University of Oulu

Hauta‐alus, H. H., Holmlund‐Suila, E. M., Valkama, S. M., Enlund‐Cerullo, M., Rosendahl, J., Coghlan, R. F., Andersson, S., & Mäkitie, O. (2022). Collagen x biomarker (cxm), linear growth, and bone development in a vitamin d intervention study in infants. Journal of Bone and Mineral Research, 37(9), 1653–1664.

Collagen X Biomarker (CXM), Linear Growth, and Bone Development in a Vitamin D Intervention Study in Infants

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Author: Hauta-Alus, Helena H.1,2,3,4; Holmlund-Suila, Elisa M.1,2; Valkama, Saara M.1,2;
Organizations: 1Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
2Research Program for Clinical and Molecular Metabolism (CAMM), Faculty of Medicine, University of Helsinki, Helsinki, Finland
3Population Health Unit, National Institute for Health and Welfare (THL), Helsinki, Finland
4PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
5Shriners Hospital for Children, Portland, OR, USA
6Department of Molecular Medicine and Surgery, Karolinska Institutet, and Clinical Genetics, Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden
7Folkhälsan Institute of Genetics, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.8 MB)
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Language: English
Published: John Wiley & Sons, 2022
Publish Date: 2022-12-12


Collagen X biomarker (CXM) is suggested to be a biomarker of linear growth velocity. However, early childhood data are limited. This study examines the relationship of CXM to the linear growth rate and bone development, including the possible modifying effects of vitamin D supplementation. We analyzed a cohort of 276 term-born children participating in the Vitamin D Intervention in Infants (VIDI) study. Infants received 10 μg/d (group-10) or 30 μg/d (group-30) vitamin D3 supplementation for the first 2 years of life. CXM and length were measured at 12 and 24 months of age. Tibial bone mineral content (BMC), volumetric bone mineral density (vBMD), cross-sectional area (CSA), polar moment of inertia (PMI), and periosteal circumference (PsC) were measured using peripheral quantitative computed tomography (pQCT) at 12 and 24 months. We calculated linear growth as length velocity (cm/year) and the growth rate in length (SD unit). The mean (SD) CXM values were 40.2 (17.4) ng/mL at 12 months and 38.1 (12.0) ng/mL at 24 months of age (p = 0.12). CXM associated with linear growth during the 2-year follow-up (p = 0.041) but not with bone (p = 0.53). Infants in group-30 in the highest tertile of CXM exhibited an accelerated mean growth rate in length compared with the intermediate tertile (mean difference [95% CI] −0.50 [−0.98, −0.01] SD unit, p = 0.044) but not in the group-10 (p = 0.062) at 12 months. Linear association of CXM and growth rate until 12 months was weak, but at 24 months CXM associated with both length velocity (B for 1 increment of √CXM [95% CI] 0.32 [0.12, 0.52] cm/yr, p = 0.002) and growth rate in length (0.20 [0.08, 0.32] SD unit, p = 0.002). To conclude, CXM may not reliably reflect linear growth from birth to 12 months of age, but its correlation with growth velocity improves during the second year of life.

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Series: Journal of bone and mineral research
ISSN: 0884-0431
ISSN-E: 1523-4681
ISSN-L: 0884-0431
Volume: 37
Issue: 9
Pages: 1653 - 1664
DOI: 10.1002/jbmr.4650
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3123 Gynaecology and paediatrics
Funding: We are also grateful for the financial support provided by the Sigrid Jusélius Foundation, the Novo Nordisk Foundation, the Folkhälsan Research Foundation, the Academy of Finland, the Foundation for Pediatric Research, the Special Governmental Subsidy for Clinical Research, Finska Läkaresällskapet, the Päivikki and Sakari Sohlberg the Foundation, Juho Vainio Foundation, and the Finnish Medical Foundation.
Copyright information: © 2022 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.