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    Comparison of clinical cut-points and treatment targets for urine NTX and plasma βCTX-I in osteoporosis. Chubb S A Paul,Mandelt Christine,Vasikaran Samuel Clinical biochemistry OBJECTIVE:We undertook to identify levels for plasma β isomerised carboxy-terminal telopeptides of type I collagen (p-βCTX-I) that are comparable to currently used urine amino-terminal telopeptides of type I collagen (u-NTX) cut-points and treatment targets in osteoporosis. DESIGN AND METHODS:Fasting morning samples were collected from patients attending tertiary hospitals and clinics for investigation of metabolic bone disease. Patients with Paget's disease or <20years of age were excluded. Second void spot urine for NTX and plasma (EDTA) samples were utilised. Urine was analysed routinely and plasma stored at -20C until analysis by enzyme-linked immunosorbent assay (ELISA) (Immunodiagnostic Systems plc), E170 (Roche Diagnostics) and IDS-iSYS (Immunodiagnostic Systems plc) methods. The relationship of u-NTX with each p-βCTX-I method's results was assessed by Passing and Bablok regression, and p-βCTX-I levels equivalent to u-NTX cut-points and targets were interpolated. RESULTS:One hundred and forty six patients were included. Spearman correlation coefficients ranged from 0.71 to 0.75 for the three βCTX-I assays. The equivalent βCTX-I concentrations for NTX/Cr values of 21 (fracture risk reduction target following risedronate therapy), 27 (healthy pre-menopausal women's mean value), and 38 (threshold for reduction of BMD on calcium alone) nmol BCE/mmol were 230, 312 and 462ng/L for the automated Roche assay and 271, 395 and 624ng/L for the automated IDS i-SYS assay respectively. CONCLUSIONS:The p-βCTX-I equivalent to the only available fracture outcome based absolute treatment threshold of 21nmol BCE/mmol established for u-NTX, is close to 250ng/L but will vary between p-βCTX-I assays. 10.1016/j.clinbiochem.2015.12.002
    Characteristics of bone biochemical indices in predicting secondary osteoporotic fracture after intertrochanteric fracture in elderly women. Yang Shaofeng,Liu Yanan,Shi Qin,Zou Jun,Yang Huilin Journal of orthopaedic translation Background:This study aimed to explore the characteristics of bone biochemical indices, including bone mineral density (BMD), metabolic markers in elderly women with osteoporotic intertrochanteric fracture and their relevance in secondary fracture. Methods:The standard for follow-up from 58 elderly women was established to analyse the BMD in the injured hip, healthy hip, and the vertebra at 1 week and 12 months after fracture. The serum levels of total procollagen type N-terminal propeptide (tPINP) and the age-related type I cross linked C-telopeptide (β-CTX) were recorded and compared between those patients with and without secondary fractures within 12 months. Results:Twelve months after fracture, the serum levels of tPINP and β-CTX were significantly higher than the baseline values ( < 0.01). The tPINP baseline in patients with secondary fracture was significantly lower than that in the rest patients without secondary fracture ( < 0.01). The β-CTX baseline was notably higher than that without secondary fracture ( < 0.01). BMD values of the three periods had no significantly difference. Conclusion:The serum levels of tPINP and β-CTX are of great value in earlier and more sensitively reflecting the condition of bone turnover in body. Meanwhile, they can predict the subsequent fracture risk more accurately combined with a lower BMD. The Translational Potential of this Article:Besides BMD, bone microstructure and remodeling levels can be accurately measured by bone biochemical indices. The main objective of this research is to explore the change of BMD and the serum level of bone biochemical indices of elderly women who suffered unilateral intertrochanteric fracture within 12 months. Simultaneously, with aim to better obtain bone remodeling level and predict more accurately the risk of a secondary osteoporotic fracture, bone biochemical indices of these patients, who undergo secondary osteoporotic fracture or not, are collected during follow-up and compared respectively. 10.1016/j.jot.2017.07.002
    The Effect of Vitamin D Supplementation on Bone Metabolic Markers in Chronic Kidney Disease. Yadav Ashok Kumar,Kumar Vivek,Kumar Vinod,Banerjee Debasish,Gupta Krishan Lal,Jha Vivekanand Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Use of active forms of vitamin D is advocated in patients with chronic kidney disease (CKD) for treatment of mineral bone disease because of the presumption that native forms of vitamin D would not undergo significant activation to calcitriol, the most active biological form of vitamin D. We present secondary analysis looking at bone turnover in subjects who completed the randomized, double blind, placebo-controlled trial investigating the effect of cholecalciferol supplementation on vascular function in nondiabetic CKD stage G3-G4 and vitamin D ≤20 ng/mL (Clinical Trials Registry of India: CTRI/2013/05/003648). Patients were randomized (1:1) to receive either two directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol group and 59 in the placebo group completed the study. At 16 weeks, the serum 25(OH)D and 1,25(OH) D levels increased in the cholecalciferol group but not in the placebo group (between-group difference in mean change: 23.40 ng/mL; 95% CI, 19.76 to 27.06; p < 0.001, and 14.98 pg/mL; 95% CI, 4.48 to 27.18; p = 0.007, respectively). Intact parathyroid hormone (iPTH) decreased in the cholecalciferol group (between-group difference in mean change -100.73 pg/mL (95% CI, -150.50 to -50.95; p < 0.001). Serum total and bone-specific alkaline phosphatase (SAP, BAP) and serum C-terminal cross-linked collagen type I telopeptides (CTX-1) were significantly reduced in cholecalciferol group (between group difference for change in mean: -20.25 U/L; 95% CI, -35.14 to -5.38 U/L; p = 0.008 for SAP; -12.54 U/L; 95% CI, -22.09 to -2.98 U/L; p = 0.013 for BAP; and -0.21 ng/mL; 95% CI, -0.38 to -0.05 ng/mL; p = 0.05 for CTX-1). Correlation analysis showed significant correlation of Δ25(OH)D with ΔiPTH (r = -0.409, p < 0.0001), Δ1,25(OH) D (r = 0.305, p = 0.001), ΔSAP (r = -0.301, p = 0.002), ΔBAP (r = -0.264, p = 0.004), and ΔCTX-1 (r = -0.210, p = 0.0230). Cholecalciferol supplementation corrects vitamin D deficiency and is effective in lowering serum intact parathyroid hormone and bone turnover markers in early stages of CKD. © 2017 American Society for Bone and Mineral Research. 10.1002/jbmr.3314
    Association of serum uric acid levels with osteoporosis and bone turnover markers in a Chinese population. Yan Dan-Dan,Wang Jie,Hou Xu-Hong,Bao Yu-Qian,Zhang Zhen-Lin,Hu Cheng,Jia Wei-Ping Acta pharmacologica Sinica Recent evidence shows that uric acid is protective against some neurological diseases, but can be detrimental in many metabolic and cardiovascular disorders. In this study, we examined the association between serum uric acid levels and bone metabolism in Chinese males and postmenopausal females. A total of 943 males and 4256 postmenopausal females were recruited in Shanghai. The levels of serum uric acid and bone turnover markers (BTMs) were detected along with other biochemical traits. In addition, the fat distribution was calculated through MRI and image analysis software, and bone mineral density (BMD) was determined using dual-energy X-ray absorptiometry. For postmenopausal females, the prevalence of osteoporosis was significantly lower in the hyperuricemia group compared with the normouricemic group (P=4.65E-06). In females, serum uric acid level was significantly associated with osteoporosis, with odds ratio (OR) and 95% confidence interval (95% CI) of 0.844 [0.763; 0.933] (P=0.0009) after adjusting for age, body mass index, HbA1c, lean mass, visceral and subcutaneous fat areas, albumin, 25-hydroxyvitamin D3 [25(OH)D3], and parathyroid hormone (PTH). In females, serum uric acid level was positively correlated with the BMD of the femoral neck (β±SE: 0.0463±0.0161; P=0.0042), total hip (β±SE: 0.0433±0.0149; P=0.0038) and L1-4 (β±SE: 0.0628±0.0165; P=0.0001) after further adjusting for age, BMI, HbA1c, lean mass, VFA, SFA, albumin, 25(OH)D3 and PTH. Regarding BTMs, serum uric acid level was negatively correlated with N-terminal procollagen of type I collagen (PINP) in females (β±SE: -0.1311±0.0508; P=0.0100). In summary, our results suggest that uric acid has a protective effect on bone metabolism independent of body composition in Chinese postmenopausal females. 10.1038/aps.2017.165