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Ulf Sennerby, MD; Håkan Melhus, MD, PhD; Rolf Gedeborg, MD, PhD; Liisa Byberg, PhD; Hans Garmo, PhD; Anders Ahlbom, PhD; Nancy L. Pedersen, PhD; Karl Michaëlsson, MD, PhD

JAMA. 2009;302(15):1666-1673.

Context  Recent studies indicate common etiologies for cardiovascular disease (CVD) and osteoporotic fractures.

Objectives  To examine the relation between CVD and risk of hip fracture in twins and evaluate the relative importance of genetics and lifestyle factors in this association.

Design, Setting, and Participants  A cohort of all 31 936 Swedish twins born from 1914-1944 was followed up from the age of 50 years. The National Patient Registry identified twins with CVDs and fractures from 1964 through 2005. Time-dependent exposures using Cox proportional hazard regression models were evaluated.

Main Outcome Measure  Time to hip fracture after diagnosis of CVD.

Results  The crude absolute rate of hip fractures was 12.6 per 1000 person-years after a diagnosis of heart failure, 12.6 per 1000 person-years after a stroke, 6.6 per 1000 person-years after a diagnosis of peripheral atherosclerosis, and 5.2 per 1000 person-years after a diagnosis of ischemic heart disease compared with 1.2 per 1000 person-years for those without a CVD diagnosis. The multivariable-adjusted hazard ratio (HR) of hip fracture after a diagnosis of heart failure was 4.40 (95% confidence interval [CI], 3.43-5.63); after a stroke, the HR was 5.09 (95% CI, 4.18-6.20); after a diagnosis of peripheral atherosclerosis, the HR was 3.20 (95% CI, 2.28-4.50); and after an ischemic heart disease event, the HR was 2.32 (95% CI, 1.91-2.84). Identical twins without heart failure and stroke also had, after their co-twins had been exposed to these respective diseases, an increased rate of hip fracture. These sibling twins pseudoexposed for heart failure had a multivariable-adjusted HR of 3.74 (95% CI, 1.97-7.10) for hip fracture, whereas pseudoexposure for stroke had an HR of 2.29 (95% CI, 1.20-4.35).

Conclusions  A diagnosis of CVD was significantly associated with risk of subsequent hip fracture. Increased risks in co-twins without an index diagnosis suggest genetic factors in the association between CVD and osteoporotic fractures.

Author Affiliations: Department of Surgical Sciences, Section of Orthopaedics (Drs Sennerby, Byberg, and Michaëlsson) and Section of Anaesthesiology and Intensive Care (Dr Gedeborg), Department of Medical Sciences, Section of Clinical Pharmacology (Dr Melhus), and Uppsala Clinical Research Center (Drs Melhus, Gedeborg, Byberg, and Michaëlsson), and Regional Oncologic Center (Dr Garmo), Uppsala University, Uppsala Sweden, King's College, School of Medicine, Division of Cancer Studies, King's College, London, UK (Dr Garmo); Department of Epidemiology, Institute of Environmental Medicine (Dr Ahlbom), Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Dr Pedersen).

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BMJ 2009;339:b4389-b4389.
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