We have shown that enhanced growth in early life is associated with greater bone size and strength as assessed by pQCT in a UK population in late middle age. Our results suggest that there is a small residual effect of early life, whereby poor growth produces weaker bone in adult life, even when adult height and weight are adjusted for. Birthweight and weight at 1 year displayed independent associations with measures of bone density and strength. Lifestyle factors such as cigarette consumption, HRT use, and obesity were associated with volumetric bone density in this population but did not explain the relationship between growth in early life and bone strength in late adulthood.
This study had a number of limitations. The individuals recruited were selected because they had been born in Hertfordshire and continued to live there at the age of 60–75 years, as in previous studies. However, we have previously demonstrated that the Hertfordshire populations studied have similar smoking characteristics and bone density to national figures 
, suggesting that selection bias is minimal. Furthermore, we ascertained that those individuals who did not complete the study had similar birthweights and weights at 1 year to those who did not. The power of the study to detect associations with fracture in men was low, due to low numbers of events.
Cadaveric studies have confirmed the high precision of pQCT and validated its use as a technique for assessing bone strength [11–14]
. Cross-sectional studies of large cohorts with a wide age range have reported that total, trabecular, and cortical bone density decrease linearly with age in both sexes, with greater declines in females 
. In women, cortical bone area decreases with age after the age of 60 years. The total cross-sectional area of the bone becomes wider with age, with greater increments in men than women, whilst the minimum moment of inertia, an index of mechanical resistance to bending, remains stable with age in men, whilst it was significantly lower in older compared with younger women. Case control studies have suggested that volumetric bone mineral content (BMC), total and trabecular volumetric BMD, and the cross-sectional moment of inertia are all significantly different in women who had sustained a low trauma Colles' fracture versus controls 
. Similarly, one Japanese study has suggested that pQCT can be used to discriminate women who have sustained vertebral fractures versus non-fractured controls 
Initial studies from Bath showed a relationship between weight at 1 year and BMC at age 21 years in women 
, whilst further work in Hertfordshire, UK went on to demonstrate an association between weight at 1 year and BMC at age 60–75 years in both sexes 
. More recent data from the US showed an association between recalled birthweight and BMC in 305 postmenopausal women 
. Typically adjustment for adult weight or height weakens but does not remove this association. Similarly, data from Sheffield demonstrated significant associations between birthweight and adult BMC (and lean mass) after adjustment for age, sex, height, and physical activity 
. Most recently, we have demonstrated independent contributions of birthweight and weight at 1 year to adult BMC and BMD in this cohort 
. Available data would therefore support the hypothesis that different mechanisms exist for establishing the adult bone envelope which encompasses not only the length of the bone, but also its width (estimated by BMC) versus its density (estimated by BMD). Each of these factors is important in establishing an individual's fracture risk. The independent effects of birthweight and weight at 1 year suggest that although genetic and/or intrauterine environmental factors that influence the foetal growth trajectory and are reflected in birthweight have long-term consequences on bone mass in late adulthood, further modification of the infant growth trajectory over the first year of life has lasting effects on adult bone mass and hence fracture risk.
It is difficult to disentangle the influences of the genome and intrauterine environment on birthweight. In a family study performed 5 decades ago, Penrose suggested that 62% of the variation in birthweight between individuals was the result of the intrauterine environment, 20% was the result of maternal genes, and 18% was the result of foetal genes 
. In addition, studies of babies born after ovum donation showed that although their birthweights were strongly related to the birthweights of the recipient mother, they were unrelated to the weight of the female donors 
. Coupled with other studies [20–22]
, these data would suggest that birth size is controlled at least in part by the intrauterine environment rather than by the genetic inheritance from both parents. Finally, a recent study that examined the association of birthweight with bone mass in a twin study of over 4000 women confirmed that bone mass and especially BMC were highly associated with birthweight in both monozygotic and dizygotic twins 
. These associations point to environmental rather than genetic factors underlying the observed relationships.
Adult bone mass is a function of both bone size and density 
; both these variables influence fracture risk [24,25]
. Both bone geometry and bone properties (including micro-architecture) are also known to be determinants of bone strength; with age, changes in the elastic modulus and toughness of bone are offset by periosteal apposition which may help to preserve bone strength 
. BMD is limited at detecting fracture risk; although risk of fracture increases with decreasing BMD, many individuals fracture with a ‘normal’ BMD. In part, this may reflect the limitations of DXA in assessing bone density (by dividing BMC by projected bone area); projected bone area will systematically underestimate the skeletal bone volume of taller subjects. Hence pQCT provides a valuable additional tool.
In conclusion, we have demonstrated independent effects of birthweight and weight at 1 year on volumetric bone size and bone strength in the seventh decade in both sexes. Lifestyle factors such as cigarette smoking were the major determinants of volumetric bone density in this population.