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American Journal of Clinical Nutrition, Vol. 88, No. 4, 1032-1039, October 2008
© 2008 American Society for Nutrition

ORIGINAL RESEARCH COMMUNICATION

Changes in bone mineral status and bone size during pregnancy and the influences of body weight and calcium intake1,2,3

Hanna Olausson, M Ann Laskey, Gail R Goldberg and Ann Prentice

1 From MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom

2 Supported by the UK Medical Research Council. HO was supported by the Henning and Johan Throne-Holst Foundation and the Swedish Council for Working Life and Social Research.

3 Address reprint requests and correspondence to H Olausson, Department of Clinical Nutrition, The Sahlgrenska Academy, University of Gothenburg, Box 459, SE-405 30 Göteborg, Sweden. E-mail: hanna.olausson{at}gu.se.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
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 ≤ 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 ≤ 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.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
In pregnancy, calcium is needed for fetal skeletal mineralization in addition to maternal calcium requirements. In theory, this additional requirement could be met by increased dietary calcium intake, greater intestinal calcium absorption efficiency, enhanced renal calcium retention, and/or mobilization of calcium from the maternal skeleton (1, 2). There is conflicting evidence about the extent to which maternal bone mineral contributes to calcium economy in human pregnancy (3). A number of prospective studies, in a relatively small number of women, have investigated the skeletal response to pregnancy by measuring bone density before pregnancy and after delivery (4–9). Some of these studies suggest that bone density may decrease in skeletal regions rich in trabecular bone, such as the spine and hip (5–11), with either no change or an increase in regions rich in cortical bone (7). Other studies did not show this pattern (5–11). In addition, these studies have suggested that there is considerable variation between women in the skeletal response to pregnancy, for reasons that are unclear (3, 8, 12). Disparities in mechanical loading resulting from differences in maternal body weight and weight gain may influence the magnitude of the skeletal response in pregnancy (3, 13). It is also plausible that the amount of skeletal calcium mobilized may depend on the calcium intake of the mother before or during pregnancy (3, 10). The limited number of studies using radiographic and absorptiometric techniques have reported no significant influence of calcium intake on maternal bone density (13, 14), whereas those conducted with quantitative ultrasound have reported that mothers consuming more calcium had smaller decreases in the measured bone variables during pregnancy (15, 16).

In the studies conducted to date, most investigators have used dual-energy X-ray absorptiometry (DXA) to investigate pregnancy-related alterations in areal bone mineral density (aBMD)—the ratio between bone mineral content (BMC) and scanned bone area (BA). This is a proxy measure for bone density that potentially masks or attenuates underlying changes in skeletal mineral content and bone size. In addition, most studies have not considered other likely influences on the maternal skeleton, independent of pregnancy, such as aging, body weight, and calcium intake.

The aims of this study were to investigate the change in whole-body and regional bone mineral status (BMC, aBMD, and BA-adjusted BMC) and in bone size (BA) prospectively from before pregnancy to after delivery in a group of British women, to compare the results with those from nonpregnant and nonlactating (NPNL) women measured contemporaneously over the same period to account for aging effects, and to consider the possible influences of body weight and calcium intake.


   SUBJECTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Subjects
Healthy, NPNL women living in Cambridge, United Kingdom, were recruited into the study by advertisement and through volunteer registers held at MRC Human Nutrition Research. Recruitment was targeted at women aged 23–37 y who were likely to become pregnant in the next few years and who were prepared to take part in a longitudinal study over several years. Potential subjects were excluded if they had a history of bone disease, were taking medication known to affect bone, had been pregnant within the previous 2 y, or had lactated within the previous year. Smokers and oral contraceptive users were not excluded. The study was approved by the Cambridge Local Research Ethics Committee, and subjects gave informed written consent.

Study design
Measurements were scheduled at 0, 6, and 12 mo after entry into the study and annually thereafter. Those subjects who became pregnant (Preg) were rescheduled for measurements during the second and third trimesters and at 2 wk postpartum. Bone densitometry was not performed during pregnancy. Data are presented here for 34 Preg women who subsequently delivered a healthy singleton baby and for 84 NPNL women who had been studied over the same time period. For the Preg group, time point 1 (T1) was defined post hoc as the measurement made before, but closest to, conception; T2 was at 2 wk postpartum. The time between T1 and T2 was 15.7 ± 3.7 mo (range: 10.8–22.8 mo). The visits during the second and third trimesters of pregnancy were at gestation weeks 20 ± 3 (range: 16–28 wk) and 32 ± 2 (range: 27–35 wk), respectively. T2 was 15 ± 5 d (range: 10–31 d) after delivery. All women initiated breastfeeding after delivery. At T2, 21 women were exclusively breastfeeding, 11 were partially breastfeeding (ie, were providing one or more bottles of formula milk per day), and 2 had stopped breastfeeding, having breastfed for <1 wk. For the NPNL group, T1 measurements were those obtained at study entry (0 mo), and measurements corresponding to T2 were a composite of those obtained at 12 and 24 mo, adjusted to match the time between Preg measurements of 15.7 mo, assuming a linear change in each variable over time. This was achieved by computing the difference in each value between 12 and 24 mo, multiplying by [(15.7–12)/12] (ie, 0.31), and adding to the value at 12 mo.

Bone mineral status, bone size, and anthropometric measures
Bone measurements were performed at each visit, except during pregnancy. BMC (g), BA (cm2), and aBMD (g/cm2) of the whole body, lumbar spine (L1-L4), left hip (femoral neck, trochanter, femoral shaft, and total hip), and left radius (wrist and shaft) were measured by DXA (Lunar MD with software 4.7e; GE Lunar Corporation, Madison, WI). Determination of z scores for aBMD of the spine and total hip at T1 was based on the English Reference Population database provided by the manufacturer.

Quality assurance procedures were performed at the start of every working day in accordance with the manufacturer's instructions. Long-term instrument performance was assessed in vitro by twice weekly measurements of the Lunar aluminum spine phantom. During the study period, there was a drift of <0.2%/y during the study period in phantom BMC and aBMD and no change in BA. Reproducibility of the DXA measurements was determined by a separate study of 30 women (mean age: 40 ± 15 y; height: 165 ± 8 cm; and body weight: 67 ± 13 kg) by duplicate measurements on the same day, with repositioning between measurements. The CVs for BMC, BA, and aBMD for the whole body were 1.6%, 2.0%, and 0.7%, respectively. The corresponding values were 1.4%, 1.1%, and 0.8% for spine; 1.8%, 1.8%, and 1.0% for total hip; 2.2%, 1.9%, and 1.7% for femoral neck; 6.3%, 5.1%, and 2.3% for trochanter; 1.6%, 1.7%, and 1.5% for femoral shaft; 1.0%, 1.1%, and 1.3% for radial shaft; and 2.5%, 2.1%, and 2.6% for radial wrist.

Height was measured to the nearest 0.1 cm with the use of a wall-mounted stadiometer at each visit. The mean of measurements made on up to 4 separate occasions was used. Body weight was measured to the nearest 0.1 kg with an electronic digital scale (Seca model 7701321004; Vogel and Halke, Hamburg, Germany) while the participants were lightly clothed.

Calcium intake
Dietary calcium intake was measured with the use of a prospective food diary over 7 consecutive days; photographs were used to assist in the selection of portion sizes and quantities described in household measures (17). Dietary supplement use was also recorded. When the data were available, customary calcium intake was the mean intake measured on 2 separate occasions (ie, 14 d of recording in total) before but closest to conception for the Preg group or at 0 and 6 mo for the NPNL group. For 8 Preg and 19 NPNL subjects, calcium intake was based on results from only one diary. Calcium intake during pregnancy was the mean intake for the Preg group measured from 2 diaries collected during the second and third trimesters. The diet records were coded by using the MRC Human Nutrition Research in-house software Diet In Data Out (18), and nutrient analysis was performed by using the in-house suite of software programs based on UK food tables (19). The intake of calcium from supplements was calculated by using packaging and manufacturers’ information provided by the volunteers and was included in the estimate of daily calcium intake.

Smoking history, oral contraceptive use, and recreational physical activity
Women were asked at T1 if they had ever smoked tobacco and if they were currently using oral contraceptives. Recreational physical activity (RPA; h/wk) over the past year was assessed by a self-completed validated questionnaire (20). RPA included non-weight-bearing and weight-bearing activities with a low, moderate, or high impact.

Statistical analysis
Statistical analysis was performed by using Linear Model software in Data Desk 6.1.1 (Data Description Inc, Ithaca, NY). This software combines elements of analysis of variance, analysis of covariance, and multiple regression analysis, as appropriate, in integrated models. Differences at T1 between the Preg and NPNL groups were investigated by using Student's 2-tailed t test. Descriptive statistics are reported as means ± SDs. Changes over time and differences between groups are reported as means ± SEs for all variables unless otherwise stated. P ≤ 0.05 was considered statistically significant; Scheffe's post hoc method was used, when appropriate, to reduce effects of multiple testing. All variables, except age, time, and parity at T1, were transformed into natural logarithms to allow the investigation of power relations between continuous variables and proportional (percentage) changes in discrete variables (21). Parity (0 or ≥ 1), current oral contraceptive use (yes or no), smoking history (ever or never) at T1, and infant feeding practice at T2 (exclusive or partial breastfeeding) were treated as discrete variables. For variables measured at both T1 and T2, the mean and the change ({Delta}) were computed after transformation to natural logarithms (eg, mean BMC = (ln[BMCT1] + ln[BMCT2])/2 and {Delta}BMC = ln[BMCT2] – ln[BMCT1]) (22). When {Delta} is calculated in this way and multiplied by 100, it approximates to percentage change ({Delta}%) (21).

Changes in bone mineral status and bone size between T1 and T2 in the Preg and NPNL groups at each skeletal site were examined in 4 ways: 1) change in BMC ({Delta}BMC) to determine whether bone mineral mass was altered; 2) change in BA ({Delta}BA) to determine whether skeletal size was altered; 3) change in aBMD ({Delta}aBMD) to determine whether there was any alteration in this marker of bone status that is commonly used as an index of fracture risk, but that is not independent of skeletal size; and 4) change in BMC after correction for BA ({Delta}BA-adjusted BMC) by using regression analysis to consider skeletal changes independently of changes in bone size (22).

First, the results were evaluated for the Preg and NPNL groups separately, by using hierarchical repeat-measures analysis of variance, to determine whether there were significant net changes in bone mineral status and bone size over the study period. For the Preg group, this enabled consideration of the net contribution of bone mineral mobilization to calcium economy in pregnancy. For the NPNL group, this enabled consideration of possible skeletal changes in women because of advancing age over the same time period and allowed for any small shifts in instrument performance. The potential influences of body weight and calcium intake at T1 were examined for each group separately by using multiple regression analysis. In addition, for the Preg group only, models were constructed to examine the influence of infant feeding practice at T2, the number of days between delivery and T2, and calcium intake during pregnancy. For the Preg group, the potential influence of calcium intake at T1 was also considered by comparing the change in bone mineral status and bone size between subjects with a calcium intake below or above the median using Student's 2-tailed t test.

Second, the data were combined and multiple regression models were constructed to determine whether there were significant differences between the Preg and NPNL groups in change between T1 and T2 and whether there were relations with other possible influences, such as body weight and calcium intake. This provided an estimate of the gross changes that could be ascribed to pregnancy, independent of other factors. In such models, when the dependent variable was transformed to natural logarithms, the coefficient for the group variable x 100 represents the difference in the changes between T1 and T2 (ie, {Delta}%Preg – {Delta}%NPNL) between the Preg and NPNL groups. These models were constructed with {Delta}BMC, {Delta}BA, or {Delta}aBMD as the dependent variables and with potential predictors as independent variables: group (Preg or NPNL), calcium intake, height, mean body weight, change in body weight ({Delta}Wt), mean age, period between T1 and T2 ({Delta}time), parity at T1, mean RPA (mRPA), RPA, smoking history at T1, and oral contraceptive use. For the analysis of {Delta}BA-adjusted BMC, mean BA and {Delta}BA were also included. For those with RPA recorded as a zero, a nominal value of 0.1 h/wk was assigned before transforming the data into natural logarithms. All variables were included simultaneously in the initial models, followed by backwards elimination of nonsignificant factors, the least significant being removed first, to produce a final parsimonious model. The value of the dependent variable at T1 was included in all models to minimize regression toward the mean. Interaction terms were included, as appropriate, to investigate whether any effects of {Delta}Wt and calcium intake differed between the groups (group x {Delta}Wt; group x calcium intake).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Subject characteristics
The characteristics of the Preg and NPNL groups are shown in Table 1Go and Table 2Go. There was no significant difference in age, parity, height, body weight, BMI, customary calcium intake, RPA, oral contraceptive use, smoking history, or calcium intake at T1 between the 2 groups of women (Table 1Go). A few subjects reported using calcium supplements at T1 (2 Preg and 8 NPNL). Overall, the contribution of supplements to the average calcium intake was small, representing 2% in both groups at T1 and in the Preg group during pregnancy. There was no significant difference in BMC, BA, or aBMD between the Preg and NPNL groups at any skeletal site at T1 (Table 2Go). The aBMD z scores at T1 for the Preg and NPNL groups, respectively, were as follows: 0.39 ± 1.08 and –0.03 ± 1.09 (P = 0.06) for the spine and 0.08 ± 0.99 and –0.03 ± 0.90 (P = 0.56) for the total hip. The z scores indicated that both groups had aBMD values at the spine and total hip that were in the normal range, with means close to those expected for their age.


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  		TABLE 1 Characteristics of subjects who became pregnant (Preg) and nonpregnant, nonlactating (NPNL) subjects1

 

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  		TABLE 2 Bone mineral content (BMC), bone area (BA), and areal bone mineral density (aBMD) at T1 for pregnant (Preg) and nonpregnant, nonlactating (NPNL) subjects1

 
Net changes in bone mineral status and BA during pregnancy
The mean changes ({Delta}%) in BMC, BA, aBMD, and BA-adjusted BMC from T1 to T2 at each skeletal site are shown in Table 3Go for the Preg and NPNL groups. The changes represent the net change in each variable over the course of the study for each group separately.


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  		TABLE 3 Percentage change ({Delta}%) in bone mineral status and bone area from T1 to T2 in pregnant (Preg) and nonpregnant, nonlactating (NPNL) subjects1

 
In the Preg group, BMC, aBMD, and BA-adjusted BMC decreased significantly at the whole body, spine, and total hip. BA decreased significantly at the spine but increased at the total hip. The pattern of change at the total hip was reflected in significant decreases in bone mineral status of the femoral shaft, femoral neck, and trochanter, but the increase in BA was observed only at the trochanter. No other significant changes were observed in the Preg group.

In the NPNL group, there were significant decreases in BMC at the femoral shaft and neck. However, in contrast with the Preg group, whole-body BMC increased significantly, and there was no significant change at the spine. BA increased significantly at the whole body, spine, radial wrist, and trochanter, with means ranging from 0.5% to 1.5%. aBMD and BA-adjusted BMC decreased significantly at the spine, total hip, femoral shaft, and femoral neck, with means ranging from –0.5% to –1.0%. No other significant changes were observed in the NPNL group.

Gross changes in bone mineral status and bone size during pregnancy
The mean percentage differences in change over time ({Delta}%Preg – {Delta}%NPNL) between the 2 groups, after adjustment for other influences, are shown in Table 3Go. The results represent the gross changes that can be ascribed to the skeletal response to pregnancy, independent of advancing age, weight gain, and other influences. The last column in Table 3Go details the factors that remained in the parsimonious models as significant predictors.

There were significant decreases in BMC at the whole body, spine, total hip, and radial wrist in the Preg group relative to the NPNL group. BMC decreased significantly at the femoral shaft, and there was a trend in this direction in the other hip regions. In general, the magnitude of these estimates was comparable with or greater than those observed in the Preg group when considered separately. There were also significant reductions in BA over time in the Preg group relative to the NPNL group at the whole body, spine, and radial wrist, but not at the hip. At most sites the pregnancy-related decrease in BMC exceeded that of BA, which resulted in a significant decrease in aBMD and BA-adjusted BMC at the whole body, spine, total hip, femoral shaft, and trochanter. There were no significant differences observed between the Preg and NPNL groups at the radial shaft or femoral neck.

Influence of body weight
There was no significant difference in body weight between the 2 groups at T1 (Table 1Go). As expected, body weight increased significantly between T1 and T2 (mean ± SD) in the Preg group (5.6 ± 0.8 kg; range: –3.2 to + 16.1; P ≤ 0.0001), but not in the NPNL group (0.5 ± 0.3 kg; range: –11.4 to 25.3; P = 0.10). Thus, {Delta}Wt was significantly greater in the Preg than in the NPNL (P ≤ 0.001) group. {Delta}Wt, but not mean body weight, was a positive predictor of some skeletal changes at the hip, spine, and radial shaft with the data from both groups combined (Table 3Go). Thus, at these sites, the increase in bone mineral status was greater (or the decrease less) in those with the greater increase in body weight over the study period. There was no evidence of a significant group x {Delta}Wt interaction at any site. At those skeletal sites where {Delta}Wt remained in the joint models, the slopes of the observed relations were comparable in each group when analyzed separately, even when no longer significant, which suggests that the correlations were not an artifact caused by the greater mean weight gain in the Preg group. For example, the slopes (coefficients) of the relation between {Delta}BMC and {Delta}Wt at the total hip were as follows: joint + 14.8 ± 5.1 (P = 0.005), Preg + 17.8 ± 9.8 (P = 0.08) and NPNL + 13.6 ± 6.2, (P = 0.03); at the femoral shaft the slopes were as follows: joint + 18.6 ± 5.4 (P ≤ 0.001), Preg + 19.4 ± 9.6 (P = 0.05) and NPNL + 18.2 ± 6.8 (P = 0.01).

When significant, adjustment for {Delta}Wt increased the estimate of the percentage decrease in bone mineral status that could be ascribed to pregnancy by {approx}1% (Table 3Go; eg {Delta}%Preg – {Delta}%NPNL in {Delta}BA-adjusted BMC: lumbar spine without correction = –2.1%, with correction = –3.0%; femoral shaft without correction = –0.6%, with correction = –1.7%).

Influence of calcium intake
There was no significant difference in mean reported customary calcium intake between the Preg (1008 ± 306 mg/d; range: 550–1748) and NPNL (1001 ± 284 mg/d; range: 438–1865) groups (Table 1Go). Reported customary calcium intake was not a significant predictor of change in bone mineral status or bone size at any site in the Preg or NPNL group considered separately or combined. This lack of effect was also observed when Preg and NPNL subjects were stratified into those with reported customary calcium intakes above or below the median intake. In addition, reported calcium intake in pregnancy was not a significant predictor of bone changes in the Preg group. No significant interaction was observed between reported calcium intake and group for any measurement at any skeletal site where significant bone changes had been observed.

Influence of other potential predictors
The independent effects of the following variables on the pregnancy-related change in bone mineral status and BA were also explored: height, age, time between T1 and T2 measurements, parity at T1, mRPA, {Delta}RPA, smoking history, and oral contraceptive use (Table 3Go). There was no significant difference in RPA between the 2 groups at T1 (Table 1Go). RPA decreased significantly between T1 and T2 in the Preg group ({Delta}RPA = median –1.1 h/wk; interquartile range: 2.7 h/wk; P = 0.02), but not in the NPNL group ({Delta}RPA = median + 0.1 h/wk; interquartile range: 4.8 h/wk; P = 0.51). Thus, {Delta}RPA was significantly different between the Preg and the NPNL groups (P = 0.005). Height, age, mRPA, and {Delta}RPA only occasionally remained significant in the parsimonious models, but no significant interactions with group were found. Height, age, mRPA, or {Delta}RPA did not materially affect the magnitude of the pregnancy-related changes in BMC and BA (Table 3Go). In addition, infant feeding practice and time between delivery and T2 were not significant predictors of the observed changes in bone mineral status and BA in the Preg group.

Heterogeneity of the changes in bone mineral status and BA
There was considerable between-subject variation in the bone changes observed between T1 and T2 in both groups. For example, the following range of values was found at the spine: {Delta}BMC (Preg: –17.9% to 4.4%; NPNL: –7.1% to 7.1%), {Delta}BA (Preg: –6.0% to 2.7%; NPNL: –3.9% to 4.5%), and {Delta}aBMD (Preg: –13.6% to 5.0%; NPNL: –5.8% to 4.5%).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
This study identified that significant changes occur in maternal bone mineral status during pregnancy, with average decreases of 1–4% in BMC, aBMD, and BA-adjusted BMC in the whole body, lumbar spine, and hip. These effects remained after allowing for skeletal changes associated with advancing age, {Delta}Wt, and other factors. The high precision of DXA allows detection of small changes in bone mineral status and BA (23). Scrutiny of DXA performance (see Methods) showed only very small changes (<0.2%/y). These will have affected both groups equally and therefore have a negligible impact on the results. Therefore, the differences in skeletal changes between the Preg and NPNL groups were due to pregnancy, not to changes in instrument performance.

Our findings are consistent with other longitudinal DXA studies of pregnant women (5–11). The strength of this study is that it included all of the following: 1) contemporaneous NPNL controls, enabling skeletal changes solely ascribed to pregnancy to be determined as well as net changes over time in pregnant women; 2) BMC and BA measurements in addition to aBMD, enabling changes in mineral content and bone size to be considered in addition to bone density; 3) body weight measurements, enabling the impact of {Delta}Wt on the observed skeletal changes to be investigated; and 4) dietary assessments, enabling the impact of calcium intake on skeletal changes to be investigated. This approach proved valuable in teasing out the multiple influences that interplay on the skeleton over time. For example, femoral neck BMC, aBMD, and BA-adjusted BMC decreased significantly in the Preg group, but the changes paralleled those in the NPNL group, and no significant differences were found between groups. Hence, the conclusion is that the decreased femoral neck bone mineral observed in the pregnant women was probably due to other factors (eg, aging) rather than to pregnancy. This study also showed that decreased aBMD at specific sites (eg, trochanter) may have been due to an increased bone size and to decreased mineral content.

This study identified significant changes in scanned BA in both groups. These may reflect skeletal effects, with a larger BA suggesting periosteal apposition or technical effects caused by changes in the orientation of the scanned bone relative to the X-ray beam and/or bone edge detection artifacts (24). In the Preg group, a net increase in BA was observed at the total hip and trochanter and a decrease was observed at the spine, whereas net BA increases were observed in the NPNL group at the whole body and several regional sites, including the spine and trochanter. Comparison of the 2 groups showed that pregnancy was associated with a significant reduction in BA, independent of advancing age and other factors, at the whole body, spine, and wrist, but not with a significant effect at the hip.

Women in both groups gained or lost weight. As expected, the Preg group gained more weight on average than did the NPNL group, although there was considerable variation between individuals. We considered it likely that {Delta}Wt would influence the interpretation of bone changes because body weight can affect DXA measurements of bone mineral status and BA, physiologically through loading effects on the skeleton and artifactually through alterations in tissue depth and bone edge detection (24, 25). This was shown to be the case at certain skeletal sites. In statistical models in which the Preg and NPNL groups were combined, {Delta}Wt was a significant positive predictor of bone mineral status at the spine and hip, such that those who gained the most weight had the greater gains (or smaller reductions) in these variables. There was no evidence of a group interaction in these relations, which suggests that there is a general effect of {Delta}Wt on these DXA measures, independent of pregnancy. Because the influence of weight gain on the bone variables was in a direction opposite that of pregnancy, correction for {Delta}Wt tended to increase the estimate of the reductions in bone mineral status in the Preg group relative to the NPNL group. If this effect was physiologic, correction for {Delta}Wt provides an estimate of the gross effects of pregnancy but overestimates the net amount of calcium released from that region of the skeleton. If it was artifactual, correction for {Delta}Wt gives a more precise estimate of the skeletal changes. At present, it is not possible to distinguish between these 2 possibilities.

Considerable interindividual variability was found in the changes in bone mineral status. Multiple regression models showed predictors at some sites included height, age, {Delta}Wt, mRPA, and {Delta}RPA, but these factors influenced the Preg and NPNL groups in a comparable manner. Calcium intake was not a significant predictor. Our study, therefore, provides evidence that skeletal changes during pregnancy are independent of calcium intake and should be regarded as physiologic rather than reflecting maternal calcium deficiency. It should be noted, however, that the women in our study were well nourished, and the majority had a calcium intake >700 mg/d (the UK reference nutrient intake for pregnant and NPNL women of this age) (26). Thus, these results may not apply to women with a very low calcium intake or from nutritionally disadvantaged backgrounds.

The mean decrease in whole-body BMC in the Preg group was –2.2%. This estimate was –2.7% relative to the change in NPNL, a value that was not significantly influenced by {Delta}Wt. These decreases are equivalent to 55 and 67 g bone mineral, respectively, for an individual with a typical whole-body BMC of 2500 g. This equates to a release of 21–25 g from the maternal skeleton based on the assumption provided by the manufacturer that calcium represents 38% of BMC measured by Lunar DXA. Given that the skeleton of an infant contains {approx}20–30 g Ca (27), our findings suggest that mobilization of mineral from the maternal skeleton could account for much of the calcium required during pregnancy for fetal growth and mineralization.

A limitation of our study was that at the 2 wk postpartum measurement, 32 of the 34 subjects were breastfeeding. The early months of human lactation are associated with considerable reductions in bone mineral status (3, 10), and it is possible that some of the changes ascribed to pregnancy were due to the skeletal response to lactation and that differences in the frequency of breastfeeding or volume of milk produced contributed to the interindividual variability.

The decreases in bone mineral status in the Preg group, although noteworthy, may not be associated with alterations in bone strength (and therefore fracture risk) to the same extent as comparable reductions in postmenopausal women. Studies of hip geometry in breastfeeding women have shown that lactation-associated bone loss occurs mainly on the endosteal surface of bone, close to the neutral axis, and therefore has a minimal effect on bone bending strength (28). It is possible that similar changes occur in pregnancy, although research is needed to confirm this.

The decreases in bone mineral during pregnancy may be temporary. In an earlier study by our group in British women during and after lactation, BA-adjusted BMC at the whole body, spine, and trochanter was greater at 12 mo postpartum or 3 mo after lactation had stopped than just after delivery (29). It is possible that these changes reflected the reversal of reductions in bone mineral that had occurred during the previous pregnancy. The magnitudes of the reported gains in bone mineral after lactation from that study correspond well with the pregnancy-related decreases observed in the present study. Evidence for postlactation compensation of pregnancy-associated bone changes is also found in studies by others that compared aBMD prepregnancy with values in the same individual measured 12 mo after delivery (5, 6). Although retrospective studies in postmenopausal women have suggested that pregnancy is not a significant risk factor for later osteoporotic fracture (3, 10), further studies are required to determine whether residual effects of pregnancy on maternal bone mineral status persist into later life.

In conclusion, our results show that decreases occur during pregnancy in BMC, aBMD, and BA-adjusted BMC at the whole body, spine, and different regions of the hip, independent of maternal calcium intake. The changes in bone mineral status are influenced by changes in body weight, a factor that needs to be considered when estimating the magnitude of the skeletal response to pregnancy. Overall, however, our study suggests that, in well-nourished women, release of calcium from the maternal skeleton is physiologic and can represent a sizeable contribution to calcium economy during pregnancy.


   ACKNOWLEDGMENTS
 
We thank the subjects for their enthusiastic participation, and we acknowledge Emily Smith and Ros Simmonds for data collection, Celia Greenberg for dietary coding and analysis, Sheila Levitt for data entry, and Ruth Webb for extracting and compiling the physical activity data.

The authors’ responsibilities were as follows: MAL and AP: conception and design of the study; MAL: coordination of volunteers and bone and anthropometric measurements; HO, MAL, GRG, and AP: data analysis and interpretation of results; and HO, MAL, GRG, and AP: draft of the manuscript. None of the authors had a financial or personal conflict of interest.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
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Received for publication April 25, 2008. Accepted for publication July 1, 2008.





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