All diseases have a genetic component, whether inherited or resulting from the body's response to environmental stresses like viruses or toxins. Explorations into the function of each human gene will therefore shed light on how genes play a role in disease causation. Molecular simulations are now being used to identify new drug pathways and gene expression profiles are being created to predict disease states such as coronary atherosclerosis, diabetes, cancer, obesity, and certain psychiatric disorders.^1,2

Osteoporosis, which typically results in bone fracture, has a profound impact on quality of life, with only one third of patients regaining their prefracture level of function. Osteoporotic patients are also at greater risk for death.³ The importance of genetic factors in an elderly individual's propensity toward bone fracture is specific to the individual's age and the site and type of the fracture, according to a study in monozygotic twins in the September 12 issue of Archives of Internal Medicine.³  This suggests that the predisposition for fractures is actually stronger than previously estimated—especially for early occurring fractures. Until now, the heritability of fractures was unknown due to the limited study size in the only previously conducted twin study.

According to the authors of this report, twin studies provide one of the most natural populations for evaluating risk. Monozygotic twins are genetically identical, whereas dizygotic twins share half of their segregating genes; therefore, if heritable factors contribute to risk of fracture, concordance should be greater among monozygotic twins. To evaluate the genetic liability to fracture in the elderly, lead author Karl Michaelsson, MD, PhD, of Uppsala University Hospital in Uppsala, Sweden, and colleagues used the Swedish Twin registry. In a cohort of all 33,432 Swedish twins born from 1896 to 1944, the researchers identified 6021 twins with any fracture at all, with a higher proportion among women than men (23% vs 14%). More than half (3599) of the twins were classified as having osteoporotic fracture, including 1055 with a hip fracture occurring after age 50.

Genetic variation differed considerably by type of fracture and age of patient, the authors reported. Less than 20% of the overall age-adjusted fracture variance was explained by genetic variation, and the age-adjusted heritability of any osteoporotic fracture was 27%. Genetic predisposition was considerably greater for first hip fracture before age 69 and between 69 and 79 years than for hip fractures after 79 years. Specifically, for hip fracture alone, heritability was 48%; 68% for hip fractures occurring before age 69, and 47% for those occurring between the ages of 69 and 79.

Further research needed

Exactly which genes confer increased risk for osteoporosis is not yet known, so the search for fracture susceptibility genes and gene-environment interaction is warranted; however, these new findings are promising.  "No specific genes have more than a marginally explained fracture risk," Dr. Michaëlsson stated. 

When asked how these genetic factors rank with other known risk factors for osteoporosis such as low body weight and smoking, Dr. Michaëlsson replied, "it depends on the type of fracture and at what age the fracture occurs," adding that "being thin is also important to consider, as well as smoking and a sedentary lifestyle."³

Concluding that the findings are important in the effort to target effective interventions against osteoporotic fractures, the authors added that hip fracture prevention strategies should be focused on lifestyle interventions in the oldest elderly. "On the other hand," they write, "especially hip, but even other types of osteoporotic fractures at younger ages seem to be strongly genetically influenced. Assessments of osteoporotic fracture risk by clinical examination may be recommended for relatives of patients with hip fractures before the age of 80 years."

References

1. Billings PR, Carlson RJ, Carlson J, et al. Ready for genomic medicine? Perspectives of health care decision makers. Arch Intern Med. 2005;165;1917-1919.

2. Rubinstein WS, HK Roy. Practicing medicine at the front lines of the genomic revolution.  Arch Intern Med. 2005;165:1815-1817.

3. Michaëlsson K, Melhus H, Ferm H, Ahlbom A, Pedersen N. Genetic liability to fractures in the elderly. Arch Intern Med. 2005;165:1825-1830.

 

Are Physicians Ready for the Genomic Revolution?

As medicine approaches the genomic era, are physicians ready? The answer is not really, according to a report on the preparedness of healthcare systems to make use of the findings of genomic medicine, published in the September 12 issue of the Archives of Internal Medicine.

The study found that only a small minority of healthcare decision makers were keenly interested in considering the implications of genomic advances, despite the large economic investments made by genomic medicine in both the public and private sectors and the tremendous enthusiasm for its promise on the part of geneticists and the makers of genomic medicine products. In order for these investments to yield improvements in healthcare, more attention must be paid to "the near-term diffusion of genomic knowledge, the barriers to its application, and the reforms needed to ensure its appropriate use," the report concluded.

To compile the report, beginning in June 2002 researchers conducted 16 workshops comprising more than 600 participants (predominantly senior executives and staff of healthcare delivery organizations and pharmaceutical, medical device, and clinical laboratory companies). Participants were questioned on their knowledge of genomics and what additional information they thought would be helpful for its medical utility.

Surprisingly, only a small minority of participants exhibited extensive knowledge regarding human genomics. "Decision makers in the healthcare system must increase their knowledge base,"¹ declared Paul R. Billings, MD, PhD, of Laboratory Corporation America Holdings, Inc, in Research Triangle Park, North Carolina.

Buyer Beware

Also in the September 12 issue of the Archives of Internal Medicine, an editorial by Wendy S. Rubinstein, MD, PhD, and Herman K. Roy, MD, of Northwestern University in Evanston, Illinois, tempered some of the enthusiasm for certain applications of genomic medicine.² Until genomic medicine is more established, they wrote, clinicians should rely on taking a family history—possibly the best tool available for a long time to come. "Clinicians should be prepared to ward off the surge of public demand for tests that are brought prematurely to the marketplace, although this may be a daunting task," they concluded.