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Genetic and Environmental Factors Affect Bone Density Variances of Families of Men and Women with Osteoporosis

INSERM U 349, Bone Pathology (C.B., M.E.C.-S., J.B., M.C.D.V.) and Fédération de Rhumatologie (M.E.C.-S., J.B., M.C.D.V.), Hôpital Lariboisière, 75475 Paris, France

Address all correspondence and requests for reprints to: Marie-Christine de Vernejoul, M.D., INSERM U349, Hôpital Lariboisière, 2 rue Ambroise Paré, 75425 Paris Cedex 10, France. E-Mail: . christine.devernejoul{at}inserm.lrb.ap-hop-paris.fr

Abstract

Our aim was to assess the relative impacts of genetics and environment in the families of osteoporotic patients and identify the best subgroup of patients to investigate the genes associated with osteoporosis. We recruited 36 men and 47 women with osteoporosis (probands), median age of 52 and 68 yr, and all their siblings (90) and offspring (83). The families were classified as young or old on the basis of the median age of the probands. We measured the bone mineral density at the femoral neck (FN) and lumbar spine (LS) adjusted for age and weight and standardized (Z-score). Physical activity, nutritional calcium, and alcohol and tobacco consumption were investigated. We compared the mean Z-score using linear mixed model and assessed the familial resemblance using intraclass correlation. The mean Z-scores of the families of osteoporotic patients were significantly negative at FN and LS, with no intergeneration or intergender differences. At FN, but not at LS, the mean Z-score was independently lower in the families of male probands (mean ± SD: -0.57 ± 0.96, female: -0.18 ± 0.85, P = 0.012) and in young families (-0.58 ± 0.94, old families: -0.11 ± 0.83, P = 0.006). This suggested that the lower Z-score in the families of men with osteoporosis was related to their younger age. There was significant phenotypic resemblance among members in the families. In the families of female probands, the correlation between the probands and her siblings was weak and disappeared after adjustment on environment, and a resemblance appeared within their children (FN: r = 0.61) suggesting that different environment had masked the resemblance in this subgroup. In the families of male probands, a strong resemblance persisted after adjusting for environment, (proband-offspring at FN: r = 0.46 and within offspring at FN: r = 0.66, at LS: r = 0.61). This showed that resemblance was independent of a common measurable environment in these families of men with osteoporosis. In conclusion, mainly young osteoporotic patients, most of whom were male in our study, are affected by the genetic component.

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