Adults with pathogenic MC4R mutations have increased final height and thereby increased bone mass

Eva W. Iepsen*, Jinyi Zhang, Mette Hollensted, Sten Madsbad, Torben Hansen, Jens J. Holst, Niklas R. Jørgensen, Jens Christian Holm, Signe S. Torekov

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Pathogenic mutations in the melanocortin-4 receptor (MC4R) are associated with obesity, increased linear growth, and higher bone mass in children, and rodent studies have indicated an effect of the MC4R on bone turnover. Furthermore, GLP-1 receptor agonists (GLP-1 RAs) may influence bone metabolism. However, these associations have not been assessed in adults with pathogenic MC4R mutations. Thus, we wished to assess the impact of the MC4R on bone mass and metabolism. Secondly, we wished to investigate the impact of the GLP-1 RA liraglutide on bone mass in adults with pathogenic MC4R mutations. 17 patients with obesity-causing MC4R mutations (BMI: 35.5 ± 7.6) and 35 matched control participants with common obesity (BMI: 34.3 ± 7.1) underwent a DEXA scan for assessment of bone mineral density (BMD), bone mineral apparent density [BMAD = (BMD/√(bone area)], and bone turnover markers (BTMs). Individuals with a BMI above 28 (14 MC4R mutation carriers and 28 matched control participants) underwent 16 weeks treatment with liraglutide 3.0 mg. The MC4R group had higher BMD [mean difference: 0.065 g/m2 (− 0.008 to 0.138), p = 0.03], but BMAD and BTMS were not different compared to the control group. In response to liraglutide, BMAD increased in the control group, compared to no change in the MC4R group [mean group difference: 0.0007 (0.0001–0.001), p = 0.04]. In conclusion, BMD is increased in MC4R causal obesity compared to common obesity, but when corrected for body size (BMAD), bone mass was not increased, and no evidence of an influence of the MC4R on bone metabolism in adults was found. Liraglutide treatment did not change bone metabolism in MC4R causal obesity, but increased bone mass as measured by BMAD in common obesity.

OriginalsprogEngelsk
TidsskriftJournal of Bone and Mineral Metabolism
Vol/bind38
Udgave nummer1
Sider (fra-til)117–125
ISSN0914-8779
DOI
StatusUdgivet - jan. 2020

Fingeraftryk

Mutation
Bone Density
Control Groups
Photon Absorptiometry
Rodentia
Liraglutide

Citer dette

Iepsen, E. W., Zhang, J., Hollensted, M., Madsbad, S., Hansen, T., Holst, J. J., ... Torekov, S. S. (2020). Adults with pathogenic MC4R mutations have increased final height and thereby increased bone mass. Journal of Bone and Mineral Metabolism, 38(1), 117–125. https://doi.org/10.1007/s00774-019-01034-8
Iepsen, Eva W. ; Zhang, Jinyi ; Hollensted, Mette ; Madsbad, Sten ; Hansen, Torben ; Holst, Jens J. ; Jørgensen, Niklas R. ; Holm, Jens Christian ; Torekov, Signe S. / Adults with pathogenic MC4R mutations have increased final height and thereby increased bone mass. I: Journal of Bone and Mineral Metabolism. 2020 ; Bind 38, Nr. 1. s. 117–125.
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title = "Adults with pathogenic MC4R mutations have increased final height and thereby increased bone mass",
abstract = "Pathogenic mutations in the melanocortin-4 receptor (MC4R) are associated with obesity, increased linear growth, and higher bone mass in children, and rodent studies have indicated an effect of the MC4R on bone turnover. Furthermore, GLP-1 receptor agonists (GLP-1 RAs) may influence bone metabolism. However, these associations have not been assessed in adults with pathogenic MC4R mutations. Thus, we wished to assess the impact of the MC4R on bone mass and metabolism. Secondly, we wished to investigate the impact of the GLP-1 RA liraglutide on bone mass in adults with pathogenic MC4R mutations. 17 patients with obesity-causing MC4R mutations (BMI: 35.5 ± 7.6) and 35 matched control participants with common obesity (BMI: 34.3 ± 7.1) underwent a DEXA scan for assessment of bone mineral density (BMD), bone mineral apparent density [BMAD = (BMD/√(bone area)], and bone turnover markers (BTMs). Individuals with a BMI above 28 (14 MC4R mutation carriers and 28 matched control participants) underwent 16 weeks treatment with liraglutide 3.0 mg. The MC4R group had higher BMD [mean difference: 0.065 g/m2 (− 0.008 to 0.138), p = 0.03], but BMAD and BTMS were not different compared to the control group. In response to liraglutide, BMAD increased in the control group, compared to no change in the MC4R group [mean group difference: 0.0007 (0.0001–0.001), p = 0.04]. In conclusion, BMD is increased in MC4R causal obesity compared to common obesity, but when corrected for body size (BMAD), bone mass was not increased, and no evidence of an influence of the MC4R on bone metabolism in adults was found. Liraglutide treatment did not change bone metabolism in MC4R causal obesity, but increased bone mass as measured by BMAD in common obesity.",
keywords = "BMAD, BMC, BMD, Bone turnover markers, GLP-1 RA, Liraglutide, MC4R mutations",
author = "Iepsen, {Eva W.} and Jinyi Zhang and Mette Hollensted and Sten Madsbad and Torben Hansen and Holst, {Jens J.} and J{\o}rgensen, {Niklas R.} and Holm, {Jens Christian} and Torekov, {Signe S.}",
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Iepsen, EW, Zhang, J, Hollensted, M, Madsbad, S, Hansen, T, Holst, JJ, Jørgensen, NR, Holm, JC & Torekov, SS 2020, 'Adults with pathogenic MC4R mutations have increased final height and thereby increased bone mass', Journal of Bone and Mineral Metabolism, bind 38, nr. 1, s. 117–125. https://doi.org/10.1007/s00774-019-01034-8

Adults with pathogenic MC4R mutations have increased final height and thereby increased bone mass. / Iepsen, Eva W.; Zhang, Jinyi; Hollensted, Mette; Madsbad, Sten; Hansen, Torben; Holst, Jens J.; Jørgensen, Niklas R.; Holm, Jens Christian; Torekov, Signe S.

I: Journal of Bone and Mineral Metabolism, Bind 38, Nr. 1, 01.2020, s. 117–125.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Adults with pathogenic MC4R mutations have increased final height and thereby increased bone mass

AU - Iepsen, Eva W.

AU - Zhang, Jinyi

AU - Hollensted, Mette

AU - Madsbad, Sten

AU - Hansen, Torben

AU - Holst, Jens J.

AU - Jørgensen, Niklas R.

AU - Holm, Jens Christian

AU - Torekov, Signe S.

PY - 2020/1

Y1 - 2020/1

N2 - Pathogenic mutations in the melanocortin-4 receptor (MC4R) are associated with obesity, increased linear growth, and higher bone mass in children, and rodent studies have indicated an effect of the MC4R on bone turnover. Furthermore, GLP-1 receptor agonists (GLP-1 RAs) may influence bone metabolism. However, these associations have not been assessed in adults with pathogenic MC4R mutations. Thus, we wished to assess the impact of the MC4R on bone mass and metabolism. Secondly, we wished to investigate the impact of the GLP-1 RA liraglutide on bone mass in adults with pathogenic MC4R mutations. 17 patients with obesity-causing MC4R mutations (BMI: 35.5 ± 7.6) and 35 matched control participants with common obesity (BMI: 34.3 ± 7.1) underwent a DEXA scan for assessment of bone mineral density (BMD), bone mineral apparent density [BMAD = (BMD/√(bone area)], and bone turnover markers (BTMs). Individuals with a BMI above 28 (14 MC4R mutation carriers and 28 matched control participants) underwent 16 weeks treatment with liraglutide 3.0 mg. The MC4R group had higher BMD [mean difference: 0.065 g/m2 (− 0.008 to 0.138), p = 0.03], but BMAD and BTMS were not different compared to the control group. In response to liraglutide, BMAD increased in the control group, compared to no change in the MC4R group [mean group difference: 0.0007 (0.0001–0.001), p = 0.04]. In conclusion, BMD is increased in MC4R causal obesity compared to common obesity, but when corrected for body size (BMAD), bone mass was not increased, and no evidence of an influence of the MC4R on bone metabolism in adults was found. Liraglutide treatment did not change bone metabolism in MC4R causal obesity, but increased bone mass as measured by BMAD in common obesity.

AB - Pathogenic mutations in the melanocortin-4 receptor (MC4R) are associated with obesity, increased linear growth, and higher bone mass in children, and rodent studies have indicated an effect of the MC4R on bone turnover. Furthermore, GLP-1 receptor agonists (GLP-1 RAs) may influence bone metabolism. However, these associations have not been assessed in adults with pathogenic MC4R mutations. Thus, we wished to assess the impact of the MC4R on bone mass and metabolism. Secondly, we wished to investigate the impact of the GLP-1 RA liraglutide on bone mass in adults with pathogenic MC4R mutations. 17 patients with obesity-causing MC4R mutations (BMI: 35.5 ± 7.6) and 35 matched control participants with common obesity (BMI: 34.3 ± 7.1) underwent a DEXA scan for assessment of bone mineral density (BMD), bone mineral apparent density [BMAD = (BMD/√(bone area)], and bone turnover markers (BTMs). Individuals with a BMI above 28 (14 MC4R mutation carriers and 28 matched control participants) underwent 16 weeks treatment with liraglutide 3.0 mg. The MC4R group had higher BMD [mean difference: 0.065 g/m2 (− 0.008 to 0.138), p = 0.03], but BMAD and BTMS were not different compared to the control group. In response to liraglutide, BMAD increased in the control group, compared to no change in the MC4R group [mean group difference: 0.0007 (0.0001–0.001), p = 0.04]. In conclusion, BMD is increased in MC4R causal obesity compared to common obesity, but when corrected for body size (BMAD), bone mass was not increased, and no evidence of an influence of the MC4R on bone metabolism in adults was found. Liraglutide treatment did not change bone metabolism in MC4R causal obesity, but increased bone mass as measured by BMAD in common obesity.

KW - BMAD

KW - BMC

KW - BMD

KW - Bone turnover markers

KW - GLP-1 RA

KW - Liraglutide

KW - MC4R mutations

U2 - 10.1007/s00774-019-01034-8

DO - 10.1007/s00774-019-01034-8

M3 - Journal article

C2 - 31471646

AN - SCOPUS:85071472471

VL - 38

SP - 117

EP - 125

JO - Journal of Bone and Mineral Metabolism

JF - Journal of Bone and Mineral Metabolism

SN - 0914-8779

IS - 1

ER -