Table 2.

Key findings from relevant studies.

Study	Population and Gender (M/F)	Key Exposures & Bone Outcomes Explored	Key Findings	Gender Differences Described	Comments
Boot et al. (1997) [41]	(n=500) Children and adolescents 4-20 years M=205 F=295	Puberty, dietary and lifestyle and current bone density (DXA)	Pubertal development in girls and current weight in boys, are main factors in current BMD Low birthweight and prematurity not significantly associated with BMD	Key factors: Tanner stage in girls versus weight in boys	Puberty and later childhood growth are key determinants of skeletal development Pubertal factors may be sex specific Large study, but limited numbers of preterm born children
Cooper et al. (2001)	(n=7086) Born in 1924-33 and residing in Finland in 1971 M=3639 F=3447	Growth measured at birth and during childhood and linked to risk of hip fracture	Children born to tall mothers and those with slow childhood growth rates have increased hip fracture risk	Fracture more likely in taller women Differing growth patterns predict risk	Measures actual fracture outcome rather than predictive markers of risk Cohort were largely working class; dietary factors and activity level may no longer be as comparable with modern patterns
Dennison et al. (2001) [50]	(n=291) Adults 61-73 years M=165 F=126	Vitamin D receptor genotype, birthweight and adult bone mass (DXA)	Significant interaction between birthweight and VDR genotype Association between lumbar BMD and VDR genotype varies according to birthweight	Women had a greater rate of bone loss over the follow-up period	Large study with later life outcomes Supports role of interactions between genetic factors and ‘programming’ of osteoporosis
Godfrey et al. (2001) [53]	(n=145) Term infants M= 81 F= 64	Maternal and paternal demographic and lifestyle factors, and neonatal bone mass (DXA)	Parental birthweight and paternal height positively correlated with neonatal total BMC Smoking during pregnancy, increased maternal exercise and decreased triceps skinfold thickness correlated with lower BMC and BMD	Gender differences in neonatal bone mineral measurements were not significant	Detailed parental exposures and good study size Suggests interaction of genetic and environmental factors on skeletal development in-utero
Javaid et al. (2004) [30]	(n=119) Term infants M=68 F=51	Umbilical cord IGF-1 and neonatal bone mass (DXA)	IGF- 1 concentration correlates with birth weight and BMC after adjustment for gestational age	Females had a greater IGF-1 level and fat mass at birth	Unable to determine interaction of growth factors and other previously measured attributes of maternal smoking, body habitus and exercise
Oliver et al. (2007) [20]	(n=631) Adults aged 65-73 years M=313 F=318	Early infant growth and adult bone strength (CT)	Strong association between birthweight or infant weight with bone length and strength, but not volumetric density in adults	Adult male BMI strongly associated with BMD Not significant in women	Large study Supports role of intrauterine and early life exposures on late adult life skeletal characteristics
Hovi et al. (2009) [28]	Adults born preterm/ VLBW (n=144) Term born controls (n=139) M=115 F=168	Low birthweight and adult bone density (DXA) at 18 - 27 years	Reduced lumbar spine and femoral neck BMD in VLBW infants 2-fold increased risk for low lumbar spine BMD after adjusting for height in VLBW infants	Gender differences not discussed	Measured around age of peak bone mass acquisition No later life follow-up of osteoporotic fractures Lower BMD compared to controls identifies birthweight as a possible risk factor
Fewtrell et al. (2009) [43]	(n=202) Adults born preterm M=87 F=115	Neonatal diet and early adult bone density (DXA)	No nutrient effect on peak bone mass between diets Positive association between proportion of human milk and later BMC No significant difference in childhood fractures	No evidence for relationship between early diet and gender on bone outcomes	Dietary intervention was brief (4 weeks) but long follow up period Maternal recall of supplemental breastfeeding may be inaccurate Potential for residual confounding of breast milk provision by socio-demographic factors
Harvey et al. (2010) [26]	(n=380) Children (age 4 years) born at term M=197 F=183	Fetal growth velocity and childhood bone density (DXA) at 4 years	Higher velocity of femur growth between 19-34 weeks positively associated with skeletal size at 4 years but not volumetric density Higher velocity of fetal abdominal growth associated with greater childhood volumetric density but not skeletal size	Gender differences not discussed	Large study with detailed measures Different mechanisms may exist for programming skeletal size and volumetric density
Steer et al. (2011) [19]	(n=6876) Children from the ALSPAC study age 9.9 years	Maternal vitamin D status and dietary factors, birthweight, and childhood bone measurements (DXA)	Association of birthweight with bone mass explained after adjusting for body size Inverse association of birthweight on bone mineral content Maternal vitamin D and folate have lasting effects on development	No difference described in intrauterine programming between genders	Large cohort Used a proxy measure of vitamin D (UVB exposure) Possible links between intrauterine environment and bone development