- Email: [email protected]
Bone loss in adolescent and adult pregnant women
Bone Loss in Adolescent and Adult Pregnant Women M. F. SOWERS, PhD, T. SCHOLL, MPH, PhD, L. HARRIS, MSN, AND M. JANNAUSCH, MS Objective: To determine the amount of change in bone ultrasound measures among pregnant adolescent girls and women and whether that change was associated with adolescence, maternal growth during pregnancy, limited weight gain during pregnancy, hypertension in pregnancy, or poor diet. Methods: We used bone ultrasound measurements of attenuation and sound velocity to assess changes in quantitative ultrasound indices of 252 pregnant adolescent girls and women age 12–34 years. Bone ultrasound measurement of the os calcis was performed at 16 ⴞ 7 weeks’ gestation (mean ⴞ standard deviation and 6 ⴞ 1 weeks postpartum. Results: On average, the bone quantitative ultrasound index was 3.6% lower 6 weeks postpartum than at entry into care (P < .001). Nulliparous patients had significantly greater bone loss than did parous subjects. Still-growing adolescents had greater quantitative ultrasound index decreases than did grown women (ⴚ ⴚ 5.5% versus ⴚ1.9%, P < .02). Patients in the upper tertile of baseline quantitative ultrasound index lost more bone than did patients in the lower tertile (ⴚ ⴚ 5% versus 0.5%, P < .02). Pregravid weight, weight change during pregnancy, gynecologic age, and age at menarche predicted bone change in subgroups defined by parity or age; however, none of the differences in those variables were statistically significant. Greater dietary calcium intake, less physical activity, and pregnancy hypertension and preeclampsia were not associated with bone change. Conclusion: There has been inconsistent evidence of maternal bone loss during pregnancy. The findings of this study challenge the assumption that because of increased calcium absorption from the maternal intestine, no transitory bone loss occurs in pregnancy. The amount of bone loss among growing adolescents and nulliparous patients was consistent with the demands of fetal mineralization and the continued demands of the maternal skeleton during growth. (Obstet Gynecol 2000;96:189 –93. © 2000 by The American College of Obstetricians and Gynecologists.)
From the Department of Epidemiology, University of Michigan, Ann Arbor, Michigan; and the Department of Obstetrics and Gynecology, University of Medicine and Dentistry of New Jersey, Camden, New Jersey. Supported by National Institutes of Health grant ES-07437.
VOL. 96, NO. 2, AUGUST 2000
Calcium metabolism in pregnancy is complex and evokes many homeostatic mechanisms, including extracellular volume expansion, increased glomerular filtration rate, and increased demand for calcium for transport to the fetus. Maternal response to that demand theoretically can involve increased absorption of calcium from the intestine, greater calcium conservation by the kidneys, or greater bone turnover.1 Calcium needed for fetal skeletal mineralization is estimated at 30 g or approximately 3% of maternal skeletal mass if maternal skeleton were the primary source of calcium for the fetus.1 Calcium metabolism and bone turnover in pregnancy might have long-term effects on maternal bone health. For example, Sowers et al2 and Fox et al3 independently reported that earlier age at first pregnancy was associated with lower cortical bone mineral density (radius) in midlife or later. In rare cases, osteoporosis has been associated with pregnancy,4,5 and calcium homeostasis has been suggested as important in other selected maternal outcomes, including preeclampsia and toxemia.6 However, bone loss during pregnancy has been believed unlikely in most women, because of absorption of calcium from the intestine in amounts that compensate for fetal demand.7 Studying calcium homeostasis during pregnancy was more difficult when studies involved measuring radioisotopes or using x-ray energy in bone densitometry. A relatively new alternative is bone ultrasound measurement, which does not involve radiation and has been reproducible in pregnant women.8 One goal of this study was to determine the amount of change in bone ultrasound measurements among female patients assessed at entry into care and 6 –7 weeks postpartum. Changes in ultrasound bone measurements also were evaluated to determine whether adolescence, maternal growth during pregnancy, poor diet, limited weight gain during pregnancy, and pregnancy hypertension were associated with greater bone loss during pregnancy.
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Materials and Methods The population comprised 252 adolescent girls and women participating in a study of pregnancy and lactation in Camden, New Jersey. Their data, including bone ultrasound results, were collected at entry into care (approximately 16 weeks’ gestation) and at 6-week postpartum checkups. Participants were 12–34 years old and identified themselves as black (40%), white (22%), or Hispanic (predominantly Puerto Rican) (38%). Patients were excluded if they had histories of serious nonobstetric conditions (including lupus, chronic hypertension, type I or type II diabetes, seizure disorders, malignancies, and drug or alcohol abuse). Subjects provided written informed consent, consistent with the policies of institutional review boards at the University of Medicine and Dentistry of New Jersey and the University of Michigan. Bone ultrasound (Sahara; Hologic Inc., Bedford, MA) was used to measure the cancellous bone of the os calcis. Two ultrasound probes were mounted on opposite sides of a well in which the heel was positioned. Contact between the transducers and the skin was maintained with ultrasound gel. Three characteristics described the sound wave pattern and by extension the architectural properties of the bone tissue. The speed of sound (in meters per second) represented the speed of signal transmission through the heel. The broadband ultrasound attenuation (in decibels per megahertz) was the degree of attenuation of the highfrequency sound waves. The quantitative ultrasound index combines the speed of sound and broadband ultrasound attenuation into a single measure. Quantitative ultrasound indices range from 0 to 170, with greater values associated with greater bone mass and lower values occurring in osteoporosis. Three women were excluded because their feet were too large (greater than size 11) to be seated appropriately in the heel well. The machine was calibrated daily using a quality control phantom. No measurements were made until the instrument was calibrated to within acceptable range. Measurements were performed at room temperature. The coefficient of variation of this measure was approximately 3%, determined from data from 280 subjects at entry into care.8 Included in this report are data from 252 of 280 subjects who had measurements at entry into care and 6-week postpartum visits. Participants were interviewed during each trimester and approximately 6 weeks postpartum, to obtain sociodemographics and medical histories. They also were measured for changes in body size and other physical characteristics at entry into care and 6 weeks postpartum. Variables included participant age at entry into care; pregravid weight, based on the individual’s recalled
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prepregnancy weight at entry into care; height, measured at entry into care; and pregravid body mass index (BMI). Pregravid BMI was used as a continuous variable in multiple variable regression modeling or trichotomized according to levels specified by the Institute of Medicine report.9 Those levels were 19.8 or less (underweight), 19.8 –26 (normal weight), and more than 26 (overweight). Weight gain during pregnancy was determined by calculating the difference between selfreported pregravid weight and weight at entry into care. Perceptions of physical activity were based on responses to the questionnaire and perceived physical activity was rated by participants in relation to their peers using a five-level variable. Current smoking behavior at entry into care was a dichotomous variable. Usual dietary calcium intake (in milligrams per day) was estimated by adding up amounts of calcium in calcium foods consumed.10 Diagnoses of hypertension in pregnancy, preeclampsia, or toxemia were abstracted from medical records. Preterm delivery was defined as delivery at less than 37 weeks’ gestation, with gestational age determined by ultrasound. Parity before the index pregnancy was treated as a dichotomous variable. Growth in pregnancy was determined by calculating the difference in knee height between entry into care and the first postpartum visit. The change in knee height was standardized to a 6-month interval, to adjust for the length of time over which change occurred. Patients age 19 years or younger who had at least 1 mm of growth were classified as growing adolescents. Differences in ultrasound bone mass were treated as continuous variables in data analysis. However, baseline bone mass was classified into tertiles to show association with bone mass change. Ultrasound bone change was adjusted for individual differences between conception and entry into care and for individual variation between date of delivery and date of the first postpartum visit in the general linear models. Unadjusted P values depicted the probability of no association between bone change and the independent variables. Adjusted P values depicted the probability of no association between bone change and the independent variables after adjusting for variations in time differences between conception and entry into care and for individual variation between date of delivery and date of the first postpartum visit. Dummy variables were used to describe categoric independent variables such as parity. Data are presented as mean ⫾ standard error of the mean (SEM) or least squares mean ⫾ SEM. After each independent variable was evaluated for association with bone ultrasound change, variables that were statistically significant at the .10 level were entered into a multiple variable regression model. All
Obstetrics & Gynecology
Table 1. Patient Characteristics, by Ethnic Group
Age (y) Age at menarche (y) Gynecologic age (y) Height (cm) Pregravid weight (kg) Weight gain in pregnancy (kg) BMI At entry into care§ At postpartum visit㛳 Daily dietary calcium intake (mg) Current smoker Growing adolescent Preterm delivery Nulliparous
Overall* (n ⫽ 252)
Black† (n ⫽ 101)
Hispanic† (n ⫽ 96)
White† (n ⫽ 55)
P‡
19.9 ⫾ 0.3 12.0 ⫾ 0.1 7.9 ⫾ 0.3 161.4 ⫾ 0.4 63.7 ⫾ 1.0 4.3 ⫾ 0.4
19.5 ⫾ 0.4 12.1 ⫾ 0.2 7.4 ⫾ 0.4 163.3 ⫾ 0.6 66.2 ⫾ 1.5 4.8 ⫾ 0.6
18.9 ⫾ 0.4 11.7 ⫾ 0.2 7.2 ⫾ 0.4 158.9 ⫾ 0.6 60.6 ⫾ 1.5 3.1 ⫾ 0.6
22.8 ⫾ 0.6 12.4 ⫾ 0.2 10.3 ⫾ 0.6 162.5 ⫾ 0.8 64.6 ⫾ 2.0 5.3 ⫾ 0.8
.001 NS .001 .001 .040 NS
24.4 ⫾ 0.3 26.7 ⫾ 0.4 1879 ⫾ 89 45 (18%) 45 (31%) 31 (13%) 159 (64%)
24.7 ⫾ 0.5 26.9 ⫾ 0.6 1811 ⫾ 144 13 (13%) 20 (33%) 12 (12%) 66 (66%)
24.0 ⫾ 0.6 26.2 ⫾ 0.6 2098 ⫾ 139 14 (15%) 17 (27%) 12 (13%) 59 (62%)
24.5 ⫾ 0.7 27.3 ⫾ 0.8 1601 ⫾ 185 18 (33%) 8 (36%) 7 (13%) 34 (62%)
NS NS NS .005 NS NS NS
NS ⫽ not significant; BMI ⫽ body mass index. * Mean ⫾ standard error of the mean or n (%). † Least squares mean ⫾ standard of the mean or n (%). ‡ Comparing least squares means or frequencies, P values reflect a test of no difference between ethnic groups. § Adjusted for the time since conception. 㛳 Adjusted for the time since delivery.
statistical analyses were done using SAS 6.10 (SAS Institute, Cary, NC).
Results As shown in Table 1, the study group had a mean (⫾ SEM) age of 19.9 ⫾ 0.3 years, a mean prepregnancy weight of 63.7 ⫾ 1.0 kg, and a mean BMI at entry into care of 24.4 ⫾ 0.3. Approximately two-thirds of participants were nulliparous. White subjects were significantly older than black or Hispanic subjects and were more likely to smoke. All bone ultrasound measures were statistically significantly lower at the postpartum visit, and the summary measure (quantitative ultrasound index) was 3.6% lower (⫺3.95 ⫾ 0.70 [mean ⫾ SEM], P ⬍ .001). Table 2 shows that all ultrasound values, after adjustment for time to entry into prenatal care and time between delivery and the first postpartum visit, remained statistically significant, with P indicating the probability that
all of the ultrasound differences were significantly different from a zero value of no change. Three factors predicted the amount of bone change: maternal growth, parity, and amount of bone mass at entry into care. Nulliparas were more likely to have greater bone change than were paras, as shown in Table 3. Adolescents who were still growing also were more likely to lose more bone, as shown in Table 4. There was more bone change among subjects with higher baseline bone ultrasound values. When bone changes were assigned to their tertiles of quantitative ultrasound index into care, it was found that patients at entry with greater baseline bone density had more bone change (Figure 1). When variables for baseline bone measure, growth, and nulliparity were entered in the regression model, the overall model explained 16% of variation in broadband ultrasound attenuation or quantitative ultrasound index, whereas it explained 22% of speed of sound change. Smoking behavior, ethnicity, weight at entry into care, weight change during pregnancy, and gyne-
Table 2. Bone Ultrasound Measures at Entry Into Care and 6 Weeks Postpartum Entry into care Broadband ultrasound attenuation (dB/mHz) Speed of sound (m/s) Quantitative ultrasound index†
6 wk postpartum
Difference
P
Adjusted P*
77.7 ⫾ 1.2
76.2 ⫾ 1.2
⫺1.47 ⫾ 0.82 (⫺1.9%)
.07
.001
1583.0 ⫾ 2.0 109.7 ⫾ 1.2
1574.70 ⫾ 1.9 105.7 ⫾ 1.2
⫺8.29 ⫾ 1.2 (⫺0.5%) ⫺3.95 ⫾ 0.70 (⫺3.6%)
.001 .001
.001 .001
Data are presented as mean ⫾ standard error of the mean. * After adjustment for weeks of gestation at entry into care and time between delivery and first postpartum visit; P values reflect a test that the mean change is not significantly different than no change. † Lower values are more likely to be noted in patients with osteoporosis.
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Table 3. Nulliparity and Bone Ultrasound Measurement Difference
Difference in quantitative ultrasound index Difference in speed of sound Difference in broadband ultrasound attenuation
Nulliparous patients (n ⫽ 159)
Parous patients (n ⫽ 93)
P*
⫺3.05 ⫾ 2.0
⫺0.05 ⫾ 2.3
.039
⫺6.93 ⫾ 3.5
⫺2.60 ⫾ 4.0
.087
⫺1.08 ⫾ 2.3
⫺0.76 ⫾ 2.6
.845
Data are presented as least squares mean ⫾ standard error of the mean. * After adjusting bone ultrasound measurement values for weeks of gestation at entry into care and weeks between delivery and first postpartum visit; P values reflect a test of no difference between parity groups.
cologic age did not predict bone loss. Patients identified as having hypertension of pregnancy or preeclampsia had a greater likelihood of more bone change, but the findings were not statistically significant. We used no direct measure of amount of bed rest; however, selfassessment of physical activity was not associated with change. Additionally, there was no evidence that preterm delivery (delivery at less than 37 weeks) was associated with greater change.
Discussion In our study, bone mass of the os calcis measured by ultrasound was lower 6 weeks postpartum than at entry into prenatal care. Two factors might explain this loss. Demand for calcium is generated by mineralization of the fetal skeleton, and expansion of plasma volume during pregnancy necessitates calcium mobilization sufficient to maintain normal circulating calcium concentrations.11 These activities are accentuated in the
Table 4. Growth in Pregnancy and Bone Ultrasound Measurement Difference
Difference in quantitative ultrasound index Difference in speed of sound Difference in broadband ultrasound attenuation
Growing adolescents (n ⫽ 45)
Grown women (n ⫽ 199)
P*
⫺5.67 ⫾ 2.4
⫺1.35 ⫾ 2.0
.020
⫺10.91 ⫾ 4.2
⫺4.43 ⫾ 3.6
.042
⫺4.96 ⫾ 2.8
0.32 ⫾ 2.3
.012
Data are presented as least squares mean ⫾ standard error of the mean. * After adjusting bone ultrasound measurement values for weeks of gestation at entry into care and weeks between delivery and first postpartum visit; P values reflect a test of no difference between growing adolescents and grown women.
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Figure 1. Differences in ultrasound bone mass change parameters, by tertile of quantitative ultrasound index (QUI) at entry into prenatal care. SOS ⫽ speed of sound; BUA ⫽ bone ultrasound attenuation.
second and third trimesters of pregnancy. In contrast, two forces tend to mitigate against bone loss in pregnancy: increased maternal weight to load bone and increased circulating estradiol concentrations in the last trimester. Findings of previous studies of bone change associated with pregnancy are inconsistent and include findings of increase at localized bone sites,12 no change,13 and bone loss.14 –16 These conflicting findings might be the result of technical limitations such as small sample size (fewer than 15 subjects)12 or cross-sectional study designs that are inadequate for describing transitional characteristics.15,17,18 Other factors that might play a role are measurement site, a mix of cortical or trabecular bone measurement sites, and different population groups. We found that patients with higher baseline bone ultrasound values were more likely to have greater bone loss during pregnancy. We believe that that is a result of having more cancellous bone surfaces available for turnover. Shahtaheri et al19 recently reported that pregnancy affects the maternal skeleton by producing fluctuations in cancellous bone volume. They identified early bone loss in bone biopsy specimens from 15 women in their first trimesters, compared with biopsy specimens from 25 nonpregnant premenopausal women. In another 13 women studied at term, those investigators found new and more numerous trabeculae, although the trabeculae were thinner. Thus, a greater bone mass might offer a more extensive periosteal bone surface and trabecular bone surface from which bone turnover then would proceed. There is increased bone turnover in the third trimester of pregnancy compared with the first trimester, as determined by measurement of urinary excretion of markers of type I collagen.20 However, the mechanism(s) whereby bone resorption might occur during pregnancy remain(s) to be delineated. The observation that bone loss was more likely in nulliparas might indicate a much more complex dy-
Obstetrics & Gynecology
namic related to calcium homeostasis. Nulliparas also were more likely to be younger and still growing, have younger gynecologic ages, and have preeclampsia and pregnancy hypertension. Nulliparity is a potential marker for increased need for calcium for adequate fetal mineralization while meeting the residual requirement for mineralization of an immature maternal skeleton. The amount of bone change reported here did not indicate osteoporosis of pregnancy.4,5 The average amount of quantitative ultrasound index change (⫺3.6%) was consistent with fetal mineralization. It is unlikely that a change of that magnitude would be associated with widespread disease. The current study did not indicate potential recovery to prepregnancy bone mass levels. Short-term reproducibility of bone ultrasound measurement was good (greater than 97%) in our sample. That degree of reproducibility was consistent with findings of other studies of ultrasound instrumentation.21,22 Reproducibility was high using the ultrasound method, but it is still not equivalent to the greater reproducibility of dual-energy x-ray absorptiometry (97–99%) observed by us and others.8 We found evidence of bone mass loss in normal pregnancy, measured with bone ultrasound technology, in an amount consistent with the demands of fetal mineralization. Three factors associated with greater loss were higher baseline bone measurement, nulliparity, and maternal growth.
References 1. Sowers M. Pregnancy and lactation as risk factors for subsequent bone loss and osteoporosis. J Bone Miner Res 1996;11:1052– 60. 2. Sowers M, Wallace RB, Lemke JH. Correlates of forearm bone mass among women during maximal bone mineralization. Prev Med 1985;14:585–96. 3. Fox KM, Magaziner J, Sherwin R, Scott JC, Plato CC, Nevitt M, et al. Reproductive correlates of bone mass in elderly women. Study of Osteoporotic Fractures Research Group. J Bone Miner Res 1993;8:901– 8. 4. Khovidhunkit W, Epstein S. Osteoporosis in pregnancy. Osteoporos Int 1996;6:345–54. 5. Dunne F, Walters B, Marshall T, Heath DA. Pregnancy associated osteoporosis. Clin Endocrinol (Oxf) 1993;39:487–90. 6. Villar J, Repke JT. Calcium supplementation during pregnancy may reduce preterm delivery in high-risk populations. Am J Obstet Gynecol 1990;163:1124 –31. 7. Kovacs CS, Kronenberg HM. Maternal-fetal calcium and bone metabolism during pregnancy, puerperium, and lactation. Endocr Rev 1997;18:832–72. 8. Sowers M, Jannausch M, Scholl T, Schall J. The reproducibility of ultrasound bone measures in a triethnic population of pregnant adolescents and adult women. J Bone Miner Res 1998;13:1768 –74. 9. Subcommittee on Nutritional Status and Weight Gain During
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10.
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Pregnancy, Institute of Medicine. Nutrition during pregnancy. Washington, DC: National Academy Press, 1990. Block G, Hartman AM, Dresser CM, Carroll MD, Gannon J, Gardner L. A data-based approach to diet questionnaire design and testing. Am J Epidemiol 1986;124:453– 69. Chesney RW, Specker BL, McKey CP. Mineral metabolism during pregnancy and lactation. In: Coe FL, Favus MJ, eds. Disorders of bone and mineral metabolism. New York: Raven, 1992:383–93. Drinkwater BL, Chesnut CH 3d. Bone density changes during pregnancy and lactation in active women: A longitudinal study. Bone Miner 1991;14:153– 60. Sowers M, Crutchfield M, Jannausch ML, Updike S, Corton G. A prospective evaluation of bone mineral change in pregnancy. Obstet Gynecol 1991;77:841–5. Aguado F, Revilla M, Hernandez ER, Menendez M, Cortes-Prieto J, Villa LF, et al. Ultrasonographic bone velocity in pregnancy: A longitudinal study. Am J Obstet Gynecol 1998;178:1016 –21. Honda A, Kurabayashi T, Yahata T, Tomita M, Takakuwa K, Tanaka K. Lumbar bone mineral density changes during pregnancy and lactation. Int J Gynaecol Obstet 1998;63:253– 8. Lamke B, Brundin J, Moberg P. Changes of bone mineral content during pregnancy and lactation. Acta Obstet Gynecol Scand 1977;56: 217–9. Yamaga A, Taga M, Minaguchi H, Sato K. Changes in bone mass as determined by ultrasound and biochemical markers of bone turnover during pregnancy and puerperium: A longitudinal study. J Clin Endocrinol Metab 1996;81:752– 6. Paparella P, Giorgino R, Maglione A, Lorusso D, Scirpa P, Del Bosco A, et al. Maternal ultrasound bone density in normal pregnancy. Clin Exp Obstet Gynecol 1995;22:268 –78. Shahtaheri SM, Aaron JE, Johnson DR, Purdie DW. Changes in trabecular bone architecture in women during pregnancy. Br J Obstet Gynaecol 1999;106:432– 8. Yamaga A, Taga M, Minaguchi H. Changes in urinary excretions of C-telopeptide and cross-linked N-telopeptide of type I collagen during pregnancy and puerperium. Endocr J 1997;44:733– 8. Yamazaki K, Kushida K, Ohmura A, Sano M, Inoue T. Ultrasound bone densitometry of the os calcis in Japanese women. Osteoporos Int 1994;4:220 –5. Naessen T, Mallmin H, Ljunghall S. Heel ultrasound in women after long-term ERT compared with bone densities in the forearm, spine and hip. Osteoporos Int 1995;5:205–10.
Address reprint requests to:
MaryFran Sowers, PhD Department of Epidemiology University of Michigan 109 South Observatory Room 3073, SPH I Ann Arbor, MI 48109-2029 E-mail: [email protected]
Received December 3, 1999. Received in revised form March 3, 2000. Accepted March 30, 2000. Copyright © 2000 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
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From the Department of Epidemiology, University of Michigan, Ann Arbor, Michigan; and the Department of Obstetrics and Gynecology, University of Medicine and Dentistry of New Jersey, Camden, New Jersey. Supported by National Institutes of Health grant ES-07437.
VOL. 96, NO. 2, AUGUST 2000
Calcium metabolism in pregnancy is complex and evokes many homeostatic mechanisms, including extracellular volume expansion, increased glomerular filtration rate, and increased demand for calcium for transport to the fetus. Maternal response to that demand theoretically can involve increased absorption of calcium from the intestine, greater calcium conservation by the kidneys, or greater bone turnover.1 Calcium needed for fetal skeletal mineralization is estimated at 30 g or approximately 3% of maternal skeletal mass if maternal skeleton were the primary source of calcium for the fetus.1 Calcium metabolism and bone turnover in pregnancy might have long-term effects on maternal bone health. For example, Sowers et al2 and Fox et al3 independently reported that earlier age at first pregnancy was associated with lower cortical bone mineral density (radius) in midlife or later. In rare cases, osteoporosis has been associated with pregnancy,4,5 and calcium homeostasis has been suggested as important in other selected maternal outcomes, including preeclampsia and toxemia.6 However, bone loss during pregnancy has been believed unlikely in most women, because of absorption of calcium from the intestine in amounts that compensate for fetal demand.7 Studying calcium homeostasis during pregnancy was more difficult when studies involved measuring radioisotopes or using x-ray energy in bone densitometry. A relatively new alternative is bone ultrasound measurement, which does not involve radiation and has been reproducible in pregnant women.8 One goal of this study was to determine the amount of change in bone ultrasound measurements among female patients assessed at entry into care and 6 –7 weeks postpartum. Changes in ultrasound bone measurements also were evaluated to determine whether adolescence, maternal growth during pregnancy, poor diet, limited weight gain during pregnancy, and pregnancy hypertension were associated with greater bone loss during pregnancy.
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Materials and Methods The population comprised 252 adolescent girls and women participating in a study of pregnancy and lactation in Camden, New Jersey. Their data, including bone ultrasound results, were collected at entry into care (approximately 16 weeks’ gestation) and at 6-week postpartum checkups. Participants were 12–34 years old and identified themselves as black (40%), white (22%), or Hispanic (predominantly Puerto Rican) (38%). Patients were excluded if they had histories of serious nonobstetric conditions (including lupus, chronic hypertension, type I or type II diabetes, seizure disorders, malignancies, and drug or alcohol abuse). Subjects provided written informed consent, consistent with the policies of institutional review boards at the University of Medicine and Dentistry of New Jersey and the University of Michigan. Bone ultrasound (Sahara; Hologic Inc., Bedford, MA) was used to measure the cancellous bone of the os calcis. Two ultrasound probes were mounted on opposite sides of a well in which the heel was positioned. Contact between the transducers and the skin was maintained with ultrasound gel. Three characteristics described the sound wave pattern and by extension the architectural properties of the bone tissue. The speed of sound (in meters per second) represented the speed of signal transmission through the heel. The broadband ultrasound attenuation (in decibels per megahertz) was the degree of attenuation of the highfrequency sound waves. The quantitative ultrasound index combines the speed of sound and broadband ultrasound attenuation into a single measure. Quantitative ultrasound indices range from 0 to 170, with greater values associated with greater bone mass and lower values occurring in osteoporosis. Three women were excluded because their feet were too large (greater than size 11) to be seated appropriately in the heel well. The machine was calibrated daily using a quality control phantom. No measurements were made until the instrument was calibrated to within acceptable range. Measurements were performed at room temperature. The coefficient of variation of this measure was approximately 3%, determined from data from 280 subjects at entry into care.8 Included in this report are data from 252 of 280 subjects who had measurements at entry into care and 6-week postpartum visits. Participants were interviewed during each trimester and approximately 6 weeks postpartum, to obtain sociodemographics and medical histories. They also were measured for changes in body size and other physical characteristics at entry into care and 6 weeks postpartum. Variables included participant age at entry into care; pregravid weight, based on the individual’s recalled
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prepregnancy weight at entry into care; height, measured at entry into care; and pregravid body mass index (BMI). Pregravid BMI was used as a continuous variable in multiple variable regression modeling or trichotomized according to levels specified by the Institute of Medicine report.9 Those levels were 19.8 or less (underweight), 19.8 –26 (normal weight), and more than 26 (overweight). Weight gain during pregnancy was determined by calculating the difference between selfreported pregravid weight and weight at entry into care. Perceptions of physical activity were based on responses to the questionnaire and perceived physical activity was rated by participants in relation to their peers using a five-level variable. Current smoking behavior at entry into care was a dichotomous variable. Usual dietary calcium intake (in milligrams per day) was estimated by adding up amounts of calcium in calcium foods consumed.10 Diagnoses of hypertension in pregnancy, preeclampsia, or toxemia were abstracted from medical records. Preterm delivery was defined as delivery at less than 37 weeks’ gestation, with gestational age determined by ultrasound. Parity before the index pregnancy was treated as a dichotomous variable. Growth in pregnancy was determined by calculating the difference in knee height between entry into care and the first postpartum visit. The change in knee height was standardized to a 6-month interval, to adjust for the length of time over which change occurred. Patients age 19 years or younger who had at least 1 mm of growth were classified as growing adolescents. Differences in ultrasound bone mass were treated as continuous variables in data analysis. However, baseline bone mass was classified into tertiles to show association with bone mass change. Ultrasound bone change was adjusted for individual differences between conception and entry into care and for individual variation between date of delivery and date of the first postpartum visit in the general linear models. Unadjusted P values depicted the probability of no association between bone change and the independent variables. Adjusted P values depicted the probability of no association between bone change and the independent variables after adjusting for variations in time differences between conception and entry into care and for individual variation between date of delivery and date of the first postpartum visit. Dummy variables were used to describe categoric independent variables such as parity. Data are presented as mean ⫾ standard error of the mean (SEM) or least squares mean ⫾ SEM. After each independent variable was evaluated for association with bone ultrasound change, variables that were statistically significant at the .10 level were entered into a multiple variable regression model. All
Obstetrics & Gynecology
Table 1. Patient Characteristics, by Ethnic Group
Age (y) Age at menarche (y) Gynecologic age (y) Height (cm) Pregravid weight (kg) Weight gain in pregnancy (kg) BMI At entry into care§ At postpartum visit㛳 Daily dietary calcium intake (mg) Current smoker Growing adolescent Preterm delivery Nulliparous
Overall* (n ⫽ 252)
Black† (n ⫽ 101)
Hispanic† (n ⫽ 96)
White† (n ⫽ 55)
P‡
19.9 ⫾ 0.3 12.0 ⫾ 0.1 7.9 ⫾ 0.3 161.4 ⫾ 0.4 63.7 ⫾ 1.0 4.3 ⫾ 0.4
19.5 ⫾ 0.4 12.1 ⫾ 0.2 7.4 ⫾ 0.4 163.3 ⫾ 0.6 66.2 ⫾ 1.5 4.8 ⫾ 0.6
18.9 ⫾ 0.4 11.7 ⫾ 0.2 7.2 ⫾ 0.4 158.9 ⫾ 0.6 60.6 ⫾ 1.5 3.1 ⫾ 0.6
22.8 ⫾ 0.6 12.4 ⫾ 0.2 10.3 ⫾ 0.6 162.5 ⫾ 0.8 64.6 ⫾ 2.0 5.3 ⫾ 0.8
.001 NS .001 .001 .040 NS
24.4 ⫾ 0.3 26.7 ⫾ 0.4 1879 ⫾ 89 45 (18%) 45 (31%) 31 (13%) 159 (64%)
24.7 ⫾ 0.5 26.9 ⫾ 0.6 1811 ⫾ 144 13 (13%) 20 (33%) 12 (12%) 66 (66%)
24.0 ⫾ 0.6 26.2 ⫾ 0.6 2098 ⫾ 139 14 (15%) 17 (27%) 12 (13%) 59 (62%)
24.5 ⫾ 0.7 27.3 ⫾ 0.8 1601 ⫾ 185 18 (33%) 8 (36%) 7 (13%) 34 (62%)
NS NS NS .005 NS NS NS
NS ⫽ not significant; BMI ⫽ body mass index. * Mean ⫾ standard error of the mean or n (%). † Least squares mean ⫾ standard of the mean or n (%). ‡ Comparing least squares means or frequencies, P values reflect a test of no difference between ethnic groups. § Adjusted for the time since conception. 㛳 Adjusted for the time since delivery.
statistical analyses were done using SAS 6.10 (SAS Institute, Cary, NC).
Results As shown in Table 1, the study group had a mean (⫾ SEM) age of 19.9 ⫾ 0.3 years, a mean prepregnancy weight of 63.7 ⫾ 1.0 kg, and a mean BMI at entry into care of 24.4 ⫾ 0.3. Approximately two-thirds of participants were nulliparous. White subjects were significantly older than black or Hispanic subjects and were more likely to smoke. All bone ultrasound measures were statistically significantly lower at the postpartum visit, and the summary measure (quantitative ultrasound index) was 3.6% lower (⫺3.95 ⫾ 0.70 [mean ⫾ SEM], P ⬍ .001). Table 2 shows that all ultrasound values, after adjustment for time to entry into prenatal care and time between delivery and the first postpartum visit, remained statistically significant, with P indicating the probability that
all of the ultrasound differences were significantly different from a zero value of no change. Three factors predicted the amount of bone change: maternal growth, parity, and amount of bone mass at entry into care. Nulliparas were more likely to have greater bone change than were paras, as shown in Table 3. Adolescents who were still growing also were more likely to lose more bone, as shown in Table 4. There was more bone change among subjects with higher baseline bone ultrasound values. When bone changes were assigned to their tertiles of quantitative ultrasound index into care, it was found that patients at entry with greater baseline bone density had more bone change (Figure 1). When variables for baseline bone measure, growth, and nulliparity were entered in the regression model, the overall model explained 16% of variation in broadband ultrasound attenuation or quantitative ultrasound index, whereas it explained 22% of speed of sound change. Smoking behavior, ethnicity, weight at entry into care, weight change during pregnancy, and gyne-
Table 2. Bone Ultrasound Measures at Entry Into Care and 6 Weeks Postpartum Entry into care Broadband ultrasound attenuation (dB/mHz) Speed of sound (m/s) Quantitative ultrasound index†
6 wk postpartum
Difference
P
Adjusted P*
77.7 ⫾ 1.2
76.2 ⫾ 1.2
⫺1.47 ⫾ 0.82 (⫺1.9%)
.07
.001
1583.0 ⫾ 2.0 109.7 ⫾ 1.2
1574.70 ⫾ 1.9 105.7 ⫾ 1.2
⫺8.29 ⫾ 1.2 (⫺0.5%) ⫺3.95 ⫾ 0.70 (⫺3.6%)
.001 .001
.001 .001
Data are presented as mean ⫾ standard error of the mean. * After adjustment for weeks of gestation at entry into care and time between delivery and first postpartum visit; P values reflect a test that the mean change is not significantly different than no change. † Lower values are more likely to be noted in patients with osteoporosis.
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Table 3. Nulliparity and Bone Ultrasound Measurement Difference
Difference in quantitative ultrasound index Difference in speed of sound Difference in broadband ultrasound attenuation
Nulliparous patients (n ⫽ 159)
Parous patients (n ⫽ 93)
P*
⫺3.05 ⫾ 2.0
⫺0.05 ⫾ 2.3
.039
⫺6.93 ⫾ 3.5
⫺2.60 ⫾ 4.0
.087
⫺1.08 ⫾ 2.3
⫺0.76 ⫾ 2.6
.845
Data are presented as least squares mean ⫾ standard error of the mean. * After adjusting bone ultrasound measurement values for weeks of gestation at entry into care and weeks between delivery and first postpartum visit; P values reflect a test of no difference between parity groups.
cologic age did not predict bone loss. Patients identified as having hypertension of pregnancy or preeclampsia had a greater likelihood of more bone change, but the findings were not statistically significant. We used no direct measure of amount of bed rest; however, selfassessment of physical activity was not associated with change. Additionally, there was no evidence that preterm delivery (delivery at less than 37 weeks) was associated with greater change.
Discussion In our study, bone mass of the os calcis measured by ultrasound was lower 6 weeks postpartum than at entry into prenatal care. Two factors might explain this loss. Demand for calcium is generated by mineralization of the fetal skeleton, and expansion of plasma volume during pregnancy necessitates calcium mobilization sufficient to maintain normal circulating calcium concentrations.11 These activities are accentuated in the
Table 4. Growth in Pregnancy and Bone Ultrasound Measurement Difference
Difference in quantitative ultrasound index Difference in speed of sound Difference in broadband ultrasound attenuation
Growing adolescents (n ⫽ 45)
Grown women (n ⫽ 199)
P*
⫺5.67 ⫾ 2.4
⫺1.35 ⫾ 2.0
.020
⫺10.91 ⫾ 4.2
⫺4.43 ⫾ 3.6
.042
⫺4.96 ⫾ 2.8
0.32 ⫾ 2.3
.012
Data are presented as least squares mean ⫾ standard error of the mean. * After adjusting bone ultrasound measurement values for weeks of gestation at entry into care and weeks between delivery and first postpartum visit; P values reflect a test of no difference between growing adolescents and grown women.
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Figure 1. Differences in ultrasound bone mass change parameters, by tertile of quantitative ultrasound index (QUI) at entry into prenatal care. SOS ⫽ speed of sound; BUA ⫽ bone ultrasound attenuation.
second and third trimesters of pregnancy. In contrast, two forces tend to mitigate against bone loss in pregnancy: increased maternal weight to load bone and increased circulating estradiol concentrations in the last trimester. Findings of previous studies of bone change associated with pregnancy are inconsistent and include findings of increase at localized bone sites,12 no change,13 and bone loss.14 –16 These conflicting findings might be the result of technical limitations such as small sample size (fewer than 15 subjects)12 or cross-sectional study designs that are inadequate for describing transitional characteristics.15,17,18 Other factors that might play a role are measurement site, a mix of cortical or trabecular bone measurement sites, and different population groups. We found that patients with higher baseline bone ultrasound values were more likely to have greater bone loss during pregnancy. We believe that that is a result of having more cancellous bone surfaces available for turnover. Shahtaheri et al19 recently reported that pregnancy affects the maternal skeleton by producing fluctuations in cancellous bone volume. They identified early bone loss in bone biopsy specimens from 15 women in their first trimesters, compared with biopsy specimens from 25 nonpregnant premenopausal women. In another 13 women studied at term, those investigators found new and more numerous trabeculae, although the trabeculae were thinner. Thus, a greater bone mass might offer a more extensive periosteal bone surface and trabecular bone surface from which bone turnover then would proceed. There is increased bone turnover in the third trimester of pregnancy compared with the first trimester, as determined by measurement of urinary excretion of markers of type I collagen.20 However, the mechanism(s) whereby bone resorption might occur during pregnancy remain(s) to be delineated. The observation that bone loss was more likely in nulliparas might indicate a much more complex dy-
Obstetrics & Gynecology
namic related to calcium homeostasis. Nulliparas also were more likely to be younger and still growing, have younger gynecologic ages, and have preeclampsia and pregnancy hypertension. Nulliparity is a potential marker for increased need for calcium for adequate fetal mineralization while meeting the residual requirement for mineralization of an immature maternal skeleton. The amount of bone change reported here did not indicate osteoporosis of pregnancy.4,5 The average amount of quantitative ultrasound index change (⫺3.6%) was consistent with fetal mineralization. It is unlikely that a change of that magnitude would be associated with widespread disease. The current study did not indicate potential recovery to prepregnancy bone mass levels. Short-term reproducibility of bone ultrasound measurement was good (greater than 97%) in our sample. That degree of reproducibility was consistent with findings of other studies of ultrasound instrumentation.21,22 Reproducibility was high using the ultrasound method, but it is still not equivalent to the greater reproducibility of dual-energy x-ray absorptiometry (97–99%) observed by us and others.8 We found evidence of bone mass loss in normal pregnancy, measured with bone ultrasound technology, in an amount consistent with the demands of fetal mineralization. Three factors associated with greater loss were higher baseline bone measurement, nulliparity, and maternal growth.
References 1. Sowers M. Pregnancy and lactation as risk factors for subsequent bone loss and osteoporosis. J Bone Miner Res 1996;11:1052– 60. 2. Sowers M, Wallace RB, Lemke JH. Correlates of forearm bone mass among women during maximal bone mineralization. Prev Med 1985;14:585–96. 3. Fox KM, Magaziner J, Sherwin R, Scott JC, Plato CC, Nevitt M, et al. Reproductive correlates of bone mass in elderly women. Study of Osteoporotic Fractures Research Group. J Bone Miner Res 1993;8:901– 8. 4. Khovidhunkit W, Epstein S. Osteoporosis in pregnancy. Osteoporos Int 1996;6:345–54. 5. Dunne F, Walters B, Marshall T, Heath DA. Pregnancy associated osteoporosis. Clin Endocrinol (Oxf) 1993;39:487–90. 6. Villar J, Repke JT. Calcium supplementation during pregnancy may reduce preterm delivery in high-risk populations. Am J Obstet Gynecol 1990;163:1124 –31. 7. Kovacs CS, Kronenberg HM. Maternal-fetal calcium and bone metabolism during pregnancy, puerperium, and lactation. Endocr Rev 1997;18:832–72. 8. Sowers M, Jannausch M, Scholl T, Schall J. The reproducibility of ultrasound bone measures in a triethnic population of pregnant adolescents and adult women. J Bone Miner Res 1998;13:1768 –74. 9. Subcommittee on Nutritional Status and Weight Gain During
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Address reprint requests to:
MaryFran Sowers, PhD Department of Epidemiology University of Michigan 109 South Observatory Room 3073, SPH I Ann Arbor, MI 48109-2029 E-mail: [email protected]
Received December 3, 1999. Received in revised form March 3, 2000. Accepted March 30, 2000. Copyright © 2000 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
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