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Biology of Reproduction 61, 1439-1444 (1999)
©Copyright 1999 Society for the Study of Reproduction, Inc.

Articles

Increased Intracortical Bone Remodeling During Lactation in Beagle Dogs1

E.G. Vajdaa,b, M. Kneissela,c, B. Muggenburgd, and S.C. Miller2,a

a Radiobiology Division, School of Medicine, University of Utah, Salt Lake City, Utah 84108-1218 b Department of Veterans Affairs Medical Center, Salt Lake City, Utah 84108 c Novartis Pharma AG, Basel, Switzerland d Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87185


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
There are substantial changes in skeletal and mineral metabolism during pregnancy and lactation. The purpose of this study was to determine the changes in intracortical bone remodeling and turnover during lactation in beagle dogs. A femur and rib were obtained from dogs near the end of lactation or soon after weaning and compared with nonlactating controls. Rib cortical bone had much higher bone turnover rates than did femoral diaphyseal cortical bone. The number of single-labeled osteons and the number of resorption spaces were significantly greater during lactation in both the rib and the femur. Additionally, the mineral apposition rate, basic multicellular unit activation frequency, and bone turnover rates were greater in the femoral cortical bone from the lactating dogs than from the controls. These data demonstrate that during lactation, intracortical bone remodeling increases, and this may provide a mechanism for the skeleton to be responsive to the calcium requirements of the mother. In addition, these data may help explain the transient decreases in cortical bone mineral density that are reported to occur during human lactation.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Substantial changes in mineral metabolism occur during pregnancy and lactation in both humans and animals. During early pregnancy in many species, the intake and intestinal absorption of calcium is increased, resulting in a positive calcium balance [1–3]. In rats, increased calcium retention during early pregnancy is associated with an increase in bone growth and mass [4], and it has been suggested that this may serve as a storage reservoir for the impending calcium requirements of fetal skeletal mineralization. A similar positive calcium balance has been reported in humans during early pregnancy [3], but measurable changes in bone mass have generally not been significant during this period [5, 6]. In later pregnancy as the fetal skeleton begins to mineralize, the bone mass of the maternal skeleton may decline as reported in both animals and humans [6, 7].

The effect of lactation on human skeletal metabolism has been inferred from serum chemistry or bone densitometry measurements because histomorphometric studies have not been conducted. Serum and urine markers of both bone formation and resorption are generally elevated during lactation [8]. Most longitudinal studies using bone densitometry performed at predominantly cancellous bone sites (e.g., vertebrae) have reported decreases in bone mass during lactation [5, 9–11], while a few studies have reported no measurable change in bone mass [12]. When measurements were made at predominantly cortical bone sites in humans, there were reports of decreases [12–14], increases [8, 12], or no changes [5, 9, 11, 12, 14, 15] in bone mass during lactation.

Studies of lactation in animal models indicate that cancellous bone loss occurs during lactation in rats [16], dogs [17], sheep [18], pigs [19], and monkeys [20]. Histomorphometry reveals that the lactation-induced decrease in bone mass is associated with a marked increase in cancellous bone remodeling as reported in dogs [17, 21] and rats [4, 22]. Cortical bone mass decreases during lactation in rats, and this has been attributed to decreased periosteal apposition coupled with increased endocortical resorption and expansion of the medullary cavity [4, 23]. Increased intracortical bone remodeling has been reported to occur in rats during multiple lactations, but only when dietary calcium is restricted [24].

The intracortical bone changes that may occur during a normal lactation in a longer-lived, normally remodeling species are not known. The purpose of this study was to determine whether there are indications of increased intracortical bone remodeling during lactation in dogs. For this, a weight-bearing (femur) and a non-weight-bearing (rib) site from a group of beagle dogs during or immediately after lactation were analyzed using histomorphometric methods.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Skeletal Tissues

The skeletal tissues were obtained from a collection of tissues that had been archived from previous studies. For this, a rib and a femur were obtained from nine normal female beagle dogs; six were unmated controls (mean age: 59 mo), and three were dogs at the end of lactation (mean age: 50 mo; Table 1). The lactating dogs had lactated from 33 to 35 days. The normal lactation period for a beagle dog is about 35 days [25]. Two additional sets of bones became available to us from dogs that were 17 days postweaning. Although this did not represent a group large enough for statistical comparison, the data from the postlactational dogs are included as a preliminary observation. All animals had been maintained at a beagle colony at the University of Utah (Salt Lake City, UT) or at the Lovelace Respiratory Research Institute (Albuquerque, NM) and were used in studies that were approved by the Institutional Animal Use and Care Committees. The beagle dogs in these colonies were a homogeneous population because of selective inbreeding and crossbreeding [26]. All dogs had reached skeletal maturity, which typically occurs at about 13 mo of age in beagles [25], and significant age-related osteopenia is unlikely, as this typically does not occur before 125 mo of age [27]. The animals were given tap water ad libitum and fed a mixture of dry dog meal and canned beef with a total calcium:phosphorous ratio of about 1.2:1.


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  		TABLE 1. Age, lactation status, and number of pups of the animals used in this study

Each dog had been given an i.v. injection of 20 mg/kg BW of tetracycline-HCl (Achromycin; Lederle Division, American Cyanamide Co., Pearl River, NY) at 18 and 17 days before necropsy. At 8 and 7 days before necropsy, the animals had been given an i.v. injection of 10 mg/kg BW calcein green (fluorescein-methylene-imino-diacetic acid; Sigma Chemical Co., St. Louis, MO).

The midfemoral diaphysis and a rib were fixed in 0.1 M phosphate-buffered 10% formalin for 24 h, dehydrated in ascending concentrations of ethanol, and embedded undecalcified in methyl methacrylate. Transverse sections of the rib and femoral shaft were cut with a low-speed saw (Isomet; Buehler Ltd., Lake Bluff, IL) and mounted on plastic slides. Slides were manually ground to approximately 30–40 µm in thickness on a rotary grinding wheel (Ecomet 5; Buehler Ltd.) and polished.

Histomorphometry

Histomorphometry was performed on one entire rib cross section (5–8 mm2 of cortical bone) and from one or two entire femur cross sections (40–110 mm2 of cortical bone). Measurements of tissue area, cortical bone area, and porosity were obtained by manual point-counting methods using a Merz (Klarmann Rulings, Inc., Manchester, NH) eyepiece reticule. Osteocyte lacunae were not counted as voids for porosity measurements. Only haversian canals and Volkmann's canals were considered to be voids. Dynamic histomorphometry measurements were performed on a fluorescence microscope equipped with a camera lucida and interfaced with a digitizing tablet and an Apple SE Computer (Apple, Cupertino, CA) running histomorphometry software (KSS Scientific Consultants, Magna, UT). Primary measured indices included the number of resorption, reversal, single-labeled (sL), and double-labeled (dL) osteons. Reversal osteons were defined as osteons containing both a resorption surface and some fluorochrome markers indicative of bone mineralization. In addition, the sL perimeter, dL perimeter, and the distance between double labels (inter-label width) were measured.

On the basis of the measured primary indices, the mineral apposition rate (MAR) was calculated as inter-label width divided by the time between labels. Because all sections were cut transverse to the long axis of the bone, MAR was not corrected for section obliquity. The volume-referent bone formation rate (BFRv) was calculated on the basis of the total mineralizing perimeter, where mineralizing perimeter equals dL perimeter + 1/2 sL perimeter, to account for label-escape.

The osteon diameter was measured using a Merz eyepiece reticule for 25 randomly selected, fluorochrome-labeled osteons from each bone, and the haversian canal diameter was measured from 25 randomly selected, unlabeled osteons. The measurement of osteon diameter from osteons that contained fluorochrome marker ensured that only osteons that had formed during the experimental period were quantified. The mean wall thickness was calculated as 1/2 (osteon diameter - haversian canal diameter), and the osteon formation time ({sigma}f) was calculated as mean wall thickness/MAR. In some bones with low bone turnover, there were fewer than 25 labeled osteons, and all labeled osteons present were measured. The activation frequency of the basic multicellular unit (BMU) was calculated as:


[28]

Histomorphometric indices conformed to the recommendations made by the American Society for Bone and Mineral Research Nomenclature Committee [29].

Statistical Analysis

For each bone, differences between lactating and control dogs were tested using an unpaired, one-tailed, Student's t-test. For the static measurements of bone size (tissue area, cortical bone area) a two-tailed t-test was used, because the effects of pregnancy and lactation might have opposite effects on these measurements when compared to those in virgin controls [4]. A P value of less than 0.05 was considered statistically significant. Because of the relatively small number of animals in the groups and the inherent variability encountered in beagle dogs, mention is made of probability values in which 0.1 > P > 0.05, and these are considered only as statistical trends. Data are expressed as the mean ± standard error of the mean.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
As expected, there were substantial differences in the static and dynamic morphometric indices between the rib and the femur in the control animals. The rib has a much greater inherent intracortical bone remodeling activity than the femur. For example, the volume-referent bone turnover rate in the rib is about 12 times greater than in the femur (Fig. 1), and similar differences were noted for many other indices of bone formation and turnover, including number of sL and dL osteons, number of resorption and reversal osteons, and activation frequency (Table 2).



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  		FIG. 1. Backscattered electron images of a control rib (a), lactating rib (b), control femur (c), and lactating femur (d). Ribs have more newly formed, poorly mineralized osteons (arrowheads) than the femur, indicating a greater remodeling rate. Lactating bones have more new osteons and resorption spaces (small arrows) than control bones. Bar width = 300 µm


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  		TABLE 2. Histomorphometric indices of intracortical bone remodeling during lactation in the rib and femur

In the rib from the lactation animals, the number of sL osteons and the number of resorption and reversal osteons were significantly greater than in the controls—160% and 100% greater, respectively. None of the other measured indices were significantly greater in lactating dog ribs.

The effects of lactation on intracortical bone remodeling were more apparent in the femoral diaphyseal shaft, probably because of the much lower basal bone remodeling rates at this site. No significant differences in tissue area were observed, but a significant decrease in cortical bone area/tissue area was observed in lactating dogs. In the femur from one of the control dogs, no dL osteons were observed although a double label was confirmed in the rib. The calculated indices of mineral apposition rate, bone turnover, and osteon formation time were performed for the remaining five control dogs. Even with this animal excluded from the statistical evaluation, BMU activation frequency and the number of sL osteons and of resorption and reversal osteons were significantly greater in lactating dog femurs than in control dog femurs (235%, 400%, and 46%, respectively). There were statistical trends in the BFRv and MAR, which were 285% and 29% greater than their respective controls. The osteon formation time was less (20%) in the lactating dogs, but not significantly less, which could be attributed to a significant increase in the MAR rather than differences in osteon size, because no differences were observed in the mean wall thickness.

In both the rib and the femur, bone formation and mineral apposition rates were greatly elevated in the postlactating dogs with respect to both control and lactating dogs. The number of resorption osteons did not show a correspondingly large increase. Although the sample was too small for statistical comparison, the data suggest that postlactation is a recovery phase, with elevated bone formation to reconstitute skeletal stores lost during pregnancy and lactation.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The need for calcium for milk production during lactation causes substantial changes in mineral and skeletal metabolism. There are substantial increases in cancellous bone remodeling [4, 17] and endocortical bone modeling [4], but decreases in endochondral growth [30] during lactation in experimental animals. Measurements of bone mass and of serum and urine markers of formation and resorption also suggest that substantial changes in skeletal metabolism occur in humans during lactation (reviewed in [31]). The present study documents increased intracortical bone remodeling and turnover in a weight-bearing (femur) and non-weight-bearing but mechanically loaded bone (rib) in lactating or immediately postlactating animals compared with nonlactating dogs.

The basal intracortical bone turnover rates in the rib were much greater than those observed in the femoral mid-diaphyseal shaft in the control animals. These site-specific differences are consistent with previous studies that have documented the rib as a relatively high-turnover bone [32]. The changes that occurred as a result of lactation were generally more evident in the femur, perhaps because of the low basal bone remodeling rates, which permitted the changes to be more detectable. In addition to the more pronounced effect observed in the femur, there was lower variability encountered in the femur than in the rib among the animals. Intracortical bone remodeling in the canine rib is, however, known to be sensitive to endocrine manipulations: Wilson et al. [32] recently reported a 7-fold increase in bone turnover in the rib at 4 mo after ovariectomy.

The increased intracortical bone remodeling that was associated with lactation in the dog is consistent with previous reports of increased cancellous bone remodeling in this species [17, 21]. Analogous to the present study, these previous studies reported increases in cancellous bone-labeled perimeter, mineral appositional rates, volume referent bone formation rates, and eroded and osteoclast perimeter, indicative of accelerated bone turnover rates. Similar to what has been reported on dog cancellous bone, increased cancellous bone turnover is documented in the rat [4]. Unlike that in the dog, however, intracortical bone remodeling in the rat has not been observed during the reproductive cycle, except during multiple reproductive cycles and when calcium is restricted in the diet [24].

There are no histological or histomorphometric data available on intracortical bone remodeling during lactation in humans. However, depending on the study design, the age of the women used, and the methods employed, some investigators have found decreased mineral density at predominantly cortical bone sites during lactation. When multiple sites are compared, however, greater changes in bone mineral content or bone mineral density were usually observed at predominantly cancellous bone rather than cortical bone sites (reviewed in [31]). Interestingly, some of the greatest cortical bone changes (about 15% loss) were observed in teenage mothers who consumed less than the recommended daily allowances of calcium [33]. While bone loss at the endocortical surface may account for some of the changes observed in humans, the activation of intracortical bone remodeling during lactation, as demonstrated in the present study, would increase the remodeling space, resulting in a transient decrease in bone mineral density. Increased intracortical bone remodeling is also consistent with the serum and urine measurements that generally show both increased bone resorption and formation during lactation in humans (reviewed in [31]).

A transient increase in bone remodeling during lactation has been proposed as a mechanism to meet the calcium demands of milk production while maintaining the structural integrity of the maternal skeleton [23]. The activation of bone remodeling would help to accommodate the immediate calcium requirements of the neonate and would also provide an increased population of osteoclasts to respond to shorter- and longer-term calcium stresses. The subsequent increase in bone formation may serve to increase the capacity of the skeleton to serve as a systemic calcium buffer, as it is generally believed that mineral exchange occurs more readily in low-density bone. Elevated bone formation may also lead to a transient decrease in bone mineral content as more new osteons are formed, which typically have less mineral than mature osteons. Newly formed bone reaches approximately 65% of full mineralization very rapidly as new mineral crystallites are formed, but complete mineralization occurs much more slowly as the mineral crystallites grow in size [34, 35]. Bone remodeling would also replace older and presumably less structurally competent bone with younger bone, which may improve skeletal integrity over the longer term. This concept is supported with some human epidemiological data that show a positive correlation between reproductive cycles and the maintenance of the maternal skeleton in later life [36, 37]. Fox et al. [38], for example, calculated a 1.4% increase in bone density measured at the wrist for each birth. The data from the present study suggest that this may also be the result of a pronounced recovery phase that restores skeletal mineral lost during pregnancy and lactation.

The animals used in this study had from 2 to 7 pups in each litter. When the bone turnover values were reviewed for each individual animal, the one with the largest number of pups also had the highest bone turnover rates (data not shown). This might be expected because this animal would also have the greatest demands placed on its calcium homeostatic system, and it is consistent with previous reports demonstrating a positive correlation between the amount of bone loss and the number of lactating offspring [7, 39]. The differences in litter size between lactating and postlactating dogs, rather than the effects of lactation versus postlactation, may explain some of the variation in intracortical remodeling between the two groups. It was not possible to account for this in the present study and the data from postlactational dogs must be viewed as a preliminary finding.

The endocrine mechanisms involved in changes in intracortical and cancellous bone remodeling during lactation are not clear. The levels of the calciotrophic hormones, 1,25 dihydroxyvitamin D, 25-hydroxyvitamin D, and parathyroid hormone (PTH) do not correlate with concentrations of bone turnover markers or changes in bone mineral density measurements during lactation in women [40]. In the rat, PTH and vitamin D levels are elevated during lactation [41], but studies suggest that bone loss is independent of PTH and vitamin D levels [42]. Lactation is also a hypoestrogenic state, and a comparison of bone dynamics in the estrogen-deficient ovariectomized beagle with the lactation-induced changes observed in the present study reveals substantial similarities. Both lactation and ovariectomy [32] have transient increases in bone formation rate and turnover rates. Ovariectomy appears to have a larger effect on bone turnover than lactation in dogs, but this would be anticipated because of the sustained depletion of serum estrogen levels that occur after ovariectomy. PTH-related peptide (PTHrP) has also been considered as a possible endocrine mediator involved in increased bone turnover during lactation. PTHrP levels are elevated in maternal serum during lactation, and the levels are negatively correlated with changes in bone mineral density in the spine and the femoral neck [43].

In summary, this study demonstrates that there are substantial increases in intracortical bone remodeling during lactation in a long-lived, normally remodeling species. These data on cortical bone are consistent with the increases in cancellous bone remodeling that occur during lactation in multiple species. An increase in intracortical bone remodeling would result in a reduction in cortical bone mineral density, consistent with many reports in the human and consistent with metabolic markers of bone formation and resorption.


   ACKNOWLEDGMENTS
 
The authors thank Mary Beth Bowman for technical assistance and Roy D. Bloebaum, Ph.D. for use of the electron microscope.


   FOOTNOTES
 
1 This work was supported by grants DE-07008 and AR44806 from the National Institutes of Health and by the Department of Veterans Affairs Office of Research and Development. Back

2 Correspondence: Scott C. Miller, Division of Radiobiology, University of Utah, 729 Arapeen Dr., Salt Lake City, UT 84108-1218. FAX: 801 581 7008; scmiller{at}hsc.utah.edu Back

Accepted: July 20, 1999.

Received: April 28, 1999.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Brommage R, Baxter DC. Elevated calcium, phosphorus, and magnesium retention in pregnant rats prior to the onset of fetal skeletal mineralization. J Bone Miner Res 1988; 3:667–672.[Medline]
  2. Goss H, Schmidt CLA. Calcium and phosphorus metabolism in rats during pregnancy and lactation and the influence of the reaction of the diet thereon. J Biol Chem 1930; 86:417–432.[Free Full Text]
  3. Heaney RP, Skillman TG. Calcium metabolism in normal human pregnancy. J Clin Endocrinol 1971; 33:661–670.[Medline]
  4. Miller SC, Shupe JG, Redd EH, Miller MA, Omura TH. Changes in bone mineral and bone formation rates during pregnancy and lactation in rats. Bone 1986; 7:283–287.[Medline]
  5. Ritchie LD, Fung EB, Halloran BP, Turnlund JR, Van Loan MD, Cann CE, King JC. A longitudinal study of calcium homeostasis during human pregnancy and lactation and after resumption of menses. Am J Clin Nutr 1998; 67:693–701.[Abstract]
  6. Sowers M. Pregnancy and lactation as risk factors for subsequent bone loss and osteoporosis. J Bone Miner Res 1996; 11:1052–1060.[Medline]
  7. Tojo Y, Kurabayashi T, Honda A, Yamamoto Y, Yahata T, Takakuwa K, Tanaka K. Bone structural and metabolic changes at the end of pregnancy and lactation in rats. Am J Obstet Gynecol 1998; 178:180–185.[CrossRef][Medline]
  8. Cross NA, Hillman LS, Allen SH, Krause GF. Changes in bone mineral density and markers of bone remodeling during lactation and postweaning in women consuming high amounts of calcium. J Bone Miner Res 1995; 10:1312–1320.[Medline]
  9. Hayslip CC, Klein TA, Wray HL, Duncan WE. The effects of lactation on bone mineral content in healthy postpartum women. Obstet Gynecol 1989; 73:588–592.[Abstract/Free Full Text]
  10. Kalkwarf HJ, Specker BL, Bianchi DC, Ranz JMH. The effect of calcium supplementation on bone density during lactation and after weaning. N Engl J Med 1997; 337:523–528.[Abstract/Free Full Text]
  11. Krebs NF, Reidinger CJ, Robertson AD, Brenner M. Bone mineral density changes during lactation: maternal, dietary, and biochemical correlates. Am J Clin Nutr 1997; 65:1738–1746.[Abstract/Free Full Text]
  12. Drinkwater BL, Chesnut CH. Bone density changes during pregnancy and lactation in active women: a longitudinal study. Bone Miner 1991; 14:153–160.[CrossRef][Medline]
  13. Atkinson PJ, West RR. Loss of skeletal calcium in lactating women. J Obstet Gynaecol Br Commonw 1970; 77:555–560.[Medline]
  14. Chan GM, Slater P, Ronald N, Roberts CC, Thomas MR, Folland D, Jackson R. Bone mineral status of lactating mothers of different ages. Am J Obstet Gynecol 1982; 144:438–441.[Medline]
  15. Frisancho AR, Garn SM, Ascoli W. Unaltered cortical area of pregnant and lactating women: studies of the second metacarpal bone in North and Central American populations. Invest Radiol 1971; 6:119–121.[Medline]
  16. Komarkova A, Zahor Z, Czabanova V. The effect of lactation on the composition of long bones in rats. J Lab Clin Med 1967; 69:102–109.
  17. Miller MA, Omura TH, Miller SC. Increased cancellous bone remodeling during lactation in beagles. Bone 1989; 10:279–285.[Medline]
  18. Benzie D, Boyne AD, Dalgarno AC, Duckworth J, Hill R, Walker DM. Studies of the skeleton of the sheep. I. The effect of different levels of dietary calcium during pregnancy and lactation on individual bones. J Agric Sci 1955; 46:425–444.
  19. Spencer GR. Pregnancy and lactational osteoporosis. Animal model: porcine lactational osteoporosis. Am J Pathol 1979; 95:277–280.[Medline]
  20. Hiyaoka A, Yoshida T, Cho F, Yoshikawa Y. Changes in bone mineral density of lumbar vertebrae after parturition in African green monkeys (Cercopithecus aethiops). Exp Anim 1996; 45:257–259.[CrossRef][Medline]
  21. Fukuda S, Iida H. Histomorphometric changes in iliac trabecular bone during pregnancy and lactation in beagle dogs. J Vet Med Sci 1993; 55:565–569.[Medline]
  22. Marie PJ, Cancela L, LeBoulch N, Miravet L. Bone changes due to pregnancy and lactation: influence of vitamin D status. Am J Physiol 1986; 251:E400-E406.
  23. Miller SC, Bowman BM. Comparison of bone loss during normal lactation with estrogen deficiency osteopenia and immobilization osteopenia in the rat. Anat Rec 1998; 251:265–274.[CrossRef][Medline]
  24. Ruth EB. Bone studies. II. An experimental study of the haversian-type vascular channels. Am J Anat 1953; 93:429–455.
  25. Parcher JW, Williams JR. Ossification. In: Anderson AC, Good LS (eds.), The Beagle as an Experimental Dog. Ames, IA: The Iowa State University Press; 1970: 158–161.
  26. Bielfelt SW, Wilson AJ, Redman HC, McClelland RO, Rosenblatt LS. A breeding program for the establishment and maintenance of a stable gene pool in a beagle dog colony to be utilized for long-term experiments. Am J Vet Res 1969; 30:2221–2229.[Medline]
  27. Jee WSS, Bartley JMH, Cooper RR, Dockum NL. Bone structure. In: Anderson AC, Good LS (eds.), The Beagle as an Experimental Dog. Ames, IA: The Iowa State University Press; 1970: 162–188.
  28. Martin RB, Burr DB. Structure, Function and Adaptation of Compact Bone. New York: Raven Press; 1989: 1–275.
  29. Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR. Bone histomorphometry: standardization of nomenclature, symbols, and units. J Bone Miner Res 1987; 2:595–610.[Medline]
  30. Redd EH, Miller SC, Jee WSS. Changes in endochondral bone elongation rates during pregnancy and lactation. Calcif Tissue Int 1984; 36:697–701.[CrossRef][Medline]
  31. Kovacs CS, Kronenberg HM. Maternal-fetal calcium and bone metabolism during pregnancy, puerperium, and lactation. Endocr Rev 1997; 18:832–872.[Abstract/Free Full Text]
  32. Wilson AK, Bhattacharyva MH, Miller S, Mani A, Sacco-Gibson N. Ovariectomy-induced changes in aged beagles: histomorphometry of rib cortical bone. Calcif Tissue Int 1998; 62:237–243.[CrossRef][Medline]
  33. Chan GM, Roberts CC, Folland D, Jackson R. Growth and bone mineralization of normal breast-fed infants and the effects of lactation on maternal bone mineral status. Am J Clin Nutr 1982; 36:438–443.[Abstract/Free Full Text]
  34. Amprino R, Engstrom A. Studies on x-ray absorption and diffraction of bone tissue. Acta Anat 1952; 15:1–22.
  35. Grynpas M. Age and disease-related changes in the mineral of bone. Calcif Tissue Int 1993; 53:S57-S64.
  36. Aloia JF, Cohn SH, Vaswani A, Yeh JK, Yuen K, Ellis K. Risk factors for postmenopausal osteoporosis. Am J Med 1985; 78:95–100.[Medline]
  37. Melton LJ, Cummings SR. Heterogeneity of age-related fractures: implications for epidemiology. Bone Miner 1987; 2:321–331.[Medline]
  38. Fox KJ, Magaziner J, Wherwin R, Scott JC, Plato CC, Nevitt M, Cummings S. Reproductive correlates of bone mass in elderly women. Study of osteoporotic fractures research group. J Bone Miner Res 1993; 8:901–908.[Medline]
  39. Peng T, Garner SC, Kusy RP, Hirsch PF. Effect of number of suckling pups and dietary calcium on bone mineral content and mechanical properties of femurs of lactating rats. Bone Miner 1988; 3:293–304.[Medline]
  40. Sowers M, Zhang D, Hollis BW, Shapiro B, Janney CA, Crutchfield M, Schork MA, Stanczyk F, Randolph J. Role of calciotrophic hormones in calcium mobilization of lactation. Am J Clin Nutr 1998; 67:284–291.[Abstract]
  41. Garner SC, Peng TC, Hirsch PF, Boass A, Toverud SU. Increase in serum parathyroid hormone concentration in the lactating rat: effects of dietary calcium and lactational intensity. J Bone Miner Res 1987; 2:347–352.[Medline]
  42. Brommage R, DeLuca HF. Regulation of bone mineral loss during lactation. Am J Physiol 1985; 248:E182-E187.
  43. Sowers MF, Hollis BW, Shapiro B, Randolph J, Janney CA, Zhang D, Schork MA, Crutchfield M, Stanczyk F, Russell-Aulet M. Elevated parathyroid hormone-related peptide associated with lactation and bone density loss. JAMA 1996; 276:549–554.[Abstract]



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E. G. Vajda, B. M. Bowman, and S. C. Miller
Cancellous and Cortical Bone Mechanical Properties and Tissue Dynamics During Pregnancy, Lactation, and Postlactation in the Rat
Biol Reprod, September 1, 2001; 65(3): 689 - 695.
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