Parental and offspring bone mass: associations and mechanisms

Introduction: Although there is evidence that measures of bone size, mineralisation and density are partly inherited, there are scant data available from which to elucidate independent associations of mother and father, and the mechanisms underlying any relationships. The aim of this work was to characterise the independent bone relationships between mother-child and father-child, as differences between the two may point towards an intrauterine effect in early life. As the placenta is the conduit for all maternal intrauterine effects, the role of placental size in offspring bone mass was also explored. Methods: Using two large prospective population-based cohorts, The Southampton Women’s Survey (SWS) and The Avon Longitudinal Study of Parents and Children (ALSPAC), relationships between offspring bone mass at birth through to 17.7 years, and placental size were assessed. Bone mass measurements were obtained using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT); placental measurements were either obtained in mid-pregnancy (SWS) using ultrasound or at delivery (ALSPAC). Subsequently, correlation and regression methods were used to assess the relationships between DXA and pQCT-derived measurements of parental and offspring bone indices. Results: Parent and offspring bone mass were positively associated, with a greater magnitude of relationship observed for measures of bone size, than bone density. Parent-child bone associations were significantly stronger for mother-child than father-child for several variables, again predominantly those associated with bone size. Placental volume was positively associated with offspring bone mass at birth, with associations remaining during puberty into late childhood. These parent-child relationships were not influenced by placental size or other environmental factors previously shown to affect offspring bone mass. Conclusions: We observed strong relationships between offspring bone mass and both placental size and parental size. Mother-child bone associations were stronger than those for father-child, and were independent of placental size. Whilst direct genetic inheritance offers one mechanistic explanation, increasing understanding of epigenetic mechanisms and the disparity between maternal and paternal associations suggest that such relationships could be in part underpinned by gene-environment interactions in early life, and an effect on placental function.