Interpretation of biomarkers of bone metabolism in children: impact of growth velocity and body size in healthy children and chronic disease.
OBJECTIVE
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.


METHODS
BSAP and DPD were measured at baseline, with growth and dual energy x-ray absorptiometry (DXA) WB-BMC measured at baseline and 6 months in 202 control subjects and 110 subjects with Crohn's disease, ages 5 to 21 years. Multivariable linear regression identified determinants of biomarkers in control subjects and subjects with Crohn's disease.


RESULTS
In control subjects, 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% to 80% of the variability in the bone biomarkers, respectively. Subjects with Crohn's disease had lower height-for-age (P < .001) and WB-BMC-for-height (P <.05) than control subjects. Crohn's disease was associated with lower BSAP (P < .001) and greater DPD (P < .001), independent of growth, maturation, baseline WB-BMC, and WB-BMC accrual, compared with control subjects.


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.
Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. tuchman@email.chop.edu
Shamir
S
Tuchman
Meena
M
Thayu
Justine
J
Shults
Babette S
BS
Zemel
Jon M
JM
Burnham
Mary B
MB
Leonard
D015502:Absorptiometry, Photon; D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism*; D000596:Amino Acids / Q000652:urine*; D015415:Biomarkers / Q000378:metabolism*; D049628:Body Size; D015519:Bone Density; D001862:Bone Resorption / Q000503:physiopathology; D002648:Child; D002657:Child Development / Q000502:physiology*; D002675:Child, Preschool; D002908:Chronic Disease; D003404:Creatinine / Q000652:urine*; D003424:Crohn Disease / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D015999:Multivariate Analysis
D000596:Amino Acids; D015415:Biomarkers; C036020:deoxypyridinoline; D003404:Creatinine; D000469:Alkaline Phosphatase