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Cited by 195Bone health and osteoporosis researchParathyroid Disorders and TreatmentsBone Metabolism and Diseases

Calcitonin Plays a Critical Role in Regulating Skeletal Mineral Metabolism during Lactation

Woodrow, Janine P., Sharpe, Christopher J., Fudge, Neva J., Hoff, Ana O., Gagel, Robert F., Kovacs, Christopher S.·2006·Endocrinology
DOI 10.1210/en.2005-1616
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Abstract

The maternal skeleton rapidly demineralizes during lactation to provide calcium to milk, responding to the stimuli of estrogen deficiency and mammary-secreted PTH-related protein. We used calcitonin/calcitonin gene-related peptide-alpha (Ctcgrp) null mice to determine whether calcitonin also modulates lactational mineral metabolism. During 21 d of lactation, spine bone mineral content dropped 53.6% in Ctcgrp nulls vs. 23.6% in wild-type (WT) siblings (P < 0.0002). After weaning, bone mineral content returned fully to baseline in 18.1 d in Ctcgrp null vs. 13.1 d in WT (P < 0.01) mice. Daily treatment with salmon calcitonin from the onset of lactation normalized the losses in Ctcgrp null mice, whereas calcitonin gene-related peptide-alpha or vehicle was without effect. Compared with WT, Ctcgrp null mice had increased circulating levels of PTH and up-regulation of mammary gland PTH-related protein mRNA. In addition, lactation caused the Ctcgrp null skeleton to undergo more trabecular thinning and increased trabecular separation compared with WT. Our studies confirm that an important physiological role of calcitonin is to protect the maternal skeleton against excessive resorption and attendant fragility during lactation and reveal that the postweaning skeleton has the remarkable ability to rapidly recover even from losses of over 50% of skeletal mineral content.

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  • Replacing missing peptide with sCT normalized bone parameters, whereas CGRP had no effect, indicating calcitonin is important for calcium balance and maternal skeleton preservation during lactation and recovery.

    “Injection of sCT normalized the bone parameters, whereas CGRP was without effect, indicating that calcitonin is the peptide that plays an important role in calcium balance and preservation of the maternal skeleton during lactation and its recovery after weaning (222).”

    From The Activity of Peptides of the Calcitonin Family in Bone (2019) · cites this paper as [222]

    The ‘Rescue of skeletal phenotype during lactation’ section reports that salmon calcitonin normalized bone mineral losses in Ctcgrp-null mice, whereas CGRPα did not. But ‘Skeletal recovery after weaning’ says calcitonin is not required for full recovery, although its absence may delay it; the claim overstates its role in postweaning recovery. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • After weaning, spine bone mineral content returned to baseline in 13 days in WT mice but took 18 days in Calca KO mice.

    “Thirteen days after weaning, spine bone mineral content returned to baseline values in the WT mice, whereas in the Calca KO mice, it took 18 days to reach these values.”

    From The Activity of Peptides of the Calcitonin Family in Bone (2019) · cites this paper as [222]

    The “BMC during pregnancy, lactation, and recovery” section says both groups regained baseline BMC after weaning, with recovery taking several more days in Ctcgrp-null mice. Figure 1’s caption distinguishes the mean days to recover baseline total-body BMC (panel B) from spine BMC (panel C). Our copy does not state the claimed 13- and 18-day figures for spine BMC. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • In Calca KO mice, spine bone mineral content dropped by over 50% during 21 days of lactation, compared with 23.6% in WT controls.

    “In the Calca KO model, deficient in both calcitonin and CGRP, spine bone mineral content dropped during 21 days of lactation by over 50%, whereas in the WT controls, the drop was only of 23.6% (222).”

    From The Activity of Peptides of the Calcitonin Family in Bone (2019) · cites this paper as [222]

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Research works printed but not linked: 4

  1. [16]16. Deftos LJ 2003 Calcitonin. In: Favus MJ, ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. 5th ed. Washington, DC: ASBMR Press; 137-141
  2. [19]19. Barlet JP, Garel JM 1975 Physiological role of calcitonin in pregnant goats and ewes. In: Talmage RV, Owen M, Parsons A, eds. Calcium regulating hormones: Proc Fifth Parathyroid Conference, Oxford, UK, 1974. 1st ed. Amsterdam: Excerpta Medica; 119 -121
  3. [39]39. Ju ¨ppner H, Kronenberg HM 2003 Parathyroid hormone. In: Favus MJ, ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. 5th ed. Washington, DC: ASBMR Press; 117-124
  4. [66]66. Kovacs CS, Kronenberg HM 2003 Skeletal physiology: pregnancy and lacta- tion. In: Favus MJ, ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. 5th ed. Washington, DC: ASBMR Press; 80 -86 Endocrinology is published monthly by The Endocrine Society (http://www.endo-society.org), the foremost professional society serving the endocrine community.

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Authors
Woodrow, J. P., Sharpe, C. J., Fudge, N. J., Hoff, A. O., Gagel, R. F., & Kovacs, C. S.
Affiliations
  • Memorial University of Newfoundland (CA)
  • The University of Texas MD Anderson Cancer Center (US)
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2006-09
Volume
147
Issue
9
Pages
4010-4021
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/en.2005-1616
OpenAlex
W2038783196
Cited by
195
References
70
Citations by year
2026: 5 · 2025: 4 · 2024: 13 · 2023: 6 · 2022: 5 · 2021: 12 · 2020: 14 · 2019: 11 · 2018: 7 · 2017: 16 · 2016: 9 · 2015: 7 · 2014: 10 · 2013: 9 · 2012: 16
FWCI
10.18
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Society for Endocrinology
  • Memorial University of Newfoundland
  • Canadian Institutes of Health Research
Topics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Keywords
calcitonin, lactation, bone demineralization, salmon calcitonin, PTH-related protein, parathyroid hormone, estrogen deficiency, trabecular bone, bone mineral content
MeSH terms
Animals, Biomechanical Phenomena, Bone and Bones, Bone Diseases, Metabolic, Bone Resorption, Calcitonin, Calcium, Duodenum, Estradiol, Female, Intestinal Absorption, Lactation, Mammary Glands, Animal, Milk, Minerals, Parathyroid Hormone, Pregnancy, RNA, Messenger, Bone Density, Calcitonin Gene-Related Peptide, Mice, Knockout, Parathyroid Hormone-Related Protein, Mice

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