Sex- and Age-Specific Reference Curves for Serum Markers of Bone Turnover in Healthy Children from 2 Months to 18 Years

Rauchenzauner, Markus; Schmid, Andrea; Heinz‐Erian, Peter; Kapelari, Klaus; Falkensammer, Gerda; Griesmacher, Andrea; Finkenstedt, G; Högler, Wolfgang

doi:10.1210/jc.2006-1706

Cited by 239 publications

(196 citation statements)

References 47 publications

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“…Our results showed that the levels of all biochemical bone markers in both patients and controls were highest in the preearly-pubertal years, followed by an overall decrease through puberty and postpubertal years, in accordance with other studies of bone markers in children, adolescents, and adults (12,(15)(16)(17)(18)(19). Previously, bone marker values have been shown to increase during early-mid puberty (Tanner breast developmental stages 2 and 3), corresponding to increasing height velocity (15,17,18).…”

Section: Rett Syndrome and Low Bone Turnoversupporting

confidence: 92%

“…Furthermore, biochemical bone markers have not been associated with measures of bone mineral density or low-energy fractures in RTT. Studies on biochemical bone markers in healthy persons have reported high levels in early childhood, peaking in puberty, and decreasing to stable levels in the mid-20s (12,(15)(16)(17)(18)(19), but the level of biochemical bone markers in children and adolescents with RTT is unknown.…”

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confidence: 99%

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Low bone turnover phenotype in Rett syndrome: results of biochemical bone marker analysis

et al. 2013

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Background:Patients with Rett syndrome (RTT) are at risk of having low bone mass and low-energy fractures. Methods: We characterized bone metabolism by both bone formation and resorption markers in blood in a RTT population of 61 girls and women and 122 well-matched healthy controls. Levels of N-terminal propeptides of collagen type 1 (P1NP), C-terminal telopeptide cross links (CTX), osteocalcin (OC), and bone-specific alkaline phosphatase (B-ALP) were compared between RTT patients and controls in regression models adjusted for BMI, vitamin D status, volumetric bone mineral apparent density of the lumbar spine (vBMAD spine ), and femoral neck (vBMAD neck ). We examined biochemical bone marker levels overall and stratified to persons younger than age 25 y or equal to or older than age 25 y. results: The RTT patients had reduced levels of all biochemical bone markers (P < 0.05), which remained significant in persons younger than 25 y (P ≤ 0.001) regarding P1NP, CTX, and OC. Bone marker levels were not significantly associated to methyl-CpG-binding protein 2 (MECP2) mutation group, walking ability, or previous low-energy fractures. conclusion: Our findings of a low bone turnover state in girls with RTT suggest critical attention to medical treatment of low bone mass in young RTT patients.

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Section: Rett Syndrome and Low Bone Turnoversupporting

confidence: 92%

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confidence: 99%

Low bone turnover phenotype in Rett syndrome: results of biochemical bone marker analysis

et al. 2013

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“…(8,(22)(23)(24)(25) Although prior studies have demonstrated that biomarkers of bone metabolism were positively correlated with growth velocity, (7,24) these studies were limited to correlations between biomarkers and growth velocity without consideration of the independent effects of pubertal maturation, bone mass, and bone accrual on biomarker levels. Our data in healthy controls demonstrates that Tanner stage, sex, WB-BMC, height velocity, and WB-BMC accrual rates were all significant and independent determinants of bone biomarker levels during childhood and adolescence.…”

Section: Discussionmentioning

confidence: 99%

“…(6,7) Biomarkers of bone metabolism in children and adolescents have traditionally been interpreted in the context of sex and age or pubertal stage. (8) However, overall skeletal mass [e.g. whole body bone mineral content (WB-BMC)], height velocity, and rates of bone accrual may also be important determinants.…”

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confidence: 99%

Interpretation of Biomarkers of Bone Metabolism in Children: Impact of Growth Velocity and Body Size in Healthy Children and Chronic Disease

Tuchman

Thayu

Shults

et al. 2008

The Journal of Pediatrics

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Objectives-To determine the effects of growth, maturation, and whole body bone mineral content (WB-BMC) accrual on biomarkers of bone formation [bone specific alkaline phosphatase (BSAP)] and resorption [urine deoxypyridinoline/creatinine (DPD)] in healthy children and children with Crohn's disease.Study design-BSAP and DPD were measured at baseline, and growth and dual energy x-ray absorptiometry (DXA) WB-BMC were measured at baseline and six months in 202 controls and 110 subjects with Crohn's disease, ages 5 to 21 years. Multivariable linear regression identified determinants of biomarkers in controls and subjects with Crohn's disease.Results-In controls, BSAP and DPD were significantly and independently associated with sex, Tanner stage, WB-BMC, height velocity, and WB-BMC accrual rates; these covariates explained 77-80% of the variability in bone biomarkers. Subjects with Crohn's disease had lower height-forage (p < 0.001) and WB-BMC-for-height (p < 0.05), compared with controls. Crohn's disease was associated with lower BSAP (p < 0.001) and greater DPD (p < 0.001), independent of growth, maturation, baseline WB-BMC, and WB-BMC accrual, compared with controls.Conclusions-These data illustrate the potential confounding effects of growth and WB-BMC on bone metabolism biomarkers in children. After adjustment for these effects, Crohn's disease was associated with lower biomarkers of bone formation and greater bone resorption. KeywordsCrohn's disease; height velocity; bone-specific alkaline phosphatase; urine deoxypyridinoline; dual energy x-ray absorptiometry; bone mineral content Corresponding/Reprint request author: Shamir Tuchman MD, MPH, Division of Pediatric Nephrology, Department of Pediatrics, The Children' s Hospital of Philadelphia, 34 th and Civic Center Blvd., Philadelphia, PA 19104, pH: (215) 590-2449, fax: (215) 590-3705, email: E-mail: tuchman@email.chop.edu. Edited by TW and WFB Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.The authors declare no conflicts of interest. Serum levels of biomarkers of bone formation were significantly reduced in children with newly diagnosed Crohn's disease, and biomarkers of bone resorption were variably reduced in comparison with controls; thus, bone remodeling may be suppressed in incident Crohn's disease due to a primary impairment in bone formation. (9) The accompanying editorial suggested that these findings support the use of anabolic agents as opposed to anti-resorptive agents in childhood Crohn's disease.(10) However, low overall bone mass (i.e. reduced numbers of osteoblasts and osteoclasts) and reduced ...

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“…Until now, paediatric reference data have mainly been used for diagnosing poor bone acquisition in children who are suffering from multiple fractures, diseases or receiving medical treatments affecting bone metabolism. 11,14 Bone reference data may be not only a diagnostic tool for children with bone diseases 15 but may also serve to monitor apparently healthy subjects and to identify those who may benefit from specific interventions to improve bone health.…”

Section: Introductionmentioning

confidence: 99%

Reference values of bone stiffness index and C-terminal telopeptide in healthy European children

et al. 2014

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,9 on behalf of the IDEFICS consortium BACKGROUND/OBJECTIVE: Quantitative ultrasound measurements and bone metabolic markers can help to monitor bone health and to detect impaired skeletal development. Population-based reference values for children may serve as a basis for preventive measures to reduce the risk of osteoporosis and osteoporotic fractures in later life. This is the first paper providing age-, sex-and height-specific reference values for bone stiffness index (SI) and serum carboxy-terminal cross-linking telopeptide of type I collagen (CTX) in healthy, apparently prepubertal children. SUBJECTS/METHODS: In the population-based IDEFICS baseline survey (2007)(2008) and follow-up (2009-2010), 18 745 children from eight European countries were newly recruited. A total of 10 791 2-10.9-year-old and 1646 3-8.9-year-old healthy children provided data on SI of the right and left calcaneus and serum CTX, respectively. Furthermore, height and weight were measured. Percentile curves were calculated using the General Additive Model for Location Scale and Shape (GAMLSS) to model the distribution of SI and CTX depending on multiple covariates while accounting for dispersion, skewness, and the kurtosis of this distribution. RESULTS: SI was negatively associated with age and height in children aged 2-5 years, whereas a positive association was observed in children aged 6-10 years. The dip in SI occurred at older age for higher SI percentiles and was observed earlier in taller children than in smaller children. The CTX reference curves showed a linear-positive association with age and height. No major sex differences were observed for the SI and CTX reference values. CONCLUSION: These reference data lay the ground to evaluate bone growth and metabolism in prepubertal children in epidemiological and clinical settings. They may also inform clinical practice to monitor skeletal development and to assess adverse drug reactions during medical treatments.

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Sex- and Age-Specific Reference Curves for Serum Markers of Bone Turnover in Healthy Children from 2 Months to 18 Years

Cited by 239 publications

References 47 publications

Low bone turnover phenotype in Rett syndrome: results of biochemical bone marker analysis

Low bone turnover phenotype in Rett syndrome: results of biochemical bone marker analysis

Interpretation of Biomarkers of Bone Metabolism in Children: Impact of Growth Velocity and Body Size in Healthy Children and Chronic Disease

Reference values of bone stiffness index and C-terminal telopeptide in healthy European children

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