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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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Efficacy and Safety of Kudzu Flower-Mandarin Peel on Hot Flashes and Bone Markers in Women during the Menopausal Transition: A Randomized Controlled Trial.
Kim, JE, Jeong, H, Hur, S, Lee, J, Kwon, O
Nutrients. 2020;(11)
Abstract
This randomized controlled study aimed to assess the efficacy and safety of an extract mixture of kudzu flower and mandarin peel (KM) on hot flashes (HFs) and markers of bone turnover in women during the menopausal transition. Healthy women aged 45-60 years with the menopausal HFs were randomly assigned in a 1:1 ratio to either KM (1150 mg/day) or placebo arms for 12 weeks (n = 84). The intent-to-treat analysis found that compared with the placebo, the KM significantly attenuated HF scores (p = 0.041) and HF severities (p < 0.001), with a mean difference from baseline to week 12. The KM also improved bone turnover markers, showing a significant reduction in bone resorption CTx (p = 0.027) and a tendency of increasing bone formation OC relative to the placebo. No serious adverse events and hormonal changes were observed in both groups. These findings suggest that KM consumption may improve the quality of life in ways that are important to symptomatic menopausal women.
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Calcium Supplementation Attenuates Disruptions in Calcium Homeostasis during Exercise.
Sherk, VD, Wherry, SJ, Barry, DW, Shea, KL, Wolfe, P, Kohrt, WM
Medicine and science in sports and exercise. 2017;(7):1437-1442
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Abstract
UNLABELLED An exercise-induced decrease in serum ionized calcium (iCa) is thought to trigger an increase in parathyroid hormone (PTH), which can stimulate bone resorption. PURPOSE The purpose of this study was to determine whether taking a chewable calcium (Ca) supplement 30 min before exercise mitigates disruptions in Ca homeostasis and bone resorption in competitive male cyclists. METHODS Fifty-one men (18 to 45 yr old) were randomized to take either 1000 mg Ca (CA) or placebo (PL) 30 min before a simulated 35-km cycling time trial. Serum iCa and PTH were measured before and immediately after exercise and a marker of bone resorption (C-terminal telopeptide of type I collagen) was measured before and 30 min after exercise. RESULTS Serum iCa decreased in both groups from before to after exercise (mean ± SD, CA = 4.89 ± 0.16 to 4.76 ± 0.11 mg·dL, PL = 4.92 ± 0.15 to 4.66 ± 0.22 mg·dL, both P ≤ 0.01); the decrease was greater (P = 0.03) in the PL group. There was a nonsignificant (P = 0.07) attenuation of the increase in PTH by Ca supplementation (CA = 30.9 ± 13.0 to 79.7 ± 42.6 pg·mL, PL = 37.1 ± 14.8 to 111.5 ± 49.4 pg·mL, both P ≤ 0.01), but no effect of Ca on the change in C-terminal telopeptide of type I collagen, which increased in both groups (CA = 0.35 ± 0.17 to 0.50 ± 0.21 ng·mL, PL = 0.36 ± 0.13 to 0.54 ± 0.22 ng·mL, both P ≤ 0.01). CONCLUSION It is possible that ingesting Ca only 30 min before exercise was not a sufficient time interval to optimize gut Ca availability during exercise. Further studies will be needed to determine whether adequate Ca supplementation before and/or during exercise can fully mitigate the exercise-induced decrease in serum iCa and increases in PTH and bone resorption.
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Effects of high-protein intake on bone turnover in long-term bed rest in women.
Heer, M, Baecker, N, Frings-Meuthen, P, Graf, S, Zwart, SR, Biolo, G, Smith, SM
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2017;(5):537-546
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Abstract
Bed rest (BR) causes bone loss, even in otherwise healthy subjects. Several studies suggest that ambulatory subjects may benefit from high-protein intake to stimulate protein synthesis and to maintain muscle mass. However, increasing protein intake above the recommended daily intake without adequate calcium and potassium intake may increase bone resorption. We hypothesized that a regimen of high-protein intake (HiPROT), applied in an isocaloric manner during BR, with calcium and potassium intake meeting recommended values, would prevent any effect of BR on bone turnover. After a 20-day ambulatory adaptation to a controlled environment, 16 women participated in a 60-day, 6° head-down-tilt (HDT) BR and were assigned randomly to 1 of 2 groups. Control (CON) subjects (n = 8) received 1 g/(kg body mass·day)-1 dietary protein. HiPROT subjects (n = 8) received 1.45 g protein/(kg body mass·day)-1 plus an additional 0.72 g branched-chain amino acids per day during BR. All subjects received an individually tailored diet (before HDTBR 1888 ± 98 kcal/day; during HDTBR 1604 ± 125 kcal/day; after HDTBR 1900 ± 262 kcal/day), with the CON group's diet being higher in fat and carbohydrate intake. High-protein intake exacerbated the BR-induced increase in bone resorption marker C-telopeptide (>30%) (p < 0.001) by the end of BR. Bone formation markers were unaffected by BR and high-protein intake. We conclude that high-protein intake in BR might increase bone loss. Further long-duration studies are mandatory to show how the positive effect of protein on muscle mass can be maintained without the risk of reducing bone mineral density.
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Bone health nutraceuticals alter microarray mRNA gene expression: A randomized, parallel, open-label clinical study.
Lin, Y, Kazlova, V, Ramakrishnan, S, Murray, MA, Fast, D, Chandra, A, Gellenbeck, KW
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2016;(1):18-26
Abstract
BACKGROUND AND OBJECTIVE Dietary intake of fruits and vegetables has been suggested to have a role in promoting bone health. More specifically, the polyphenols they contain have been linked to physiological effects related to bone mineral density and bone metabolism. In this research, we use standard microarray analyses of peripheral whole blood from post-menopausal women treated with two fixed combinations of plant extracts standardized to polyphenol content to identify differentially expressed genes relevant to bone health. METHODS In this 28-day open-label study, healthy post-menopausal women were randomized into three groups, each receiving one of three investigational fixed combinations of plant extracts: an anti-resorptive (AR) combination of pomegranate fruit (Punica granatum L.) and grape seed (Vitis vinifera L.) extracts; a bone formation (BF) combination of quercetin (Dimorphandra mollis Benth) and licorice (Glycyrrhiza glabra L.) extracts; and a fixed combination of all four plant extracts (AR plus BF). Standard microarray analysis was performed on peripheral whole blood samples taken before and after each treatment. Annotated genes were analyzed for their association to bone health by comparison to a gene library. RESULTS The AR combination down-regulated a number of genes involved in reduction of bone resorption including cathepsin G (CTSG) and tachykinin receptor 1 (TACR1). The AR combination also up-regulated genes associated with formation of extracellular matrix including heparan sulfate proteoglycan 2 (HSPG2) and hyaluronoglucosaminidase 1 (HYAL1). In contrast, treatment with the BF combination resulted in up-regulation of bone morphogenetic protein 2 (BMP-2) and COL1A1 (collagen type I α1) genes which are linked to bone and collagen formation while down-regulating genes linked to osteoclastogenesis. Treatment with a combination of all four plant extracts had a distinctly different effect on gene expression than the results of the AR and BF combinations individually. These results could be due to multiple feedback systems balancing activities of osteoblasts and osteoclasts. CONCLUSION In summary, this ex-vivo microarray study indicated that the pomegranate, grape seed, quercetin and licorice combinations of plant extracts modulated gene expression for both osteoclastic and osteogenic processes.
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Intermittent zoledronic Acid prevents bone loss in adults after allogeneic hematopoietic cell transplantation.
Hari, P, DeFor, TE, Vesole, DH, Bredeson, CN, Burns, LJ
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2013;(9):1361-7
Abstract
Bone mineral density (BMD) loss is common in survivors of allogeneic hematopoietic cell transplantation (alloHCT). We performed a multicenter, phase II, randomized open-label trial of intravenous zoledronic acid (ZA) to prevent BMD loss in adult recipients of alloHCT with osteopenia before HCT. The treatment group received ZA 4 mg intravenously within 28 days pre-HCT and at 3 and 6 months after HCT. Both treatment and control groups received calcium carbonate and vitamin D supplements. Of 61 patients, 32 were randomized to the ZA cohort and 29 to the control cohorts. More patients in the ZA group had an HCT comorbidity index high-risk score of ≥3 (50% versus 21%, P < .01). Baseline BMD, T-scores, serum osteocalcin, bone alkaline phosphatase, and urine N-telopeptide (UNTX) levels were similar in both cohorts. Thirty patients were evaluable for outcomes (11 from the treatment and 19 from the control group). At 12 months, subjects in the treatment group had an improvement in BMD at the femoral neck (mean change, .018 for ZA group versus -.054 for controls; P = .04) and a significant decline in levels of UNTX (-56 for ZA group versus -9 for control; P = .04) compared with baseline. ZA was well tolerated and not associated with any cases of osteonecrosis of jaw or renal impairment. Lower survival observed in the ZA cohort was likely related to baseline imbalance in HCT-CI scores. Intermittent ZA is effective in preserving long-term bone health in adult alloHCT recipients at risk for osteoporosis.
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Effect of methylprednisolone pulse therapy with and without alendronate on biochemical markers of bone turnover in patients with Graves' ophthalmopathy.
Gasińska, T, Borowska, A, Wichary, H, Dec, R
Polskie Archiwum Medycyny Wewnetrznej. 2012;(7-8):341-7
Abstract
INTRODUCTION Immunosuppression with glucocorticoids is the method of choice in the treatment of active Graves' ophthalmopathy (GO). However, glucocorticoid therapy may have side effects, among others, it affects bone metabolism. OBJECTIVES The aim of the study was to compare the effect of methylprednisolone pulse therapy (MPPT) with and without alendronate on bone turnover markers in patients with GO with normal and reduced bone mineral density (BMD). PATIENTS AND METHODS The study included 53 patients with GO and 20 sex- and age‑matched healthy controls. Twenty patients with normal BMD (17 women, 3 men, aged 45 ±1.0 years) received only MPPT (8 g intravenously during 4 weeks). The remaining patients, with reduced BMD, were randomly assigned either to MPPT without alendronate (10 women, 2 men, aged 47 ±1.0 years) or MPPT with alendronate (18 women, 3 men, aged 47 ±1.0 years). BMD of the lumbar spine and femoral neck was assessed using dual energy X‑ray absorptiometry (DEXA) before treatment. The markers of bone formation (serum osteocalcin, carboxyterminal propeptide of type I collagen [PICP], alkaline phospatase) and the markers of bone resorption (serum carboxyterminal telopeptide of type I collagen [ICTP], cross‑linked C‑terminal telopeptide of type I collagen [CTX], serum calcium [Ca] and potassium [P], as well as urinary excretion of deoxypyridinoline, Ca, and P) were determined before and after treatment. RESULTS MPPT caused a decrease in bone formation markers and an increase in some bone resorption markers. MPPT with alendronate decreased bone formation and bone resorption markers. CONCLUSIONS A negative effect of MPPT on bone turnover is observed both in patients with GO with normal and with reduced BMD. Simultaneous use of MPPT and alendronate in patients with GO and reduced BMD suppresses bone resorption caused by methylprednisolone.
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Weight-loss-associated changes in bone mineral density and bone turnover after partial weight regain with or without aerobic exercise in obese women.
Hinton, PS, Rector, RS, Linden, MA, Warner, SO, Dellsperger, KC, Chockalingam, A, Whaley-Connell, AT, Liu, Y, Thomas, TR
European journal of clinical nutrition. 2012;(5):606-12
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Abstract
BACKGROUND/OBJECTIVES Moderate, long-term weight loss results in the loss of bone mass in overweight or obese premenopausal women. However, whether these changes persist during weight maintenance or regain remains to be determined. SUBJECTS/METHODS Overweight or obese (body mass index: 25.8-42.5 kg/m(2)) women (n=40) with at least two risk factors for the metabolic syndrome participated in this 12-month study that examined the effects of prescribed weight loss and regain, with or without exercise, on bone turnover and on bone mineral density (BMD) in a subset of participants (n=24). During the first 6 month, participants lost ≈ 10% of their initial body weight via energy restriction and supervised aerobic exercise. Following weight loss, participants were randomly assigned to either an exercise or a no exercise treatment for the regain (+50% of weight lost) phase. A one-way (time) repeated measures one-factor analysis of variance (RMANOVA) tested the effects of weight loss on BMD and bone turnover, and a two-way RMANOVA (time, exercise) was used to examine the effects of exercise during weight regain. RESULTS Hip (P=0.007) and lumbar spine (P=0.05) BMD decreased with weight loss, and remained reduced after weight regain with or without exercise. Likewise, the weight-loss-associated increases in osteocalcin (P<0.001) and C-terminal peptide of type I collagen (P<0.001) persisted following weight regain, independent of exercise. CONCLUSIONS The results of the present study, which is the first to examine changes in bone mass and turnover during carefully controlled weight regain, suggest that weight-loss-induced perturbations in bone mass and turnover persist after partial weight regain, regardless of whether regular weight-bearing aerobic exercise was continued.
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Flavonoid intake and bone health.
Weaver, CM, Alekel, DL, Ward, WE, Ronis, MJ
Journal of nutrition in gerontology and geriatrics. 2012;(3):239-53
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Abstract
Flavonoids, found in a wide diversity of plant foods from fruits and vegetables, herbs and spices, essential oils, and beverages, have the most potential of dietary components for promotion of bone health beyond calcium and vitamin D. Recent epidemiological studies show flavonoid consumption to have a stronger association with bone than general fruit and vegetable consumption. Bioactive flavonoids are being assessed for properties beyond their chemical antioxidant capacity, including anti-inflammatory actions. Some have been reported to enhance bone formation and to inhibit bone resorption through their action on cell signaling pathways that influence osteoblast and osteoclast differentiation. Future research is needed to determine which of the flavonoids and their metabolites are most effective and at what dose, as well as the mechanism of modulating cellular events, in order to set priorities for clinical trials.
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Prevention of bone resorption by intake of phytoestrogens in postmenopausal women: a meta-analysis.
Salari Sharif, P, Nikfar, S, Abdollahi, M
Age (Dordrecht, Netherlands). 2011;(3):421-31
Abstract
Phytoestrogens as selective estrogen receptor modulators like compounds may consider as a therapeutic option in osteoporosis. In this regard, the effect of phytoestrogens on bone biomarkers was examined in several trials which their results are controversial. We aimed this meta-analysis to evaluate the net effect of phytoestrogens on bone markers. A thorough search was conducted from 2000 to 2010 in English articles. All randomized clinical trials were reviewed, and finally, 11 eligible randomized clinical trials were selected for meta-analysis. Totally 1,252 postmenopausal women were enrolled in the study by considering the changes of pyridinoline (Pyd), desoxypyridinoline (Dpyd), bone alkaline phosphatase, and osteocalcin concentrations in urine and serum after phytoestrogens consumption. The urine Pyd and Dpyd levels decreased significantly in phytoestrogens consumers. Effect size and effect size for weighted mean difference of urine Pyd levels showed -1.229171 (95% confidence interval (CI) = -1.927639 to -0.530703) and -9.780623 (95% CI = -14.240401 to -5.320845), respectively, a significant results in comparison to control group and significant results for Dpyd -0.520132 (95% CI = -0.871988 to -0.168275) and -0.818582 (95% CI = -1.247758 to -0.389407), respectively. Meta-analysis indicates that phytoestrogens intake can prevent bone resorption, but its benefits on bone formation are not significant. This favorable effect was observed in low doses and in at least 3 weeks of phytoestrogens intake.