GIF of 2.51 (P < .001 for overall GIF), suggesting "a significant excess of relationships among patients compared with controls."

The investigators relied on International Classification of Diseases, Ninth Revision, codes to identify patients, so diagnostic accuracy may have varied, depending on physician specialty and experience, they noted. Also, they were unable to determine disease severity and response to treatment. Genetically, the population of Utah is similar to the US population and to the northern European population from which the founders of Utah came, so the findings may be generalized to those groups.

Now that a genetic predisposition to lumbar disc disease has been identified, the authors conclude, "identification of the specific genetic products responsible for lumbar disc disease may help in the development of potential biologic interventions to prevent and/or treat lumbar disc disease in the population at large."

In an accompanying editorial published online, David A. Wong, MD, from the Denver Spine Center, Greenwood Village, Colorado, commends Dr. Patel and colleagues for their study design and conclusion. Dr. Wong remarks on the future possibilities that may lead researchers to identify specific genes responsible for spine and other musculoskeletal disorders, akin to what is currently known about breast cancer. He states: "We can look forward to more genetic research in the area of the spine. Inevitably better treatments are likely to be found. Perhaps the treatment for so-called black disc disease is lurking on the horizon."

J Bone Joint Surg Am. 2011;93:225-229. Abstract