MRC Environmental Epidemiology Unit, University of Southampton, Southampton, UK
Correspondence to: C. Cooper. E-mail: cc{at}mrc.soton.ac.uk
SIR, We were delighted to read the study by Dr Antoniades and colleagues confirming that birth weight is an important predictor of skeletal size and areal bone mineral density (BMD) [1]. This observation adds support to the notion that the intrauterine environment might programme the later risk of osteoporosis and fracture. As with our own data [2], the authors found that the relationship of birth weight with bone mineral content was substantially stronger than that with bone mineral density, although even the second of these relationships remained statistically significant after adjustment for current body size. Although areal BMD is an important determinant of fracture risk, bone size and geometry are emerging as equally important independent determinants, and our most recent findings suggest that poor growth in infancy has persisting effects on proximal femoral geometry and derived mechanical strength during the sixth and seventh decades of life [3]. Furthermore, data from Finland have demonstrated that individuals with poor height gain during childhood have a 1.9-fold increase in their risk of hip fracture several decades later [4]. Hence, effects on height and bone size should not be discounted when considering the early determinants of future fracture risk.
We were surprised that Dr Antoniades and colleagues infer that the strong intra-pair association between birth weight and adult skeletal status in their twins represents a principally genetic effect. We would have viewed the data as strongly supportive of a predominantly environmental influence, given the control for genetic influences using the twin model. Although aspects of maternal lifestyle, for example smoking and nutrition, are discussed in their abstract, we were uncertain how information on these attributes was ascertained in their study. In a detailed study contrasting maternal lifestyle with skeletal development in the neonate, we have previously demonstrated that maternal smoking, nutritional status and physical activity during late pregnancy are important correlates of neonatal bone mass [5].
Extrapolation from our studies of hip fracture suggest that a considerable population attributable risk arises through such early exposures. The epigenetic mechanisms whereby the maternal environment interacts with the fetal genome in determining the skeletal growth trajectory seems to us a critical area for future research, in order that preventive strategies against osteoporotic fracture might be targeted at this early stage of development.
References