The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations.

Lifestyle choices influence 20-40 % of adult peak bone mass. Therefore, optimization of lifestyle factors known to influence peak bone mass and strength is an important strategy aimed at reducing risk of osteoporosis or low bone mass later in life. The National Osteoporosis Foundation has issued this scientific statement to provide evidence-based guidance and a national implementation strategy for the purpose of helping individuals achieve maximal peak bone mass early in life. In this scientific statement, we (1) report the results of an evidence-based review of the literature since 2000 on factors that influence achieving the full genetic potential for skeletal mass; (2) recommend lifestyle choices that promote maximal bone health throughout the lifespan; (3) outline a research agenda to address current gaps; and (4) identify implementation strategies. We conducted a systematic review of the role of individual nutrients, food patterns, special issues, contraceptives, and physical activity on bone mass and strength development in youth. An evidence grading system was applied to describe the strength of available evidence on these individual modifiable lifestyle factors that may (or may not) influence the development of peak bone mass (Table 1). A summary of the grades for each of these factors is given below. We describe the underpinning biology of these relationships as well as other factors for which a systematic review approach was not possible. Articles published since 2000, all of which followed the report by Heaney et al. [1] published in that year, were considered for this scientific statement. This current review is a systematic update of the previous review conducted by the National Osteoporosis Foundation [1]. [Table: see text] Considering the evidence-based literature review, we recommend lifestyle choices that promote maximal bone health from childhood through young to late adolescence and outline a research agenda to address current gaps in knowledge. The best evidence (grade A) is available for positive effects of calcium intake and physical activity, especially during the late childhood and peripubertal years-a critical period for bone accretion. Good evidence is also available for a role of vitamin D and dairy consumption and a detriment of DMPA injections. However, more rigorous trial data on many other lifestyle choices are needed and this need is outlined in our research agenda. Implementation strategies for lifestyle modifications to promote development of peak bone mass and strength within one's genetic potential require a multisectored (i.e., family, schools, healthcare systems) approach.

Anthropometric models of bone mineral content and areal bone mineral density based on the bone mineral density in childhood study.

UNLABELLED: New models describing anthropometrically adjusted normal values of bone mineral density and content in children have been created for the various measurement sites. The inclusion of multiple explanatory variables in the models provides the opportunity to calculate Z-scores that are adjusted with respect to the relevant anthropometric parameters. INTRODUCTION: Previous descriptions of children's bone mineral measurements by age have focused on segmenting diverse populations by race and sex without adjusting for anthropometric variables or have included the effects of a single anthropometric variable. METHODS: We applied multivariate semi-metric smoothing to the various pediatric bone-measurement sites using data from the Bone Mineral Density in Childhood Study to evaluate which of sex, race, age, height, weight, percent body fat, and sexual maturity explain variations in the population's bone mineral values. By balancing high adjusted R(2) values with clinical needs, two models are examined. RESULTS: At the spine, whole body, whole body sub head, total hip, hip neck, and forearm sites, models were created using sex, race, age, height, and weight as well as an additional set of models containing these anthropometric variables and percent body fat. For bone mineral density, weight is more important than percent body fat, which is more important than height. For bone mineral content, the order varied by site with body fat being the weakest component. Including more anthropometrics in the model reduces the overlap of the critical groups, identified as those individuals with a Z-score below -2, from the standard sex, race, and age model. CONCLUSIONS: If body fat is not available, the simpler model including height and weight should be used. The inclusion of multiple explanatory variables in the models provides the opportunity to calculate Z-scores that are adjusted with respect to the relevant anthropometric parameters.

Changes in DXA and quantitative CT measures of musculoskeletal outcomes following pediatric renal transplantation.

This prospective study evaluated changes in dual energy X-ray absorptiometry (DXA) whole body bone mineral content (WB-BMC) and spine areal bone mineral density (spine-BMD), and tibia quantitative computed tomography (QCT) trabecular and cortical volumetric BMD and cortical area in 56 children over 12 months following renal transplantation. At transplant, spine-BMD Z-scores were greater in younger recipients (<13 years), versus 898 reference participants (p < 0.001). In multivariate models, greater decreases in spine-BMD Z-scores were associated with greater glucocorticoid dose (p < 0.001) and declines in parathyroid hormone levels (p = 0.008). Changes in DXA spine-BMD and QCT trabecular BMD were correlated (r = 0.47, p < 0.01). At 12 months, spine-BMD Z-scores remained elevated in younger recipients, but did not differ in older recipients (≥ 13) and reference participants. Baseline WB-BMC Z-scores were significantly lower than reference participants (p = 0.02). Greater glucocorticoid doses were associated with declines in WB-BMC Z-scores (p < 0.001) while greater linear growth was associated with gains in WB-BMC Z-scores (p = 0.01). Changes in WB-BMC Z-scores were associated with changes in tibia cortical area Z-scores (r = 0.52, p < 0.001), but not changes in cortical BMD Z-scores. Despite resolution of muscle deficits, WB-BMC Z-scores at 12 months remained significantly reduced. These data suggest that spine and WB DXA provides insight into trabecular and cortical outcomes following pediatric renal transplantation.

Fitting of bone mineral density with consideration of anthropometric parameters.

UNLABELLED: A new model describing normal values of bone mineral density in children has been evaluated, which includes not only the traditional parameters of age, gender, and race, but also weight, height, percent body fat, and sexual maturity. This model may constitute a better comparative norm for a specific child with given anthropometric values. INTRODUCTION: Previous descriptions of children's bone mineral density (BMD) by age have focused on segmenting diverse populations by race and gender without adjusting for anthropometric variables or have included the effects of anthropometric variables over a relatively homogeneous population. METHODS: Multivariate semi-metric smoothing (MS(2)) provides a way to describe a diverse population using a model that includes multiple effects and their interactions while producing a result that can be smoothed with respect to age in order to provide connected percentiles. We applied MS(2) to spine BMD data from the Bone Mineral Density in Childhood Study to evaluate which of gender, race, age, height, weight, percent body fat, and sexual maturity explain variations in the population's BMD values. By balancing high adjusted R (2) values and low mean square errors with clinical needs, a model using age, gender, race, weight, and percent body fat is proposed and examined. RESULTS: This model provides narrower distributions and slight shifts of BMD values compared to the traditional model, which includes only age, gender, and race. Thus, the proposed model might constitute a better comparative standard for a specific child with given anthropometric values and should be less dependent on the anthropometric characteristics of the cohort used to devise the model. CONCLUSIONS: The inclusion of multiple explanatory variables in the model, while creating smooth output curves, makes the MS(2) method attractive in modeling practically sized data sets. The clinical use of this model by the bone research community has yet to be fully established.

Fracture risk in children with a forearm injury is associated with volumetric bone density and cortical area (by peripheral QCT) and areal bone density (by DXA).

UNLABELLED: Children who sustain a forearm fracture when injured have lower bone density throughout their skeleton, and have a smaller cortical area and a lower strength index in their radius. Odds ratios per SD decrease in bone characteristics measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA) were similar (1.28 to 1.41). INTRODUCTION: Forearm fractures are common in children. Bone strength is affected by bone mineral density (BMD) and bone geometry, including cross-sectional dimensions and distribution of mineral. Our objective was to identify bone characteristics that differed between children who sustained a forearm fracture compared to those who did not fracture when injured. METHODS: Children (5-16 years) with a forearm fracture (cases, n = 224) and injured controls without fracture (n = 200) were enrolled 28 ± 8 days following injury. Peripheral QCT scans of the radius (4% and 20% sites) were obtained to measure volumetric BMD (vBMD) of total, trabecular and cortical bone compartments, and bone geometry (area, cortical thickness, and strength strain index [SSI]). DXA scans (forearm, spine, and hip) were obtained to measure areal BMD (aBMD) and bone area. Receiver operating characteristic (ROC) analyses were used to assess screening performance of bone measurements. RESULTS: At the 4% pQCT site, total vBMD, but not trabecular vBMD or bone area, was lower (-3.4%; p = 0.02) in cases than controls. At the 20% site, cases had lower cortical vBMD (-0.9%), cortical area (-2.8%), and SSI (-4.6%) (p < 0.05). aBMD, but not bone area, at the 1/3 radius, spine, and hip were 2.7-3.3% lower for cases (p < 0.01). Odds ratios per 1 SD decrease in bone measures (1.28-1.41) and areas under the ROC curves (0.56-0.59) were similar for all bone measures. CONCLUSIONS: Low vBMD, aBMD, cortical area, and SSI of the distal radius were associated with an increased fracture risk. Interventions to increase these characteristics are needed to help reduce forearm fracture occurrence.

Special report on the 2007 adult and pediatric Position Development Conferences of the International Society for Clinical Densitometry.

The International Society for Clinical Densitometry (ISCD) conducts Position Development Conferences (PDCs) for the purpose of establishing standards and guidelines in the field of bone densitometry. Topics for consideration are selected according to clinical relevance, a perceived need for standardization, and the likelihood of achieving agreement. Questions regarding nomenclature, indications, acquisition, analysis, quality control, interpretation, and reporting of bone density tests for each topic area are assigned to task forces for a comprehensive review of the scientific literature. The findings of the review and recommendations are then presented to an international panel of experts at the PDC. The expert panel votes on potential Official Positions for appropriateness, necessity, quality of the evidence, strength of the recommendation, and applicability (worldwide or variable according to local requirements). Recommendations that are approved by the ISCD Board of Directors become Official Positions. The first Pediatric PDC was 20-21 June 2007 in Montreal, QC, Canada. The most recent Adult PDC was held 20-22 July 2007, in Lansdowne, VA, USA. This Special Report summarizes the methodology of the ISCD PDCs and presents selected Official Positions of general interest.

Bone density in relation to alcohol intake among men and women in the United States.

UNLABELLED: Studies of postmenopausal women have shown a positive association between BMD and alcohol intake. We found that BMD was higher in men, and possibly postmenopausal women, who drank alcohol compared with those who abstained. Drinking alcohol, but not binge drinking, may benefit bone health of men and postmenopausal women. INTRODUCTION: Osteoporotic fractures account for over 2.5 million physician visits annually for persons ages >or=45 years in the United States. Studies of postmenopausal women show a positive association between bone mineral density (BMD) and alcohol intake, but for men and premenopausal women, the bone-alcohol relationship remains unclear. We examined the association between total hip (TH) and femoral neck (FN) BMD and alcohol intake of men and pre- and postmenopausal women. METHODS: We conducted multiple regression analyses using data from 13,512 persons ages >or=20 years from the Third National Health and Nutrition Examination Survey, 1988-1994. Alcohol intake and binge drinking were measured by questionnaire and hip BMD by dual energy X-ray absorptiometry (DXA). RESULTS: Accounting for covariates, TH BMD was higher in men (n = 6,868) who had 5-29 (+2.1%, p < 0.01) and >29 drinking occasions/month (+1.7%, p < 0.05) than men who abstained. BMD of premenopausal women (n = 4,136) who drank alcohol did not differ from those who abstained. FN BMD was 3.8% higher in postmenopausal women (n = 2,043) who had >29 drinking occasions/month than those who abstained (p = 0.06). Binge drinking was not associated with BMD of men or women. CONCLUSIONS: Drinking alcohol, but not binge drinking, appears to be beneficial to bone health of men and possibly postmenopausal women.

Consequences of smoking and caffeine consumption during pregnancy in women with type 1 diabetes.

OBJECTIVE: To test the hypothesis that, in women with type 1 diabetes, prenatal smoking and caffeine consumption during pregnancy are associated with an increased risk of adverse maternal and perinatal outcomes. METHODS: A secondary analysis of data on pregnant women with type 1 diabetes from an interdisciplinary program of Diabetes in Pregnancy. Women were interviewed monthly, by a trained non-medical member of the research team, using a standardized questionnaire, to ascertain daily smoking habits and caffeine consumption. RESULTS: Smoking and caffeine information were available on 191 pregnancies, 168 progressing beyond 20 weeks of gestation. Early pregnancy smoking (OR 3.3, 95% CI 1.2, 8.7) and caffeine consumption (OR 4.5, 95% CI 1.2, 16.8) were associated with increased risk of spontaneous abortion when controlling for age, years since diagnosis of diabetes, previous spontaneous abortion, nephropathy and retinopathy. Smoking throughout pregnancy was significantly associated with decreased birth weight and prolonged neonatal hospital stay. Smoking throughout pregnancy (OR 0.2, 95% 0.1, 1.0) and caffeine consumption after 20 weeks (OR 0.3, 95% CI 0.1, 1.0) were associated with reduced risk of pre-eclampsia. CONCLUSIONS: Caffeine consumption during early pregnancy, regardless of glycemic control, increases the risk of spontaneous abortion. Smoking throughout pregnancy and caffeine consumption are associated with reduced risk of pre-eclampsia.

Pediatric motor vehicle related injuries in the Navajo Nation: the impact of the 1988 child occupant restraint laws.

BACKGROUND: Navajo motor vehicle mortality is the highest among the 12 Indian Health Service (IHS) administrative areas. In July 1988, the Navajo Nation enacted a primary enforcement safety belt use and a child restraint law. OBJECTIVE: Assess the impact of the laws on the rate and severity of pediatric (0-19 years) motor vehicle injury resulting in hospitalizations in the Navajo Nation. METHODS: Hospitalizations associated with motor vehicle related injury discharges were identified by International Classification of Diseases, 9th revision, CM E codes, 810-825 (.0,.1) from the Navajo IHS hospital discharge database. Age specific rates for the period before the law, 1983-88, were compared with those after enactment and enforcement, 1991-95. Severity of injury, measured by the abbreviated injury scale (AIS) score and new injury severity score (NISS), was determined with ICDMAP-90 software. Wilcoxon rank sum and chi(2) tests were used for analysis. RESULTS: Discharge rates (SE) for motor vehicle injury (per 100 000) decreased significantly in all age groups: 0-4 years (62 (7) to 28 (4)), 5-11 years (55.3 (6) to 26 (4)), and 15-19 years (139 (14) to 68 (7)); p=0.0001. In children 0-4 years, the median AIS score decreased from 1.5 (1,3) (25th, 75th centile) to 1 (1,2), p=0.06, and the median NISS decreased from 3.5 (1,9) to 2 (1,5), p=0.07. The proportion of children with NISS scores >4 decreased significantly for the 0-4 year age group (p=0.03). CONCLUSIONS: Concurrent with enactment of the Navajo Nation occupant and child restraint laws there was a reduction in the rate of motor vehicle related hospital discharges for children. Severity of injury declined in very young Navajo children. The effect of enactment and enforcement of this Native American child occupant restraint law may serve as an example of an effective injury control effort directed at Native American children.

Dietary fiber intakes and insulin requirements in pregnant women with type 1 diabetes.

OBJECTIVE: To determine whether higher dietary fiber intake (water soluble and insoluble) is associated with lower insulin requirements and better glycemic control in pregnant women with type 1 diabetes consuming a self-selected diet. DESIGN: A longitudinal, observational study. SUBJECTS: Pregnant women (n=141) with type 1 diabetes participating in an interdisciplinary program examining the effects of glycemic control on pregnancy outcome (Diabetes and Pregnancy Program, University of Cincinnati Medical Center). MEASUREMENTS: We determined total, water soluble and insoluble fiber intakes from 3-day food records kept each trimester during pregnancy. Outcome measures were insulin dose, pre-meal blood glucose, and glycated hemoglobin concentrations. STATISTICAL ANALYSES: Correlation coefficients, multiple regression, mixed-model analysis of variance. RESULTS: Mean intakes (g/day) of total, water soluble fiber, and insoluble fiber were 14.0 (range, 1.8-33.1), 4.8 (range, 0.6-10.5) and 9.0 (range, 1.1-24.0), respectively. In the second and third trimesters of pregnancy, insulin requirements were inversely associated with total, water soluble, and insoluble fiber intakes; the correlation coefficients ranged from -0.22 to -0.17 (P=.02 to .08). Insulin requirements associated with a higher fiber intake (20.5 g/day) were 16% to 18% lower than for a lower fiber intake (8.1 g/day). These relations remained after adjustment for body weight, disease severity and duration, insulin type, and study year in the second (P=.03 to .10) but not in the third trimester. Pre-meal blood glucose and glycated hemoglobin concentrations were not associated with fiber intake. CONCLUSIONS: Among pregnant women with type 1 diabetes, higher fiber intake is associated with lower daily insulin requirements. Dietary fiber intake should be considered when counseling patients about the management of blood glucose concentrations.

Trends and patterns of playground injuries in United States children and adolescents.

OBJECTIVE: To determine the prevalence, trends, and severity of injuries attributable to playground falls relative to other common unintentional mechanisms that resulted in an emergency department (ED) visit in the United States. DESIGN AND SETTING: Data from the emergency subset of the National Hospital Ambulatory Medical Care Survey collected from 1992 to 1997 for children <20 years. METHODS: Injury rates and 95% confidence intervals (CIs) were estimated and injury severity scores were computed. RESULTS: There were 920551 (95% CI: 540803 to 1300299) ED visits over the 6-year study period by children and adolescents that were attributable to falls from playground equipment. The annual incidence of visits for playground injuries did not significantly decrease over the course of the study (187000 to 98000, P =.053). Injury visits for playground falls were twice as prevalent as pedestrian mechanisms, but they were less prevalent than visits for motor vehicle-- and bicycle-related injuries. A larger proportion of playground falls resulted in "moderate-to-severe" injury than did bicycle or motor vehicle injuries. Children aged 5 to 9 years had the highest number of playground falls (P =.0014). Playground falls were most likely to occur at school compared to home, public, and other locations (P =.0016). CONCLUSIONS: Playground injury emergency visits have not significantly declined and remain a common unintentional mechanism of injury. Injury visits for playground falls were proportionally more severe than injury visits attributable to other common unintentional mechanisms. Interventions targeting schools and 5- to 9-year-old children may have the greatest impact in reducing emergency visits for playground injuries.

The role of calcium in health and disease.

Skeletal fragility at the end of the life span (osteoporosis) is a major source of morbidity and mortality. Adequate calcium intake from childhood to the end of the life span is critical for the formation and retention of a healthy skeleton. High intakes of calcium and vitamin D potentiate the bone loss prevention effects of hormone replacement therapy in postmenopausal women. Pregnancy and lactation are not risk factors for skeletal fragility, although lactation is associated with a transient loss of bone that cannot be prevented by calcium supplementation. Low calcium intake has been implicated in the development of hypertension, colon cancer, and premenstrual syndrome, and it is associated with low intakes of many other nutrients. Encouragement of increased consumption of calcium-rich foods has the potential to be a cost-effective strategy for reducing fracture incidence later in life and for increasing patients' dietary quality and overall health.

Hormonal and dietary regulation of changes in bone density during lactation and after weaning in women.

Lactating women secrete approximately 250 mg of calcium in breast milk each day. Some of the calcium used for milk production comes from bone as women experience a transient 3-9% decrease in bone density during lactation. This loss appears to be obligatory and under hormonal regulation as lactation-induced bone loss occurs even when calcium intake is high. Bone mineral is recovered after lactation ceases or menses resume. Recovery of bone mineral appears to be complete even when pregnancies and lactations are closely spaced, and lactation does not increase future risk of osteoporotic fracture. Current data point to estrogen and parathyroid hormone-related peptide as regulating bone mobilization during lactation. The typical calcium regulatory hormones, parathyroid hormone, calcitriol and calcitonin, do not appear to stimulate bone resorption during lactation. Restoration of ovarian hormone production and decreased production of PTHrP2 are likely to result in the recovery of bone mineral after lactation has ceased.

Effects of calcium supplementation on calcium homeostasis and bone turnover in lactating women.

Lactation is a time of calcium flux, because women secrete approximately 210 mg calcium/day in breast milk, and they experience a transient bone loss. The objectives of this study were to determine the effect of calcium supplementation on adaptive responses in calcium homeostasis during lactation and after weaning. Two cohorts of women participated in a 6-month randomized calcium supplementation trial. Lactation cohort women (97 lactating, 99 nonlactating) were studied during the first 6 months post partum, and weaning cohort women (95 lactating, 92 nonlactating) were studied during the second 6 months post partum. Lactating women in the weaning cohort weaned approximately 1.5 months after enrollment. PTH was 18-30% lower in lactating than in nonlactating women (P < 0.01). Serum 1,25-dihydroxyvitamin D was 11-16% higher in lactating than in nonlactating women and remained elevated for approximately 1.5 months after weaning (P = 0.06). Calcium supplementation decreased serum PTH and 1,25-dihydroxyvitamin D in lactating and nonlactating women similarly. At 6 months, the calciuric response to calcium supplementation was less in lactating (compared with nonlactating) women (P = 0.06). Biomarkers of bone turnover were higher in lactating than in nonlactating women during lactation and after weaning but were not effected by calcium supplementation. Calcium supplementation has little effect on lactation-induced changes in the calcium economy.

Randomized trial of magnesium administration to prevent hypocalcemia in infants of diabetic mothers.

OBJECTIVE: Hypocalcemia is common in infants of diabetic mothers (IDMs) and may be caused by secondary hypoparathyroidism related to hypomagnesemia. This study was designed to test the hypothesis that prophylactic magnesium sulfate (MgSO4) administration at birth in IDMs with low cord magnesium concentrations will prevent neonatal hypocalcemia. STUDY DESIGN: In this randomized trial conducted in IDMs with a cord magnesium concentration of <0.74 mM (1.8 mg/dl), 26 subjects received 6 mg/kg elemental magnesium and 23 subjects received no treatment. Serum concentrations of total and ionized calcium, phosphorus, and magnesium were recorded at birth, by measuring the concentrations within the umbilical cord, and at 24 and 72 hours of age. RESULTS: The incidence of hypocalcemia at 72 hours was 0% (0 of 23) in the magnesium-treated group and 12.5% (2 of 16) in the group with no treatment (p = 0.16). There was no difference in mean serum calcium concentration at 72 hours between infants in the treated group and the group with no treatment (2.28 +/- 0.04 vs 2.22 +/- 0.05 mM; p = 0.39). The drop in serum calcium concentration from birth to 72 hours of age was less for the treated group (0.30 +/- 0.05 mM [1.23 +/- 0.18 mg/dl]) than the group with no treatment (0.45 +/- 0.05 mM [1.81 +/- 0.21 mg/dl]; p = 0.04). CONCLUSION: Administration of intramuscular MgSO4 to IDMs with cord magnesium <0.74 mM (1.8 mg/dl) does not reduce the incidence of hypocalcemia in infants of well-controlled diabetic mothers.

Effects of calcium supplementation and lactation on iron status.

Calcium has been shown to inhibit iron absorption. The consequences of chronic calcium supplementation on iron status are unclear, however. As part of a randomized calcium-supplementation trial in lactating and nonlactating women in the postpartum period, we determined whether long-term calcium supplementation and lactation status affected iron stores as measured by serum ferritin concentrations. Subjects (95 lactating and 92 nonlactating) were enrolled at approximately 6 mo postpartum and then randomly assigned to receive either 500 mg Ca as calcium carbonate or a placebo twice daily with meals for 6 mo. Lactating women weaned their infants approximately 2 mo after enrollment (ie, approximately 8 mo postpartum). Calcium supplementation had no effect on serum ferritin concentrations. At the end of the study, geometric mean serum ferritin concentrations were 28.4 microg/L in the calcium-supplemented group and 27.5 microg/L in the placebo group (P > 0.5). Lactation status was significantly related to serum ferritin concentrations. At baseline, serum ferritin concentrations were higher in lactating women than in nonlactating women (47.7 compared with 31.5 microg/L, P < 0.001). In lactating women, serum ferritin concentrations decreased by a mean of 17 microg/L after weaning. By 12 mo postpartum, mean serum ferritin concentrations in women who were previously lactating were not significantly higher than those of nonlactating women (30.5 compared with 25.5 microg/L). These findings provide reassurance that long-term calcium supplementation does not impair iron stores. Furthermore, lactation status should be considered when assessing iron nutriture of women and determinants of iron status in populations.

Effects of gestational age, maternal diabetes, and intrauterine growth retardation on markers of fetal bone turnover in amniotic fluid.

Little is known about the dynamics of bone formation and bone resorption in utero, particularly the normal changes that occur throughout gestation and in clinical situations that result in low bone mass at birth. The objectives of this study were to describe the effects of gestational age on markers of fetal bone turnover, and to investigate whether the reported low bone mass at birth in small-for-gestational-age (SGA) infants and infants of diabetic mothers (IDMs) was associated with biochemical markers of decreased bone formation or increased bone resorption in utero. Bone formation and resorption were assessed by measurement of carboxyterminal propeptide of type I procollagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP), respectively, in 201 amniotic fluid samples. These markers are by-products of type I collagen formation and degradation, respectively, and have been used in the assessment of bone metabolism ex utero. Both PICP and ICTP concentrations in amniotic fluid were inversely associated with gestational age (P < 0.0001). Amniotic fluid concentrations of PICP increased exponentially in relation to infant birthweight (P = 0.008), and SGA infants had lower amniotic fluid PICP concentrations than controls (P = 0.07). The presence of diabetes in the mother was not associated with alterations in amniotic fluid PICP or ICTP concentrations. Although maturational effects on clearance of bone markers from amniotic fluid cannot be excluded, these data are consistent with a high turnover of bone matrix early in fetal life, and a reduction in bone formation when fetal growth is compromised.

The effect of calcium supplementation on bone density during lactation and after weaning.

BACKGROUND: Women may lose bone during lactation because of calcium lost in breast milk. We studied whether calcium supplementation prevents bone loss during lactation or augments bone gain after weaning. METHODS: We conducted two randomized, placebo-controlled trials of calcium supplementation (1 g per day) in postpartum women. In one trial (the study of lactation), 97 lactating and 99 nonlactating women were enrolled a mean (+/-SD) of 16+/-2 days post partum. In the second trial (the study of weaning), 95 lactating women who weaned their infants in the 2 months after enrollment and 92 nonlactating women were enrolled 5.6+/-0.8 months post partum. The bone density of the total body, lumbar spine, and forearm was measured at enrollment and after three and six months. RESULTS: The bone density of the lumbar spine decreased by 4.2 percent in the lactating women receiving calcium and by 4.9 percent in those receiving placebo and increased by 2.2 and 0.4 percent, respectively, in the nonlactating women (P<0.001 for the effect of lactation; P= 0.01 for the effect of calcium). After weaning, the bone density of the lumbar spine increased by 5.9 percent in the lactating women receiving calcium and by 4.4 percent in those receiving placebo; it increased by 2.5 and 1.6 percent, respectively, in the nonlactating women (P<0.001 for the effects of lactation and calcium). There was no effect of either lactation or calcium supplementation on bone density in the forearm, and there was no effect of calcium supplementation on the calcium concentration in breast milk. CONCLUSIONS: Calcium supplementation does not prevent bone loss during lactation and only slightly enhances the gain in bone density after weaning.