Longitudinal Lactation Bone Density Study

NCT01630629 | Completed

• 1 other identifier: PRO12050600
• Study Type: observational
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

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 fragility 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 Dual X-Ray Absorbiometry (DXA)Scans 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).

Conditions

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

Keywords

Lactation; Weaning; Bone Density; Endocrine; Physiological Properties; Bone Metabolism

Outcome Measures

Primary Outcomes (1)

• Change from baseline in bone density measurements (BMD)

  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.

  Change from baseline in BMD at 2,12, 24 weeks postpartum, and six months after weaning.

Secondary Outcomes (1)

• Change from baseline of bone metabolism measurements

  Change from baseline at 2, 12,and 24 weeks postpartum, and six months after weaning.

Study Arms (2)

African-American Lactating Women

Healthy African-American women who are exclusively breast-feeding.

Caucasian Lactating Women

Healthy Caucasian women who are exclusively breast-feeding.

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (31)

• Kovacs CS. Calcium and bone metabolism during pregnancy and lactation. J Mammary Gland Biol Neoplasia. 2005 Apr;10(2):105-18. doi: 10.1007/s10911-005-5394-0.

  PMID: 16025218 BACKGROUND

• 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.

  PMID: 8709404 BACKGROUND

• Kovacs CS, Kronenberg HM. Maternal-fetal calcium and bone metabolism during pregnancy, puerperium, and lactation. Endocr Rev. 1997 Dec;18(6):832-72. doi: 10.1210/edrv.18.6.0319. No abstract available.

  PMID: 9408745 BACKGROUND

• 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. doi: 10.1210/jcem.80.7.7608281.

  PMID: 7608281 BACKGROUND

• 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. doi: 10.1210/en.2003-0892. Epub 2003 Sep 18.

  PMID: 14500568 BACKGROUND

• 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. doi: 10.1172/JCI19504.

  PMID: 14597768 BACKGROUND

• 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. doi: 10.1210/jc.2009-1518. Epub 2010 Feb 11.

  PMID: 20150580 BACKGROUND

• 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. doi: 10.1359/JBMR.041016. Epub 2004 Oct 25.

  PMID: 15619664 BACKGROUND

• 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. doi: 10.1210/endo.138.11.5505.

  PMID: 9348185 BACKGROUND

• van der Horst G, Farih-Sips H, Lowik CW, Karperien M. Multiple mechanisms are involved in inhibition of osteoblast differentiation by PTHrP and PTH in KS483 Cells. J Bone Miner Res. 2005 Dec;20(12):2233-44. doi: 10.1359/JBMR.050821. Epub 2005 Aug 29.

  PMID: 16294276 BACKGROUND

• Cosman F, Nieves J, Dempster D, Lindsay R. Vitamin D economy in blacks. J Bone Miner Res. 2007 Dec;22 Suppl 2:V34-8. doi: 10.1359/jbmr.07s220.

  PMID: 18290719 BACKGROUND

• 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. doi: 10.1210/jcem.86.8.7783.

  PMID: 11502814 BACKGROUND

• 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. doi: 10.1002/jbmr.5650080912.

  PMID: 8237481 BACKGROUND

• 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. doi: 10.1210/jcem.79.6.7989469.

  PMID: 7989469 BACKGROUND

• 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. doi: 10.1002/jbmr.5650100515.

  PMID: 7639113 BACKGROUND

• 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. doi: 10.1359/jbmr.2003.18.12.2238.

  PMID: 14672360 BACKGROUND

• Thomas PA. Racial and ethnic differences in osteoporosis. J Am Acad Orthop Surg. 2007;15 Suppl 1:S26-30. doi: 10.5435/00124635-200700001-00008.

  PMID: 17766786 BACKGROUND

• 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. doi: 10.1359/jbmr.1997.12.6.958.

  PMID: 9169356 BACKGROUND

• 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. doi: 10.1210/jcem.83.4.4737.

  PMID: 9543117 BACKGROUND

• 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. doi: 10.1210/jc.2002-020773.

  PMID: 12679445 BACKGROUND

• 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. doi: 10.1210/jcem-55-2-219.

  PMID: 7085851 BACKGROUND

• 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. doi: 10.1210/jcem.87.7.8654.

  PMID: 12107201 BACKGROUND

• 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. doi: 10.1210/jcem.81.3.8772584.

  PMID: 8772584 BACKGROUND

• 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. doi: 10.1359/JBMR.050602. Epub 2005 Jun 6.

  PMID: 16160737 BACKGROUND

• 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. doi: 10.1210/jcem.84.2.5451.

  PMID: 10022402 BACKGROUND

• 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. doi: 10.1359/jbmr.2000.15.10.1992.

  PMID: 11028452 BACKGROUND

• 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. doi: 10.1210/jcem.86.4.7406.

  PMID: 11297578 BACKGROUND

• Burtis WJ, Brady TG, Orloff JJ, Ersbak JB, Warrell RP Jr, Olson BR, Wu TL, Mitnick ME, Broadus AE, Stewart AF. Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer. N Engl J Med. 1990 Apr 19;322(16):1106-12. doi: 10.1056/NEJM199004193221603.

  PMID: 2320080 BACKGROUND

• 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. doi: 10.1210/jcem.81.8.8768857.

  PMID: 8768857 BACKGROUND

• 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. doi: 10.1007/s00198-008-0634-y. Epub 2008 Jul 16.

  PMID: 18629572 BACKGROUND

• 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. doi: 10.1359/jbmr.080411.

  PMID: 18442309 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood and breast milk

MeSH Terms

Conditions

Breast Feeding

Condition Hierarchy (Ancestors)

Feeding Behavior; Behavior

Study Officials

• Mara Horwitz

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: June 20, 2012
• First Posted: June 28, 2012
• Study Start: August 1, 2012
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: June 16, 2016

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)