M. Ann Laskey

Symposium on ‘Nutrition and health in children and adolescents’ Session 1: Nutrition in growth and development: Nutrition and bone growth and development

The growth and development of the human skeleton requires an adequate supply of many different nutritional factors. Classical nutrient deficiencies are associated with stunting (e.g. energy, protein, Zn), rickets (e.g. vitamin D) and other bone abnormalities (e.g. Cu, Zn, vitamin C). In recent years there has been interest in the role nutrition may play in bone growth at intakes above those required to prevent classical deficiencies, particularly in relation to optimising peak bone mass and minimising osteoporosis risk. There is evidence to suggest that peak bone mass and later fracture risk are influenced by the pattern of growth in childhood and by nutritional exposures in utero, in infancy and during childhood and adolescence. Of the individual nutrients, particular attention has been paid to Ca, vitamin D, protein and P. There has also been interest in several food groups, particularly dairy products, fruit and vegetables and foods contributing to acid–base balance. However, it is not possible at the present time to define dietary reference values using bone health as a criterion, and the question of what type of diet constitutes the best support for optimal bone growth and development remains open. Prudent recommendations (Department of Health, 1998; World Health Organization/Food and Agriculture Organization, 2003) are the same as those for adults, i.e. to consume a Ca intake close to the reference nutrient intake, optimise vitamin D status through adequate summer sunshine exposure (and diet supplementation where appropriate), be physically active, have a body weight in the healthy range, restrict salt intake and consume plenty of fruit and vegetables.

Bone mineral changes during and after lactation.

OBJECTIVE To assess bone mineral changes during and after lactation. METHODS Fifty-nine breast-feeding women, 11 formula-feeding women, and 22 nonpregnant, nonlactating women had dual-energy x-ray absorptiometry measurements of the whole body, spine, hip, and forearm at 0.5 (baseline), 3, 6, and 12 months postpartum, with an additional measurement at 3 months after lactation for women who had breast-fed for more than 9 months. RESULTS Lactation was associated with decreases in bone mineral at the whole body, spine, femoral neck, total hip, and radial wrist, which reversed as lactation declined and menstruation resumed. These changes were not seen in formula-feeding women. The magnitude and duration of the response were greater for women who breast-fed for a longer time. After lactation had stopped for at least 3 months, bone mineral, adjusted for bone area, had increased significantly above baseline at the whole body (+1.44%; 95% confidence interval [CI] +0.97%, +1.91%; P < .001), spine (+2.66%; 95% CI +1.60%, +3.72%; P < .001), and greater trochanter (+3.55%; 95% CI +2.53%, +4.57%; P < .001), was not different at the total hip and radial shaft, but was lower at the femoral neck (-2.07%; 95% CI -3.21%, -0.93%; P < .001) and radial wrist (-1.23%; 95% CI -1.99%, -0.47%; P < .01). Changes after lactation were largely independent of the duration of lactation or amenorrhea, and similar effects were observed in formula-feeding women. CONCLUSION Lactation was associated with temporary decreases in bone mineral. After lactation, there were significant residual effects on bone mineral that were unrelated to the duration of lactation and may be related to having been pregnant. The long-term effect of lactation on the femoral neck requires further investigation.

The calcium and phosphorus intakes of rural Gambian women during pregnancy and lactation

The Ca and P intakes of 148 pregnant and lactating women in a rural village in The Gambia, West Africa, have been estimated by direct weighing of food on a total of 4188 d. The Ca and P contents of local foods were determined by analysis of raw ingredients, snack foods and prepared dishes. Information about the contribution of mineral-rich seasonings was obtained. Efforts were made to discover unusual sources of Ca that might not be perceived as food by subject or observer. The main contributors to daily Ca intake were shown to be leaves, fish, cereals, groundnuts and local salt. Cows milk accounted for only 5% of Ca intake. Unusual sources of Ca were discovered, namely baobab (Adansonia digitata) fruit and selected earths, but these were consumed infrequently and their contributions to Ca intakes were small. Cereals and groundnuts were the main sources of P. Ca and P intakes (mg/d) were shown to average 404 (SD 110) and 887 (SD 219) respectively. Seasonal changes in the availability of leaves, cereals and groundnuts resulted in variations in Ca and P intakes. The rainy season was associated with increased Ca intakes (by 16%) but decreased P consumption (by 15%). No difference was observed in Ca intake between pregnant and lactating women but P intake in lactation was 11% higher than that in pregnancy during the post-harvest season. The implications of these low Ca intakes require investigation.

Bone mineral content of British and rural Gambian women aged 18-80+years

The bone mineral content (BMC) of the mid-shaft radius was measured in 446 rural Gambian and 349 British women aged 18-80+ years using single-photon absorptiometry. The two groups of women differed substantially in habitual calcium intake, calcium requirements for reproduction, physical activity and incidence of minimal-trauma fractures. The relationships of BMC with bone width (BW) and with body weight and height were explored using stepwise multiple regression analysis. The pattern of BMC with age was similar in The Gambia and Britain; BMC increased slightly to a peak at the end of the fourth decade followed by a decrease of about 30% between 40 and 70+ years. Gambian women had significantly lower BMC than British women of the same age (-5.6%, P less than 0.001) but after adjusting for weight, height and BW, the BMC of Gambian women was shown to be slightly higher than that of British women (+2.1%, P less than 0.05).

Effect of calcium supplementation in pregnancy on maternal bone outcomes in women with a low calcium intake

Background: Mobilization of maternal bone mineral partly supplies calcium for fetal and neonatal bone growth and development. Objective: We investigated whether pregnant women with low calcium intakes may have a more extensive skeletal response postpartum that may compromise their short- or long-term bone health. Design: In a subset of participants (n = 125) in a double-blind, randomized, placebo-controlled trial (International Trial Registry: ISRCTN96502494) in pregnant women in The Gambia, West Africa, with low calcium intakes (≈350 mg Ca/d), we measured bone mineral status of the whole body, lumbar spine, and hip by using dual-energy X-ray absorptiometry and measured bone mineral status of the forearm by using single-photon absorptiometry at 2, 13, and 52 wk lactation. We collected blood and urine from the subjects at 20 wk gestation and at 13 wk postpartum. Participants received calcium carbonate (1500 mg Ca/d) or a matching placebo from 20 wk gestation to parturition; participants did not consume supplements during lactation. Results: Women who received the calcium supplement in pregnancy had significantly lower bone mineral content (BMC), bone area (BA), and bone mineral density (BMD) at the hip throughout 12 mo lactation (mean ± SE difference: BMC = −10.7 ± 3.7%, P = 0.005; BA = −3.8 ± 1.9%, P = 0.05; BMD = −6.9 ± 2.6%, P = 0.01). The women also experienced greater decreases in bone mineral during lactation at the lumbar spine and distal radius and had biochemical changes consistent with greater bone mineral mobilization. Conclusions: Calcium supplementation in pregnant women with low calcium intakes may disrupt metabolic adaptation and may not benefit maternal bone health. Further study is required to determine if such effects persist long term or elicit compensatory changes in bone structure.

Calcium economy in human pregnancy and lactation

Pregnancy and lactation are times of additional demand for Ca. Ca is transferred across the placenta for fetal skeletal mineralisation, and supplied to the mammary gland for secretion into breast milk. In theory, these additional maternal requirements could be met through mobilisation of Ca from the skeleton, increased intestinal Ca absorption efficiency, enhanced renal Ca retention or greater dietary Ca intake. The extent to which any or all of these apply, the underpinning biological mechanisms and the possible consequences for maternal and infant bone health in the short and long term are the focus of the present review. The complexities in the methodological aspects of interpreting the literature in this area are highlighted and the inter-individual variation in the response to pregnancy and lactation is reviewed. In summary, human pregnancy and lactation are associated with changes in Ca and bone metabolism that support the transfer of Ca between mother and child. The changes generally appear to be independent of maternal Ca supply in populations where Ca intakes are close to current recommendations. Evidence suggests that the processes are physiological in humans and that they provide sufficient Ca for fetal growth and breast-milk production, without relying on an increase in dietary Ca intake or compromising long-term maternal bone health. Further research is needed to determine the limitations of the maternal response to the Ca demands of pregnancy and lactation, especially among mothers with marginal and low dietary Ca intake, and to define vitamin D adequacy for reproductive women.

Bone mineral content of Gambian and British children aged 0-36 months

The influence of age, sex and body size on the bone mineral content of the radius (BMC) measured by single-photon absorptiometry has been studied in 134 British and 243 rural Gambian children aged 0-36 months. Growth rates and childhood nutrition, including calcium intakes, were markedly different in the two communities. In both groups BMC increased with age and was higher in boys (8%, P less than 0.001). Adjustment for body size (height, weight, bone width), using multiple regression analysis, removed the age effect and reduced the sex difference to 4% (P less than 0.01). Gambian children had significantly lower BMCs than British children of the same age (P less than 0.001), averaging 11% close to birth and diverging to a calculated difference of 31% at 36 months. The differential was reduced after adjustment for body size but remained significant (P less than 0.01) with BMC values diverging from birth to a predicted difference of 12% at 15 kg body weight. The extent to which these results reflect the low calcium intakes of Gambian children requires further study.

Unexpected long-term effects of calcium supplementation in pregnancy on maternal bone outcomes in women with a low calcium intake: a follow-up study

Background: Calcium supplementation of pregnant Gambian women with a low calcium intake results in lower maternal bone mineral content in the subsequent lactation. Objective: The objective was to investigate whether the lower bone mineral content persists long term. Design: All women in the calcium supplementation trial (International Trial Registry ISRCTN96502494) who had been scanned with dual-energy X-ray absorptiometry at 52 wk of lactation (L52; n = 79) were invited for follow-up when neither pregnant nor lactating for ≥3 mo (NPNL) or at 52 wk postpartum in a future lactation (F52). Bone scans and anthropometric and dietary assessments were conducted. Results: Sixty-eight women participated (35 at both NPNL and F52 and 33 at only one time point): n = 59 NPNL (n = 31 calcium, n = 28 placebo) and n = 44 F52 (n = 24 calcium, n = 20 placebo). The mean (±SD) time from L52 was 4.9 ± 1.9 y for NPNL and 5.0 ± 1.3 y for F52. Size-adjusted bone mineral content (SA-BMC) was greater at NPNL than at L52 in the placebo group (P ≤ 0.001) but not in the calcium group (P for time-by-group interaction: lumbar spine, 0.002; total hip, 0.03; whole body, 0.03). No significant changes in SA-BMC from L52 to F52 were observed in either group. Consequently, the lower SA-BMC in the calcium group at L52 persisted at NPNL and F52 (P ≤ 0.001): NPNL (lumbar spine, −7.5 ± 0.7%; total hip, −10.5 ± 1.0%; whole body, −3.6 ± 0.5%) and F52 (lumbar spine, −6.2 ± 0.9%; total hip, −10.3 ± 1.4%; whole body, −3.2 ± 0.6%). Conclusion: In rural Gambian women with a low-calcium diet, a calcium supplement of 1500 mg/d during pregnancy resulted in lower maternal bone mineral content in the subsequent lactation that persisted long term. This trial was registered at www/controlled-trials.com/mrct/ as ISRCTN96502494.

Birth weight predicts bone size in young adulthood at cortical sites in men and trabecular sites in women from The Gambia

Fracture risk is determined by bone mass, size and architecture. Birth weight (Bwt) is reported to predict adult bone mass and density. Early life environment may therefore be a determinant of bone strength in later life. However such evidence was obtained using dual energy X-ray absorptiometry (DXA), which is known to be dependent on size. We used peripheral quantitative computed tomography (pQCT) and DXA to investigate Bwt as a determinant of bone size and cross section area (CSA), bone mineral content (BMC) and volumetric bone mineral density (vBMD) and areal BMD (aBMD) independent of current weight, height and age. The study population consisted of 68 males and 52 nulliparous females aged 17 to 21years from Keneba, The Gambia. This population has a high prevalence of factors likely to influence skeletal development (poor nutrition, low calcium intake, late puberty and high physical activity). Measures of bone size and CSA, BMC and BMD were obtained using pQCT (Stratec 2000; at 4% and 66% radius; 4% and 50% tibia) and DXA (Lunar DPX; spine, hip, forearm and whole body). Sequential univariable (influence of Bwt on bone variables) and multivariable linear regression analyses (influence of Bwt on bone variables after adjusting for current height, weight and age) were used to investigate the independent effects of Bwt and attained size. Analyses were performed separately by sex. Bwt was a significant positive predictor of CSA at appendicular cortical sites in males and CSA and bone area at appendicular and most axial trabecular sites in females before and after adjustment for current height, weight and age. Bwt was not consistently related to BMC, vBMD or aBMD as measured by pQCT or DXA. Current weight was a positive predictor of aBMD and pQCT- and DXA-derived BMC in males and females. Height predicted aBMD and trabecular vBMD in males. In summary, Bwt significantly predicted attained CSA at cortical sites in males and at trabecular sites in females. Current weight was a positive predictor of BMC and aBMD in both sexes. This suggests that pre-natal factors affecting fetal growth may influence adult bone strength independently of post-natal factors.

Comparison of Narrow-Angle Fan-Beam and Pencil-Beam Densitometers: In Vivo and Phantom Study of the Effect of Bone Density, Scan Mode, and Tissue Depth on Spine Measurements

This study compared the in vivo and in vitro performances of the Lunar MD and Prodigy dual-energy X-ray absorptiometers (DXAs). Ten volunteers and three different spine phantoms were studied to determine the effect of scan mode, tissue depth, and bone density on measures of spine bone area (BA), bone mineral content (BMC), and areal bone mineral density (BMD). These studies demonstrated that the choice of scan mode was most important for the Prodigy and for subjects who were thin, obese, or had low BMD. Increase in tissue depth caused an increase in measured BMC and BMD for the MD but had a small effect on Prodigy results if the appropriate scan mode was selected. BA was dependent on the BMD for both DXA systems. Results using a hydroxyapatite phantom demonstrated that after correcting for the calibration of Lunar systems, the BMC measured by the MD and Prodigy was similar to the calculated hydroxyapatite content of the phantom. In vivo studies confirmed the in vitro findings and demonstrated that even when the appropriate scan mode was selected, the BMC, BMD, and T-scores were significantly higher on the Prodigy than MD.