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Genetic Liability to Fractures in the Elderly
Karl Michaëlsson, MD, PhD;
Håkan Melhus, MD, PhD;
Helene Ferm, MD;
Anders Ahlbom, PhD;
Nancy L. Pedersen, PhD
Arch Intern Med. 2005;165:1825-1830.
Background The genetic impact on the causation of osteoporotic fractures is unclear. A large twin study is ideally suited to determine the genetic liability to categories of fracture at various ages.
Methods A cohort of all 33 432 Swedish twins born from 1896 to 1944 was used to evaluate the genetic liability to fracture occurrence in the elderly. The Swedish Inpatient Registry and computer-assisted telephone interviews enabled us to identify 6021 twins with any fracture, 3599 with an osteoporotic fracture, and 1055 with a hip fracture after the age of 50 years.
Results Genetic variation in liability to fracture differed considerably by type of fracture and age. Less than 20% of the overall age-adjusted fracture variance was explained by genetic variation. The age-adjusted heritability of any osteoporotic fracture was slightly greater (0.27; 95% confidence interval [CI], 0.09-0.28), and for hip fracture alone, it was 0.48 (95% CI, 0.28-0.57). Heritability was not attenuated after further adjustment for several known osteoporotic covariates but was considerably greater for first hip fractures before the age of 69 years (0.68; 95% CI, 0.41-0.78) and between 69 and 79 years (0.47; 95% CI, 0.04-0.62) than for hip fractures after 79 years of age (0.03; 95% CI, 0.00-0.26).
Conclusions The importance of genetic factors in propensity to fractures depends on fracture site and age. The search for susceptibility genes and environmental factors that may modulate expression of these genes in younger elderly patients with hip fracture, the most devastating osteoporotic fracture, should be encouraged. Prevention of fractures in the oldest elderly should focus on lifestyle interventions.
Author Affiliations: Departments of Surgical Sciences (Drs Michaëlsson and Ferm) and Medical Pharmacology (Dr Melhus), Uppsala University Hospital, Uppsala, Sweden; and Departments of Environmental Medicine (Dr Ahlbom) and Medical Epidemiology and Biostatistics (Dr Pedersen), Karolinska Institute, Stockholm, Sweden.
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