{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:42:08Z","timestamp":1774658528617,"version":"3.50.1"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Breast milk is the best nutrition for newborns. Its composition is dynamic and adapted to the newborn\u2019s individual needs. A variety of bioactive compounds, including bone-related molecules, have been described in breast milk. Osteocalcin (OCN) is a small non-collagenous, bone-derived protein. In its carboxylated form (cOCN) it plays a crucial role in bone metabolism and calcium homeostasis. The undercarboxylated form of osteocalcin (ucOCN) is suggested to have endocrine functions such as influencing neurotransmitter synthesis and glucose homeostasis. This study aimed to analyze whether the bone-related proteins cOCN and ucOCN are present in breast milk at different time points of the lactation phase and whether the amount is affected by lifestyle factors, such as dietary behavior, physical activity, BMI, age, or number of parities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>98 mothers, aged 31.8 \u00b1 4.7 years, participated in the study. Breast milk was collected at four points during the breastfeeding period (T1: 1\u20133 days postpartum (pp); T2: 7 days pp; T3: 14 days pp; T4: 3 months pp). Total protein, ucOCN and cOCN were analyzed by BCA (bicinchoninic acid) assay and enzyme immunoassay, respectively. Dietary habits, physical activity, and BMI were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The median concentration of cOCN in relation to the total amount of protein decreased only marginally during the breastfeeding period (T1: 0.068 [0.021-0.207] ng\/mg protein; T4: 0.045 [0.026-0.196] ng\/mg protein), with total protein concentrations in breast milk decreasing. In contrast, the relative ucOCN concentration in relation to the total protein concentration was twice as high in the colostrum (0.125 [0.043-0.223] ng\/mg protein) compared to mature breast milk (0.055 [0.028-0.091] ng\/mg protein). The concentration of ucOCN in colostrum from primiparous women (0.138 [0.041 \u2013 0.342] ng\/mg protein) tended to be higher than the concentration in colostrum of multiparous women (0.062 [0.034 \u2013 0.151] ng\/mg protein, p = 0.094). This also applied for the cOCN concentration. Other lifestyle factors, e.g., physical activity, BMI, or age showed no associations with ucOCN concentrations in breast milk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study indicates that ucOCN and cOCN are components of breast milk. The function of both molecules in infants and mothers, still needs to be uncovered.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.bfarm.de<\/jats:ext-link>\n                      , identifier DRKS00023072.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1715553","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T05:16:02Z","timestamp":1764134162000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Osteocalcin in human breast milk over the course of lactation"],"prefix":"10.3389","volume":"16","author":[{"given":"Olivier","family":"Prosperi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Hanusch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophia","family":"Naber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"L\u00fccke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"Sinningen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.770913","article-title":"Association between breastmilk microbiota and food allergy in infants","volume":"11","author":"Wang","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01024-7","article-title":"Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect","volume":"387","author":"Victora","year":"2016","journal-title":"Lancet (London England)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"14804","DOI":"10.3390\/ijerph192214804","article-title":"Exclusive breastfeeding and childhood morbidity: A narrative review","volume":"19","author":"Hossain","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"B4","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/978-1-4757-4242-8_7","article-title":"The optimal duration of exclusive breastfeeding: a systematic review","volume":"554","author":"Kramer","year":"2004","journal-title":"Adv Exp Med Biol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/APA.13133","article-title":"Long-term consequences of breastfeeding on cholesterol, obesity, systolic blood pressure and type 2 diabetes: a systematic review and meta-analysis","volume":"104","author":"Horta","year":"2015","journal-title":"Acta Paediatr (Oslo Norway 1992)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/J.PCL.2012.10.002","article-title":"Human milk composition: nutrients and bioactive factors","volume":"60","author":"Ballard","year":"2013","journal-title":"Pediatr Clinics North America"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2328","DOI":"10.3390\/nu12082328","article-title":"Circadian variation in human milk composition, a systematic review","volume":"12","author":"Italianer","year":"2020","journal-title":"Nutrients"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.115.120881","article-title":"Impact of maternal nutrition on breast-milk composition: a systematic review","volume":"104","author":"Bravi","year":"2016","journal-title":"Am J Clin Nutr"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/mcn.13168","article-title":"Acute changes to breast milk composition following consumption of high-fat and high-sugar meals","volume":"17","author":"Ward","year":"2021","journal-title":"Maternal Child Nutr"},{"key":"B10","doi-asserted-by":"publisher","first-page":"279","DOI":"10.3390\/nu8050279","article-title":"Review of infant feeding: key features of breast milk and infant formula","volume":"8","author":"Martin","year":"2016","journal-title":"Nutrients"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s10911-005-5394-0","article-title":"Calcium and bone metabolism during pregnancy and lactation","volume":"10","author":"Kovacs","year":"2005","journal-title":"J Mammary Gland Biol Neoplasia"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/S00404-023-07189-0","article-title":"Bone turnover in lactating and nonlactating women","volume":"308","author":"Nerius","year":"2023","journal-title":"Arch Gynecol Obstet"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-012-2062-2","article-title":"Changes in calcitropic hormones, bone markers and insulin-like growth factor I (IGF-I) during pregnancy and postpartum: a controlled cohort study","volume":"24","author":"M\u00f8ller","year":"2013","journal-title":"Osteoporos Int J Established As Result Cooperation Between Eur Foundation Osteoporos Natl Osteoporos Foundation USA"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.72.10.3925","article-title":"Direct identification of the calcium-binding amino acid, gamma-carboxyglutamate, in mineralized tissue","volume":"72","author":"Hauschka","year":"1975","journal-title":"Proc Natl Acad Sci United States America"},{"key":"B15","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/BF00441848","article-title":"Evaluation of serum osteocalcin as an index of altered bone metabolism","volume":"145","author":"Kruse","year":"1986","journal-title":"Eur J Pediatr"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1021\/BI00539A038","article-title":"Calcium-dependent alpha-helical structure in osteocalcin","volume":"21","author":"Hauschka","year":"1982","journal-title":"Biochemistry"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2020.129809","article-title":"The carboxylation status of osteocalcin has important consequences for its structure and dynamics","volume":"1865","author":"Kapoor","year":"2021","journal-title":"Biochim Biophys Acta Gen Subj"},{"key":"B18","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.cell.2010.06.003","article-title":"Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism","volume":"142","author":"Ferron","year":"2010","journal-title":"Cell"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELL.2013.08.042","article-title":"Maternal and offspring pools of osteocalcin influence brain development and functions","volume":"155","author":"Oury","year":"2013","journal-title":"Cell"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELL.2007.05.047","article-title":"Endocrine regulation of energy metabolism by the skeleton","volume":"130","author":"Lee","year":"2007","journal-title":"Cell"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711119105","article-title":"Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice","volume":"105","author":"Ferron","year":"2008","journal-title":"Proc Natl Acad Sci United States America"},{"key":"B22","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.bone.2014.09.006","article-title":"Oral administration of osteocalcin improves glucose utilization by stimulating glucagon-like peptide-1 secretion","volume":"69","author":"Mizokami","year":"2014","journal-title":"Bone"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.3390\/nu16101487","article-title":"Bioactive components of human milk and their impact on child's health and development, literature review","volume":"16","author":"Szyller","year":"2024","journal-title":"Nutrients"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/apa.12771","article-title":"Biochemical markers of bone resorption are present in human milk: implications for maternal and neonatal bone metabolism","volume":"103","author":"Bouroutzoglou","year":"2014","journal-title":"Acta Paediatr (Oslo Norway 1992)"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000127014.22068.15","article-title":"Osteoprotegerin in human milk: a potential role in the regulation of bone metabolism and immune development","volume":"55","author":"Vidal","year":"2004","journal-title":"Pediatr Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"8","DOI":"10.34763\/jmotherandchild.20202403.2032.d-20-00001","article-title":"Immunoglobulins content in colostrum, transitional and mature milk of Bangladeshi mothers: Influence of parity and sociodemographic characteristics","volume":"24","author":"Akhter","year":"2020","journal-title":"J Mother Child"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3255","DOI":"10.3390\/NU14163255","article-title":"Association between maternal characteristics and immune factors TGF-\u03b21, TGF-\u03b22, and igA in colostrum: an exploratory study in Japan","volume":"14","author":"Hirata","year":"2022","journal-title":"Nutrients"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s00103-012-1498-z","article-title":"DEGS: Studie zur Gesundheit Erwachsener in Deutschland. Bundesweite Quer- und L\u00e4ngsschnittstudie im Rahmen des Gesundheitsmonitorings des Robert Koch-Instituts","volume":"55","author":"G\u00f6\u00dfwald","year":"2012","journal-title":"Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz"},{"key":"B29","volume-title":"Entwicklung eines Index zur Bewertung der Ern\u00e4hrungsqualit\u00e4t in der Studie zur Gesundheit Erwachsener in Deutschland (DEGS1)","author":"Kuhn","year":"2018"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.3390\/nu11081889","article-title":"Associations between the prenatal diet and neonatal outcomes-A secondary analysis of the cluster-randomised geliS trial","volume":"11","author":"G\u00fcnther","year":"2019","journal-title":"Nutrients"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports-2020-102955","article-title":"World Health Organization 2020 guidelines on physical activity and sedentary behaviour","volume":"54","author":"Bull","year":"2020","journal-title":"Br J Sports Med"},{"key":"B32","volume-title":"BMI Classification Percentile and Cut Off Points","author":"Weir","year":"2023"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.20344\/amp.11057","article-title":"Advanced maternal age: adverse outcomes of pregnancy, A meta-analysis","volume":"32","author":"Pinheiro","year":"2019","journal-title":"Acta Med Port"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1159\/000243909","article-title":"Osteocalcin and human milk","volume":"63","author":"Pittard","year":"1993","journal-title":"Biol Neonate"},{"key":"B35","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1016\/j.cmet.2019.08.012","article-title":"Mediation of the acute stress response by the skeleton","volume":"30","author":"Berger","year":"2019","journal-title":"Cell Metab"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115818","article-title":"Osteocalcin and its forms respond similarly to exercise in males and females","volume":"144","author":"Hiam","year":"2021","journal-title":"Bone"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.repbio.2021.100566","article-title":"The role of osteocalcin in placental function in gestational diabetes mellitus","volume":"21","author":"Song","year":"2021","journal-title":"Reprod Biol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/s0169-6009(08)80013-x","article-title":"Stress decreases the serum level of osteocalcin","volume":"21","author":"Napal","year":"1993","journal-title":"Bone Miner"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.17264","article-title":"How should we interpret lactate in labour? A reference study","volume":"129","author":"Dockree","year":"2022","journal-title":"BJOG an Int J Obstet Gynaecol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.22.01028","article-title":"Lactate mediates the bone anabolic effect of high-intensity interval training by inducing osteoblast differentiation","volume":"105","author":"Zhu","year":"2023","journal-title":"J Bone Joint Surg Am Volume"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1210\/EN.2014-1083","article-title":"FGF-21 and skeletal remodeling during and after lactation in C57BL\/6J mice","volume":"155","author":"Bornstein","year":"2014","journal-title":"Endocrinology"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1210\/JCEM.80.7.7608281","article-title":"Biochemical markers of bone turnover in lactating and nonlactating postpartum women","volume":"80","author":"Sowers","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1121579","article-title":"Crosstalk within a brain-breast-bone axis regulates mineral and skeletal metabolism during lactation","volume":"14","author":"Athonvarangkul","year":"2023","journal-title":"Front Physiol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/apa.70259","article-title":"Parity influences the immune profile of human milk via increased T lymphocyte content","volume":"114","author":"Tomaszewska","year":"2025","journal-title":"Acta Paediatr (Oslo Norway 1992)"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.2147\/PPA.S374628","article-title":"Psychological status during the second pregnancy and its influencing factors","volume":"16","author":"Cai","year":"2022","journal-title":"Patient Prefer Adherence"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.wombi.2020.09.021","article-title":"The childbirth experience: A systematic review of predictors and outcomes","volume":"34","author":"McKelvin","year":"2021","journal-title":"Women Birth J Aust Coll Midwives"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2020.104878","article-title":"Serum osteocalcin is associated with subjective stress in people with depression and type 2 diabetes","volume":"122","author":"Nguyen","year":"2020","journal-title":"Psychoneuroendocrinology"},{"key":"B48","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1007\/s12020-017-1384-4","article-title":"Association between serum osteocalcin and body mass index: a systematic review and meta-analysis","volume":"58","author":"Kord-Varkaneh","year":"2017","journal-title":"Endocrine"},{"key":"B49","doi-asserted-by":"publisher","first-page":"45","DOI":"10.3109\/17477161003792564","article-title":"Gestational weight gain and overweight in children: Results from the cross-sectional German KiGGS study","volume":"6","author":"Kries","year":"2011","journal-title":"Int J Pediatr Obes IJPO"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/oby.20197","article-title":"Late pregnancy reversal from excessive gestational weight gain lowers risk of childhood overweight\u2013a cohort study","volume":"21","author":"Kries","year":"2013","journal-title":"Obes (Silver Spring Md.)"},{"key":"B51","doi-asserted-by":"publisher","first-page":"e12776","DOI":"10.1111\/bjhp.12776","article-title":"Associations between lifestyle and well-being in early and late pregnancy in women with overweight or obesity: Secondary analyses of the PEARS RCT","volume":"30","author":"Philippe","year":"2025","journal-title":"Br J Health Psychol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1840","DOI":"10.1038\/s41598-020-58760-7","article-title":"Circulating undercarboxylated osteocalcin as estimator of cardiovascular and type 2 diabetes risk in metabolic syndrome patients","volume":"10","author":"Riquelme-Gallego","year":"2020","journal-title":"Sci Rep"},{"key":"B53","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1111\/CEN.15036","article-title":"Reference limits for osteocalcin in infancy and early childhood: A longitudinal birth cohort study","volume":"100","author":"Berggren","year":"2024","journal-title":"Clin Endocrinol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2024.120067","article-title":"Osteocalcin: A bone protein with multiple endocrine functions","volume":"567","author":"Determe","year":"2025","journal-title":"Clin Chim Acta Int J Clin Chem"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1055\/a-0713-1058","article-title":"Diet and lifestyle before and during pregnancy - practical recommendations of the Germany-wide healthy start - young family network","volume":"78","author":"Koletzko","year":"2018","journal-title":"Geburtshilfe Und Frauenheilkunde"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1002\/fsn3.3482","article-title":"Adherence to recommendations for nutrient supplementation related to pregnancy in Germany","volume":"11","author":"Doru","year":"2023","journal-title":"Food Sci Nutr"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1715553\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T05:16:04Z","timestamp":1764134164000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1715553\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":56,"alternative-id":["10.3389\/fendo.2025.1715553"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1715553","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,26]]},"article-number":"1715553"}}