scholarly journals Octreotide Abolishes the Acute Decrease in Bone Turnover in Response to Oral Glucose

2003 ◽  
Vol 88 (10) ◽  
pp. 4867-4873 ◽  
Author(s):  
Jackie A. Clowes ◽  
Heather C. Allen ◽  
Donna M. Prentis ◽  
Richard Eastell ◽  
Aubrey Blumsohn

Abstract Feeding or oral intake of glucose results in an acute suppression of bone turnover. This does not appear to be mediated by insulin. Several gastrointestinal hormones modulate bone turnover in vitro and may mediate this response. We examined whether inhibiting the production of gastrointestinal hormones using octreotide could block glucose-mediated suppression of bone turnover. Fifteen subjects were each studied on four occasions in a randomized, single-blind, crossover study after receiving 1) oral placebo, iv saline; 2) oral glucose, iv saline; 3) oral glucose, iv octreotide; or 4) iv octreotide alone. We measured serum C-terminal telopeptide of type I collagen, urinary N-terminal telopeptide of type I collagen, osteocalcin, procollagen type I N-terminal propeptide, PTH, insulin, ionized calcium, and glucose over 4 h. All bone turnover markers decreased significantly after oral glucose (P < 0.001). At 120 min serum C-terminal telopeptide decreased by 45 ± 2%, urinary N-terminal telopeptide by 31 ± 7%, osteocalcin by 16 ± 1%, and procollagen type I N-terminal propeptide by 8 ± 1%. There was no significant decrease in bone turnover in response to oral glucose during octreotide infusion. Octreotide alone resulted in a significant increase in all bone turnover markers (P < 0.05) and PTH (P < 0.01). We conclude that octreotide completely abolishes the bone turnover response to glucose intake and increases PTH secretion. The apparent bone turnover response to feeding is probably mediated by an octreotide-inhibitable endocrine factor.

2002 ◽  
Vol 87 (7) ◽  
pp. 3324-3329 ◽  
Author(s):  
Jackie A. Clowes ◽  
Robert T. Robinson ◽  
Simon R. Heller ◽  
Richard Eastell ◽  
Aubrey Blumsohn

Bone turnover is acutely suppressed after feeding or oral glucose. Insulin infusion suppresses bone turnover and might mediate this effect, but this is confounded by a possible direct effect of hypoglycemia. We examined the effect of euglycemic hyperinsulinemia and hypoglycemic hyperinsulinemia on bone turnover using an insulin clamp. Sixteen men participated in this double-blind crossover study. Clamp induction involved infusion of insulin (80 mU/m2·min) while maintaining euglycemia (5 mmol/liter) for 40 min with a variable rate dextrose infusion. Glucose was lowered to 2.5 mmol/liter (hypoglycemic clamp) or maintained at 5 mmol/liter (euglycemic clamp) for a further 105 min. Nine controls received a matched saline infusion. Measurements included serum C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide, osteocalcin, and PTH. Induction of hyperinsulinemia resulted in a reduction in PTH (27% ± 5; P < 0.01), but no significant change in bone turnover from baseline. Hypoglycemic clamp resulted in suppression of serum C-terminal telopeptide of type I collagen by 34% ± 3, procollagen type I N-terminal propeptide by 15% ± 1, osteocalcin by 5% ± 1, and PTH by a further 12% ± 5 (all P < 0.05). By contrast, there was no significant change in any marker of bone turnover during euglycemic clamp. Postprandial hyperinsulinemia is unlikely to explain the acute suppression of bone turnover with feeding. The reduction in bone turnover during hypoglycemia may be related to hypoglycemia itself, acute changes in PTH, or other hormones released in response to hypoglycemia.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 358.2-358
Author(s):  
S. Shevchuk ◽  
L. Denyshchych

Background:Osteoporosis and fractures associated with it are considered to be one of the most severe complications of systemic lupus erythematosus (SLE). The role of a systemic inflammatory process, vitamin D deficiency, hypogonadism and peculiarities of disease treatment in reduced bone mineral density (BMD) is being discussed. Even though the frequency of osteoporosis in patients with SLE is being studied extensively by scientists from different countries, data on the peculiarities of bone tissue metabolism and the factors that provoke disorders of bone remodeling in such individuals are quite limited. The association between markers of bone tissue metabolism and BMD, and how they change during an inflammatory process is poorly studied.Objectives:The objective of our research is to study the levels of osteocalcin (OC) and procollagen type I C-terminal propeptide (PICP) in patients with systemic lupus erythematosus and to estimate their association with BMD and inflammatory activity based on the levels of interleukin-6 (IL-6).Methods:A total of 58 women with SLE (the average age was 45.11 ± 1.03 years old) and 29 individuals from the control group (the average age was 46.79 ± 2.30 years old) were examined. The diagnosis of SLE was established on the basis of 2019 EULAR/ACR classification criteria for SLE. Levels of IL-6, OC and PICP in serum were determined by enzyme immunoassay. Changes in BMD of the lumbar spine at the level of L1-L4 and the proximal femur were determined by dual-energy X-ray absorptiometry. In postmenopausal women, the diagnosis of osteoporosis was established by the T-score ≤ -2.5 SD. Osteopenia met T-score from -1 to -2.5 SD. In women of reproductive age, the Z-score was used to determine BMD. Values of the Z-score ≤ -2.0 SD were considered as “below expected range for age”.Results:The average OC level in serum of practically healthy individuals equaled 17.64 ± 0,59 ng/ml, and in patients with SLE it was 13.96 ± 0.40 ng/ml, i.e. it was 20.9% lower. The average PICP level in the control group equaled 107.8 ± 4.28 ng/ml, in the main group it was 92.9 ± 5.01 ng/ml, i.e. 16% lower. Overall, the decrease in the bone turnover markers (PICP and/or OC) was noticed in 28 patients with SLE (48.3%) and only in 4 practically healthy individuals (13.8%).In women with decreased bone turnover markers, the T-score of the lumbar spine and hip was 2.3-2.6 times lower (p < 0.05) than in the group with adequate levels of bone turnover markers. Z-score was also lower among patients with decreased levels of OC and PICP. In this group, the average BMD level was 0.81 ± 0.05 g/cm2and was 13.8% lower than in the group of patients with no signs of bone tissue metabolism disorder – 0.94 ± 0.02 g/cm2. Among the group of women with signs of suppression of biosynthetic processes in bone tissue, there were twice more individuals with decreased BMD. In patients with critically high levels of IL-6 (above 20.0 ng/L), OC level was lower than in patients with high (12.5-20.0 ng/L) and adequate (< 12.5 ng/L) levels of IL-6 (by 17.3 and 19% respectively). The proportion of individuals with low OC levels increased from 31.2% in the last group to 70.6% among patients with critically high levels of IL-6.PICP level was also lower (38.1% and 39.7% respectively) in case of critically high IL-6 levels compared to its high and adequate levels. The proportion of individuals with low PICP levels increased from 6.3% in the group with adequate IL-6 level to 58.8% in the group with critically high IL-6 level.Conclusion:Women with SLE have bone tissue metabolism disorder in the form of decreased bone turnover markers (procollagen type I C-terminal propeptide and osteocalcin) associated with the inflammatory activity. In the group of patients with the signs of suppression of biosynthetic processes in the bone tissue, there were more individuals with decreased BMD.Disclosure of Interests:Sergii Shevchuk Grant/research support from: Celltrion, Inc, Liudmyla Denyshchych: None declared


Author(s):  
Jan Mieszkowski ◽  
Andrzej Kochanowicz ◽  
Elżbieta Piskorska ◽  
Bartłomiej Niespodziński ◽  
Joanna Siódmiak ◽  
...  

Abstract Purpose/introduction To compare serum levels of bone turnover markers in athletes and non-athletes, and to evaluate the relationship between serum levels of vitamin D metabolites and exercise-induced changes in biomarker levels. Methods Sixteen elite male artistic gymnasts (EG; 21.4 ± 0.8 years-old) and 16 physically active men (the control group, PAM; 20.9 ± 1.2 years-old) performed lower and upper body 30-s Wingate anaerobic tests (LBWT and UBWT, respectively). For biomarker analysis, blood samples were collected before, and 5 and 30 min after exercise. Samples for vitamin D levels were collected before exercise. N-terminal propeptide of type I collagen (PINP) was analysed as a marker of bone formation. C-terminal telopeptide of type I collagen (CTX) was analysed as a marker of bone resorption. Results UBWT fitness readings were better in the EG group than in the PAM group, with no difference in LBWT readings between the groups. UBWT mean power was 8.8% higher in subjects with 25(OH)D3 levels over 22.50 ng/ml and in those with 24,25(OH)2D3 levels over 1.27 ng/ml. Serum CTX levels increased after both tests in the PAM group, with no change in the EG group. PINP levels did not change in either group; however, in PAM subjects with 25(OH)D3 levels above the median, they were higher than those in EG subjects. Conclusion Vitamin D metabolites affect the anaerobic performance and bone turnover markers at rest and after exercise. Further, adaptation to physical activity modulates the effect of anaerobic exercise on bone metabolism markers.


2016 ◽  
Vol 101 (8) ◽  
pp. 3222-3230 ◽  
Author(s):  
Jean Redmond ◽  
Anthony J. Fulford ◽  
Landing Jarjou ◽  
Bo Zhou ◽  
Ann Prentice ◽  
...  

Context: Ethnic groups differ in fragility fracture risk and bone metabolism. Differences in diurnal rhythms (DRs) of bone turnover and PTH may play a role. Objective: We investigated the DRs of plasma bone turnover markers (BTMs), PTH, and 1,25(OH)2D in three groups with pronounced differences in bone metabolism and plasma PTH. Participants: Healthy Gambian, Chinese, and white British adults (ages 60–75 years; 30 per country). Interventions: Observational study with sample collection every 4 hours for 24 hours. Main Outcomes: Levels of plasma C-terminal telopeptide of type I collagen, procollagen type-1 N-propeptide, N-mid osteocalcin, bone alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D were measured. DRs were analyzed with random-effects Fourier regression and cross-correlation and regression analyses to assess associations between DRs and fasting and 24-hour means of BTMs and PTH. Results: Concentrations of BTMs, PTH, and 1,25-dihydroxyvitamin D were higher in Gambians compared to other groups (P &lt; .05). The DRs were significant for all variables and groups (P &lt; .03) and were unimodal, with a nocturnal peak and a daytime nadir for BTMs, whereas PTH had two peaks. The DRs of BTMs and PTH were significantly cross-correlated for all groups (P &lt; .05). There was a significant positive association between C-terminal telopeptide of type I collagen and PTH in the British and Gambian groups (P = .03), but not the Chinese group. Conclusions: Despite ethnic differences in plasma BTMs and PTH, DRs were similar. This indicates that alteration of rhythmicity and loss of coupling of bone resorption and formation associated with an elevated PTH in other studies may not uniformly occur across different populations and needs to be considered in the interpretation of PTH as a risk factor of increased bone loss.


2014 ◽  
Vol 112 (10) ◽  
pp. 1611-1620 ◽  
Author(s):  
Sarah M. Bristow ◽  
Greg D. Gamble ◽  
Angela Stewart ◽  
Lauren Horne ◽  
Meaghan E. House ◽  
...  

Ca supplements are used for bone health; however, they have been associated with increased cardiovascular risk, which may relate to their acute effects on serum Ca concentrations. Microcrystalline hydroxyapatite (MCH) could affect serum Ca concentrations less than conventional Ca supplements, but its effects on bone turnover are unclear. In the present study, we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca, phosphate, parathyroid hormone and bone turnover markers. We randomised 100 women (mean age 71 years) to 1 g/d of Ca as citrate or carbonate (citrate–carbonate), one of two MCH preparations, or a placebo. Blood was sampled for 8 h after the first dose, and after 3 months of daily supplementation. To determine whether the acute effects changed over time, eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months. There were no differences between the citrate and carbonate groups, or between the two MCH groups, so their results were pooled. The citrate–carbonate dose increased ionised and total Ca concentrations for up to 8 h, and this was not diminished after 3 months. MCH increased ionised Ca concentrations less than the citrate–carbonate dose; however, it raised the concentrations of phosphate and the Ca–phosphate product. The citrate–carbonate and MCH doses produced comparable decreases in bone resorption (measured as serum C-telopeptide (CTX)) over 8 h and bone turnover (CTX and procollagen type-I N-terminal propeptide) at 3 months. These findings suggest that Ca preparations, in general, produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jakob Kau Starup-Linde ◽  
Rikke Viggers ◽  
Bente Langdahl ◽  
Soeren Gregersen ◽  
Simon Lykkeboe ◽  
...  

ObjectiveCirculating osteoglycin may facilitate the crosstalk between bone and pancreas to empower adaptation of bone mass to whole body energy balance. We aimed to examine whether osteoglycin is associated with bone and metabolic parameters and if osteoglycin levels differ between patients with type 1 and 2 diabetes (T1D and T2D).Design and methodsA cross-sectional study of 190 patients with diabetes mellitus and stable hemoglobin A1c (HbA1c) (97 T1D and 93 T2D) was conducted. S-osteoglycin was analyzed by ELISA. Unpaired t-tests were performed to test differences between patients with T1D and T2D and linear regression analyses were performed to investigate associations between osteoglycin, glycemic markers, bone turnover markers and characteristics.ResultsS-osteoglycin did not differ between patients with T1D and T2D (p=0.10). No associations were present between osteoglycin and age, gender, microvascular complications, HbA1c, or plasma glucose in T1D or T2D patients (p&gt;0.05 for all). S-osteoglycin was not associated with levels of bone turnover markers (C-terminal cross-linked telopeptide of type-I collagen (CTX), P-procollagen type 1 amino terminal propeptide (P1NP), P-osteocalcin (OC), P-sclerostin, S-osteoprotegerin (OPG) or S-Receptor Activator of Nuclear factor Kappa beta Ligand (RANKL)) in neither T1D or T2D patients (p&gt;0.05 for all).ConclusionOsteoglycin levels were similar in T1D and T2D patients. Osteoglycin did not correlate with glucose, HbA1c or any other biochemical marker of bone turnover. Thus, we did not find evidence supporting the existence of an osteoglycin-bone-pancreas axis.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT01870557.


2019 ◽  
Vol 10 (Vol.10, No.3) ◽  
pp. 243-251
Author(s):  
Alina Deniza CIUBEAN ◽  
Laszlo IRSAY ◽  
Rodica Ana UNGUR ◽  
Viorela Mihaela CIORTEA ◽  
Ileana Monica BORDA ◽  
...  

Introduction: Osteoporosis has a strong genetic contribution, and several genes have been shown to influence bone mineral density. Variants in the human genome are considered important causes of differences in drug responses observed in clinical practice. In terms of bone mineral density, about 26–53% of patients do not respond to amino-bisphosphonate therapies, of which alendronate is the most widely used. Material and method: The current study is prospective, observational, analytical, longitudinal and cohort type. It included 25 postmenopausal women treated with alendronate for 1 year. Bone mineral density at lumbar spine and proximal femur was measured and bone turnover markers (C-terminal telopeptide of type I collagen and procollagen 1N-terminal propeptide) were evaluated at 0 and 12 months of treatment. Six single nucleotide polymorphisms in osteoporosis-candidate genes were genotyped (FDPS rs2297480, LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438, GGPS1 rs10925503 and RANKL rs2277439). Treatment response was evaluated by percentage changes in bone mineral density and bone turnover markers. Results: The heterozygous CT of FDPS rs2297480 showed lower increases in BMD values in the lumbar spine region and the homozygous CC of the GGPS1 rs10925503 showed lower increases in terms of BMD at the total hip region. No association was found for LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438 and RANKL rs2277439. Conclusions: Romanian postmenopausal women with osteoporosis carrying the CT genotype of FDPS rs2297480 or the CC genotype of GGPS1 rs10925503 could have an unsatisfactory response to alendronate treatment. Key words: osteoporosis; genetic polymorphism; alendronate; bone mineral density; bone turnover markers,


2006 ◽  
Vol 154 (5) ◽  
pp. 745-751 ◽  
Author(s):  
Andrea Dovio ◽  
Laura Perazzolo ◽  
Laura Saba ◽  
Angela Termine ◽  
Marco Capobianco ◽  
...  

Objective: Glucocorticoids (GCs) at pharmacological doses stimulate bone resorption. Mechanisms of this action are unclear. The osteoclastogenic cytokine interleukin (IL)-6 acts through an oligomeric receptor consisting of two subunits, gp80 (or IL-6 receptor α, IL-6Rα) and gp130; both exist in membrane and soluble forms. Soluble IL-6Rα (sIL-6Rα) enhances, while sgp130 inhibits IL-6 signalling. In vitro, GCs enhance many effects of IL-6 by up-regulation of IL-6Rα. The aim of the present study was to assess acute changes of IL-6 system in the peripheral blood of patients given high-dose GCs. Subjects and methods: Serum levels of IL-6, sIL-6Rα, sgp130 and bone turnover markers were assessed before and each day during treatment in 24 multiple sclerosis (MS) patients undergoing high-dose (prednisolone, 15 mg/kg per day), short-term (3 to 5 days) intravenous GC therapy for relapse at the Regional Multiple Sclerosis Centre. Results: An immediate and marked fall of osteocalcin and an early increase of C-terminal telopeptide of type I collagen were already noticed at day 2 (P < 0.001 and P < 0.02, respectively); both became more apparent in the subsequent days. IL-6 was always below or near the detection limit of our ELISA. sgp130 showed a slight increase. sIL-6Rα significantly increased, peaking at day 4 (P < 0.01). However, inter-individual variability of response was noticed. Four patients showed a slight decrease, while no change was observed in one patient and an increase was noticed in the remaining nineteen (maximum change ranging from +10% to +67% with respect to baseline). In these patients, a significant increase of sIL-6Rα/sgp130 ratio was apparent. No correlation was found between bone turnover markers and any measured component of the IL-6 system. Conclusions: sIL-6Rα and sIL-6Rα/sgp130 ratio are precociously increased in the peripheral blood of the vast majority of patients given high-dose, intravenous GCs. The increase of systemically available sIL-6Rα conceivably results in the enhancement of IL-6-dependent osteoclastogenesis. The role of such a mechanism in the bone loss observed in inflammatory and immune-mediated diseases (where abundancy of IL-6 in the bone microenvironment is expected) requires further investigation.


Author(s):  
A. Gaudio ◽  
R. Rapisarda ◽  
A. Xourafa ◽  
L. Zanoli ◽  
V. Manfrè ◽  
...  

Abstract Background Irisin, a myokine, is a polypeptide derived from the cleavage of the extracellular domain of fibronectin domain-containing protein 5, a receptor that is present on different tissues (skeletal muscle, pericardium, myocardium, and brain), whose functions are not yet fully defined. Purpose The main aim of our study was to evaluate the effect of competitive physical activity on serum irisin levels and bone turnover markers. Methods Fifteen male footballers and an equal number of subjects of the same age and gender, but with a predominantly sedentary lifestyle, had their serum levels of irisin and bone turnover markers measured. Bone mineral status was evaluated in both groups by quantitative bone ultrasound of the calcaneus. In addition, only in footballers, biochemical analyses were repeated after 3 months. Results We did not observe significant differences in the serum levels of calcium, phosphorus, and parathyroid hormone between the two groups. The footballers had significantly higher quantitative bone ultrasound, 25-OH vitamin D, and creatinine values than the controls. There were also no significant differences in the bone alkaline phosphatase, carboxy-terminal telopeptide of type I collagen, osteoprotegerin, sclerostin or Dkk-1 values, while the irisin levels (+ 89%, p < 0.001) and RANKL were significantly higher in the footballers compared to those in the controls. Conclusion Our study shows that footballers have significantly higher serum irisin values than the general population. Irisin could be the "trait d’union" between bone health and physical activity.


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