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.

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.

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 (approximately 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.

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.

Changes in bone mineral status and bone size during pregnancy and the influences of body weight and calcium intake.

BACKGROUND: Calcium may be mobilized from the maternal skeleton during pregnancy, which may be influenced by several factors. OBJECTIVE: The objective was to investigate changes in bone mineral status and size during pregnancy and to consider the influences of body weight and calcium intake. DESIGN: Thirty-four British women were studied before pregnancy and 2 wk postpartum (Preg). Eighty-four nonpregnant, nonlactating (NPNL) women were studied over a corresponding time. Bone mineral content (BMC), bone area (BA), areal bone mineral density (aBMD), and BA-adjusted BMC of the whole-body, lumbar spine, radius, and hip were measured by dual-energy X-ray absorptiometry. RESULTS: The Preg group experienced significant decreases in BMC, aBMD, and BA-adjusted BMC at the whole-body, spine, and total hip of between 1% and 4%. Whole-body BMC increased in the NPNL group, and aBMD and BA-adjusted BMC decreased at the spine and hip by 0.5% to 1%. Whole-body BMC decreased in the Preg group by -2.16 +/- 0.46%, equivalent to -2.71 +/- 0.43% relative to the NPNL group (P < or = 0.001). Weight change was a positive predictor of skeletal change at the spine, hip, and radius in both groups. Differences between the Preg and NPNL groups in change in BA-adjusted BMC, after correction for weight change and other influences, were as follows (P < or = 0.01): whole-body, -1.70 +/- 0.25%; spine, -3.03 +/- 0.72%; and total hip, -1.87 +/- 0.60%. Calcium intake was not a significant predictor of skeletal change in either group. CONCLUSIONS: Pregnancy is associated with decreases in whole-body and regional bone mineral status sufficient to make a sizeable contribution to maternal and fetal calcium economy. Calcium intake is not a significant predictor of the skeletal response to pregnancy in well-nourished women.

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.

Fruit and vegetable intakes and bone mineral status: a cross sectional study in 5 age and sex cohorts.

BACKGROUND: Evidence is increasing for positive effects of fruit and vegetable intakes on bone health. However, most of the studies to date were conducted in adults, and few reports included adolescents. OBJECTIVE: We explored the association between bone mineral status and fruit and vegetable intakes in adolescent boys and girls (aged 16-18 y), young women (aged 23-37 y), and older men and women (aged 60-83 y). DESIGN: Bone mineral measurements of the whole body, hip, and spine were made in all subjects by using dual-energy X-ray absorptiometry. Information on health and lifestyle and physical activity was obtained by questionnaire. Fruit, vegetable, and nutrient intakes were ascertained from 7-d food diaries. RESULTS: In adolescent boys and girls and older women, significant positive associations were observed between spine size-adjusted bone mineral content (SA-BMC) and fruit intake. In boys only, femoral neck SA-BMC was also significantly and positively associated with the intakes of both fruit and dietary vitamin C. No significant associations were found in the young women or older men, or between bone measurements and intake of vegetables alone (after adjustments) in any of the groups. CONCLUSIONS: Higher fruit and vegetable intakes may have positive effects on bone mineral status in both younger and older age groups, especially at the spine and femoral neck. The specific mechanisms remain to be ascertained, but vitamin C, other fruit-specific antioxidants, and lifestyle may play a role.

Randomized, placebo-controlled, calcium supplementation study in pregnant Gambian women: effects on breast-milk calcium concentrations and infant birth weight, growth, and bone mineral accretion in the first year of life.

BACKGROUND: Growth and bone mineral accretion in Gambian infants are poorer than those in Western populations. The calcium intake of Gambian women is low, typically 300-400 mg Ca/d, and they have low breast-milk calcium concentrations, which result in low calcium intakes for their breastfed infants. A low maternal calcium supply in pregnancy may limit fetal mineral accretion and breast-milk calcium concentrations and thereby affect infant growth and bone mineral accretion. OBJECTIVE: We investigated the effects of calcium supplementation in Gambian women during pregnancy on breast-milk calcium concentrations and infant birth weight, growth, and bone mineral accretion. DESIGN: A randomized, double-blind, placebo-controlled supplementation study was conducted in 125 Gambian women who received 1500 mg Ca/d (as calcium carbonate) or placebo from 20 wk of gestation until delivery. Infant birth weight and gestational age were recorded. Breast milk was collected, and infant anthropometric and bone measurements were performed at 2, 13, and 52 wk after delivery. Infant bone mineral status was assessed by using single-photon absorptiometry of the radius and whole-body dual-energy X-ray absorptiometry. RESULTS: Compliance with the supplement was high. No significant differences were detected between the groups in breast-milk calcium concentration, infant birth weight, or growth or bone mineral status during the first year of life. A slower rate of increase in infant whole-body bone mineral content and bone area was found in the supplement group than in the placebo group (group x time interaction: P = 0.03 and 0.02, respectively). CONCLUSION: Calcium supplementation of pregnant Gambian women had no significant benefit for breast-milk calcium concentrations or infant birth weight, growth, or bone mineral status in the first year of life.

Calcium supplementation increases stature and bone mineral mass of 16- to 18-year-old boys.

The effect of calcium carbonate supplementation on bone growth and mineral accretion was studied in 143 boys aged 16-18 yr, randomized to 1000 mg Ca/d or a matching placebo for 13 months. Anthropometry and dual-energy x-ray absorptiometry of the whole body, lumbar spine, hip, and forearm were performed before, during, and after the intervention. The intervention resulted in greater bone mineral content (BMC) of the whole body (+1.3%, P = 0.02), lumbar spine (+2.5%, P = 0.004), and hip (total +2.3%, P = 0.01; neck +2.4%, P = 0.02; intertrochanter +2.7%, P = 0.01). This was associated with greater height (+0.4%, P = 0.0004, equivalent to 7 mm), lean mass (+1.3%, P = 0.02), and lumbar spine bone area (+1.5%, P = 0.003). The increases in BMC diminished after size adjustment, suggesting that the intervention effect was mediated through an effect on growth. The BMC response at the intertrochanter was greater in subjects with high physical activity (+4.4%, P = 0.05). There were no other significant interactions with physical activity, plasma testosterone, calcium intake, or tablet compliance. We conclude that calcium carbonate supplementation of adolescent boys increased skeletal growth, resulting in greater stature and bone mineral acquisition. Follow-up studies will determine whether this reflects a change in the tempo of growth or an effect on skeletal size that persists into adulthood.

Do appendicular bone measurements reflect changes in the axial skeleton?: the use of dual-energy X-ray absorptiometry and ultrasound measurements during lactation.

The ability of different bone measurement techniques to monitor changes in bone mineral was studied. Lactation was used as a model because large, rapid, but reversible decreases in bone mineral content (BMC) occur in breast-feeding women. Spine and forearm dual-energy X-ray absorptiometry (DXA) and calcaneal quantitative ultrasound (QUS) measurements were made during 30 lactations. During the first 3 mo of lactation, decreases in the BMC, adjusted for area, were significant at the spine (-2.8%; standard error [SE] = 0.6; p < 0.001) but not the wrist (p = 0.40). Nonsignificant increases in normalized broadband ultrasound attenuation (nBUA) and velocity of sound (VOS) were observed at the calcaneus using QUS. From peak lactation to postlactation, the BMC increases at the spine were significant (4.1%; SE = 0.6; p < 0.001) but not those at the wrist (p = 0.17). Nonsignificant decreases were observed using QUS. Eleven breast-feeding women had longitudinal calcaneal and spine DXA measurements from peak lactation to postlactation. Significant BMC increases were observed at both sites (calcaneus: 2.4%, SE = 0.7, p < 0.01; spine: 3.3%, SE = 1.3, p < 0.03). The similarity of DXA calcaneal changes to spine changes indicates that DXA calcaneal measurements could be a useful alternative tool when it is difficult to monitor BMC at axial sites.

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.