A Single 60 mg Dose of Denosumab Might Improve Hepatic Insulin Sensitivity in Postmenopausal Nondiabetic Severe Osteoporotic Women

Background. The RANKL/RANK/OPG signaling pathway is crucial for the regulation of osteoclast activity and bone resorption being activated in osteoporosis. The pathway has been also suggested to influence glucose metabolism as observed in chronic low inflammation. Aim. To test whether systemic blocka...

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Main Authors: Elena Passeri, Stefano Benedini, Elena Costa, Sabrina Corbetta
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2015/352858
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author Elena Passeri
Stefano Benedini
Elena Costa
Sabrina Corbetta
author_facet Elena Passeri
Stefano Benedini
Elena Costa
Sabrina Corbetta
author_sort Elena Passeri
collection DOAJ
description Background. The RANKL/RANK/OPG signaling pathway is crucial for the regulation of osteoclast activity and bone resorption being activated in osteoporosis. The pathway has been also suggested to influence glucose metabolism as observed in chronic low inflammation. Aim. To test whether systemic blockage of RANKL by the monoclonal antibody denosumab influences glucose metabolism in osteoporotic women. Study Design. This is a prospective study on the effect of a subcutaneously injected single 60 mg dose of denosumab in 14 postmenopausal severe osteoporotic nondiabetic women evaluated at baseline and 4 and 12 weeks after their first injection by an oral glucose tolerance test. Results. A single 60 mg dose of denosumab efficiently inhibited serum alkaline phosphatase while it did not exert any significant variation in fasting glucose, insulin, or HOMA-IR at both 4 and 12 weeks. No changes could be detected in glucose response to the glucose load, Matsuda Index, or insulinogenic index. Nonetheless, 60 mg denosumab induced a significant reduction in the hepatic insulin resistance index at 4 weeks and in HbA1c levels at 12 weeks. Conclusions. A single 60 mg dose of denosumab might positively affect hepatic insulin sensitivity though it does not induce clinical evident glucose metabolic disruption in nondiabetic patients.
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spelling doaj-art-e0fca4fe0d824eeb98e87260f260babf2025-02-03T01:25:50ZengWileyInternational Journal of Endocrinology1687-83371687-83452015-01-01201510.1155/2015/352858352858A Single 60 mg Dose of Denosumab Might Improve Hepatic Insulin Sensitivity in Postmenopausal Nondiabetic Severe Osteoporotic WomenElena Passeri0Stefano Benedini1Elena Costa2Sabrina Corbetta3Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, 20097 San Donato Milanese, ItalyEndocrinology and Diabetology Unit, Department of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, 20097 San Donato Milanese, ItalyClinical Laboratory, IRCCS Policlinico San Donato, 20097 San Donato Milanese, ItalyEndocrinology and Diabetology Unit, Department of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, 20097 San Donato Milanese, ItalyBackground. The RANKL/RANK/OPG signaling pathway is crucial for the regulation of osteoclast activity and bone resorption being activated in osteoporosis. The pathway has been also suggested to influence glucose metabolism as observed in chronic low inflammation. Aim. To test whether systemic blockage of RANKL by the monoclonal antibody denosumab influences glucose metabolism in osteoporotic women. Study Design. This is a prospective study on the effect of a subcutaneously injected single 60 mg dose of denosumab in 14 postmenopausal severe osteoporotic nondiabetic women evaluated at baseline and 4 and 12 weeks after their first injection by an oral glucose tolerance test. Results. A single 60 mg dose of denosumab efficiently inhibited serum alkaline phosphatase while it did not exert any significant variation in fasting glucose, insulin, or HOMA-IR at both 4 and 12 weeks. No changes could be detected in glucose response to the glucose load, Matsuda Index, or insulinogenic index. Nonetheless, 60 mg denosumab induced a significant reduction in the hepatic insulin resistance index at 4 weeks and in HbA1c levels at 12 weeks. Conclusions. A single 60 mg dose of denosumab might positively affect hepatic insulin sensitivity though it does not induce clinical evident glucose metabolic disruption in nondiabetic patients.http://dx.doi.org/10.1155/2015/352858
spellingShingle Elena Passeri
Stefano Benedini
Elena Costa
Sabrina Corbetta
A Single 60 mg Dose of Denosumab Might Improve Hepatic Insulin Sensitivity in Postmenopausal Nondiabetic Severe Osteoporotic Women
International Journal of Endocrinology
title A Single 60 mg Dose of Denosumab Might Improve Hepatic Insulin Sensitivity in Postmenopausal Nondiabetic Severe Osteoporotic Women
title_full A Single 60 mg Dose of Denosumab Might Improve Hepatic Insulin Sensitivity in Postmenopausal Nondiabetic Severe Osteoporotic Women
title_fullStr A Single 60 mg Dose of Denosumab Might Improve Hepatic Insulin Sensitivity in Postmenopausal Nondiabetic Severe Osteoporotic Women
title_full_unstemmed A Single 60 mg Dose of Denosumab Might Improve Hepatic Insulin Sensitivity in Postmenopausal Nondiabetic Severe Osteoporotic Women
title_short A Single 60 mg Dose of Denosumab Might Improve Hepatic Insulin Sensitivity in Postmenopausal Nondiabetic Severe Osteoporotic Women
title_sort single 60 mg dose of denosumab might improve hepatic insulin sensitivity in postmenopausal nondiabetic severe osteoporotic women
url http://dx.doi.org/10.1155/2015/352858
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