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

Abstract

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 ...

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

“…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).…”

“…Generally, bone markers are known to be related to changes in bone remodeling and in bone mass in elderly postmenopausal women (23,25) but not in young premenopausal women (28). Studies of the association between markers of bone turnover and subsequent bone gain in healthy girls have shown conflicting results (15,17,22,29). An association between bone markers and bone gain should be examined prospectively in a larger group of patients with RTT of different ages and pubertal stages.…”

“…However, limitations of the cross sectional design made it impossible to evaluate the influence on previous shown determinants of bone markers in children and adolescents, as height velocity and bone mineral accrual (15). It is feasible that those determinants are also relevant for bone marker levels in RTT.…”

“…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.…”

Biochemical markers of bone turnover in children with clinical bone fragility

“…During remodeling, which is seen in adults, bone formation and resorption are tightly coupled. In contrast, bone modeling during growth in children results in new bone formation at a different site than the site of resorption and at a faster rate, leading to alterations in bone shape and bone mass accrual [13]. Interpretation of biochemical markers of bone turnover [bone turnover markers (BTMs)] in children is therefore more challenging than that in adults as biomarkers of bone metabolism represent the combined effects of bone formation, skeletal growth and bone remodeling.…”