Longitudinal Lactation Bone Density Study - Full Text View

Purpose

Changes in maternal calcium metabolism are necessary during lactation to provide adequate calcium in breast milk for development of the newborn skeleton. The calcium in milk is derived from the maternal skeleton, resulting in significant bone loss, a process thought to be mediated by the actions of parathyroid hormone-related protein (PTHrP) in combination with a decreased estrogen levels. After weaning, bone lost during lactation is rapidly regained.

Differences between African-American and Caucasian bone metabolism are well documented and include higher bone mineral density (BMD), lower risk of fragily fracture, lower 25-hydroxyvitamin D (25(OH) D), and higher PTH in African-Americans compared to Caucasians. Most studies of bone metabolism in lactating women have been done in Caucasians. Because of differences in bone metabolism between African-Americans and Caucasians, we do not know whether African-Americans will have similar findings.

The primary aim of this study is to compare the changes in bone mineral density (BMD) during lactation in African-Americans with those in Caucasians. It is not known whether the loss in BMD during lactation will be the same for both races. African-Americans display skeletal resistance to PTH with short-term infusions and have lower bone resorption, higher BMD and lower fracture risk than Caucasians. A recent study by our group indicated that lactating African-American mothers had slightly lower bone resorption but quantitatively similar bone formation compared to Caucasians. However, there was a significant increase of 2-3 fold in markers of bone formation and resorption in both groups. Therefore, it is currently not known whether the loss in BMD during lactation will be the same for both races. Primary outcome measures in this study will include spine, hip and radius BMD by DXA during lactation (at 2,12 and 24 weeks postpartum or at weaning if prior to 24 weeks postpartum, and six months after weaning (+1 week). This longitudinal protocol will distinguish between two hypotheses. Either: a) as measured by BMD, bone loss in African-Americans during lactation will be equal to that in Caucasians, and skeletal recovery will be the same or possibly accelerated compared to Caucasians; or, b) African-Americans will be resistant to bone loss during lactation compared to Caucasians because of resistance to Parathyroid Hormone-related Protein (PTHrP).

Condition
Lactation Other Disorders of Bone Density and Structure Endocrine; Complications

Study Type:	Observational
Study Design:	Observational Model: Cohort Time Perspective: Prospective
Official Title:	"Bone Density and Calcitropic Hormones During Lactation in African-American and Caucasian Women"

Resource links provided by NLM:

MedlinePlus related topics: Bone Density Bone Diseases Breast Feeding

U.S. FDA Resources

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:

Change from baseline in bone density measurements (BMD) [ Time Frame: Change from baseline in BMD at 2,12, 24 weeks postpartum, and six months after weaning. ] [ Designated as safety issue: No ]
Primary outcome measures will include spine, hip and radius BMD by DXA at 2, 12, and 24 weeks post-partum and 6 months post-weaning.

Secondary Outcome Measures:

Change from baseline in bone metabolism parameters [ Time Frame: Change from baseline at 2, 12,and 24 weeks postpartum, and six months after weaning. ] [ Designated as safety issue: No ]
measurement of markers of bone turnover, other calcium metabolic parameters such as calcium, phosphorus, fractional excretion of calcium, PTH(1-84), PTHrP, vitamin D metabolites, estradiol, SHBG, prolactin, and breast milk calcium levels.

Biospecimen Retention: Samples Without DNA

Blood and breast milk

Estimated Enrollment:	80
Study Start Date:	August 2012
Estimated Study Completion Date:	December 2014
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Groups/Cohorts
African-American Lactating Women Healthy African-American women who are exclusively breast-feeding.
Caucasian Lactating Women Healthy Caucasian women who are exclusively breast-feeding.

Show Detailed Description

Eligibility

Ages Eligible for Study:	21 Years to 45 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

New mothers will be recruited from UPMC hospital population, primarily Magee Womens Hospital. As this is a study which aims to describe racial differences in bone metabolism during lactation in African-Americans and Caucasians, subjects must identify themselves as belonging to one of these groups.

Criteria

Inclusion Criteria:

21-45 years old
Post-partum after a singleton pregnancy
Exclusively breast-feeding (not more than one supplemental bottle of formula per day)
African-American or Caucasian by self-identification

Exclusion Criteria:

Subjects with cardiac, hypertensive, vascular, renal (serum creatinine of >1.5), pulmonary, endocrine, musculoskeletal, hepatic, hematologic, malignant or rheumatologic disease
Fractures or bone surgery within the past 12 months
Smokers and subjects with history of significant alcohol or drug use
Pregnant women
Women who achieved pregnancies with IVF or other hormonal manipulation
Women who had significant complications with the most recent pregnancy or who are unable to exclusively breastfeed beginning at birth
Subjects on chronic medications other than
stable doses of thyroid hormone
oral contraceptives
vitamin supplements
Women on Depo-Provera will be excluded
Receiving an investigational drug within 90 days
Weight greater than 130 kg
Z-score -3.0 or less (hip or spine) on initial DXA

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01630629

Contacts

Contact: Mary Beth Tedesco, MNED, CRNP	412-864-3265	tedesco@pitt.edu
Contact: Angela Laslavic, MS	412-578-9259	and70@pitt.edu

Locations

United States, Pennsylvania
University of Pittsburgh Medical Center	Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15213
Sub-Investigator: Marilyn Augustine, MD
Principal Investigator: Mara J Horwitz, MD
Sub-Investigator: Andrew F Stewart, MD
Sub-Investigator: Mary Beth Tedesco, MNEd, CRNP
Sub-Investigator: Angela Laslavic, MS
Sub-Investigator: Susan M Sereika, PhD

Sponsors and Collaborators

University of Pittsburgh

Investigators

Principal Investigator:

Mara Horwitz

University of Pittsburgh

More Information

Publications:

Kovacs CS. Calcium and bone metabolism during pregnancy and lactation. J Mammary Gland Biol Neoplasia. 2005 Apr;10(2):105-18. Review.

Sowers MF, Hollis BW, Shapiro B, Randolph J, Janney CA, Zhang D, Schork A, Crutchfield M, Stanczyk F, Russell-Aulet M. Elevated parathyroid hormone-related peptide associated with lactation and bone density loss. JAMA. 1996 Aug 21;276(7):549-54.

Kovacs CS, Kronenberg HM. Maternal-fetal calcium and bone metabolism during pregnancy, puerperium, and lactation. Endocr Rev. 1997 Dec;18(6):832-72. Review. No abstract available.

Sowers M, Eyre D, Hollis BW, Randolph JF, Shapiro B, Jannausch ML, Crutchfield M. Biochemical markers of bone turnover in lactating and nonlactating postpartum women. J Clin Endocrinol Metab. 1995 Jul;80(7):2210-6.

VanHouten JN, Wysolmerski JJ. Low estrogen and high parathyroid hormone-related peptide levels contribute to accelerated bone resorption and bone loss in lactating mice. Endocrinology. 2003 Dec;144(12):5521-9. Epub 2003 Sep 18.

VanHouten JN, Dann P, Stewart AF, Watson CJ, Pollak M, Karaplis AC, Wysolmerski JJ. Mammary-specific deletion of parathyroid hormone-related protein preserves bone mass during lactation. J Clin Invest. 2003 Nov;112(9):1429-36.

Carneiro RM, Prebehalla L, Tedesco MB, Sereika SM, Hugo M, Hollis BW, Gundberg CM, Stewart AF, Horwitz MJ. Lactation and bone turnover: a conundrum of marked bone loss in the setting of coupled bone turnover. J Clin Endocrinol Metab. 2010 Apr;95(4):1767-76. Epub 2010 Feb 11.

Wang YH, Liu Y, Buhl K, Rowe DW. Comparison of the action of transient and continuous PTH on primary osteoblast cultures expressing differentiation stage-specific GFP. J Bone Miner Res. 2005 Jan;20(1):5-14. Epub 2004 Oct 25.

Dobnig H, Turner RT. The effects of programmed administration of human parathyroid hormone fragment (1-34) on bone histomorphometry and serum chemistry in rats. Endocrinology. 1997 Nov;138(11):4607-12.

Cosman F, Nieves J, Dempster D, Lindsay R. Vitamin D economy in blacks. J Bone Miner Res. 2007 Dec;22 Suppl 2:V34-8. Review.

Harris SS, Soteriades E, Dawson-Hughes B; Framingham Heart Study; Boston Low-Income Elderly Osteoporosis Study. Secondary hyperparathyroidism and bone turnover in elderly blacks and whites. J Clin Endocrinol Metab. 2001 Aug;86(8):3801-4.

Bell NH, Yergey AL, Vieira NE, Oexmann MJ, Shary JR. Demonstration of a difference in urinary calcium, not calcium absorption, in black and white adolescents. J Bone Miner Res. 1993 Sep;8(9):1111-5.

Fuleihan GE, Gundberg CM, Gleason R, Brown EM, Stromski ME, Grant FD, Conlin PR. Racial differences in parathyroid hormone dynamics. J Clin Endocrinol Metab. 1994 Dec;79(6):1642-7.

Nelson DA, Jacobsen G, Barondess DA, Parfitt AM. Ethnic differences in regional bone density, hip axis length, and lifestyle variables among healthy black and white men. J Bone Miner Res. 1995 May;10(5):782-7.

George A, Tracy JK, Meyer WA, Flores RH, Wilson PD, Hochberg MC. Racial differences in bone mineral density in older men. J Bone Miner Res. 2003 Dec;18(12):2238-44.

Thomas PA. Racial and ethnic differences in osteoporosis. J Am Acad Orthop Surg. 2007;15 Suppl 1:S26-30.

Cosman F, Morgan DC, Nieves JW, Shen V, Luckey MM, Dempster DW, Lindsay R, Parisien M. Resistance to bone resorbing effects of PTH in black women. J Bone Miner Res. 1997 Jun;12(6):958-66.

Prentice A, Jarjou LM, Stirling DM, Buffenstein R, Fairweather-Tait S. Biochemical markers of calcium and bone metabolism during 18 months of lactation in Gambian women accustomed to a low calcium intake and in those consuming a calcium supplement. J Clin Endocrinol Metab. 1998 Apr;83(4):1059-66.

Horwitz MJ, Tedesco MB, Sereika SM, Hollis BW, Garcia-Ocana A, Stewart AF. Direct comparison of sustained infusion of human parathyroid hormone-related protein-(1-36) [hPTHrP-(1-36)] versus hPTH-(1-34) on serum calcium, plasma 1,25-dihydroxyvitamin D concentrations, and fractional calcium excretion in healthy human volunteers. J Clin Endocrinol Metab. 2003 Apr;88(4):1603-9.

Stewart AF, Vignery A, Silverglate A, Ravin ND, LiVolsi V, Broadus AE, Baron R. Quantitative bone histomorphometry in humoral hypercalcemia of malignancy: uncoupling of bone cell activity. J Clin Endocrinol Metab. 1982 Aug;55(2):219-27.

Finkelstein JS, Lee ML, Sowers M, Ettinger B, Neer RM, Kelsey JL, Cauley JA, Huang MH, Greendale GA. Ethnic variation in bone density in premenopausal and early perimenopausal women: effects of anthropometric and lifestyle factors. J Clin Endocrinol Metab. 2002 Jul;87(7):3057-67.

Perry HM 3rd, Horowitz M, Morley JE, Fleming S, Jensen J, Caccione P, Miller DK, Kaiser FE, Sundarum M. Aging and bone metabolism in African American and Caucasian women. J Clin Endocrinol Metab. 1996 Mar;81(3):1108-17.

Horwitz MJ, Tedesco MB, Sereika SM, Syed MA, Garcia-Ocana A, Bisello A, Hollis BW, Rosen CJ, Wysolmerski JJ, Dann P, Gundberg C, Stewart AF. Continuous PTH and PTHrP Infusion Causes Suppression of Bone Formation and Discordant Effects on 1,25(OH)(2)Vitamin D. J Bone Miner Res. 2005 Oct;20(10):1792-803. Epub 2005 Jun 6.

Kalkwarf HJ, Specker BL, Ho M. Effects of calcium supplementation on calcium homeostasis and bone turnover in lactating women. J Clin Endocrinol Metab. 1999 Feb;84(2):464-70.

Nelson DA, Barondess DA, Hendrix SL, Beck TJ. Cross-sectional geometry, bone strength, and bone mass in the proximal femur in black and white postmenopausal women. J Bone Miner Res. 2000 Oct;15(10):1992-7.

Syed MA, Horwitz MJ, Tedesco MB, Garcia-Ocana A, Wisniewski SR, Stewart AF. Parathyroid hormone-related protein-(1--36) stimulates renal tubular calcium reabsorption in normal human volunteers: implications for the pathogenesis of humoral hypercalcemia of malignancy. J Clin Endocrinol Metab. 2001 Apr;86(4):1525-31.

Luckey MM, Wallenstein S, Lapinski R, Meier DE. A prospective study of bone loss in African-American and white women--a clinical research center study. J Clin Endocrinol Metab. 1996 Aug;81(8):2948-56.

Cauley JA, Wampler NS, Barnhart JM, Wu L, Allison M, Chen Z, Hendrix S, Robbins J, Jackson RD; Women's Health Initiative Observational Study. Incidence of fractures compared to cardiovascular disease and breast cancer: the Women's Health Initiative Observational Study. Osteoporos Int. 2008 Dec;19(12):1717-23. Epub 2008 Jul 16.

Cauley JA, Palermo L, Vogt M, Ensrud KE, Ewing S, Hochberg M, Nevitt MC, Black DM. Prevalent vertebral fractures in black women and white women. J Bone Miner Res. 2008 Sep;23(9):1458-67.

Responsible Party:	Mara Horwitz, Associate Professor of Medicine, University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT01630629 History of Changes
Other Study ID Numbers:	PRO12050600
Study First Received:	June 20, 2012
Last Updated:	June 26, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Pittsburgh:

Lactation
Weaning
Bone Density

Endocrine
Physiological Properties
Bone Metabolism

Additional relevant MeSH terms:

Bone Diseases
Musculoskeletal Diseases

ClinicalTrials.gov processed this record on May 23, 2013