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1.
Effects of endogenous GIP in patients with type 2 diabetes.
Stensen, S, Gasbjerg, LS, Krogh, LL, Skov-Jeppesen, K, Sparre-Ulrich, AH, Jensen, MH, Dela, F, Hartmann, B, Vilsbøll, T, Holst, JJ, et al
European journal of endocrinology. 2021;(1):33-45
Abstract
OBJECTIVE The insulinotropic effect of exogenous, intravenously infused glucose-dependent insulinotropic polypeptide (GIP) is impaired in patients with type 2 diabetes. We evaluated the effects of endogenous GIP in relation to glucose and bone metabolism in patients with type 2 diabetes using a selective GIP receptor antagonist and hypothesized that the effects of endogenous GIP were preserved. DESIGN A randomized, double-blinded, placebo-controlled, crossover study. METHODS Ten patients with overweight/obesity and type 2 diabetes (mean±s.d.; HbA1c 52 ± 11 mmol/mol; BMI 32.5 ± 4.8 kg/m2) were included. We infused a selective GIP receptor antagonist, GIP(3-30)NH2 (1200 pmol/kg/min), or placebo (saline) during two separate, 230-min, standardized, liquid mixed meal tests followed by a meal ad libitum. Subcutaneous adipose tissue biopsies were analyzed. RESULTS Compared with placebo, GIP(3-30)NH2 reduced postprandial insulin secretion (Δbaseline-subtracted area under the curve (bsAUC)C-peptide% ± s.e.m.; -14 ± 6%, P = 0.021) and peak glucagon (Δ% ± s.e.m.; -11 ± 6%, P = 0.046) but had no effect on plasma glucose (P = 0.692). Suppression of bone resorption (assessed by circulating carboxy-terminal collagen crosslinks (CTX)) was impaired during GIP(3-30)NH2 infusion compared with placebo (ΔbsAUCCTX; ±s.e.m.; -4.9 ± 2 ng/mL × min, P = 0.005) corresponding to a ~50% reduction. Compared with placebo, GIP(3-30)NH2 did not affect plasma lipids, meal consumption ad libitum or adipose tissue triglyceride content. CONCLUSIONS Using a selective GIP receptor antagonist during a meal, we show that endogenous GIP increases postprandial insulin secretion with little effect on postprandial glycaemia but is important for postprandial bone homeostasis in patients with type 2 diabetes.
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2.
Supplementary Energy Increases Bone Formation during Arduous Military Training.
O'Leary, TJ, Walsh, NP, Casey, A, Izard, RM, Tang, JCY, Fraser, WD, Greeves, JP
Medicine and science in sports and exercise. 2021;(2):394-403
Abstract
PURPOSE This study aimed to investigate the effect of supplementary energy on bone formation and resorption during arduous military training in energy deficit. METHODS Thirty male soldiers completed an 8-wk military combat course (mean ± SD, age = 25 ± 3 yr, height = 1.78 ± 0.05 m, body mass = 80.9 ± 7.7 kg). Participants received either the habitual diet (control group, n = 15) or an additional 5.1 MJ·d-1 to eliminate the energy deficit (supplemented group, n = 15). Circulating markers of bone formation and resorption, and reproductive, thyroid, and metabolic status, were measured at baseline and weeks 6 and 8 of training. RESULTS Bone-specific alkaline phosphatase decreased in controls (-4.4 ± 1.9 μg·L-1) and increased in the supplemented group (16.0 ± 6.6 μg·L-1), between baseline and week 8 (P < 0.001). Procollagen type 1 N-terminal propeptide increased between baseline and week 6 for both groups (5.6 ± 8.1 μg·L-1, P = 0.005). Beta carboxy-terminal cross-linking telopeptide of type 1 collagen decreased between baseline and week 8 for both groups (-0.16 ± 0.20 μg·L-1, P < 0.001). Prolactin increased from baseline to week 8 for the supplemented group (148 ± 151 IU·L-1, P = 0.041). The increase in adiponectin from baseline to week 8 was higher in controls (4.3 ± 1.8 mg·L-1, P < 0.001) than that in the supplemented group (1.4 ± 1.0 mg·L-1, P < 0.001). Insulin-like growth factor binding protein-3 was lower at week 8 than baseline for controls (-461 ± 395 ng·mL-1, P < 0.001). CONCLUSION The increase in bone-specific alkaline phosphatase, a marker of bone formation, with supplementation supports a role of energy in osteoblastic activity; the implications for skeletal adaptation and stress fracture risk are unclear. The mechanism is likely through protecting markers of metabolic, but not reproductive or thyroid, function.
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3.
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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4.
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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5.
Bone Health Following Bariatric Surgery: An Update.
Saad, R, Habli, D, El Sabbagh, R, Chakhtoura, M
Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2020;(2):165-181
Abstract
Obesity rates are increasing rapidly, and bariatric surgery is currently the most effective tool for weight loss. Recently, bariatric surgery induced bone loss has gained attention. Such detrimental effect on bone is multifactorial and causes may include nutrient deficiencies, gut and gonadal hormonal changes, mechanical unloading, loss of lean mass, increased bone marrow fat, and increased risk of fall. This review describes the available evidence on bone loss and fracture risk following bariatric surgery and summarizes the guidelines on the topic. Increased bone resorption starts early postsurgery, and bone markers peak at 1-2 yr. Across studies, the drop in areal bone mineral density is inconsistent at the lumbar spine, while a 2%-5% drop at 6 mo and a 6%-10.5% at 9-12 mo are observed at the total hip. Conversely, studies using quantitative CT showed a 6%-7% decrease in volumetric bone mineral density at the lumbar spine at 6-12 mo postsurgery. These studies also report significant bone loss at the radius and tibia, in addition to alteration in bone microarchitecture. Fracture risk increases 2 yr after surgery, more so following malabsorptive procedures. Fractures were reported at axial, weight bearing sites and at appendicular sites. The available evidence is very heterogeneous, and mostly derived from studies on Roux-en-y gastric bypass in premenopausal women. Data on restrictive procedures is scarce. Our findings suggest that the early postoperative phase represents the "golden window" to intervene and promote bone health. More research is needed to determine the effect of different bariatric procedures on bone, to identify optimal interventions to prevent bone loss and to characterize high risk individuals who should be targeted.
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6.
Soy isoflavones prevent bone resorption and loss, a systematic review and meta-analysis of randomized controlled trials.
Akhlaghi, M, Ghasemi Nasab, M, Riasatian, M, Sadeghi, F
Critical reviews in food science and nutrition. 2020;(14):2327-2341
Abstract
BACKGROUND Osteoporosis is a common bone disease characterized by reduced bone mass resulting from continuous bone resorption. METHODS PubMed, Scopus, and Embase were searched to find published trials on the effect of soy isoflavones on bone mineral density (BMD) and bone turnover markers (bone-specific alkaline phosphatase, osteocalcin, osteoprotegerin, pyridinoline, deoxypyridinoline, C-telopeptide, and N-telopeptide). Random-effects inverse-variance model was used to calculate the pooled effects. RESULTS A total of 5313 articles were found, screened, and assessed for eligibility, and finally 52 trials were included in the meta-analysis. Consumption of soy isoflavones caused significant improvement in BMD of lumbar spine (mean difference (MD) = 0.76%; 95% CI: 0.09, 1.42%; p = 0.03), hip (MD = 0.22%; 95% CI: 0.02, 0.42%; p = 0.04), and femoral neck (MD = 2.27%; 95% CI: 1.22, 3.31%; p < 0.001). Subgroup analysis showed that in all 3 sites, the improvement was significant in normal weight subjects and interventions longer than a year, although trial location and dosage were also factors influencing isoflavones' impact on BMD. Among markers of bone turnover, osteoprotegerin (MD = 5.79; 95% CI: 3.08, 8.51 pg/ml; p < 0.001), pyridinoline (MD = -5.13; 95% CI: -7.76, -2.50 nmol/mmol; p < 0.001), and C-telopeptides (MD = -0.08; 95% CI: -0.16, -0.00 ng/ml; p = 0.04) were favorably affected by isoflavones while osteocalcin and bone alkaline phosphatase did not change. Subgroup analysis of bone markers showed that in overweight/obese individuals and dosages <90 mg/day, isoflavones are more effective. CONCLUSIONS Soy isoflavones prevent osteoporosis-related bone loss in any weight status or treatment duration. They increase BMD in normal weight subjects and diminish bone resorption in overweight/obese individuals. Although bone resorption may be decelerated over short-term isoflavone consumption, periods longer than a year are probably needed to affect BMD. Isoflavones also appear benefits on bone in any dose or subjects' ethnicity.
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7.
Does the Use of a "Walking Bleaching" Technique Increase Bone Resorption Markers?
Bersezio, C, Vildósola, P, Sáez, M, Sánchez, F, Vernal, R, Oliveira, OB, Jorquera, G, Basualdo, J, Loguercio, A, Fernández, E
Operative dentistry. 2018;(3):250-260
Abstract
OBJECTIVE This randomized clinical trial evaluated the effect of 35% hydrogen peroxide in comparison with 37% carbamide peroxide in a nonvital bleaching technique of "walking bleaching" (four sessions of treatment) on periodontal markers: nuclear factor kappa B-ligand (RANK-L-process of root resorption marker) and interleukin 1β (IL-1β-inflammatory response marker). METHODS AND MATERIALS Fifty volunteers presenting with discoloration of nonvital teeth and endodontic treatment in good condition participated. Fifty teeth were randomly divided into two study groups according to bleaching gel: HP = 35% hydrogen peroxide (n=25) and 37% carbamide peroxide (n=25). Nonvital bleaching was performed with a walking bleaching technique consisting of four sessions of bleach application. Gingival crevicular fluid samples were taken in order to quantify the RANK-L and IL-1β levels by enzyme-linked immunosorbent assay. Samples were obtained from six periodontal sites for each bleached tooth: three vestibular and three palatine (mesial, middle, and distal) at seven time periods: baseline, after each of the four sessions of nonvital bleaching, at one week, and at one month after nonvital bleaching. Tooth color variations were analyzed in each session by VITA Bleachedguide 3D-MASTER (ΔSGU). RESULTS Significant increments in the RANK-L and IL-1β levels were detected in each evaluated time compared with baseline ( p<0.05); however, no differences were detected between hydrogen peroxide and carbamide peroxide on increments of the biomarkers studied. The change of color was effective for both nonvital bleaching therapies ( p<0.05). CONCLUSIONS Nonvital bleaching induced a significant increment in the RANK-L and IL-1β levels in periodontal tissues around bleached, nonvital teeth.