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Effects of a Lifestyle Intervention on Bone Turnover in Persons with Type 2 Diabetes: A Post Hoc Analysis of the U-TURN Trial.
Abildgaard, J, Johansen, MY, Skov-Jeppesen, K, Andersen, LB, Karstoft, K, Hansen, KB, Hartmann, B, Holst, JJ, Pedersen, BK, Ried-Larsen, M
Medicine and science in sports and exercise. 2022;(1):38-46
Abstract
INTRODUCTION/PURPOSE The increased risk of fractures with type 2 diabetes (T2D) is suggested to be caused by decreased bone turnover. Current international guidelines recommend lifestyle modifications, including exercise, as first-line treatment for T2D. The aim of this study was to investigate the effects of an exercise-based lifestyle intervention on bone turnover and bone mineral density (BMD) in persons with T2D. METHODS Persons with T2D were randomized to either a 12-month lifestyle intervention (n = 64) or standard care (n = 34). The lifestyle intervention included five to six weekly aerobic training sessions, half of them combined with resistance training. Serum markers of bone turnover (osteocalcin, N-terminal propeptide of type-I procollagen, reflecting bone formation, and carboxyterminal collagen I crosslinks, reflecting bone resorption) and BMD (by DXA) were measured before the intervention and at follow-up. RESULTS From baseline to follow-up, s-propeptide of type-I procollagen increased by 34% (95% confidence interval [CI], 17%-50%), serum-carboxyterminal collagen I crosslink by 36% (95% CI, 1%-71%), and s-osteocalcin by 31% (95% CI, 11-51%) more in the lifestyle intervention group compared with standard care. Loss of weight and fat mass were the strongest mediators of the increased bone turnover. Bone mineral density was unaffected by the intervention (ΔBMD, 0.1%; 95% CI, -1.1% to 1.2%). CONCLUSIONS A 12-month intensive exercise-based lifestyle intervention led to a substantial but balanced increase in bone turnover in persons with T2D. The increased bone turnover combined with a preserved BMD, despite a considerable weight loss, is likely to reflect improved bone health and warrants further studies addressing the impact of exercise on risk of fractures in persons with T2D.
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Liraglutide does not change bone turnover in clozapine- and olanzapine-treated schizophrenia overweight patients with prediabetes - randomized controlled trial.
Maagensen, H, Larsen, JR, Jørgensen, NR, Fink-Jensen, A, Vilsbøll, T
Psychiatry research. 2021;:113670
Abstract
Schizophrenia is associated with a lowered bone mineral density. The antidiabetic and body weight lowering glucagon-like peptide-1 receptor agonist liraglutide has shown to mitigate overweight and impaired glucose tolerance associated with olanzapine and clozapine. As liraglutide has been proposed to affect bone metabolism, we evaluated the effect of liraglutide on bone turnover markers (BTM) in patients with prediabetes and schizophrenia treated with olanzapine or clozapine. Patients diagnosed with a schizophrenia spectrum disorder treated with the antipsychotic compounds clozapine and/or olanzapine, having prediabetes and a BMI above 27 kg/m2 were randomized to 16 weeks of treatment with liraglutide or placebo. Fasting state serum sampled in the morning from patients (n=78) were analysed for the BTM collagen type 1 C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP). After 16 weeks of treatment, no significant changes of neither P1NP nor CTX were observed when comparing liraglutide to placebo. No association between changes of bone turnover markers and change of body weight were found in the group treated with liraglutide. In conclusion, no treatment effect on CTX nor P1NP was observed, and thus, this study does not raise any concerns in patients with schizophrenia and prediabetes treated with liraglutide regarding bone-related adverse effects.
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Effect of Vitamin D-Enriched Gouda-Type Cheese Consumption on Biochemical Markers of Bone Metabolism in Postmenopausal Women in Greece.
Moschonis, G, van den Heuvel, EG, Mavrogianni, C, Manios, Y
Nutrients. 2021;(9)
Abstract
Considering the role of bone metabolism in understanding the pathogenesis of osteoporosis, the aim of the present study was to examine the effects of vitamin D-enriched cheese on the serum concentrations of the parathyroid hormone (PTH) and certain bone remodeling biomarkers in postmenopausal women in Greece. In a randomised, controlled dietary intervention, 79 postmenopausal women (55-75 years old) were randomly allocated either to a control (CG: n = 39) or an intervention group (IG: n = 40), consuming 60 g of either non-enriched or vitamin D3-enriched Gouda-type cheese (5.7 μg of vitamin D3), respectively, daily and for eight weeks during the winter. The serum concentrations of 25-hydroxy vitamin D (25(OH)D), PTH, bone formation (i.e., osteocalcin, P1NP) and bone resorption (i.e., TRAP-5b) biomarkers were measured. Consumption of the vitamin D-enriched cheese led to higher serum 25(OH)D concentrations of 23.4 ± 6.39 (p = 0.022) and 13.4 ± 1.35 (p < 0.001) nmol/L in vitamin D-insufficient women being at menopause for less and more than 5 years, respectively. In vitamin D-insufficient women that were less than 5 years at menopause, consumption of vitamin D-enriched cheese was also associated with lower serum PTH (Beta -0.63 ± 1.11; p < 0.001) and TRAP-5b (Beta -0.65 ± 0.23; p = 0.004) levels at follow-up, compared with the CG. The present study showed that daily intake of 5.7 μg of vitamin D through enriched cheese increased serum 25(OH)D concentrations, prevented PTH increase and reduced bone resorption in vitamin D-insufficient early postmenopausal women, thus reflecting a potential food-based solution for reducing the risk of bone loss occurring after menopause.
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Effects of a whey protein pre-meal on bone turnover in participants with and without type 2 diabetes-A post hoc analysis of a randomised, controlled, crossover trial.
Bjørnshave, A, Lykkeboe, S, Hartmann, B, Holst, JJ, Hermansen, K, Starup-Linde, J
Diabetic medicine : a journal of the British Diabetic Association. 2021;(6):e14471
Abstract
AIMS: Whey protein may improve bone turnover and have anti-osteoporotic effects. The aim of the present randomised, controlled, crossover trial was to evaluate the effects of a whey protein pre-meal on bone turnover in people with type 2 diabetes and controls. METHODS Two groups, matched on sex, age and body mass index, comprising 12 participants with and 12 participants without type 2 diabetes were randomly given a pre-meal of whey protein (20 g) or water, which was consumed 15 min before a fat-rich meal or a fat-rich meal supplemented with 20 g whey protein. During a 360-min period, postprandial responses in bone turnover were examined. RESULTS Osteocalcin, P-procollagen type 1 amino terminal propeptide (P1NP), C-terminal cross-linked telopeptide of type-I collagen (CTX) and parathyroid hormone (PTH) were lower at baseline and PTH, osteocalcin and P1NP were lower during the entire postprandial phase in participants with type 2 diabetes than in participants without type 2 diabetes. We observed similar postprandial responses in bone turnover markers between persons with and without type 2 diabetes. We observed no effect of the whey protein or the water pre-meal on bone turnover markers. The changes were unrelated to secretion of hormones of the gut-bone axis. CONCLUSION Osteocalcin, P1NP, CTX and PTH all decreased following meal ingestion. We observed no convincing effect of a whey protein pre-meal on bone turnover. However, these results confirm that people with type 2 diabetes have low bone turnover and that the decreased bone formation markers are also extend into the postprandial responses.
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Associations between Postprandial Gut Hormones and Markers of Bone Remodeling.
Jensen, NW, Clemmensen, KKB, Jensen, MM, Pedersen, H, Færch, K, Diaz, LJ, Quist, JS, Størling, J
Nutrients. 2021;(9)
Abstract
Gut-derived hormones have been suggested to play a role in bone homeostasis following food intake, although the associations are highly complex and not fully understood. In a randomized, two-day cross-over study on 14 healthy individuals, we performed postprandial time-course studies to examine the associations of the bone remodeling markers carboxyl-terminal collagen type I crosslinks (CTX) and procollagen type 1 N-terminal propeptide (P1NP) with the gut hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) using two different meal types-a standardized mixed meal (498 kcal) or a granola bar (260 kcal). Plasma concentrations of total GIP, total GLP-1, total PYY, CTX, and P1NP were measured up to 240 min after meal intake, and the incremental area under the curve (iAUC) for each marker was calculated. The iAUC of CTX and P1NP were used to assess associations with the iAUC of GIP, GLP-1, and PYY in linear mixed effect models adjusted for meal type. CTX was positively associated with GIP and GLP-1, and it was inversely associated with PYY (all p < 0.001). No associations of P1NP with GIP or GLP-1 and PYY were found. In conclusion, the postprandial responses of the gut hormones GIP, GLP-1, and PYY are associated with the bone resorption marker CTX, supporting a link between gut hormones and bone homeostasis following food intake.
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Effect of Vitamin E Supplement on Bone Turnover Markers in Postmenopausal Osteopenic Women: A Double-Blind, Randomized, Placebo-Controlled Trial.
Vallibhakara, SA, Nakpalat, K, Sophonsritsuk, A, Tantitham, C, Vallibhakara, O
Nutrients. 2021;(12)
Abstract
Vitamin E is a strong anti-oxidative stress agent that affects the bone remodeling process. This study evaluates the effect of mixed-tocopherol supplements on bone remodeling in postmenopausal osteopenic women. A double-blinded, randomized, placebo-controlled trial study was designed to measure the effect of mixed-tocopherol on the bone turnover marker after 12 weeks of supplementation. All 52 osteopenic postmenopausal women were enrolled and allocated into two groups. The intervention group received mixed-tocopherol 400 IU/day, while the control group received placebo tablets. Fifty-two participants completed 12 weeks of follow-up. Under an intention-to-treat analysis, vitamin E produced a significant difference in the mean bone resorption marker (serum C-terminal telopeptide of type I collagen (CTX)) compared with the placebo group (-0.003 ± 0.09 and 0.121 ± 0.15, respectively (p < 0.001)). In the placebo group, the CTX had increased by 35.3% at 12 weeks of supplementation versus baseline (p < 0.001), while, in the vitamin E group, there was no significant change of bone resorption marker (p < 0.898). In conclusion, vitamin E (mixed-tocopherol) supplementation in postmenopausal osteopenic women may have a preventive effect on bone loss through anti-resorptive activity.
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Clinical Research of the Application of Bone Turnover Markers in Monitoring the Short-Term Therapeutic Efficacy of Vitamin D in Postmenopausal Osteoporotic women in Harbin, China.
Zhang, Y, Wang, Y
The journal of nutrition, health & aging. 2020;(5):485-493
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Abstract
BACKGROUND The incidence of osteoporosis (OP) is increasing year by year. researches have shown that there was an intense link between the vitamin D (VitD) status and the efficacy of zoledronate (ZOL) in patients with osteoporosis. Since VitD is related to the geogen, its promotion effect on zoledronate has regional specificity. AIM: Combining dual-energy X-ray and bone turnover markers (BTM) to explore the VitD level in postmenopausal osteoporosis patients in Harbin and monitor its effect on the anti-osteoporosis effect of ZOL. METHODS A total of 120 patients with postmenopausal osteoporosis (PMO) were enrolled .These patients were divided into two groups with 25(OH)D levels = 10ng/ml as a critical point, and each group was randomly divided into experimental groups and control groups). All of the patients were conducted 5 mg ZOL. Then the experimental group was given calcitriol and calcium carbonate, and the control group was only given calcium carbonate. BTM were measured at baseline, 24h, 3 months and 6 months. We also measured bone mineral density (BMD) of bilateral hips (TH BMD) and lumbar spine (LS BMD) at baseline and 6 months. RESULTS The VitD deficiency rates of the patients enrolled were 84.1%. There was an inverse relationship between the baseline level of VitD and the serum levels of P1NP / β-CTX, (r=-0.452,p=0.00; r=-0.225, p=0.01). Comparing with baseline, the level of serum P1NP,β-CTX in each group declined significantly after the treatment (P<0.05). The mean decreasing rates of P1NP and β-CTX in the both experimental groups were significantly higher than that of the corresponding control groups at the same time point (P<0.05), after 6 months of medication. Both TH BMD and LS BMD at 6 months increased significantly. The increase rate of LS BMD in the high VitD experimental group was significantly higher than the other three groups (P<0.05), the increase rates of TH BMD in the low VitD control group were significantly lower than the other three groups (P<0.05). CONCLUSIONS The levels of serum VitD in the patients enrolled in this study were generally low. VitD could increase the therapeutic effect of ZOL on osteoporosis.
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Ubiquinol supplementation modulates energy metabolism and bone turnover during high intensity exercise.
Diaz-Castro, J, Mira-Rufino, PJ, Moreno-Fernandez, J, Chirosa, I, Chirosa, JL, Guisado, R, Ochoa, JJ
Food & function. 2020;(9):7523-7531
Abstract
Bone and energy metabolism are profoundly influenced by exercise. The objective of this study was to determine for the first time whether a short-term supplementation with ubiquinol could have a modulating effect on bone turnover and energy metabolism associated with strenuous exercise. The participants (n = 100 healthy and well-trained firemen) were randomly divided into two groups: ubiquinol group (ubiquinol (200 mg day-1)) and control group (placebo) for two weeks. The protocol consisted of conducting two identical strenuous exercise tests with a rest period between tests of 24 h. Blood samples were collected before supplementation (basal value) (T1), after supplementation (T2), after the first physical exercise test (T3), after 24 h of rest (T4), and after the second physical exercise test (T5). Parathyroid hormone (PTH), osteocalcin (OC), osteoprotegerin (OPG), osteopontin (OPN), sclerotin (SOST), alkaline phosphatase (AP), adrenocorticotropin (ACTH), insulin, leptin, adrenaline, noradrenaline and peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) were determined. Our protocol increased ACTH, SOST, PTH and OC levels, while it decreased OPN. This protocol also increased adrenaline, noradrenaline and PCG-1α, and decreased insulin. After ubiquinol supplementation, PTH, OC, OPG, alkaline phosphatase, leptin, insulin, noradrenaline and PGC-1α levels increased in the supplemented group compared to the control group after the exercise protocol. Strenuous exercise has a clear effect on energy metabolism and bone turnover. These effects are modulated by ubiquinol supplementation, which especially increases the biomarkers of bone formation during strenuous exercise. In addition, ubiquinol has a beneficial effect on the mobilization of energy sources, fact that it could represent an ergogenic and physiological advantage for skeletal muscles.
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Consumption of Greek yogurt during 12 weeks of high-impact loading exercise increases bone formation in young, adult males - a secondary analysis from a randomized trial.
Bridge, AD, Brown, J, Snider, H, Ward, WE, Roy, BD, Josse, AR
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2020;(1):91-100
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Abstract
Exercise combined with protein and calcium has been shown to benefit bone turnover and bone metabolism. Greek yogurt (GY) contains important nutrients that support bone but has yet to be studied with exercise for this purpose. Thirty untrained, university-aged, males were randomized to 2 groups (n = 15/group): GY (20 g protein, 208 mg calcium/dose) or placebo pudding (PP; 0 g protein, 0 g calcium/dose) consumed 3×/day on training days and 2×/day on nontraining days. Both groups underwent a resistance/plyometric training program for 12 weeks. Blood was obtained at weeks 0, 1, and 12 to measure procollagen-type-I-N-terminal-propeptide (P1NP) and C-terminal-telopeptide (CTX). After outlier treatment, P1NP increased more over time in GY versus PP (p = 0.002; interaction). Both groups decreased CTX over time (p = 0.046; time effect). Following 1 week of training, there was a trend towards a significant increase in CTX in PP with no change in GY (p = 0.062; interaction). P1NP changed more in GY than PP (baseline to week 12; p = 0.029) as did the P1NP/CTX ratio (p = 0.015) indicating a greater increase in formation with GY. Thus, GY added to a high-load, high-impact exercise program positively shifted bone turnover towards increased formation while attenuating resorption. GY could be a plausible postexercise food to support bone health in young adult males. Novelty Greek yogurt, with exercise, increased bone formation in young adult males over 12 weeks. After 1 week of an osteogenic exercise program, Greek yogurt tended to blunt a rise in bone resorption seen with the placebo. Greek yogurt is a plausible postexercise food that supports bone.
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Changes in serological bone turnover markers in bisphosphonate induced osteonecrosis of the jaws: A case control study.
Demircan, S, Isler, SC
Nigerian journal of clinical practice. 2020;(2):154-158
Abstract
BACKGROUND There are a lot study confirmed the relationship of bone serum markers changes and skeletal irregularities. But there is no sufficient case control studies about the role of these markers on bisphosphonate induced osteonecrosis of jaws (BRONJ). AIMS The aim of this study is to find out if there is any derangement of bone markers in bisphosphonate-treated patients with ONJ. METHODS We obtained serum bone markers and other relevant endocrine assays on 20 patients with osteonecrosis of the jaw (ONJ) and 20 randomized healthy volunteers. All of the ONJ group treated with zoledronic acid and had been withdrawn from bisphosphonate for at least 6 months. Diagnostic criteria for ONJ were those formulated by the American Association of Oral and Maxillofacial Surgeons. Serum levels of several indices of bone remodeling were evaluated using commercial enzyme-linked immunosorbent assays. The biochemical assays were performed on N-Telopeptides of type I collagen (NTX), bone-specific alkaline phosphatase (ALP), calcitonin, osteocalcin, intact parathyroid hormone (PTH), T3, T4, TSH, and Vitamin D 25 hydroxy (Vit-D). RESULTS In ONJ group, PTH level is statistically higher and TSH, Vit-D, osteocalcin and NTX levels statistically lower compared to control group. CONCLUSION We conclude that these changes in PTH, Vit-D, TSH, osteocalcin and NTX levels maybe have a role in the pathophysiology of BRONJ. But the data need to be confirmed by future studies.