scholarly journals Associations between Postprandial Gut Hormones and Markers of Bone Remodeling

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3197
Author(s):  
Nina Wittorff Jensen ◽  
Kim Katrine Bjerring Clemmensen ◽  
Marie Møller Jensen ◽  
Hanne Pedersen ◽  
Kristine Færch ◽  
...  
Keyword(s):  
Food Intake ◽  
Bone Remodeling ◽  
Time Course ◽  
Plasma Concentrations ◽  
Gut Hormones ◽  
Bone Resorption Marker ◽  
Type I ◽  
Bone Homeostasis ◽  
Mixed Effect ◽  
Bone Remodeling Markers

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.

scholarly journals SUN-352 The Effects of Acute Hyponatremia on Bone Remodeling Markers in Patients with Subarachnoid Hemorrhage

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Aoife Garrahy ◽  
Iona Galloway ◽  
Anne Marie Hannon ◽  
Rose Dineen ◽  
K J Gan ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Bone Formation ◽  
Bone Remodeling ◽  
Serum Cortisol ◽  
Plasma Sodium ◽  
Type I ◽  
Amino Terminal ◽  
Bone Remodeling Markers ◽  
Significant Difference ◽  
Acute Hyponatremia

Abstract Animal data and cross-sectional human studies have established that chronic hyponatremia predisposes to osteoporosis; the effects of acute hyponatremia on bone remodeling are unknown. Serum markers of bone remodeling (total procollagen type 1 amino-terminal propeptide (P1NP), bone specific alkaline phosphatase (bone ALP), N-mid-osteocalcin (OCI) and C-terminal teleopeptides of type I collagen (CTX-1)) were assessed in a cohort of patients admitted with subarachnoid hemorrhage (SAH), who were prospectively studied over seven days. The ratio of P1NP:CTX-1 was calculated to report a bone formation index. Twenty-two patients (13 women), median (IQR) age 53 (47, 62) years were recruited. Patients who developed post-SAH ACTH deficiency and those treated with glucocorticoids, or continuous enteral feeding were excluded. All patients were eunatremic on initial assessment. Eight patients developed acute hyponatremia, median nadir plasma sodium concentration (pNa) 131 (128, 132) mmol/L, and 14 remained eunatremic, nadir pNa 136 (133, 137) mmol/L. The groups were matched for age, 25-hydroxy Vitamin D, PTH, WFSS and Fischer scores. Serum cortisol concentration was greater in the hyponatremic group, 571 (504, 671) nmol/L, than the eunatremic group, 449 (400, 501) nmol/L, p=0.008. Bone remodeling markers and bone formation index (P1NP:CTX-1 ratio) were similar in the two groups at baseline. There was a significant rise in CTX-1 in both hyponatremic patients, +0.15 (0.09, 0.37) μg/l, p = 0.009, and patients who remained eunatremic, +0.11 (-0.02, 0.23) μg/l, p = 0.04, with no significant difference between the groups. There was, however, a significant fall in P1NP:CTX-1 ratio in patients with acute hyponatremia, p = 0.02, but no significant change in eunatraemic patients, with significant between group difference, p = 0.02. Changes in P1NP and OCI correlated positively with nadir pNa; r = 0.43, p = 0.04 and r = 0.61, p = 0.001 respectively. In addition, there was a positive correlation between change in P1NP:CTX-1 ratio and nadir pNa, r = 0.43, p = 0.04. There was no correlation between change in OCI or CTX-1 and nadir pNa. Serum cortisol was strongly negatively correlated with change in P1NP (r = -0.64, p = 0.001) but not with change in other bone remodeling markers. Acute hyponatremia following SAH is associated with a fall in bone formation index; physiological hypercortisolemia may contribute to this. Further analysis with larger numbers will help us determine whether hyponatremia is an independent risk factor.

scholarly journals Pharmacokinetic Properties of a Sufentanil Sublingual Tablet Intended to Treat Acute Pain

2018 ◽  
Vol 128 (5) ◽  
pp. 943-952 ◽  
Author(s):  
Dennis M. Fisher ◽  
Peter Chang ◽  
D. Russell Wada ◽  
Albert Dahan ◽  
Pamela P. Palmer
Keyword(s):  
Plasma Concentration ◽  
Acute Pain ◽  
Healthy Subjects ◽  
Time Course ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Rapid Onset ◽  
Maximum Plasma ◽  
Mixed Effect ◽  
Sublingual Tablet

Abstract Background Desirable product attributes for treatment of moderate-to-severe acute pain in many medically supervised settings are rapid onset and a route of administration not requiring intravenous access. The pharmacokinetic characteristics of sublingually administered tablets containing 15 or 30 µg of sufentanil are described. Methods Blood was sampled from healthy subjects (four studies, 122 subjects) and patients (seven studies, 944 patients). Studies in healthy subjects determined bioavailability, effect of inhibition of cytochrome P450 3A4, and the plasma concentration profile with single and hourly sublingual doses. Studies in patients evaluated effects of weight, age, sex, and organ impairment on apparent clearance. Noncompartmental and mixed-effect population methods were used. Results Bioavailability of a single sublingual tablet was 52%, decreasing to 35% with repeat dosing. Ketoconazole (CYP3A4 inhibitor) increased maximum plasma concentration 19% and increased the area under the curve 77%. After a single 30-µg dose, plasma concentrations reached the published sufentanil analgesic threshold (24 pg/ml) within 30 min, peaked at 1 h, and then decreased below therapeutic concentrations by ~3 h. With hourly administration, plasma concentrations plateaued by the fifth dose. Time for concentrations to decrease 50% from maximal values was similar after 1 dose (2.5 ± 0.85 h) and 12 doses (2.5 ± 0.72 h). Clearance increased with weight, decreased with age, and was not affected by renal or hepatic impairment. Conclusions The time course of a single 30-µg dose was consistent with onset of analgesia and redosing frequency observed in clinical trials. Sublingual sufentanil tablets provide the opportunity to noninvasively and rapidly treat moderate-to-severe pain in a monitored setting.

scholarly journals Alterations of Bone Metabolism in Patients with Diabetes Mellitus

2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Sain S. Safarova
Keyword(s):  
Bone Mineral Density ◽  
Bone Metabolism ◽  
Bone Remodeling ◽  
Bone Mineral ◽  
Type I Collagen ◽  
Bone Microarchitecture ◽  
Type I ◽  
Mineral Density ◽  
Bone Remodeling Markers ◽  
Patients With Diabetes

Aim. The study aims to develop a practical model for screening bone turnover state in patients with diabetes and evaluate its clinical usefulness to identify diabetic osteopathy. Materials. The study was conducted in 2015–2017 in the Endocrinology Department of the Therapeutic Clinic of AM University. A total of 235 patients were assessed in the study (98 with T1DM and 137 with T2DM). 89 nondiabetic subjects served as controls. Bone mineral density (BMD) [by dual energy X-ray absorptiometry (DXA)] and serum markers of bone remodeling [aminoterminal propeptide of procollagen type I (P1NP) and c-terminal telopeptide of type I collagen (CTX)], parathyrin, and 25(OH)D were measured in all 235 patients. Results. Our results show that patients with T2DM have lower b-CTx values and relatively higher levels of P1NP, reflecting less pronounced changes in bone metabolism compared to patients with T1DM, regardless of age or duration of the disease. Osteoporosis was detected in 50% of patients with T1DM, compared to 13% of patients with T2DM. Conclusion. In some cases, bone remodeling markers are useful for improving the assessment of the state of bone tissue in early stages of diabetes, while alterations in bone microarchitecture may not always be captured by bone mineral density measurements.

scholarly journals Bone Remodelling Markers in Rheumatoid Arthritis

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Patrice Fardellone ◽  
Alice Séjourné ◽  
Julien Paccou ◽  
Vincent Goëb
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Resorption ◽  
Bone Remodeling ◽  
Type I Collagen ◽  
Bone Alkaline Phosphatase ◽  
Collagen I ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Bone Remodeling Markers

Bone loss in rheumatoid arthritis (RA) patients results from chronic inflammation and can lead to osteoporosis and fractures. A few bone remodeling markers have been studied in RA witnessing bone formation (osteocalcin), serum aminoterminal propeptide of type I collagen (PINP), serum carboxyterminal propeptide of type I collagen (ICTP), bone alkaline phosphatase (BAP), osteocalcin (OC), and bone resorption: C-terminal telopeptide of type 1 collagen (I-CTX), N-terminal telopeptide of type 1 collagen (I-NTX), pyridinolines (DPD and PYD), and tartrate-resistant acid phosphatase (TRAP). Bone resorption can be seen either in periarticular bone (demineralization and erosion) or in the total skeleton (osteoporosis). Whatever the location, bone resorption results from activation of osteoclasts when the ratio between osteoprotegerin and receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) is decreased under influence of various proinflammatory cytokines. Bone remodeling markers also allow physicians to evaluate the effect of drugs used in RA like biologic agents, which reduce inflammation and exert a protecting effect on bone. We will discuss in this review changes in bone markers remodeling in patients with RA treated with biologics.

scholarly journals Interleukin-6 May Not Affect Bone Resorption Marker CTX or Bone Formation Marker P1NP in Humans

2020 ◽  
Vol 4 (9) ◽  
Author(s):  
Louise L Lehrskov ◽  
Sasha Kjeldsen ◽  
Mark P Lyngbæk ◽  
Regitse Højgaard Chirstensen ◽  
Anne-Sophie Wedell-Neergaard ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Crossover Study ◽  
Bone Remodeling ◽  
Interleukin 6 ◽  
Plasma Concentrations ◽  
Bone Resorption Marker ◽  
Healthy Individuals ◽  
Bone Formation Marker ◽  
Double Blinded

Abstract Context Interleukin 6 (IL-6) contributes to bone remodeling in preclinical studies. Clinical trials investigating the role of IL-6 in bone remodeling are limited. Objective To investigate if IL-6 regulates bone remodeling in humans. Design Plasma concentrations of the bone resorption marker carboxy-terminal type I collagen crosslinks (CTX) and of the bone formation marker procollagen type 1 N-terminal propeptide (P1NP) were measured during a mixed-meal tolerance test (MMTT) in 3 placebo-controlled human studies. Participants Five healthy individuals participated in study 1; 52 obese individuals, in study 2; and 10 healthy individuals, in study 3. Interventions Study 1 was a single-blinded crossover study consisting of a 1-h infusion of saline (placebo) or the IL-6 receptor antibody tocilizumab followed by an exercise bout. Study 2 was a randomized, double-blinded 12-week exercise training intervention study. Participants received infusions of saline or tocilizumab. Study 3 was a randomized, double-blinded, crossover study consisting of 30 min infusion of saline or IL-6. Main outcomes measures Effect of IL-6 on CTX levels. Results CTX was significantly (P &lt; 0.01) decreased during MMTTs in all 3 studies. Treatment with tocilizumab did not affect exercise or meal induced changes in plasma CTX or P1NP concentrations acutely (study 1) or after a 12-week treatment period (study 2). Exogenous IL-6 had no effect on CTX or P1NP plasma concentrations (study 3). Conclusions IL-6 may not regulate bone remodeling in humans.

scholarly journals Traditional and Novel Bone Remodeling Markers in Premenopausal and Postmenopausal Women

2013 ◽  
Vol 98 (11) ◽  
pp. E1740-E1748 ◽  
Author(s):  
Sonsoles Botella ◽  
Patricia Restituto ◽  
Ignacio Monreal ◽  
Inmaculada Colina ◽  
Amparo Calleja ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Acid Phosphatase ◽  
Postmenopausal Women ◽  
Bone Remodeling ◽  
Bone Mineral ◽  
Analytical Performance ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Mineral Density ◽  
Bone Remodeling Markers

Context: Bone turnover markers (BTMs) may identify changes in bone remodeling within a relatively short time interval before changes in bone mineral density can be detected. New markers such as osteoprotegerin, receptor activator of nuclear factor-κB ligand, and sclerostin have emerged, but there is little information about their potential use in clinical practice. Objectives: The aim of this study was to analyze the ability of several BTMs to predict bone loss in pre- and postmenopausal women and to monitor the efficacy of treatment in osteoporotic women. Design, Patients, and Setting: We performed an observational prospective study in pre- and postmenopausal ambulatory women (n = 72 and n = 152, respectively). Intervention: Postmenopausal women with osteoporosis (n = 18) were treated with risedronate and calcium. Women filled out a questionnaire and underwent bone mineral density measurement using dual-energy x-ray absorptiometry at the time of enrollment and after 1 year of follow-up. BTMs were measured at baseline, at 6 months, and after 1 year. Results: Increased levels of N-terminal propeptide of type 1 procollagen (P1NP) and β-type I collagen telopeptides (CTXs) were associated with low bone mineral density in the premenopausal (P = .02 and P = .04, respectively) and postmenopausal (P = .03 and P = .02) groups. The best analytical performance to diagnose osteoporosis was for β-CTX, osteocalcin, and P1NP, with areas under the curve of 0.70 (P = .005), 0.64 (P = .048), and 0.71 (P = .003). A significant decrease was found in P1NP, osteocalcin, tartrate-resistant acid phosphatase-5b, β-CTX, and bone alkaline phosphatase after 1 year of treatment (all P &lt; .05). Conclusions: Our data suggest that measurement of β-CTX and P1NP shows adequate analytical performance and could potentially be included in algorithms for the screening of osteoporosis. Furthermore, these two markers, along with osteocalcin and tartrate-resistant acid phosphatase-5b, are useful to monitor the response to risedronate.

Increased Concentrations of Prostaglandin D2 During Post-Fracture Bone Remodeling

2010 ◽  
Vol 37 (3) ◽  
pp. 644-649 ◽  
Author(s):  
MAXIME A. GALLANT ◽  
ESTELLE CHAMOUX ◽  
MARTINE BISSON ◽  
CATARINA WOLSEN ◽  
JEAN-LUC PARENT ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Type I Collagen ◽  
Bone Cells ◽  
Bone Alkaline Phosphatase ◽  
Positive Influence ◽  
Fracture Repair ◽  
Prostaglandin D2 ◽  
Type I ◽  
Bone Homeostasis

Objective.To test the hypothesis that increased concentrations of prostaglandin D2 (PGD2) correlate with bone remodeling. Studies using isolated bone cells indicate that PGD2 may be implicated in the regulation of bone homeostasis, with a positive influence on bone anabolism. We studied patients with traumatic fractures and age- and sex-matched healthy controls as an in vivo model of increased bone remodeling.Methods.Thirty-five patients with bone fracture and matched controls were recruited. Urine and sera samples were collected. Urinary 11ß-PGF2α, a PGD2 metabolite, and PGE2 metabolites (PGEM), serum lipocalin-type PGD2 synthase (L-PGDS), bone alkaline phosphatase (bone ALP), and crosslinked C-telopeptides of type I collagen (CTX) were measured.Results.At 5–6 weeks post-fracture, 11ß-PGF2α, L-PGDS, bone ALP, and CTX were significantly increased in the fracture patients compared to controls. PGEM levels were not different between groups. Levels of 11ß-PGF2α and bone ALP were positively correlated, suggesting that PGD2 may be implicated in fracture repair.Conclusion.These results support our working hypothesis that PGD2 could be implicated in the control of bone anabolism in humans.

scholarly journals The Bone Extracellular Matrix as an Ideal Milieu for Cancer Cell Metastases

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1020 ◽  
Author(s):  
Alexus D. Kolb ◽  
Karen M. Bussard
Keyword(s):  
Extracellular Matrix ◽  
Cancer Cells ◽  
Bone Remodeling ◽  
Cancer Cell ◽  
Metastatic Cancer ◽  
Bone Matrix ◽  
Type I ◽  
Bone Homeostasis ◽  
Inorganic Components ◽  
Metastatic Cancer Cells

Bone is a preferential site for cancer metastases, including multiple myeloma, prostate, and breast cancers.The composition of bone, especially the extracellular matrix (ECM), make it an attractive site for cancer cell colonization and survival. The bone ECM is composed of living cells embedded within a matrix composed of both organic and inorganic components. Among the organic components, type I collagen provides the tensile strength of bone. Inorganic components, including hydroxyapatite crystals, are an integral component of bone and provide bone with its rigidity. Under normal circumstances, two of the main cell types in bone, the osteoblasts and osteoclasts, help to maintain bone homeostasis and remodeling through cellular communication and response to biophysical signals from the ECM. However, under pathological conditions, including osteoporosis and cancer, bone remodeling is dysregulated. Once in the bone matrix, disseminated tumor cells utilize normal products of bone remodeling, such as collagen type I, to fuel cancer cell proliferation and lesion outgrowth. Models to study the complex interactions between the bone matrix and metastatic cancer cells are limited. Advances in understanding the interactions between the bone ECM and bone metastatic cancer cells are necessary in order to both regulate and prevent metastatic cancer cell growth in bone.

scholarly journals Short-Term Variations in Bone Remodeling Biochemical Markers: Cyclical Etidronate and Alendronate Effects Compared

1997 ◽  
Vol 82 (9) ◽  
pp. 3034-3039 ◽  
Author(s):  
P. Bettica ◽  
M. Bevilacqua ◽  
T. Vago ◽  
M. Masino ◽  
E. Cucinotta ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Calcium Carbonate ◽  
Bone Remodeling ◽  
Bone Alkaline Phosphatase ◽  
Time Interval ◽  
Short Time Interval ◽  
Type I ◽  
Short Term ◽  
Bone Remodeling Markers ◽  
Cyclical Etidronate

Abstract Bone-remodeling markers have been proposed to monitor antiosteoporotic therapy, as substantial changes in these markers usually occur in a relatively short time interval. In this study we have evaluated the short term effects of two bisphosphonates on bone-remodeling markers with the aim of 1) defining the shortest reliable time interval after which markers should be measured, and 2) comparing the effects of different bisphophonates. To do so, 74 postmenopausal women with a lumbar spine t score of at least −1 were randomly allocated to 4 different treatments: calcium carbonate (500 mg/day; n = 18), 5 mg/day alendronate (A5; n = 18), 10 mg/day alendronate (A10; n = 20), and cyclical etidronate (CE; n = 18). Serum and 24-h urine samples were collected at baseline and 14, 28, 56, and 84 days after the beginning of therapy. Type I collagen N-terminal (NTx) and C-terminal (CTx) telopeptides and total deoxypyridinoline (tDPD) were measured in urine and normalized for urinary creatinine excretion. Osteocalcin and bone alkaline phosphatase in serum were measured. Alendronate (at both doses) and CE significantly decreased bone-remodeling markers, whereas calcium carbonate did not. Bone resorption markers reduction reached a plateau 14 (A10) or 28 (A5 and CE) days after the beginning of treatment, whereas osteocalcin and bone alkaline phosphatase were significantly reduced at 56 (A10) and 84 (CE) days. The global effects of alendronate and CE on NTx and CTx (calculated as the area under the curve) were significantly different from those of calcium (P &lt; 0.05), but were not significantly different from each other. The percent change from baseline obtained with tDPD, NTx, or CTx during bisphosphonate treatment were significantly different (P &lt; 0.05), but this difference disappeared when the variability in the calcium carbonate group was taken into account. In conclusion, this study shows that 1) etidronate and alendronate induce a significant and rapid reduction in bone-remodeling markers; 2) the changes in NTx, CTx, and tDPD urinary excretions reach a plateau after 2–4 wk of treatment; and 3) short term treatments with CE or alendronate induce similar changes in the urinary excretion of NTx and CTx.

Processes of Bone Remodeling in Patients with Cardiovascular Diseases and Manifestations of Chronic Heart Failure

10.12737/3315 ◽  
2014 ◽  
Vol 21 (1) ◽  
pp. 63-66
Author(s):  
Хестанова ◽  
Madina Khestanova
Keyword(s):  
Heart Failure ◽  
Bone Mineral Density ◽  
Chronic Heart Failure ◽  
Bone Remodeling ◽  
Bone Mineral ◽  
Type I Collagen ◽  
Control Group ◽  
Type I ◽  
Mineral Density ◽  
Bone Remodeling Markers

Recently, secondary osteoporosis attracted the attention of many researchers. The paper presents the results of a study of bone remodeling processes in patients with pathology of the cardiovascular system associated with the manifestations of chronic heart failure. Among 114 patients with ischemic heart disease and hypertensive disease with manifestations of chronic heart failure, the study of bone mineral density and bone remodeling markers in serum: osteocalcin and C-terminal telopeptide, formed during the degradation of type I collagen was carried out. The results of osteodensitometry in various areas of the skeleton of examined patients revealed a significant decrease in bone mineral density at the femoral neck compared with the control group. Study of the content of osteocalcin in serum of patients in comparison with the data of the control group demonstrated unsignificant difference. However, when comparing the content of the C-terminal telopeptide of type I collagen in serum of patients with data of the control group revealed significant differences. The obtained data proved the formation of osteoporosis as a risk factor for fractures background progressive resorption.

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