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The Journal of Clinical Endocrinology and Metabolism logoLink to The Journal of Clinical Endocrinology and Metabolism
. 2012 Dec 28;98(2):523–532. doi: 10.1210/jc.2012-2118

Evaluation of Markers of Bone Turnover During Lactation in African-Americans: A Comparison With Caucasian Lactation

Raquel M Carneiro 1, Linda Prebehalla 1, Mary Beth Tedesco 1, Susan M Sereika 1, Caren M Gundberg 1, Andrew F Stewart 1, Mara J Horwitz 1,✉
PMCID: PMC3565113  PMID: 23275526

Abstract

Context:

The African-American skeleton is resistant to PTH; whether it is also resistant to PTHrP and the hormonal milieu of lactation is unknown.

Objectives:

The objective of the study was to assess bone turnover markers in African-Americans during lactation vs Caucasians.

Design and Participants:

A prospective cohort study with repeated measures of markers of bone turnover in 60 African-American women (3 groups of 20: lactating, bottle feeding, and healthy controls), compared with historic Caucasian women.

Setting:

The study was conducted at a university medical center.

Outcome Measures:

Biochemical markers of bone turnover and calcium metabolism were measured.

Results:

25-Hydroxyvitamin D (25-OHD) and PTH were similar among all 3 African-American groups, but 25-OHD was 30%–50% lower and PTH 2-fold higher compared with Caucasians (P < .001, P < .002), with similar 1,25 dihydroxyvitamin D [1,25(OH)2D] values. Formation markers [amino-terminal telopeptide of procollagen-1 (P1NP) and bone-specific alkaline phosphatase (BSAP)] increased significantly (2- to 3-fold) in lactating and bottle-feeding African-American women (P1NP, P < .001; BSAP, P < .001), as did resorption [carboxy-terminal telopeptide of collagen-1 (CTX) and serum amino-terminal telopeptide of collagen 1 (NTX), both P < .001]. P1NP and BSAP were comparable in African-American and Caucasian controls, but CTX and NTX were lower in African-American vs Caucasian controls. African-American lactating mothers displayed quantitatively similar increases in markers of bone formation but slightly lower increases in markers of resorption vs Caucasians (P = .036).

Conclusions:

Despite reported resistance to PTH, lactating African-American women have a significant increase in markers of bone resorption and formation in response the hormonal milieu of lactation. This response is similar to that reported in Caucasian women despite racial differences in 25-OHD and PTH. Whether this is associated with similar bone loss in African-Americans as in Caucasians during lactation is unknown and requires further study.

The skeleton is in a catabolic state during normal lactation, a well-documented physiological requirement for providing calcium to the rapidly mineralizing neonatal skeleton. Thus, during 6 months of lactation, women have been reported to lose up to 10% of bone mineral density (BMD) to provide 200–300 mg/d of calcium for breast milk (1–3). This extensive bone loss is thought to be mediated largely by the combination of systemic secretion of mammary-derived PTHrP coupled with the low estrogen levels characteristic of lactation (3–5). However, the bone cell-based mechanisms underlying this skeletal loss are not completely understood. Markers of bone resorption are markedly increased in lactation, reflecting both osteoclast-mediated bone resorption and possible osteocytic osteolysis as well (6). Several studies also report increases in markers of bone formation (7–9) despite the fall in BMD. As suggested by histological studies (10, 11), the increase in formation markers may reflect effective recruitment of osteoblast lineage cells into the bone formation program but with incomplete differentiation into mature osteoblasts, such that whereas formation markers are increased, complete osteoid synthesis and mineralization do not occur during lactation. Unlike other states of rapid bone loss, repeated epidemiological and observational studies indicate that bone density is usually regained rapidly after weaning, and there appears to be no major impact of lactation on the risk of developing osteoporosis in Caucasians (1, 12).

Most lactational bone studies have been performed in women of European descent. However, bone metabolism in African-Americans differs from Caucasians in many quantitatively important respects. African-Americans display higher bone density and a lower incidence of osteoporosis and osteoporotic fracture as compared with Caucasians (13–17). Despite lower 25-hydroxyvitamin D (25-OHD), higher PTH levels (18, 19), and lower urinary calcium excretion in African-Americans compared with Caucasians (20–23), biochemical markers of bone turnover have generally been reported to be lower in African-Americans (24–26). Lower bone turnover in African-Americans has been confirmed by bone histomorphometric studies (25). This attenuated bone turnover has been attributed to skeletal resistance to PTH in African-Americans (27). If the African-American skeleton is indeed resistant to the effect of PTH, one must wonder what the response of the African-American skeleton may be to the hormonal milieu of lactation.

To our knowledge, studies in lactating Blacks have been limited to Black Gambian women (29–31), compared with Caucasians in Great Britain. In these studies, in contrast to African-Americans, Black Gambian women displayed lower BMD than Caucasians and demonstrated significant additional losses in whole-body and hip BMD during lactation, as measured by dual-energy x-ray absorptiometry (29). Interestingly, and in contrast to what has been reported in Caucasians, there was little evidence of bone mass regain following lactation: in fact, there appeared to be continued loss at the hip. Thus, the Gambian studies may not be generalizable to the African-American population in the United States because the Gambian population ingests a very low-calcium diet, and the level of nutrition is suboptimal as compared with that of African-Americans.

With the above considerations in mind and with the essential absence of data on mineral metabolism and bone turnover in well-nourished African-Americans, we sought to explore markers of bone turnover and calcium metabolism in African-Americans during lactation in this pilot study. Specifically we sought to determine whether markers of bone formation and resorption are increased in African-American women during lactation compared with nonlactating African-American women and postpartum women who were not lactating. In addition, using historical controls from a previously published study with the same design (7), we explored how bone turnover markers in African-Americans compare with Caucasians during lactation.

Subjects and Methods

Study subjects

Sixty African-American women, aged 21–38 years, were enrolled into 1 of 3 study groups (n = 20 each). The first group included postpartum subjects who were exclusively lactating or using a maximum of 1 bottle of supplemental formula per day. The second group included subjects who were bottle feeding exclusively for at least 4 weeks prior to enrollment. The third group consisted of healthy nonpregnant control subjects who were age matched to the lactating mothers and who had not been pregnant or breast-feeding for at least 1 year prior to enrollment. Control subjects were recruited within the same month of the first visit of a lactating subject. Subjects were excluded from the study if they had any chronic diseases, were taking medications other than stable doses of thyroid hormone or oral contraceptives, were using tobacco or consuming significant amounts of alcohol, had had multiple pregnancies, had not conceived spontaneously, or had any complication of pregnancy or delivery. The study was done over a period of 1 year, and data were collected throughout the different seasons. All subjects gave written informed consent to participate in the study, which had been previously approved by the University of Pittsburgh Institutional Board Review.

Study design

This was a prospective cohort study in African-American lactating women compared with African-American postpartum bottle feeding and African-American healthy controls. Bone metabolism in this cohort of African-American women was also compared with a cohort of mostly Caucasian women from our previously published study with an identical design (7). Volunteers were recruited through fliers and from local obstetric clinics and postpartum wards. All subjects had 2 outpatient visits at the Clinical and Translational Research Center at the University of Pittsburgh. For postpartum women, visits occurred 6–8 weeks and 12–14 weeks after delivery. For controls, visits occurred during the follicular phase of their menstrual cycle, 6–8 weeks apart. At each visit, a medical history, a dietary calcium intake questionnaire, height, weight, and vital signs were obtained. In addition, fasting blood and urine specimens were collected for measurement of the following: serum ionized and total calcium, phosphorus, creatinine, albumin, PTH(1–84), 25-OHD, 1,25 dihydroxyvitamin D [1,25(OH)2D], serum carboxy-terminal telopeptide of telopeptide of collagen-1 (CTX), serum amino-terminal telopeptide of collagen 1 (NTX), and procollagen-1 (P1NP), bone-specific alkaline phosphatase (BSAP), urinary calcium, creatinine, and phosphorus. Estradiol and TSH were also measured at the first visit.

Biochemical assays

Serum ionized and total calcium, phosphorus, creatinine, albumin, TSH, and urine calcium, creatinine, and phosphorus were analyzed on the day of the visit using standard automated chemistries in the University of Pittsburgh Medical Center Clinical Chemistry Laboratory. The tubular maximum for phosphorus (TmP/GFR) and fractional excretion of calcium (FECa) were calculated as previously described (32, 33). The other laboratory assays were performed in 1 batch at the conclusion of the study on blood samples that had been processed and stored in temperatures of −80°C. Archived samples from a subset of the prior Caucasian study (6) were also included in the same assays to ensure reproducibility of the assays (see Supplemental Data, published on The Endocrine Society's Journals Online web site at http://jcem.endojournals.org). Endogenous PTH(1–84) was measured by a solid-phase chemiluminometric assay [Siemens Immunolite 2500, Tarrytown, New York; coefficient of variation (CV) 12.5%]. Plasma 25-OHD was measured using the DiaSorin Liason 25-OHD total assay (Stillwater, Minnesota; CV 9.4%) (34–36) and 1,25(OH)2D was measured using a previously described competitive RIA assay (CV 9.7%) (37). P1NP, NTX, CTX, and BSAP were measured using commercial kits from Orion Diagnostics RIA (Espoo, Finland; CV 4.9%), Osteomark ELISA (Ostex International, Seattle, Washington; CV 14%), Crosslaps ELISA (Nordic Bioscience Diagnostics, Herlev, Denmark; CV 16.5%), and Ostase enzyme immunoassay (Hybritech Inc, Fullerton, California; CV 5.3%), respectively.

Statistical analysis

This was a descriptive and exploratory study by design. Data were analyzed using SAS (version 9.1.3; SAS Institute, Inc, Cary, North Carolina). Two-sided hypotheses were tested with a significance level of P = .05. A feasible sample size of 20 women per group was determined so that means and SDs could be estimated with precisions of 0.468 σ and 0.350 σ respectively, with a confidence coefficient of 0.95. Descriptive data analysis was done initially using exploratory data analytical techniques to look for possible data anomalies. Group outcome variables were compared using standard comparative statistics regarding subject descriptors, baseline values, and changes from 6–8 weeks to 12–14 weeks postpartum. For continuous normally distributed variables, ANOVA with F-tests was performed. For nonnormally distributed or ordinally scaled data, a nonparametric Kruskal-Wallis test was performed. For categorical variables, a contingency table with χ2-type tests or Fisher's exact test was used. Tukey's multiple comparison procedure or a nonparametric Mann-Whitney U test was used for post hoc pairwise comparisons to explore differences among the 3 groups being compared. The data from this study were concatenated with an existing data set from an exploratory, group comparative study in which the same design was implemented and the same end points were measured in Caucasian women (7). When descriptively comparing bone metabolism end points from African-American participants with those from Caucasian participants, differences in means between racial groups for each study group were estimated with a 0.640 σ precision.

Results

Demographics

As shown in Table 1, the 3 groups of African-American women were similar with regard to age, height, weight, and body mass index (BMI). Parity was also similar when comparing the lactation and bottle-feeding groups but higher in the bottle-feeding group as compared with African-American controls (P = .002). Total daily dietary calcium intake was higher in the lactation group as compared with controls (P = .044). Mean estradiol concentrations were lower in both lactating (mean 51.5 ± 7.79 pmol/mL) and bottle-feeding (mean 81.1 ± 14.20 pmol/L) women as compared with African-American controls (mean 120.3 ± 20.26 pmol/L, P = .008 and P = .018, respectively).

Table 1.

Baseline Demographics of African-American Women

Control (n = 20) Bottle (n = 20) Lactation (n = 20)
Age, y
    Mean ± SE 28 ± 1.25 26.2 ± 1.17 27.3 ± 1.00
    Median (range) 27 (21–38) 24 (21–38) 27 (21–38)
Height, m
    Mean ± SE 1.65 ± 0.02 1.63 ± 0.01 1.63 ± 0.01
    Median (range) 1.64 (1.55–1.79) 1.65 (1.54–1.74) 1.61 (1.50–1.73)
Weight, kg
    Mean ± SE 74.2 ± 3.04 83.9 ± 05.02 86.8 ± 5.05
    Median (range) 73.5 (52.8–108.7) 75 (54.1–132) 81.4 (55.1–135.7)
BMI, kg/m2
    Mean ± SE 27.3 ± 1.31 31.6 ± 1.98 32.6 ± 1.97
    Median (range) 26.8 (19.0–41.9) 29.3 (21.4–55.6) 31.5 (22.3–50.9)
Parity
    Mean ± SE 1 ± 0.3 3 ± 0.5a 2 ± 0.2
    Median (range) 1.0 (0–4) 2.0 (1–9) 2.0 (1–5)
Total dietary daily calcium intake, mg/d
    Mean ± SE 639.2 ± 90.9 648.3 ± 94.8 1020 ± 137.2b
    Median (range) 487.3 (200–1912) 491.3 (111–1330) 827 (121–2613)
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a

P = .002 bottle vs control.

b

P = .044 lactation vs control.

When compared with the prior Caucasian cohort (7), African-American women were younger (mean age African-American 27 years vs Caucasian 31.7 years, P < .001), had higher BMI (mean African-American BMI, 30.6 vs Caucasian, 25.9, P = .005), and had lower total daily dietary calcium intake (mean intake African-American 769 vs. Caucasian 1075 mg/d, P = .02). Estradiol levels were similar in African-American and Caucasian lactating women (7).

Serum and urine minerals

As shown in the dark gray bars in Fig. 1A, mean total serum calcium was within the normal range and similar in all 3 groups of African-American women. When compared with Caucasians (light gray bars), bottle-feeding African-American women had a slightly lower total calcium (P = .049). Mean ionized calcium was normal and not different among groups or races (data not shown). Serum phosphorus was slightly higher in lactating and bottle-feeding African-American women as compared with African-American controls (P = .001 and P = .038, respectively, Fig. 1B). Serum phosphorus was also higher in African-American lactating and bottle-feeding women when compared with Caucasian (P < .001 and P = .019, respectively), but there was no difference between the control groups. FECa was similar among the 3 groups of African-American women (Fig. 1C) but was lower in African-American vs Caucasian lactating and control women (P = .005 and P = .002, respectively). The relatively low FECa in the Caucasian bottle feeders is presumed to reflect the small sample size in this group (7). The tubular maximum for phosphorus (TmP/GFR) was higher in African-American lactating and bottle-feeding women as compared with African-American controls (P = .001 and P = .038, respectively, Fig. 1D) and when compared with the same groups of Caucasian mothers (P < .001 and P = .019, respectively). Again, there was no difference between the 2 control groups.

Figure 1.

Figure 1.

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Serum total calcium (A), serum phosphorus (B), FECa (C), and the TmP/GFR (D) in lactating, bottle-feeding, and control African-American and Caucasian women. The first bar (dark gray) of each study group represents the mean and SE of the 2 time points studied for African-American women. The second bar (light gray) of each group represents the same data for Caucasian women. A, There were no differences in total serum calcium among the 3 African-American groups. There was a slight statistical difference in serum total calcium between African-American and Caucasian bottle-feeding women (P = .049). B, Serum phosphorus was higher in bottle-feeding and lactating African-American women as compared with African-American controls (P = .038 and P = .001 respectively). In addition, serum phosphorus was higher in bottle-feeding and lactating African-American women as compared with their Caucasian counterparts (P = .019 and P = .001 respectively). C, FECa was similar among the 3 groups of African-American women but was lower in both control and lactating African-American women compared with Caucasian women (P = .002 and P = .005, respectively). D, There was no difference between the African-American and Caucasian control groups for TmP/GFR. TmP/GFR was slightly higher in the African-American lactating and bottle-feeding mothers both compared with African-American controls (P = .001 and P = .038, respectively) and compared the same groups of Caucasian women (P < .001 and P = .019, respectively).

PTH and vitamin D metabolites

As shown in Fig. 2, there were no differences in PTH, plasma 25-OHD, or 1,25(OH)2D among study groups in African-American women. As expected, African-American controls displayed strikingly higher PTH (Fig. 2A) and markedly lower plasma 25-OHD (Fig. 2B) as compared with Caucasian controls (P < .002 and P < .001, respectively). This pattern of higher PTH and lower 25-OHD was also seen when comparing African-American lactating and bottle-feeding women with the Caucasian groups (for PTH, P = .022 and P = .002, respectively, and for 25-OHD, P < .001 and P = .009, respectively). As shown in Fig. 2C, African-Americans and Caucasians displayed similar 1,25(OH)2D in all three study groups, with no racial differences.

Figure 2.

Figure 2.

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PTH, 25-OHD, and 1,25(OH)2D in lactating, bottle-feeding, and control African-American and Caucasian women. The 2 bars for each group represent the mean and SE of the 2 time points studied in African-Americans and Caucasians as previously described for Fig. 1. There were no differences in PTH, plasma 25-OHD, or 1,25(OH)2D between study groups in African-American women. A, PTH was strikingly higher in the 3 African-American as compared with Caucasian groups (P = .002). B, Plasma 25-OHD was markedly lower in the three African-American as compared with Caucasian groups (P < .001, control; P = .009, bottle; P < .001, lactating). C, African-Americans and Caucasians displayed similar 1,25(OH)2D in all 3 study groups, with no racial differences.

Bone turnover

Figure 3 shows the results for plasma P1NP and BSAP, the current standard markers of bone formation. Bone formation markers rose markedly after delivery: African-American lactating and bottle-feeding mothers displayed marked increases in P1NP as compared with African-American controls (P < .001 and P < .001, respectively, Fig. 3A). Similarly, BSAP was markedly higher in African-American lactating and bottle-feeding women as compared with African-American controls (P < .001 and P = .006, respectively, Fig. 3B). In control African-Americans and Caucasians, bone formation markers were not different, and there were no ethnic differences in these increases in bone formation because lactating African-Americans responded similarly to lactating Caucasian mothers.

Figure 3.

Figure 3.

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Markers of bone formation in lactating, bottle-feeding, and control African-American and Caucasian women. The 2 bars for each group represent the mean and SE of the 2 time points studied in African-Americans and Caucasians as previously described in Fig. 1. A and B, P1NP and BSAP, bone formation markers, were significantly higher in the African-American lactating and bottle-feeding mothers as compared with the African-American controls (P = .001 both for P1NP, and P < .001 and P = .006 for BSAP). However, there were no racial differences among the groups.

Figure 4 shows the concentrations of serum CTX and NTX, current markers of bone resorption, which clearly increased by some 2- to 3-fold in the African-American lactating and bottle-feeding mothers as compared with the African-American controls (P < .01 and P = .002, Fig. 4A, and P < .001 for both, Fig. 4B). As with bone formation, this increase in markers of bone resorption is comparable with events in Caucasian women. As anticipated, baseline bone resorption was substantially and significantly attenuated in African-American controls as compared with Caucasian controls (CTX, P = .003, NTX, P < .01, Fig. 4, A and B). Lactating African-American women displayed significantly lower levels of CTX than lactating Caucasian women (P = .036, Fig. 4A), a difference not observed for NTX.

Figure 4.

Figure 4.

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Markers of bone resorption in lactating, bottle-feeding, and control African-American and Caucasian women. The 2 bars for each group represent the mean and SE of the 2 time points studied in African-American and Caucasians as previously described in Fig. 1. A, Baseline CTX was lower in African-American controls as compared with Caucasian controls (P = .003). In addition, CTX was 2- to 3-fold higher in African-American lactating and bottle-feeding mothers as compared with the African-American controls (P < .001 and P = .002). Finally, CTX was higher in lactating Caucasian as compared with African-American women (P = .036). B, Baseline NTX was also lower in African-American controls as compared with Caucasian controls (P < .01). In addition, NTX was higher in lactating and bottle-feeding African-American women as compared with African-American controls (P < .001 for both).

Discussion

Despite the large database regarding lactational mineral mobilization and bone loss in Caucasians, there are no studies, to the best of our knowledge, exploring lactational bone loss and bone turnover in African-Americans or Blacks elsewhere in the developed world. The current study begins to dissect and describe the similarities and differences in lactation, uniquely exploring an African-American population, and using state-of-the-art bone turnover markers. We used a prospective cohort design that we have used previously to study lactational mineral metabolism in Caucasian and compare these events in African-Americans with those previously observed in Caucasians (7). Although comparing current studies in African-Americans with historic controls in Caucasians can be hazardous, we took care to ensure that older Caucasian and newer African-American samples were rerun in the same assays and to confirm that repeat assay results of Caucasian samples were comparable with the original assay results (7), which are reported in the Supplemental Data. Thus, this study provides a database of markers of bone turnover from which to generate hypotheses and extend the understanding of bone and mineral metabolism during lactation in African-Americans. This is important because African-Americans evidently have a more successful skeletal phenotype (higher BMD, fewer fractures) than Caucasians despite higher PTH and despite vitamin D deficiency: there perhaps are lessons that can be learned that will help to augment bone health in all populations.

In baseline observations in control, nonlactating African-American young women, we confirm results reported in prior studies: among healthy African-American controls, PTH is markedly higher, 25-OHD is substantially lower, renal calcium excretion is lower, and bone resorption is also lower than in Caucasians. These events have been interpreted to indicate that African-Americans are resistant to PTH (lower bone resorption) and are also relatively vitamin D deficient, have secondary hyperparathyroidism, and reflect lower intestinal calcium absorption. An alternate interpretation, because African-Americans have higher BMD and fewer fractures, might be that Caucasians are profligate with respect to renal calcium handling and are abnormally PTH sensitive, a hypothesis that resonates with the observations that higher bone turnover leads to menopausal bone loss (38, 39) and that active bone resorption enhances osteoporotic fracture risk, independent of BMD (40).

More importantly, we demonstrate that despite the well-documented resistance to PTH in African-Americans (21, 27, 41), markers of bone resorption increase dramatically in African-Americans with lactation, presumably in response to a rise in PTHrP and a decline in estrogen, as has been described in rodents and Caucasian humans (3–5). We also find that baseline markers of bone formation appears comparable in African-Americans and Caucasians, despite the relative increase in markers bone resorption in Caucasian control subjects, suggesting a net higher formation to resorption marker ratio in African-Americans vs Caucasians. Finally, we also observe that bone formation markers increase dramatically in African-Americans during lactation and do so in a manner that is indistinguishable from events in Caucasians during lactation. That is, despite resistance to PTH in African-Americans, markers of bone turnover increase comparably in African-American and Caucasians in response to the hormonal milieu of lactation.

Seen from the standpoint of the well-documented PTH resistance in African-Americans (21, 27, 41), the substantial rise in bone turnover markers in African-Americans presents interesting hypotheses. First, it may signify that although African-Americans display skeletal resistance to PTH, African-Americans remain sensitive to the effects of PTHrP, despite its structural similarities to PTH. Alternatively, African-Americans may produce greater amounts of PTHrP during lactation as compared with Caucasians, which may overcome a putative skeletal PTHrP resistance. Finally, because PTH is higher in African-Americans than Caucasians during lactation, it may be that the combination of increases of PTHrP together with the higher levels of PTH characteristic of African-Americans subjects may overcome potential skeletal PTH/PTHrP resistance during lactation. Unfortunately, currently available PTHrP assays are insufficiently sensitive to address this question and were therefore not measured in this or our prior Caucasian study (7). On the other hand, direct evaluation of skeletal resistance to PTH vs PTHrP in African-Americans vs Caucasians using PTH vs PTHrP infusions is both attractive and feasible (21, 43) and may be used to address this question in future studies.

Serum minerals and their renal handling in African-Americans and Caucasians revealed similarities and differences. The fractional excretion of calcium was lower in African-Americans as compared with Caucasians controls and remained constant in both groups during lactation. This is in agreement with prior studies in African-Americans across all age groups, which show that average calcium excretion is approximately half that of Caucasians (20, 22, 23). This has been attributed to relative secondary HPT in African-Americans, lower dietary calcium intake, and inefficient calcium absorption in African-Americans (20, 21). Yet, during lactation, despite presumed net skeletal delivery of calcium into extracellular fluid and despite this limited renal ability to clear calcium, total serum calcium remains within normal limits for both groups, events that presumably reflect net efflux of calcium from extracellular fluid into milk.

Serum phosphorus and TmP/GFR were higher in the lactating groups as compared with controls, particularly in the African-Americans. These findings have been documented in previous epidemiological studies involving Caucasian women (5). Increased phosphorus delivery into extracellular fluid from bone resorption may contribute to the rise in serum phosphorus in both lactating groups, whereas the higher TmP/GFR in African-Americans presumably accounts for the even higher serum phosphorus in this group. The mechanism of the relatively reduced phosphate excretion in African-American is unclear. Perhaps renal resistance to the phosphaturic effects of PTH or PTHrP, other differences in phosphorus-regulating factors not measured (eg, prolactin, GH, or fibroblast growth factor-23) may also play a role in differential regulation of phosphate excretion during lactation in African-Americans.

Surprisingly, despite differences in PTH, 1,25(OH)2D did not differ between African-Americans and Caucasians in any of the groups. This finding differs from some previous studies, which revealed higher 1,25(OH)2D in African-Americans (28, 42), but agrees with others that demonstrate comparable 1,25(OH)2D concentrations in African-Americans and Caucasians (26). The differences among reports may reflect differences in 1,25(OH)2D assay techniques and the difficulties inherent in measuring this hormone. The measurements here were performed using an established competitive RIA (37).

These collective observations raise several more interesting questions. First, if bone turnover is increased in African-Americans, and comparably with Caucasians, does BMD decline in African-Americans as it does in Caucasians during lactation? Or if African-Americans are resistant to PTH and PTHrP, does BMD remain elevated and unchanged in African-Americans as compared with Caucasians during lactation? The answers to these questions are unknown and can be directly addressed only with future longitudinal studies comparing BMD in Caucasians vs African-Americans during lactation.

Our study has limitations. First, the African-American and Caucasian cohorts were recruited and assays performed a few years apart. As mentioned above, we attempted to correct for this by repeating all bone turnover markers and calciotropic hormones from the lactation groups in the 2 studies in the same assay and found that the interassay variation was small. Second, we did not measure BMD in these subjects to assess whether bone loss occurred in African-Americans as previously described in Caucasians, nor did we perform bone biopsies to evaluate skeletal histomorphometry. Third, due to a current lack of sufficiently sensitive and specific assays, we were unable to measure PTHrP during lactation in these studies. Dietary calcium intake differed between the racial groups, which may have affected bone turnover markers and PTH levels. Lastly, we looked at only 2 time points during lactation: future longitudinal studies are necessary to further investigate the dynamic state of bone metabolism.

In summary, this study provides an evaluation of bone turnover markers and measures of mineral metabolism in lactating African-Americans. It confirms previously described baseline differences in PTH, 25-OHD, and renal calcium handling between African-Americans and Caucasian subjects. More importantly, it reveals that during lactation, bone turnover markers are increased in African-Americans as they are in Caucasians. It also serves as a platform for hypothesis generation regarding African-Americans vs Caucasian skeletal mineral and calcium-regulating hormones during lactation. Although the study did not include measurements of PTHrP, BMD, or bone histology, we suspect that the general mechanisms underlying skeletal mobilization during lactation in African-Americans are likely the same as in Caucasians. However, the extent of skeletal calcium/BMD loss in African-Americans vs Caucasians and the degree of skeletal resistance to PTH vs PTHrP in African-Americans vs Caucasians during lactation remains unknown. Future larger, longitudinal studies of pregnancy, lactation, and BMD in African-Americans are needed to further explore this question.

Acknowledgments

We acknowledge Ronald Horst for his valuable assistance in performing the vitamin D assays. We thank the nurses on the postpartum wards at Magee's Women's Hospital for their help with recruiting for this study and the Clinical Translational Research Center staff for their outstanding support with this study. We also thank the study participants who kindly volunteered their time and made this study possible. This study is registered with Clinical Trials (NCT 00785824).

This work was supported by National Institutes of Health Grants DK 51081, DK 073039, and DK071158 as well as the University of Pittsburgh Clinical Translational Sciences Award, National Institutes of Health/National Center for Research Resources/Clinical and Translational Science Awards UL1 RR024153 and MO-1 RR000056.

Disclosure Summary: R.M.C., L.P., M.B.T., S.M.S., C.M.G., A.F.S., and M.J.H. have nothing to declare.

Footnotes

Abbreviations:
BMD
Bone mineral density
BMI
body mass index
BSAP
bone-specific alkaline phosphatase
CTX
carboxy-terminal telopeptide of telopeptide of collagen-1
CV
coefficient of variation
FECa
fractional excretion of calcium
NTX
serum amino-terminal telopeptide of collagen 1
1,25(OH)2D
1,25 dihydroxyvitamin D
25-OHD
25-hydroxyvitamin D
P1NP
amino-terminal telopeptide of procollagen-1
TmP/GFR
tubular maximum for phosphorus.

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