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Bone formation and resorption markers at 7 years of age: Relations with growth and bone mineralization.

ABSTRACT: PURPOSE:We aimed to describe bone formation and resorption markers in generally healthy prepubertal children using total alkaline phosphatase (tALP), osteocalcin (OC) and ?-isomerized C-terminal telopeptides of type I collagen (?-CTx) serum concentrations and to estimate markers' correlations with anthropometric growth (height, weight, body mass index and trajectories of weight gain) as well as bone mineral content (BMC) and areal density (aBMD). METHODS:We assessed 395 7-year-old children from the Generation XXI cohort with tALP, OC and ?-CTx concentrations determined from a fasting venous blood sample and BMC/aBMD measured by dual-energy X-ray absorptiometry. Gender-specific reference intervals for tALP, OC and ?-CTx in 7-year-old children were established by calculating the 2.5th and 97.5th percentiles. Pearson and partial correlation coefficients (controlling for sex, age, body size and season) between bone markers and growth measures were computed. RESULTS:tALP increased with height (rpartial controlled for sex = 0.26, 95%CI: 0.17, 0.35), was higher in overweight than in healthy weight children, and in children who gained weight above average during infancy. No correlations were found between OC or ?-CTx and growth. In girls, OC was slightly correlated with subtotal BMC (rpartial = 0.22, 95%CI: 0.08, 0.35), subtotal aBMD (rpartial = 0.20, 95%CI: 0.06, 0.33) and lumbar spine aBMD (rpartial = 0.23, 95%CI: 0.09, 0.36). tALP and ?-CTx were not correlated with any of the DXA-derived bone measures. CONCLUSION:This study contributed to the description of bone turnover at 7 years of age and suggested that bone metabolism markers measured in a single point in time have limited ability to describe anthropometric growth and overall bone status in generally healthy prepubertal children.

SUBMITTER: Monjardino T

PROVIDER: S-EPMC6705799 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Bone formation and resorption markers at 7 years of age: Relations with growth and bone mineralization.

Monjardino Teresa T Silva Poliana P Amaro Joana J Carvalho Ofélia O Guimarães João Tiago JT Santos Ana Cristina AC Lucas Raquel R

PloS one 20190822 8

<h4>Purpose</h4>We aimed to describe bone formation and resorption markers in generally healthy prepubertal children using total alkaline phosphatase (tALP), osteocalcin (OC) and β-isomerized C-terminal telopeptides of type I collagen (β-CTx) serum concentrations and to estimate markers' correlations with anthropometric growth (height, weight, body mass index and trajectories of weight gain) as well as bone mineral content (BMC) and areal density (aBMD).<h4>Methods</h4>We assessed 395 7-year-old ...[more]

PMID: 31437153

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Project description:Bone remodeling is characterized by the sequential, local tethering of osteoclasts and osteoblasts, and is key to the maintenance of bone integrity. While bone matrix-mobilized growth factors, such as TGF-β, are proposed to regulate remodeling, no in vivo evidence exists that an osteoclast-produced molecule is the enigmatic coupling factor. We have identified Cthrc1, a protein secreted by mature bone-resorbing osteoclasts, that targets stromal cells so as to stimulate osteogenesis. The expression of Cthrc1 is robustly induced when mature osteoclasts are placed on dentin or hydroxyapatite, and also by increasing extracellular calcium. Cthrc1 expression in bone increases in a high turnover state, such as that which is induced by RANKL injections in vivo, whereas it decreases with aging or following alendronate treatment, conditions associated with suppressed bone turnover. The targeted deletion of the Cthrc1 gene eliminates Cthrc1 expression in bone, whereas its deficiency in osteoblasts does not exert any significant effect. Osteoclast-specific deletion of the Cthrc1 gene results in osteopenia due to reduced bone formation: it also impairs the coupling process following resorption induced by RANKL injections, with a resultant impairment of bone mass recovery. Thus, Cthrc1 is an osteoclast-secreted “coupling factor” that regulates bone remodeling and hence, skeletal integrity. Total bone marrow cells were prepared from the femurs and tibias of 8-10-week-old C57BL/6 mice and cultured in the presence of M-CSF (100ng/ml) for 3 days as described previously (Takeshita et al., 2000 JBMR 15:1477-1488). Cells were harvested with 0.02% EDTA/PBS and used as bone marrow macrophages (BMMs). These BMMs were cultured in the presence of M-CSF (100 ng/ml) and RANKL (100ng/ml) for 2 days. TRAP positive mononuclear cells were harvested and used as pre-osteoclasts (pOC). These pOC cells were further cultured in the presence of M-CSF and RANKL for 2 days in normal plastic plate or on dentin slices. After 2 days, multinucleated TRAP positive mature osteoclasts were generated as mature osteoclasts on plate (mOCp) and mature resorbing osteoclasts on dentin (mOCd), respectively. RNAs were extracted from four different stages of osteoclast lineage cells; BMMs, pOC, mOCp and mOCd, and used for microarray analysis.

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Bone formation and resorption markers at 7 years of age: Relations with growth and bone mineralization.

Publications

Bone formation and resorption markers at 7 years of age: Relations with growth and bone mineralization.

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