Differential impact of glucose administered intravenously or orally on bone turnover markers in healthy male subjects

Westberg-Rasmussen, Sidse; Starup-Linde, Jakob; Hermansen, Kjeld; Holst, Jens J.; Hartmann, Bolette; Vestergaard, Peter; Gregersen, Søren

doi:10.1016/j.bone.2017.01.027

Cited by 47 publications

(49 citation statements)

References 25 publications

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“…Furthermore, it might have been beneficial to increase the duration of the observation period because the CTX levels did not return (increase) to fasting levels following the GLP‐1‐mediated decrease in bone resorption. However, in previous studies of longer duration the nadir of CTX was reached at 120 min after oral glucose intake . Another limitation is the possible effect of GLP‐1 on the kidneys.…”

Section: Discussionmentioning

confidence: 90%

“…JBMR Plus (WOA) Previous studies of postprandial bone remodeling show that oral glucose (eg, in the form of an oral glucose tolerance test) can lead to a decrease in bone resorption as measured by CTX levels to as low as 50% of the fasting level (baseline level). (14,34) Here a decrease to 74% of the baseline level was reached after injections of GLP-1 (7-36)amide, which indicates that GLP-1 is not responsible for the entire postprandial inhibition of bone resorption. This leaves room for an effect of other gut hormones, such as GIP and GLP-2, which both have been suggested as major players in the gut-bone axis.…”

Section: Discussionmentioning

confidence: 96%

“…However, in previous studies of longer duration the nadir of CTX was reached at 120 min after oral glucose intake. (14,34) Another limitation is the possible effect of GLP-1 on the kidneys. In theory, the observed effect on CTX levels could be caused by increased clearance induced by GLP-1 of collagen degradation fragments, which are normally eliminated by glomerular filtration.…”

Section: Discussionmentioning

confidence: 99%

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A Pilot Study Showing Acute Inhibitory Effect of GLP‐1 on the Bone Resorption Marker CTX in Humans

et al. 2019

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Bones have been suggested to be a target for glucagon‐like peptide ‐1 (GLP‐1); however, studies of the effects on human bones so far have given diverging results. We hypothesized that GLP‐1, together with glucagon‐like peptide‐2 and glucose‐dependent insulinotropic polypeptide, plays a role in the gut–bone axis. We examined the acute effect of three GLP‐1 receptor ligands [GLP‐1 (7‐36)amide, GLP‐1 (9‐36)amide, and exenatide] on markers of bone remodeling. Eight healthy, normal‐weight participants, with a mean age of 24.3 years, were studied for 4 days in a double‐blinded, randomized clinical trial. Blood was collected before and after s.c. injection of GLP‐1 (7‐36)amide (1.5 nmol/kg), GLP‐1 (9‐36)amide (1.5 nmol/kg), exenatide (2.4 nmol/subject), or saline. Plasma was analyzed for bone markers and for osteoprotegerin (OPG), PTH, and IGF‐1 levels. All ligands were tested in vitro for their cAMP‐inducing activity on the human GLP‐1 receptor. GLP‐1 (7‐36)amide decreased CTX‐levels, compared with placebo (area under the curve [AUC] ±SD 0 to 120 min = –2143 ± 1294 % × min versus –883 ± 1557 % × min; p < 0.05). No difference was observed between placebo and GLP‐1 (9‐36)amide, or between placebo and exenatide, although exenatide had a similar potency as GLP‐1 (7‐36)amide for cAMP formation in vitro (EC50 of 0.093 and 0.054 nmol/L). However, exenatide reached maximum plasma concentration at 90 min versus 15 min for GLP‐1 (7‐36)amide, and plasma CTX was significantly decreased during the second hour of the study after exenatide injections compared with placebo (AUC ±SD –463.1 ± 218 % × min and –136 ± 91 % × min; p < 0.05). There was no effect of the injections on bone formation markers (P1NP and osteocalcin) or on OPG, PTH and IGF‐1 levels. In conclusion, we show that GLP‐1 receptor agonists, but not the primary metabolite GLP‐1 (9‐36)amide, decrease bone resorption, and suggest that GLP‐1 may be part of the gut–bone axis. © 2019 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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A Pilot Study Showing Acute Inhibitory Effect of GLP‐1 on the Bone Resorption Marker CTX in Humans

et al. 2019

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“…The STROBE guidelines were followed (Supplemental Table 1 ). The study design has been described previously in detail ( 8 ). In the study we included relatively young individuals and to avoid potential effects of fluctuations in sex hormones on bone markers during the menstrual cycle we only enrolled males.…”

Section: Methodsmentioning

confidence: 99%

“…An oral glucose tolerance test (OGTT) and an intravenous isoglycemic glucose infusion (IIGI) results in differential insulin and incretin hormone responses despite comparable levels of plasma glucose ( 7 , 8 ). The aim of the present study is to investigate whether administration of glucose by two different routes resulting in differential incretin and insulin responses differentially influences osteocalcin and undercarboxylated osteocalcin levels.…”

Section: Introductionmentioning

confidence: 99%

Glucose Tolerance Tests and Osteocalcin Responses in Healthy People

et al. 2018

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Aim: Osteocalcin and undercarboxylated osteocalcin are suggested to be endocrine messengers from the bones and have been shown to stimulate insulin secretion from pancreatic β-cells. Insulin is hypothesized to increase the osteoblastic production of osteocalcin. The aim of the study was to investigate whether the route of glucose administration influence the circulating levels of osteocalcin and undercarboxylated osteocalcin.Methods: Twelve healthy males were enrolled in an acute cross-over study where they underwent an oral glucose tolerance test (OGTT), an isoglycemic intravenous glucose infusion (IIGI) and a fasting period (control). Blood samples were collected throughout 180 min and analyzed for osteocalcin and undercarboxylated osteocalcin and compared to insulin, glucose, and gastro-intestinal hormone responses.Results: Neither osteocalcin levels nor undercarboxylated osteocalcin levels over time differed between the OGTT, IIGI, and fasting. Baseline insulin levels and glucose levels were not associated with osteocalcin or undercarboxylated osteocalcin levels. Increases in insulin and glucose levels were neither associated with altered osteocalcin nor undercarboxylated osteocalcin levels.Conclusion: The route of glucose administration does not influence the circulating levels of osteocalcin and undercarboxylated osteocalcin despite the differential insulin and incretin responses. In the acute setting this suggests that insulin does not increase osteoblastic production of osteocalcin in healthy human males.

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Effects of Incretin Therapy on Skeletal Health in Type 2 Diabetes—A Systematic Review

Viggers,

Rasmussen,

Vestergaard

2023

JBMR Plus

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Diabetes poses a significant risk to bone health, with Type 1 diabetes (T1D) having a more detrimental impact than Type 2 diabetes (T2D). The group of hormones known as incretins, which includes gastric inhibitory peptide (GIP) and glucagon‐like peptide 1 (GLP‐1), play a role in regulating bowel function and insulin secretion during feeding. GLP‐1 receptor agonists (GLP‐1 RAs) are emerging as the primary treatment choice in T2D, particularly when atherosclerotic cardiovascular disease is present. Dipeptidyl peptidase 4 inhibitors (DPP‐4is), although less potent than GLP‐1 RAs, can also be used. Additionally, GLP‐1 RAs, either alone or in combination with GIP, may be employed to address overweight and obesity. Since feeding influences bone turnover, a relationship has been established between incretins and bone health. To explore this relationship, we conducted a systematic literature review following the PRISMA guidelines. While some studies on cells and animals have suggested positive effects of incretins on bone cells, turnover, and bone density, human studies have yielded either no or limited and conflicting results regarding their impact on bone mineral density (BMD) and fracture risk. The effect on fracture risk may vary depending on the choice of comparison drug and the duration of follow‐up, which was often limited in several studies. Nevertheless, GLP‐1 RAs may hold promise for people with T2D who have multiple fracture risk factors and poor metabolic control. Furthermore, a potential new area of interest is the use of GLP‐1 RAs in fracture prevention among overweight and obese people. Based on this systematic review, existing evidence remains insufficient to support a positive or a superior effect on bone health to reduce fracture risk in people with T2D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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Differential impact of glucose administered intravenously or orally on bone turnover markers in healthy male subjects

Cited by 47 publications

References 25 publications

A Pilot Study Showing Acute Inhibitory Effect of GLP‐1 on the Bone Resorption Marker CTX in Humans

A Pilot Study Showing Acute Inhibitory Effect of GLP‐1 on the Bone Resorption Marker CTX in Humans

Glucose Tolerance Tests and Osteocalcin Responses in Healthy People

Effects of Incretin Therapy on Skeletal Health in Type 2 Diabetes—A Systematic Review

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