The effect of prepubertal calcium carbonate supplementation on skeletal development in Gambian boys-a 12-year follow-up study.

CONTEXT: Calcium intake during growth is essential for future bone health but varies widely between individuals and populations. The impact on bone of increasing calcium intake is unknown in a population where low calcium intake, stunting, and delayed puberty are common. OBJECTIVE: To determine the effect of prepubertal calcium supplementation on mean age at peak velocity for bone growth and mineral accrual. DESIGN AND SETTING: Prospective follow-up of boys in rural Gambia, West Africa, who had participated in a double-blind, randomized, placebo-controlled trial of calcium supplementation. PARTICIPANTS: Eighty boys, initially aged 8.0-11.9 years, were followed up for 12 years. INTERVENTIONS: Subjects received 1 year of calcium carbonate supplementation (1000 mg daily, 5 d/wk). MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry measurements were carried out for whole body (WB), lumbar spine, and total hip bone mineral content, bone area (BA), and WB lean mass. Super imposition by translation and rotation models was made to assess bone growth. RESULTS: Age at peak velocity was consistently earlier in the calcium group compared to the placebo group, for WB bone mineral content (mean, -6.2 [SE, 3.1]; P = .05), WB BA (mean, -7.0 [SE, 3.2] mo; P = .03), lumbar spine and total hip BA. By young adulthood, supplementation did not change the amount of bone accrued (mineral or size) or the rate of bone growth. CONCLUSIONS: Twelve months of prepubertal calcium carbonate supplementation in boys with a low calcium diet advanced the adolescent growth spurt but had no lasting effect on bone mineral or bone size. There is a need for caution when applying international recommendations to different populations.

Bone mineral changes after lactation in Gambian women accustomed to a low calcium intake.

BACKGROUND/OBJECTIVES: Previous studies in Gambian women with a low calcium intake have described decreases in whole-body and regional bone mineral content (BMC) and areal bone mineral density (aBMD) during the first year of lactation. The aim of this study was to examine whether these effects are reversed after lactation. SUBJECTS/METHODS: Thirty-three Gambian women who had a previous dual-energy X-ray absorptiometry (DXA) scan at 52 weeks lactation (L52) were invited to participate in a follow-up study when neither pregnant nor lactating (NPNL) for ≥3 months and/or when 52 weeks postpartum in a subsequent lactation (F52). Whole body, lumbar spine and hip bone mineral were measured by DXA. Anthropometry and dietary assessments were also conducted. Repeated-measures analysis of covariance was used to determine differences from L52 at NPNL and F52. RESULTS: Twenty-eight women were scanned at NPNL and 20 at F52. The mean±s.d. calcium intake of the 33 women at NPNL and F52 was 360±168 mg/day. BMC, aBMD and size-adjusted BMC (SA-BMC) at all sites were higher at NPNL than L52. Percent increases in SA-BMC (mean±s.e.m.) were significant (P<0.0001): whole body=2.7±0.4%; lumbar spine=4.9±1.0%; total hip=3.7±1.0%. There were no significant differences in any measurements between the two lactation time points (L52 and F52). CONCLUSIONS: This study of Gambian women with low calcium intakes demonstrates that bone mineral mobilised during lactation is recovered after lactation. Successive periods of long lactation are not associated with progressive skeletal depletion.

Proximal femur structural geometry changes during and following lactation.

Human lactation is associated with transient decreases in bone mineral density (BMD). Bone strength is related to both mass and structural geometry. This study investigated longitudinal changes of hip bone strength during lactation using hip structural analysis (HSA), which determines hip structural geometry (including areal BMD, BMDa) from dual-energy X-ray absorptiometry scans (DXA). Forty-eight lactating women were studied longitudinally at the proximal femur using DXA at approximately 2 weeks postpartum, peak-lactation and post-lactation. Nonpregnant, nonlactating women (NPNL, n=23) were studied concurrently at baseline and after 1 year. Hip scans were analysed using HSA at the narrow neck, intertrochanter and proximal shaft. No significant change (>0.05) was observed in NPNL women for any measurement. In contrast, for lactating women BMDa decreased significantly from 2 weeks postpartum to peak-lactation at narrow neck (-2.8%), intertrochanter (-3.2%) and shaft (-1.4%). Cross-sectional area (CSA) decreased at narrow neck (-3.4%) and intertrochanter (-2.7%). There were no significant changes in bone width. Section modulus decreased at intertrochanter (-2.1%). At shaft, cortical thickness decreased (-1.7%) and buckling ratio increased (2.3%). By post-lactation, measurements were not significantly different from 2 weeks postpartum except for decrements in BMDa (-1.1%) and CSA (-1.2%) at the shaft. During the study, lactating women lost 5% of their body weight. Adjusting for weight changes decreased the magnitude and significance of HSA changes at peak-lactation and by post-lactation there were no significant differences from 2 weeks postpartum. Calcium intake was not a significant predictor of changes in HSA variables. In conclusion, lactation is associated with significant but transient changes in hip BMD and structural geometry. Changes in body weight but not calcium intake were associated with these changes. These small changes at the hip during lactation occurred mainly at internal surfaces and had minimal impact on bending or compressive strength.

Older people in China and the United Kingdom differ in the relationships among parathyroid hormone, vitamin D, and bone mineral status.

To explore whether there are ethnic differences in relationships among parathyroid hormone (PTH), vitamin D, and bone mineral status, 352 healthy volunteers, 60-83 years old, were studied in Shenyang, Peoples' Republic of China (108 men, 110 women), and in Cambridge, UK (67 men, 67 women), in late winter. Early morning fasting blood and 2-h fasting urine were analyzed for 25-hydroxyvitamin D (25OH-D), PTH, and free deoxypyridinoline (DPD). Hip bone mineral status was measured using dual-energy X-ray absorptiometry (Lunar). There were significant differences (P < 0.001) in plasma 25OH-D and PTH concentrations between Shenyang and Cambridge [25OH-D nmol/L: Shenyang = 29.0 (SD 12.7), Cambridge = 35.7 (12.9)]; PTH ng/L: Shenyang = 34.3 (13.4), Cambridge = 25.2 (11.0)]. PTH was negatively related to 25OH-D in both populations. The relationship was exponential, best described by an inverse log-log equation with no break point (P < 0.001), indicating that the exponential curve did not tend toward a low plateau. PTH was higher for a given 25OH-D and decreased less with increasing 25OH-D in Shenyang than in Cambridge (country-ln25OH-D interaction, P = 0.0005). After adjusting for bone area, weight, height, age, and sex, hip bone mineral content (BMC) was significantly related to PTH concentration in Cambridge but not in Shenyang [femoral neck coefficient: Cambridge = -0.064 (SE 0.027), P = 0.02; Shenyang = -0.027 (0.028), P = 0.3; trochanter: Cambridge = -0.116 (0.034), P = 0.001; Shenyang = -0.019 (0.027), P = 0.5]. There was a significant country-lnPTH interaction at the trochanter (P = 0.02), but not at the femoral neck (P = 0.7). A weak positive association between BMC at the femoral neck and 25OH-D concentration was found in Cambridge [coefficient: 0.054 (0.028), P = 0.05] but not in Shenyang (coefficient: -0.013, P = 0.5; country-ln25OH-D interaction, P = 0.07). Urinary DPD concentration was also positively related to plasma PTH concentration in Cambridge subjects only [coefficient: 0.2 (0.08), P = 0.02]. These data suggest that although PTH increases when 25OH-D decreases, and Chinese people have a higher PTH for a given 25OH-D, older Chinese adults may be more resistant than Britons to the effects of PTH on bone.

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.

An investigation of ethnic differences in bone mineral, hip axis length, calcium metabolism and bone turnover between West African and Caucasian adults living in the United Kingdom.

The aim of the study was to investigate factors relating to calcium and bone metabolism which might explain the low incidence of osteoporotic fracture among Africans. Adult bone mineral status, hip axis length and biochemical indices were investigated in 20 Caucasians (10 male, 10 female) and 19 Gambians (12 male, 7 female) living in the UK. Bone mineral content (BMC), bone mineral density (BMD) and BMC adjusted for bone area, body weight and height (size-adjusted BMC) were measured for the whole-body, lumbar spine, femoral neck, trochanter, radius shaft and radius wrist using dual-energy X-ray absorptiometry. There were no significant differences in whole body or regional BMC; values tended to be lower in the Gambians. Gambian men had higher size-adjusted BMC at the femoral neck (Gambian-British = 21%, 95% CI = 6 to 36%, p < 0.01), associated with a smaller bone area (Gambian-British = -11%, 95% CI = -20 to -2%, p = 0.02). BMD was affected similarly. No other significant differences in BMD or size-adjusted BMC were observed. Gambians had shorter hip axis length (Gambian British, after accounting for sex, = -5%, 95% CI = -9 to -1%, p = 0.02). There were no significant differences in bone turnover (osteocalcin, bone isoenzyme of alkaline phosphatase, urinary deoxypyridinoline) or calciotropic hormone levels (parathyroid hormone, 1,25-dihydroxyvitamin D, calcitonin). Gambian men had lower 25-hydroxyvitamin D concentrations (Gambian = 26.3 SD 12.0 nmol/L, British = 55.5 SD 13.9 nmol/L, p < 0.0001), a difference not seen among the women. Gambian men and women excreted significantly less phosphate and potassium than British subjects by 30-60%; urinary calcium and sodium excretion were similar in the two groups. This study revealed few ethnic differences that could account for the disparity in osteoporotic fracture rates between Africans and Caucasians, with the possible exception of anatomical differences in the hip.

Anomalies in dual energy X-ray absorptiometry measurements of total-body bone mineral during weight change using Lunar, Hologic and Norland instruments.

A previous study showed that measurements of total-body bone mineral changes made with a Hologic QDR 1000W were unreliable when the subjects underwent weight change. The study has been extended to dual energy X-ray absorptiometry (DXA) apparatus from other manufacturers. Re-analysis of published results during weight loss using a Lunar DPX showed that they varied with the software used. Using the Extended mode, there was a 1% loss of bone mineral areal density (BMD), but no significant change in bone mineral content (BMC) or bone area (BA) following a weight loss of 16 kg, whereas the use of the Standard mode led to a larger fall of BMC and BMD. Similar findings arose from the consideration of two studies using Norland XR 26 HS absorptiometers. On the other hand, separation of two groups with similar weight changes from the population studied with a Hologic QDR 1000W confirmed that BMC changed directly with weight, but there was an inverse relationship for BMD, owing to an inappropriate change of BA. The use of Hologic Enhanced and Standard software modes led to significant differences in initial readings and measured changes. With each instrument there was a strong correlation between changes in BA and changes in BMC. When 6 kg of lard was wrapped around the limbs of volunteers or a semi-anthropomorphic phantom to simulate weight change, there were spurious increases of measured BMC and BA by about 5% with each instrument. There were no changes of BMD with Lunar, variable results with Norland, but decreases with Hologic. The results observed in vivo could be explained by the effects of fat changes, without there being any real change of bone mineral. Changes of BMD in the skeleton of the phantom were underestimated with all three brands. The anomaly observed with the Hologic QDR 1000W is less apparent with a Lunar DPX or a Norland XR 26, but there are sufficient uncertainties for all total-body measurements during weight change to be treated with suspicion.

Comparison of adult and paediatric spine and whole body software for the Lunar dual energy X-ray absorptiometer.

Simple phantoms were devised to compare the performance of adult (software 3.64) and paediatric (software 3.8 g) spine and whole body software developed for the Lunar dual energy X-ray absorptiometer. Rectangular slabs of aluminium with high (1.18 g cm-2) and low (0.57 g cm-2) density were used to represent bone mineral. For spine measurements, the phantoms were scanned in water at depths of 5-20 cm. For whole body measurements, the phantoms were scanned with known amounts of oil and water to represent fat and lean tissue. This simulated tissue depths of 5.5-19.7 cm and body composition ranging from 14-29% fat. There were systematic differences in spine and whole body bone mineral content (BMC), bone area (BA) and bone mineral density (BMD) measurements and also between adult and paediatric software versions. The magnitude and direction of these differences were dependent on BMD of the phantom and tissue depth. Similar systematic differences were observed in vivo when volunteers were scanned using adult and paediatric software. Paediatric software enabled measurements to be made at low tissue depths. The weights of fat, lean and total soft tissue measured by the adult and paediatric whole body software were similar to the values calculated from the known composition of the phantom. Precision estimates for all softwares were excellent. In conclusion, paediatric software should improve bone mineral measurements of children but the discrepancies between adult and paediatric softwares may cause problems in longitudinal studies of skeletal growth and when compiling reference data from infancy through to adulthood.

Changes in body fat: measurements by neutron activation, densitometry and dual energy X-ray absorptiometry.

The measurement of body fat in ten subjects (BMI from 22 to 43 kg/m2), and in particular the changes arising from a ketogenic diet, by the techniques of in vivo neutron activation analysis (NAA), densitometry (using two- and four-compartment models) by under water weighing (UWW) and dual energy X-ray absorptiometry (DXA) was compared. The association between techniques for the fat changes was generally high (r = 0.70 to 0.98) and significant (p < 0.05). Assessment of agreement between DXA and the other techniques revealed discrepancies with significant slope and high association (r = -0.81 and -0.64). Whilst NAA and UWW appeared to measure similar changes, DXA underestimated small changes.

Bone changes after 3 mo of lactation: influence of calcium intake, breast-milk output, and vitamin D-receptor genotype.

Factors influencing the change in bone mineral after 3 mo of lactation were investigated in 47 breast-feeding mothers, 11 formula-feeding mothers, and 22 nonpregnant, nonlactating control subjects. At 6-8 wk postpartum, the breast-feeding group had a mean (+/-SD) calcium intake of 34.8+/-13.2 mmol/d and breast-milk volume, calcium concentration, and calcium output of 0.865+/-0.230 L/d, 7.41+/-1.25 mmol/L, and 6.41+/-2.00 mmol/d, respectively. There was no relation between calcium intake and any breast-milk variable. Dual-energy X-ray absorptiometry of the whole body, spine, hip, and forearm was performed at 0.5 and 3 mo. There were significant decreases in bone mineral content at the spine (3.96%; 95% CI: 4.86%, 3.06%), femoral neck (2.39%; 95% CI: 3.61%, 1.17%), total hip (1.51%; 95% CI: 2.45%, 0.60%), and whole body (0.86%; 95% CI: 1.29%, 0.43%) in breast-feeding mothers but not in formula-feeding mothers or nonpregnant, nonlactating women. These changes were not related to calcium intake, breast-milk calcium concentration, vitamin D-receptor genotype, postpartum weight change, or use of the progesterone-only contraceptive pill. After adjustment for bone area, breast-milk volume and height were identified as significant predictors at the spine, such that greater decreases were associated with taller mothers (P = 0.007) and those with greater breast-milk volume (P = 0.001). This finding suggests that the marked bone mineral changes observed in breast-feeding mothers represented a physiologic response to lactation that was independent of dietary calcium supply.

Vitamin D status does not influence the breast-milk calcium concentration of lactating mothers accustomed to a low calcium intake.

Plasma 25-hydroxy-vitamin D and breast-milk calcium concentration were measured at 3 months of lactation in 60 Gambian mothers accustomed to a low calcium diet, of whom 30 were consuming a calcium supplement and 30 were receiving a placebo, and in 48 British mothers. The plasma 25-hydroxy-vitamin D concentration of the Gambian women was not affected by either calcium supplementation (supplemented, 64.4 +/- 2.5 nmol l(-1); placebo, 64.9 +/- 3.5 nmol l(-1); mean +/- SE) or season. The British average was lower (53.9 +/- 3.0 nmol l(-1), p = 0.004), owing to marked seasonal effects. The breast-milk calcium concentration was lower in The Gambia (supplemented, 5.38 +/- 0.13 mmol l(-1); placebo, 5.10 +/- 0.13 mmol l(-1); British, 6.93 +/- 0.15 mmol l(-1), p < 0.0001). There was no relationship between plasma 25-hydroxy-vitamin D and breast-milk calcium concentration in any group. There was no trend towards lower breast-milk calcium concentration in women with vitamin D status towards the bottom of the normal range or in British women during the winter. This study provides no support for the hypothesis that breast-milk calcium concentration is influenced by vitamin D status or that lactating women with a low calcium intake are at particular risk of vitamin D deficiency.

Prediction of body composition in elderly men over 75 years of age.

A comprehensive number of body composition predictions (involving weight, height, skinfold thicknesses, bioelectrical impedance and near-infrared interactance-NIRI) were evaluated against total body water (TBW from isotope dilution), in 23 randomly selected men over 75 years old, and dual-energy X-ray absorptiometry (DXA), in 15 volunteers from this group. Comparisons were made between anthropometric and impedance methods for estimating limb muscle mass (obtained using DXA). Bias and 95% limits of agreement between measured TBW and DXA estimates were -2.1 kg and 3.1 kg, respectively (for fat, 5.4% and 6.1% body weight). Agreement between TBW predictions and reference measurements was remarkably variable, irrespective of whether TBW was predicted from TBW-specific equations or indirectly from estimates of fat or fat-free mass: for predictions using anthropometry, bias ranged from -4.7 kg to 1.6 kg and 95% limits of agreement from bias +/- 3.8 kg to +/- 5.0 kg; using impedance, bias was -8.8 kg to 3.2 kg and 95% limits of agreement were bias +/- 3.6 kg to +/- 7.8 kg; corresponding values for NIRI were -5.3 kg and +/- 5.4 kg. Although some non-age-specific equations appeared valid, age-specific equations generally predicted TBW better. Limb muscle mass (DXA) was predicted better using the segmental impedance method, from indices of limb muscle area (r = 0.76; SEE = 1.9 kg) and volume (r = 0.86; SEE = 1.6 kg), than by anthropometry alone (r = 0.61 and 0.71; SEE = 2.3 kg and 2.1 kg, respectively). In conclusion, some body composition predictions are unacceptable (at least for TBW) in older men, and care is recommended when selecting from these methods or equations. Also, the segmental impedance method is as good as, if not better than, anthropometry alone in predicting limb muscle mass (DXA) in older men.

Dual-energy X-ray absorptiometry and body composition.

This review describes the advantages and limitations of dual-energy absorptiometry (DXA), a technique that is widely used clinically to assess a patient's risk of osteoporosis and to monitor the effects of therapy. DXA is also increasingly used to measure body composition in terms of fat and fat-free mass. There are three commercial manufacturers of DXA instruments: Lunar, Hologic, and Norland. All systems generate X-rays at two different energies and make use of the differential attenuation of the X-ray beam at these two energies to calculate the bone mineral content and soft tissue composition in the scanned region. Most DXA instruments measure bone mineral in the clinically important sites of the spine, hip, and forearm. More specialized systems also perform whole-body scans and can be used to determine the bone and soft tissue composition of the whole body and subregions such as arms, legs, and trunk. The effective dose incurred during DXA scanning is very small, and, consequently, DXA is a simple and safe technique that can be used for children and the old and frail. Precision of all DXA measurements is excellent but varies with the region under investigation. Precision is best for young healthy subjects (coefficient of variation is about 1% for the spine and whole body bone measurements) but is less good for osteoporotic and obese subjects. The accuracy of DXA measurements, however, can be problematic. Marked systematic differences in bone and soft tissue values are found between the three commercial systems due to differences in calibration, bone edge detection, and other factors. In addition, differences in reference data provided by each manufacturer can lead to an individual appearing normal on one machine but at risk of osteoporosis on another. At present, DXA cannot be regarded as a "gold standard" for body composition. However, the continuing development of DXA and the introduction of new software is greatly improving the performance of this increasingly important technique.

Effect of exercise training programme on bone mineral density in novice college rowers.

Exercise has important effects on skeletal mineralization. Changes in bone mineral density (BMD) and bone mineral content (BMC) as measured by dual energy X-ray absorptiometry were investigated in a group of 17 male novice college oarsmen over a 7-month period and were compared with eight age-matched controls. The rowing training programme consisted of approximately 8 h rowing, 1 h weight training, and 1 h running per week. After 7 months training the mean BMD of the lumbar spine (L1-L4) had increased significantly by 2.9% (P < 0.001) and the mean BMC had increased by 4.2% (P < 0.001). There was no significant change in the control group. Neither group showed a significant change in BMD or BMC in the femoral neck, greater trochanter or Ward's triangle. This study provides further evidence that exercise plays an important role in bone mineral formation.