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      Chinese Bone Turnover Marker Study: Reference Ranges for C-Terminal Telopeptide of Type I Collagen and Procollagen I N-Terminal Peptide by Age and Gender

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          Abstract

          Background

          Bone formation marker procollagen I N-terminal peptide (PINP) and resorption marker C-terminal telopeptide of type I collagen (β-CTX) are useful biomarkers for differential diagnosis and therapeutic evaluation of osteoporosis, but reference values are required.

          Methods

          The multi-center, cross-sectional Chinese Bone Turnover Marker Study included 3800 healthy volunteers in 5 Chinese cities. Serum PINP, β-CTX, parathyroid hormone (PTH) and 25OHD levels were measured by chemiluminescence assay. Lumbar spine and proximal femur BMD were measured by dual-energy X-ray absorptiometry. Serum PINP and β-CTX levels were assessed by age, gender, weight, recruitment latitude, levels of PTH and 25OHD.

          Results

          Subjects ( n = 1436, M∶F, 500∶936; mean age 50.6±19.6 years) exhibited non-normally distributed PINP and β-CTX peaking between 15–19 years, gradually declining throughout adulthood, elevating within 10 years of postmenopause, and then declining by age 70. In women between the age of 30 and menopause, median PINP and β-CTX levels were 40.42 (95% CI: 17.10–102.15) and 0.26 (95% CI: 0.08–0.72) ng/mL, respectively. β-CTX and PINP were positively linearly correlated ( r = 0.599, P<0.001). β-CTX correlated positively ( r = 0.054 and 0.093) and PINP correlated negatively ( r = −0.012 and −0.053) with 25OHD and PTH ( P<0.05).

          Conclusions

          We established Chinese reference ranges for PINP and CTX. Chinese individuals exhibited high serum PINP and β-CTX levels between 15 and 19 years of age and at menopause, which gradually declined after 70 years of age.

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          Most cited references32

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          Biochemical markers of bone turnover: part I: biochemistry and variability.

          With the ageing population in most countries, disorders of bone and mineral metabolism are becoming increasingly relevant to every day clinical practice. Consequently, the interest in, and the need for effective measures to be used in the screening, diagnosis and follow-up of such pathologies has markedly grown. Together with clinical and imaging techniques, biochemical tests play an important role in the assessment and differential diagnosis of metabolic bone disease. In recent years, the isolation and characterisation of cellular and extracellular components of the skeletal matrix have resulted in the development of molecular markers that are considered to reflect either bone formation or bone resorption. These biochemical indices are non-invasive, comparatively inexpensive and, when applied and interpreted correctly, helpful tools in the diagnostic and therapeutic assessment of metabolic bone disease. Part I of this article provides an overview of the basic biochemistry of bone markers, and sources of non-specific variability. Part II (to be published in a subsequent issue of this journal) will review the current evidence regarding the clinical use of biochemical markers of bone remodelling in metabolic and metastatic bone disease.
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            New insights into osteoporosis: the bone-fat connection.

            Osteoporosis and obesity are chronic disorders that are both increasing in prevalence. The pathophysiology of these conditions is multifactorial and includes genetic, environmental and hormonal determinants. Although it has long been considered that these are distinct disorders rarely found in the same individual, emerging evidence from basic and clinical studies support an important interaction between adipose tissue and the skeleton. It is proposed that adiposity may influence bone remodelling through three mechanisms: (i) secretion of cytokines that directly target bone, (ii) production of adipokines that influence the central nervous system thereby changing sympathetic impulses to bone and (iii) paracrine influences on adjacent skeletal cells. Here we focus on the current understanding of bone-fat interactions and the clinical implications of recent studies linking obesity to osteoporosis. © 2012 The Association for the Publication of the Journal of Internal Medicine.
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              Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate.

              Changes in the level of biochemical markers of bone resorption with risedronate treatment for osteoporosis were examined as a surrogate for the decrease in fracture risk. Greater decreases in bone resorption markers were associated with greater decreases in vertebral (and nonvertebral) fractures. Antifracture efficacy of antiresorptive therapies is only partially explained by increases in bone mineral density. Early decreases in bone resorption may also play a role. We tested this hypothesis by measuring two bone resorption markers, the C-telopeptide of type I collagen (CTX) and the N-telopeptide of type I collagen (NTX), in osteoporotic patients in risedronate vertebral fracture trials. We studied 693 women with at least one vertebral deformity (mean age, 69 +/- 7 years) who received calcium (and vitamin D if required) and placebo or risedronate 5 mg daily for 3 years. The reductions in urinary CTX (median, 60%) and NTX (51%) at 3-6 months with risedronate therapy were significantly associated (p < 0.05) with the reduction in vertebral fracture risk (75% over 1 year and 50% over 3 years). The changes in both CTX and NTX accounted for approximately one-half (CTX, 55%; NTX, 49%) of risedronate's effect in reducing the risk of vertebral fractures in the first year and approximately two-thirds (CTX, 67%; NTX, 66%) over 3 years compared with placebo. The changes in CTX and NTX accounted for 77% and 54%, respectively, of risedronate's effect in reducing the risk of nonvertebral fractures over 3 years compared with placebo. The relationships between vertebral fracture risk and changes from baseline in CTX and NTX were not linear (p < 0.05). There was little further improvement in fracture benefit below a decrease of 55-60% for CTX and 35-40% for NTX. The decrease in bone resorption in patients taking risedronate accounts for a large proportion of the reduction in fracture risk. There may be a level of bone resorption reduction below which there is no further fracture benefit.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                12 August 2014
                : 9
                : 8
                : e103841
                Affiliations
                [1 ]Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
                [2 ]Department of Laboratory, People's Hospital, Hubei Province, Wuhan, China
                [3 ]Department of Geriatrics, General Hospital of Guangzhou Military Command, Guangzhou, China
                [4 ]Department of Osteoporosis, Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China
                [5 ]Department of Orthopedics, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
                [6 ]Department of Obstetrics and Gynecology, Chinese Academy of Medical Sciences, Peking Union Medical College, Peking Union Medical College Hospital, Beijing, China
                National University of Ireland, Galway (NUI Galway), Ireland
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: WX LX. Performed the experiments: ML YL WD ZZ ZD YH. Analyzed the data: ML. Contributed reagents/materials/analysis tools: ML WX. Wrote the paper: ML.

                Article
                PONE-D-13-54394
                10.1371/journal.pone.0103841
                4130521
                25117452
                d1143556-91f9-4127-b140-ac2cbe3cc159
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 January 2014
                : 2 July 2014
                Page count
                Pages: 7
                Funding
                This study was supported by national natural science foundation of China (No. 81100623) and the Beijing Natural Science Foundation (No. 7121012). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Biochemistry
                Medicine and Health Sciences
                Endocrinology

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