Obese children have disadvantageous bone geometry, bone of low quality, and reduced strength at non-weight-bearing skeletal sites. The aim of our study was to investigate the role of parathormone (PTH) and the Wnt/β-catenin signaling pathway and its inhibitors, sclerostin and Dickkopf-1 (DKK1), as negative modulators of fat mass on bone. This was a cross-sectional observational study performed in 44 (26 males and 18 females) obese subjects, aged 11.41 ± 2.61 years. Thirty-seven normal-weight, healthy children (22 males and 15 females) of the same chronological age served as controls for the biochemical parameters and bone markers, while the data on bone geometry were evaluated according to our normative data obtained previously in a group of 325 control children. Digitalized X-rays were evaluated at the level of the second metacarpal bone for the determination of bone geometry: total cross-sectional area (TCSA), cortical area (CA), medullary area (MA), and bone strength (bending breaking resistance index [BBRI]). Serum bone markers (intact procollagen-1N-terminal propeptide [P1NP] and serum carboxy-terminal telopeptide of collagen-1 [CTX]), sclerostin, DKK1, PTH, 25-hydroxyvitamin D and were also measured. Data for TCSA, CA, MA, and BBRI are expressed as a standard deviation score in order to normalize them for age and sex. TCSA (mean ± SD, -2.92 ± 2.71), CA (-0.60 ± 0.82), MA (-0.45 ± 1.14), and BBRI (-2.65 ± 2.31) were all significantly smaller than in controls (p < 0.01). Serum PTH (36.27 ± 23.89 vs. 19.33 ± 11.37 pg/mL) and CTX (1.55 ± 0.44 vs. 1.34 ± 0.46 ng/mL) were significantly increased (p < 0.05) in the obese children compared to controls, while sclerostin was significantly decreased (24.67 ± 10.06 vs. 30.42 ± 11.01 pmol/L, p < 0.05). P1NP was also significantly increased (p < 0.01). PTH was negatively correlated with TCSA, CA, and BBRI. Bone turnover is higher in obese children than in controls, and this is associated with smaller and apparently weaker bones. Higher PTH and lower sclerostin levels may be responsible for these findings.
Higher circulating parathormone is associated with smaller and weaker bones in obese children.
ADAMI, Silvano;ROSSINI, Maurizio;GATTI, Davide
2014-01-01
Abstract
Obese children have disadvantageous bone geometry, bone of low quality, and reduced strength at non-weight-bearing skeletal sites. The aim of our study was to investigate the role of parathormone (PTH) and the Wnt/β-catenin signaling pathway and its inhibitors, sclerostin and Dickkopf-1 (DKK1), as negative modulators of fat mass on bone. This was a cross-sectional observational study performed in 44 (26 males and 18 females) obese subjects, aged 11.41 ± 2.61 years. Thirty-seven normal-weight, healthy children (22 males and 15 females) of the same chronological age served as controls for the biochemical parameters and bone markers, while the data on bone geometry were evaluated according to our normative data obtained previously in a group of 325 control children. Digitalized X-rays were evaluated at the level of the second metacarpal bone for the determination of bone geometry: total cross-sectional area (TCSA), cortical area (CA), medullary area (MA), and bone strength (bending breaking resistance index [BBRI]). Serum bone markers (intact procollagen-1N-terminal propeptide [P1NP] and serum carboxy-terminal telopeptide of collagen-1 [CTX]), sclerostin, DKK1, PTH, 25-hydroxyvitamin D and were also measured. Data for TCSA, CA, MA, and BBRI are expressed as a standard deviation score in order to normalize them for age and sex. TCSA (mean ± SD, -2.92 ± 2.71), CA (-0.60 ± 0.82), MA (-0.45 ± 1.14), and BBRI (-2.65 ± 2.31) were all significantly smaller than in controls (p < 0.01). Serum PTH (36.27 ± 23.89 vs. 19.33 ± 11.37 pg/mL) and CTX (1.55 ± 0.44 vs. 1.34 ± 0.46 ng/mL) were significantly increased (p < 0.05) in the obese children compared to controls, while sclerostin was significantly decreased (24.67 ± 10.06 vs. 30.42 ± 11.01 pmol/L, p < 0.05). P1NP was also significantly increased (p < 0.01). PTH was negatively correlated with TCSA, CA, and BBRI. Bone turnover is higher in obese children than in controls, and this is associated with smaller and apparently weaker bones. Higher PTH and lower sclerostin levels may be responsible for these findings.
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