Family history of appendicular fracture and risk of osteoporosis: A population-based study

Family and twin studies demonstrate a strong genetic component to osteoporo sis, suggesting that a positive family history for this disease may be an i mportant clinical risk factor. We have therefore explored the extent to whi ch a history of wrist fracture in a female first-degree relative was associ ated with an increased risk of prevalent fracture at both appendicular and vertebral sites in a cross-sectional study design. One thousand and three C aucasian women (age range 45-64 years) were studied from a UK population co hort. Bone mineral density (BMD) was measured at the lumbar spine and femor al neck using dual-energy X-ray absorptiometry. Appendicular fractures (wri st and hip) were recorded by questionnaire and validated from radiographs a nd hospital records. Vertebral fractures were assessed using radiologic sur vey of the thoracolumbar spine and semi-automated morphometric analysis. A positive family history of osteoporotic fracture (hip and/or wrist) in eith er a mother and/or sister was reported in 138 of the 1003 women. When compa red with those with a negative family history of fracture, BMD was signific antly reduced in those with a positive history at both the spine (p = 0.02) and the hip (p = 0.02). In total, there were 63 validated fragility fractu res found in the 1003 women (16 wrist, 6 hip and 41 vertebral). Family hist ory of osteoporotic fracture was associated with an increased total risk fo r osteoporotic fracture, with an odds ratio (95% confidence interval) of 2. 02 (1.02, 3.78). Site-specific analysis showed that a positive family histo ry of wrist fracture was associated with a considerably elevated risk of wr ist fracture, with an odds ratio of 4.24 (1.44, 12.67). These increases in risk remained after adjustment for BMD, suggesting that other genetic facto rs account for the familial risk of osteoporosis and fracture.