Ryan F Coghlan1, Robert C Olney2, Bruce A Boston3, Daniel T Coleman4, Brian Johnstone5, William A Horton1,6. 1. Research Center, Shriners Hospitals for Children, Portland, Oregon. 2. Division of Endocrinology, Nemours Children's Specialty Care, Jacksonville, Florida. 3. Department of Pediatrics, Oregon Health & Science University, Portland, Oregon. 4. Graduate School of Social Service, Fordham University, New York, New York. 5. Department of Orthopaedics & Rehabilitation, Oregon Health & Science University, Portland, Oregon. 6. Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, Oregon.
Abstract
CONTEXT: Height velocity (HV) is difficult to assess because growth is very slow. The current practice of calculating it from measurements taken at several-month intervals is insufficient for managing children with growth disorders. We identified a bone growth by-product (collagen X biomarker, CXM) in blood that in preliminary analysis in healthy children correlated strongly with conventionally determined HV and displayed a pattern resembling published norms for HV vs age. OBJECTIVE: The goal was to confirm our initial observations supporting the utility of CXM as an HV biomarker in a larger number of individuals and establish working reference ranges for future studies. DESIGN, SETTINGS, AND PARTICIPANTS: CXM was assessed in archived blood samples from 302 healthy children and 10 healthy adults yielding 961 CXM measurements. A total of 432 measurements were plotted by age, and sex-specific reference ranges were calculated. Serial values from 116 participants were plotted against observed HV. Matched plasma, serum, and dried blood spot readings were compared. RESULTS: A correlation of blood CXM with conventional HV was confirmed. Scatter plots of CXM vs age showed a similar pattern to current HV norms, and CXM levels demarcated the pubertal growth spurt both in girls and boys. CXM levels differed little in matched serum, plasma, and dried blood spot samples. CONCLUSIONS: Blood CXM offers a potential means to estimate HV in real time. Our results establish sex-specific, working reference ranges for assessing skeletal growth, especially over time. CXM stability in stored samples makes it well suited for retrospective studies.
CONTEXT: Height velocity (HV) is difficult to assess because growth is very slow. The current practice of calculating it from measurements taken at several-month intervals is insufficient for managing children with growth disorders. We identified a bone growth by-product (collagen X biomarker, CXM) in blood that in preliminary analysis in healthy children correlated strongly with conventionally determined HV and displayed a pattern resembling published norms for HV vs age. OBJECTIVE: The goal was to confirm our initial observations supporting the utility of CXM as an HV biomarker in a larger number of individuals and establish working reference ranges for future studies. DESIGN, SETTINGS, AND PARTICIPANTS: CXM was assessed in archived blood samples from 302 healthy children and 10 healthy adults yielding 961 CXM measurements. A total of 432 measurements were plotted by age, and sex-specific reference ranges were calculated. Serial values from 116 participants were plotted against observed HV. Matched plasma, serum, and dried blood spot readings were compared. RESULTS: A correlation of blood CXM with conventional HV was confirmed. Scatter plots of CXM vs age showed a similar pattern to current HV norms, and CXM levels demarcated the pubertal growth spurt both in girls and boys. CXM levels differed little in matched serum, plasma, and dried blood spot samples. CONCLUSIONS: Blood CXM offers a potential means to estimate HV in real time. Our results establish sex-specific, working reference ranges for assessing skeletal growth, especially over time. CXM stability in stored samples makes it well suited for retrospective studies.
Authors: Ravi Savarirayan; Melita Irving; Carlos A Bacino; Bret Bostwick; Joel Charrow; Valerie Cormier-Daire; Kim-Hanh Le Quan Sang; Patricia Dickson; Paul Harmatz; John Phillips; Natalie Owen; Anu Cherukuri; Kala Jayaram; George S Jeha; Kevin Larimore; Ming-Liang Chan; Alice Huntsman Labed; Jonathan Day; Julie Hoover-Fong Journal: N Engl J Med Date: 2019-06-18 Impact factor: 91.245
Authors: Robert C Olney; Joseph W Permuy; Timothy C R Prickett; Joan C Han; Eric A Espiner Journal: Clin Endocrinol (Oxf) Date: 2012-09 Impact factor: 3.478
Authors: R J Kuczmarski; C L Ogden; L M Grummer-Strawn; K M Flegal; S S Guo; R Wei; Z Mei; L R Curtin; A F Roche; C L Johnson Journal: Adv Data Date: 2000-06-08
Authors: Ryan F Coghlan; Jon A Oberdorf; Susan Sienko; Michael D Aiona; Bruce A Boston; Kara J Connelly; Chelsea Bahney; Jeremie LaRouche; Sarah M Almubarak; Daniel T Coleman; Irute Girkontaite; Klaus von der Mark; Gregory P Lunstrum; William A Horton Journal: Sci Transl Med Date: 2017-12-06 Impact factor: 17.956
Authors: L E Nicol; R F Coghlan; D Cuthbertson; Sandesh C S Nagamani; B Lee; R C Olney; W Horton; E Orwoll Journal: Bone Date: 2021-04-28 Impact factor: 4.626
Authors: Ricki S Carroll; Robert C Olney; Angela L Duker; Ryan F Coghlan; William G Mackenzie; Colleen P Ditro; Cassondra J Brown; David A O'Connell; William A Horton; Brian Johnstone; Eric A Espiner; Timothy C R Prickett; Michael B Bober Journal: Calcif Tissue Int Date: 2022-03-11 Impact factor: 4.000
Authors: Ming Liang Chan; Yulan Qi; Kevin Larimore; Anu Cherukuri; Lori Seid; Kala Jayaram; George Jeha; Elena Fisheleva; Jonathan Day; Alice Huntsman-Labed; Ravi Savarirayan; Melita Irving; Carlos A Bacino; Julie Hoover-Fong; Keiichi Ozono; Klaus Mohnike; William R Wilcox; William A Horton; Joshua Henshaw Journal: Clin Pharmacokinet Date: 2021-08-25 Impact factor: 6.447
Authors: Helena H Hauta-Alus; Elisa M Holmlund-Suila; Saara M Valkama; Maria Enlund-Cerullo; Jenni Rosendahl; Ryan F Coghlan; Sture Andersson; Outi Mäkitie Journal: J Bone Miner Res Date: 2022-08-04 Impact factor: 6.390