Genetic determinants of bone mass in adult women: A reevaluation of the twin model and the potential importance of gene interaction on heritability estimates

Abstract

We estimated genetic effects on bone density in pre- and postmenopausal twins and critically considered the assumptions of the twin model. Bone mass in the radius, lumbar spine, and hip, anthropometric measurements, usual calcium and caffeine intake, tobacco and alcohol use, number of pregnancies and live births, menstrual history, usual physical activity, and medical history were measured in a volunteer sample of 171 twin pairs [124 monozygotic (MZ) and 47 dizygotic (DZ)], aged 25-80, free of diseases known to affect bone mass or mineral metabolism. At all skeletal sites, MZ intraclass correlations exceeded DZ correlations for both pre- and postmenopausal women, yielding highly significant estimates of heritability for bone mass. Adjustments for height, age, and environmental characteristics did not reduce the heritability estimates. However, many of these estimates were unrealistically high, suggesting some violation(s) of the assumptions of the twin model. Thus, the familial resemblance in bone mass is due primarily to genetic effects at all skeletal sites and at all ages, although the importance of genetic effects is diminished with aging, as evidenced by increasing within-MZ pair variability in older women. Because of failures in the assumptions of the twin model, however, particularly the greater MZ environmental similarity and the probability of gene interaction, heritability estimates are probably too high and require cautious interpretation.

Oxidative stress and bone mineral density in elderly men: Antioxidant activity of alpha-tocopherol

“…Osteoporosis is a disease resulting from a decreased renewal of bone, which leads to a fragile skeleton and increased risk of fractures. The etiology of osteoporosis is complex and the fracture risk is influenced both by the genetic constitution and by environmental factors, with lifestyle becoming more important for bone mass and osteoporotic fractures with increasing age [1,2].…”

Whole Bone Mechanics and Bone Quality

“…Bone mass is influenced highly by genetics (eg, [33,64,112,121]), although this impact appears to diminish with aging [53,112]. Bone morphology, particularly hip axis length and femoral head width, is highly heritable [44,71].…”

Interaction Between Clinical and Laboratorys Indicators and Genetic Polymorphysms of the Calcaneal Bone Mineral Density in Children Starting Puberty. Is this a Time for Intervention?

“…Many factors affect bone growth, BMC and BMD, such as birth weight, maternal ultraviolet B exposure during pregnancy [10], and behavioural factors like physical activity [9,11], diet [7], vitamin D [12] and calcium intake [13,14], alcohol consumption [7] and carbonated soft drinks [15]. Hormonal balance and its fine interplay are also very important and necessary for normal bone development, primarily sex hormones, growth hormone (GH) [16] and insulin-like growth factors (IGFs) [17].…”