Contribution of Gender‐Specific Genetic Factors to Osteoporosis Risk

Abstract

SummaryCommon diseases result from the complex relationship between genetic and environmental factors. The aim of this review is to provide perspective for a conceptual framework aimed at studying the interplay of gender-specific genetic and environmental factors in the etiology of complex disease, using osteoporosis as an example.In recent years, gender differences in the heritability of the osteoporosis-related phenotypes have been reported and sex-specific quantitative-trait loci were discovered by linkage studies in humans and mice. Results of numerous allelic association studies also differed by gender. In most cases, it was not clear whether or not this phenomenon should be attributed to the effect of sex-chromosomes, sex hormones, or other intrinsic or extrinsic differences between the genders, such as the level of bioavailable estrogen and of physical activity. We conclude that there is need to consider gender-specific genetic and environmental factors in the planning of future association studies on the etiology of osteoporosis and other complex diseases prevalent in the general population.

Role of Plasminogen Activator Inhibitor-1 in Glucocorticoid-Induced Diabetes and Osteopenia in Mice

“…We previously reported that PAI-1 is involved in the pathogenesis of type 1 diabetic osteoporosis in female mice but not in male mice (16). Studies have suggested that a protein linked to the sex chromosomes is associated with the sex differences in the prevalence of metabolic abnormality and osteoporosis (49,50). This suggests that a protein linked to a sex chromosome might be responsible for the sex differences observed in the current study.…”

Identification of homogeneous genetic architecture of multiple genetically correlated traits by block clustering of genome-wide associations

“…We did not apply a similar threshold to the phenotypes, whose selection was based on availability and epidemiologic evidence of their associations with fracture rather than on correlations among them. Because musculoskeletal traits are sexually dimorphic and likely to be influenced by sex-specific genetic mechanisms, (50) the analyses were performed separately in men and women; however, we presented results from the women because the sample size was greater, and women experience more fractures than men. Results in men appear similar; however, our study has insufficient power for a formal comparison of the clustering results between the sexes.…”

“…Because musculoskeletal traits are sexually dimorphic and the genetic mechanisms are likely to be sex-specific, (50) the analyses were performed separately in men and women. We focused on results from the 2038 women because osteoporotic fractures are more common in women, genetic regulation has been shown to differ by gender, (50,51) and our sample size for women was greater than for men. …”

Sex and Gender Differences in Endocrinology

“…223 Males have larger bones at all ages compared to females, resulting in an increase of whole body strength. Based on remodeling differences, females displayed faster expansion of the femoral neck, leading to potentially increased bone fragility.…”