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1.
Low bone turnover is associated with plain X-ray vascular calcification in predialysis patients.
Neto, R, Pereira, L, Magalhães, J, Quelhas-Santos, J, Frazão, J
PloS one. 2021;(10):e0258284
Abstract
BACKGROUND Vascular calcification (VC) is a common finding in chronic kidney disease (CKD) patients and predicts subsequent cardiovascular morbidity and mortality in this population. Vascular calcification is linked to disordered mineral metabolism and has been associated with bone histomorphometry changes in CKD. However, data on predialysis patients is scarce. METHODS A cross-sectional study was conducted on a cohort of 56 CKD patients not yet on dialysis, who underwent a transiliac bone biopsy for histomorphometric evaluation after double tetracycline labeling. Patients had no previous exposure to calcium salts, vitamin D agents, steroids or bisphosphonates. Vascular calcification was assessed at the time of biopsy, using Kauppila (plain X-ray of the lateral lumbar spine) and Adragão (plain X-ray of the pelvis and hands) scores. RESULTS Vascular calcification was seen in two-thirds of the cohort. Subjects with VC were more likely to be male and have diabetes, and had significantly higher sclerostin and osteoprotegerin circulating levels than those without VC. The histomorphometric analysis showed that bone formation rate was significantly lower in VC compared to non-VC patients. In the multivariable logistic regression analysis, bone formation rate was independently associated with the presence of VC. CONCLUSIONS Vascular calcification is highly prevalent in predialysis patients, especially in those with diabetes. The independent association between bone formation rate and VC provides evidence of an important interaction between bone and vessel in CKD. Our results suggest that low bone turnover is a non-traditional risk factor for cardiovascular disease in predialysis patients.
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2.
Bone metabolism markers are associated with neck circumference in adult Arab women.
Albassam, RS, Sabico, S, Alnaami, AM, Khattak, MNK, Lei, KY, Al-Daghri, NM, Reginster, JY, Alokail, MS
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2019;(4):845-852
Abstract
UNLABELLED The study aimed to determine whether neck circumference is associated with bone metabolism markers among adult Arab women and found modest but significant associations with bone resorption markers, suggesting that neck circumference, a surrogate measure of upper subcutaneous fat, influences bone turnover expression among adult females. INTRODUCTION Body fat distribution is associated with decreased bone resorption and neck circumference (NC), a surrogate measure for upper body fat, has never been tested as a marker that can reflect bone turnover. This is the first study aimed to analyze the associations between NC and several bone biomarkers among adult Saudi women. METHODS This cross-sectional study included a total of 265 middle-aged Saudi women [86 non-obese (mean age 52.7 ± 8.1; mean BMI 26.9 ± 2.3) and 179 obese (mean age 50.6 ± 7.5; mean BMI 35.7 ± 4.5)] recruited from primary care centers in Riyadh, Saudi Arabia. Anthropometrics included BMI, NC, waist and hip circumferences, total body fat percentage (%), and blood pressure. Biochemical parameters included glucose and lipid profile which were measured routinely. Serum levels of 25(OH) D, parathyroid hormone, RANKl, sclerostin, C-terminal telopeptide of collagen I (CTX-I), Dkk1, IL1β, osteoprotegerin, osteopontin, and osteocalcin were measured using commercially available assays. RESULTS In all groups, NC was inversely associated with PTH (R = - 0.22; p < 0.05) and positively associated with osteoprotegerin (R = 0.20; p < 0.05) even after adjustments for age and BMI. Using all anthropometric indices as independent variables showed that only NC explained the variance perceived in CTX-I (p = 0.049). In the non-obese, waist-hip ratio (WHR) was significantly associated with sclerostin (R = 0.40; p < 0.05) and body fat was significantly associated with osteopontin (R = 0.42; p < 0.05). CONCLUSION NC is modestly but significantly associated with bone biomarkers, particularly the bone resorption markers, among adult Arab women. The present findings highlight the importance of NC as measure of upper body subcutaneous fat in influencing bone biomarker expression in adult females.
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3.
Effects of Biliopancreatic Diversion on Bone Turnover Markers and Association with Hormonal Factors in Patients with Severe Obesity.
Turcotte, AF, Grenier-Larouche, T, Ung, RV, Simonyan, D, Carreau, AM, Carpentier, AC, Mac-Way, F, Michou, L, Tchernof, A, Biertho, L, et al
Obesity surgery. 2019;(3):990-998
Abstract
BACKGROUND This study evaluated early and medium-term changes in bone turnover markers, and their associations with weight loss, total bone mineral density (BMD), and hormonal changes after biliopancreatic diversion (BPD). METHODS Ancillary study from a one-year prospective cohort of 16 individuals assessed before, 3 days, 3 and 12 months after BPD. Bone turnover markers (C-terminal telopeptide (CTX), intact osteocalcin (OC), sclerostin, and osteoprotegerin (OPG)) and several hormones were measured at each visit. Total BMD by DXA was assessed at baseline, 3 and 12 months after BPD. Three participants were lost to follow-up. RESULTS CTX increased significantly at 3 days (+ 66%), 3 months (+ 219%), and 12 months (+ 295%). OC decreased at 3 days (- 19%) then increased at 3 months (+ 69%) and 12 months (+ 164%). Change in sclerostin was only significant between 3 days and 3 months (+ 13%), while change in OPG was significant between baseline and 3 days (+ 48%) and baseline and 12 months (+ 45%). CTX increase correlated negatively with weight loss at 3 (r = - 0.63, p = 0.009) and 12 months (r = - 0.58, p = 0.039), and total BMD decrease (r = - 0.67, p = 0.033) at 12 months. Change in insulin and adiponectin correlated with changes in bone turnover markers independently of weight loss. CONCLUSION BPD causes an earlier and greater increase in bone resorption over bone formation markers and a decrease in total BMD. Sclerostin did not increase as expected following extensive weight loss. Changes in insulin and adiponectin seem to play a role in the activation of bone remodeling after BPD.
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4.
Bone Turnover Markers in Men and Women with Impaired Fasting Glucose and Diabetes.
Holloway-Kew, KL, De Abreu, LLF, Kotowicz, MA, Sajjad, MA, Pasco, JA
Calcified tissue international. 2019;(6):599-604
Abstract
Bone turnover markers (BTMs) are reduced in diabetes, but whether BTM changes occur in impaired fasting glucose (IFG) is unknown. The aim of this study was to investigate whether BTMs are altered in IFG and diabetes compared to normoglycaemia. For men and women (n = 2222) in the Geelong Osteoporosis Study, IFG was defined as fasting plasma glucose (FPG) 5.5-6.9 mmol/L and diabetes as FPG ≥ 7.0 mmol/L, use of antihyperglycemic medication and/or self-report. Serum C-terminal telopeptide (CTx) and procollagen type 1 N-terminal propeptide (P1NP) were measured. After natural log transformation to normalise the data, multivariable regression was used to examine the relationship between glycaemia status and bone turnover markers (BTMs), before and after adjusting for other confounders. There were 643 men and 682 women with normoglycaemia, 355 men and 391 women with IFG and 97 men and 54 women with diabetes. Men with IFG or diabetes had lower adjusted ln(CTx) and ln(P1NP) compared to normoglycaemia (all p < 0.05). Women with IFG or diabetes had lower adjusted ln(CTx) and ln(P1NP) (all p < 0.05) except for ln(P1NP) when comparing diabetes with normoglycaemia, which showed a trend for lower ln(P1NP) (p = 0.053). In both sexes, an age * glycaemia interaction term indicated between-group differences in BTMs diminished with increasing age. No other confounders were identified. Bone turnover was lower in those with either IFG or diabetes compared to normoglycaemia.
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5.
Bariatric Roux-En-Y Gastric Bypass Surgery: Adipocyte Proteins Involved in Increased Bone Remodeling in Humans.
Biagioni, MFG, Mendes, AL, Nogueira, CR, Leite, CV, Gollino, L, Mazeto, GM
Obesity surgery. 2017;(7):1789-1796
Abstract
PURPOSE Bariatric surgery has been associated with bone remodeling changes. The action of adipokines on the expression of receptor activator of nuclear factor kappa β ligand (RANKL) and osteoprotegerin (OPG) and on an increase in sclerostin could be related to these changes. MATERIALS AND METHODS This study aimed to assess the repercussions of weight loss, fat mass (FM), and fat-free mass (FFM) loss and biochemical and hormonal changes on bone remodeling markers after Roux-en-Y gastric bypass (RYGB). Anthropometric data, parathyroid hormone (PTH), bone-specific alkaline phosphatase (BSAP), collagen type 1 C-telopeptide (CTX), 25-hydroxy vitamin D (25-OH-VitD), leptin, adiponectin, RANKL, OPG, and sclerostin of 30 menstruating women were measured preoperatively (Pre), and 3, 12, and 24 months (m) after RYGB. RESULTS Leptin (34.4 (14.7; 51.9) vs. 22.5 (1.9; 52.7) ng/mL) and OPG (3.6 (1.1; 11.5) vs. 3.4 (1.5; 6) pmol/L) decreased, and adiponectin (7.4 (1.7; 18.4) vs. 13.8 (3.0; 34.6) μg/mL), CTX (0.2 (0.1; 2.2) vs. 0.6 (0.4; 6.0) ng/mL), RANKL (0.1 (0.0; 0.5) vs. 0.3 (0.0; 2.0) pmol/L), and sclerostin (21.7 (3.2; 75.1) vs. 34.8 (6.4; 80.5) pmol/L) increased after 3 m. BSAP increased after 12 m (10.1 (5.4; 18.9) vs. 13.9 (6.9; 30.2) μg/mL) (p < 0.005). CTX correlated positively with adiponectin at 24 m and inversely with leptin Pre; OPG at 3 m; weight, FM, FFM, and leptin at 24 m. RANKL correlated directly with weight at 3 m. Sclerostin correlated inversely with weight Pre and FM at 3 m. BSAP correlated negatively with 25-OH-VitD at 12 m, and positively with PTH at 24 m. CONCLUSIONS RYGB induced weight loss, and biochemical, hormonal, and body composition changes are associated with higher bone remodeling.
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6.
[Effect of tumour necrosis factor α blockade on bone metabolism in chronic inflammatory joint diseases].
Aguilar Del Rey, FJ, García Portales, R, Haro Liger, M, Rodríguez Andreu, J, Casals Sánchez, JL, Pérez González, R
Medicina clinica. 2016;(2):56-62
Abstract
BACKGROUND AND OBJECTIVE To evaluate the effect of anti-TNF treatments on bone mineral density (BMD), bone remodelling markers (BRM) and receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) in patients with chronic inflammatory joint diseases. METHODS A longitudinal prospective study was performed under clinical practice conditions on 31 patients diagnosed of rheumatoid arthritis, psoriatic arthropathy and ankylosing spondylitis who had received treatment with anti-TNF alpha drugs for one year. BMD, OPG and RANKL soluble form (sRANKL) were studied at the onset and end of the study. During the study (0, 3, 6, 9 and 12 month), disease activity (SDAI, BASDAI and CRP), functional capacity (HAQ, BASFI), BRM and vitamin D were studied. RESULTS BMD was not modified after one year of treatment. The patients who took corticosteroids had a mean bone mass loss of 3% in the lumbar spine (±1.6, P=.02). In regards to the BRM, did not experience significant changes over the course of the study. Disease activity, both SDAI (P=.002) and BASDAI (P=.002), decreased. OPG was maintained without changes during the year of treatment while both the sRANKL (0.28±0.22, P=.013) and sRANKL/OPG ratio significantly decreased (0.04±0.03, P=.031). CONCLUSION The patients being treated with anti-TNF did not present with a significant loss of DMO during the study (one year), at the same time experiencing an improvement in disease activity. This protection has been clearer in the responding patients.
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7.
[Utility of bone turnover markers in metabolic bone disease detection in patients with phenylketonuria].
Mirás, A, Freire Corbacho, A, Rodríguez García, J, Leis, R, Aldámiz-Echevarría, L, Fraga, JM, Couce, ML
Medicina clinica. 2015;(5):193-7
Abstract
BACKGROUND AND OBJECTIVE Mineral bone disease is more common in phenylketonuric patients. The objectives of this study were to determine the usefulness of biochemical bone markers to identify phenylketonuric patients with mineral bone disease (MBD) and know the underlying bone remodeling alterations. PATIENTS AND METHOD Cross-sectional study of 43 phenylketonuric patients>7 years (range: 7.1-41 years). A nutritional survey was performed and bone alkaline phosphatase (BAP), procollagen type 1 N-terminal propeptide (PNP-1), beta-crosslaps and ratio calcium/creatinine in urine were determined. RESULTS A percentage of 20.9 of patients had pathological biochemical bone markers, 90% of them being adults. BAP was decreased in 70% of them and beta-crosslaps in 42.8%. BAP values were more often pathological in phenylketonuric patients with a late diagnosis (41.7 vs. 10.7%; P<.05) and in patients with MBD (60 vs. 14.3%; P<.05). PNP-1 values and calcium/creatinine were similar among all phenylketonuric patients regardless of presenting MBD, late diagnosis or tetrahydrobipterin treatment (enzyme cofactor). Patients with decreased BAP and beta-crosslaps had lower natural protein intake: BAP (0.21 ± 0.13 vs. 0.65 ± 0.65 g/kg; P<.05); beta-crosslaps (0.29 ± 0.23 vs. 0.65 ± 0.66 g/kg; P<.05). None of the tetrahydrobiopterin treated patients showed altered values of BAP, PNP-1 or calcium/creatinine. CONCLUSIONS Adult phenylketonuric patients with lower natural protein intake tend to have lower values of BAP, which is a marker that may be useful to identify patients at risk for MBD.
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8.
Interrelationship between bone turnover markers, calciotropic hormones and leptin in obese Saudi children.
Saber, LM, Mahran, HN, Baghdadi, HH, Al Hawsawi, ZM
European review for medical and pharmacological sciences. 2015;(22):4332-43
Abstract
OBJECTIVE Fat-bone relationship involves the interaction among endocrine, inflammatory, immune processes and bone turnover. We tried to assess the association between Leptin and bone turnover markers (OCN, β-CTx, ALP), calciotropic hormones PTH and 25(OH)D in obese Saudi children. PATIENTS AND METHODS A cross-sectional study performed with 60 obese children and 36 lean children. For all subjects, OCN, ALP, β-CTx, PTH, 25(OH)D, leptin, Ca and Pi were investigated. Levels of leptin were measured by [ELISA] method, and OCN, β-CTx, PTH and 25-(OH)D by an electrochemiluminescence immunoassay. RESULTS Sixty obese Saudi children had means weight (38.3 vs. 13.8 kg), height (121.0 vs. 91.8 cm) leptin (23.04 vs.16.88 ng/ml), PTH (31.5 vs. 14.7 pg/ml), Pi (1.67 vs. 1.54 mmol/l) were significantly higher and 25(OH)D (21.02 vs. 29.45 ng/ml) was significantly lower than controls. There was no difference in serum OCN, β-CTx, ALP and calcium between groups (p > 0.05). In the correlation study, OCN were significantly positively correlated with height, ALP, age, PTH, and β-CTx (r = 0.347, 0.32, p < 0.05), (r = 0.35, 0.51, 0.66, p < 0.01 respectively), while serum 25(OH)D was negatively correlated with PTH, weight, height and BMI (r = -0.45, -0.55, -0.55, -0.47, p < 0.01 respectively). PTH was positively correlated with leptin and β-CTx (r = 0.41, 0.44, p < 0.01), but not to ALP and BMI percentile. β-CTx correlated significantly positive with Pi (r = 0.34 p < 0.05) and ALP with BMI percentile (r = 0.42, p < 0.05). Multiple regression analysis demonstrated that PTH was predicted by leptin and β-CTx (R2 = 0.55); β-CTx by leptin and OCN (R2 = 0.498); OCN by PTH and β-CTx (R2 = 0.47); and 25(OH)D by PTH (R2 = 0.21). CONCLUSIONS The obese children had increased levels of leptin and PTH with strong associated with bone turn over markers OCN, β-CTx and deficiency of 25(OH)D which may be playing an important role in the pathogenesis of obesity and related bone metabolic risk diseases as osteoporosis and fractures.