No evidence for alteration in early secondary mineralization by either alendronate, teriparatide or combination of both in transiliac bone biopsy samples from postmenopausal osteoporotic patients

The influence of treatment with alendronate (ALN), teriparatide (TPTD) or concurrent treatment with both on the human bone matrix mineralization has not yet been fully elucidated. For this purpose we analyzed quadruple fluorochrome labelled transiliac bone biopsy samples (n = 66) from postmenopausal...

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Main Authors: Barbara M. Misof, Paul Roschger, Hua Zhou, Jeri W. Nieves, Mathias Bostrom, Felicia Cosman, Robert Lindsay, Klaus Klaushofer, David W. Dempster
Format: Article
Language:English
Published: Elsevier 2020-06-01
Series:Bone Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2352187220300139
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author Barbara M. Misof
Paul Roschger
Hua Zhou
Jeri W. Nieves
Mathias Bostrom
Felicia Cosman
Robert Lindsay
Klaus Klaushofer
David W. Dempster
author_facet Barbara M. Misof
Paul Roschger
Hua Zhou
Jeri W. Nieves
Mathias Bostrom
Felicia Cosman
Robert Lindsay
Klaus Klaushofer
David W. Dempster
author_sort Barbara M. Misof
collection DOAJ
description The influence of treatment with alendronate (ALN), teriparatide (TPTD) or concurrent treatment with both on the human bone matrix mineralization has not yet been fully elucidated. For this purpose we analyzed quadruple fluorochrome labelled transiliac bone biopsy samples (n = 66) from postmenopausal osteoporotic women with prior and ongoing ALN (ALN-Rx arm) or without ALN (Rx-Naïve arm) after 7 months treatment with cyclic or daily TPTD or without TPTD using quantitative backscattered electron imaging and confocal scanning laser microscopy. Additionally to the bone mineralization density distribution (BMDD) of entire cancellous and cortical compartments, we measured the mineralization kinetics, i.e. the calcium concentration between the younger (Ca_DL2) and older double labels (Ca_DL1), and in interstitial bone (Ca_int) in a subset of the biopsy cohort.We found the BMDD from the patients with prior and ongoing ALN generally shifted to higher calcium concentrations compared to those without ALN (average degree of mineralization in cancellous bone Cn.CaMean + 3.1%, p<0.001). The typical BMDD changes expected by cyclic or daily TPTD treatment due to the increased bone turnover/formation, e.g. an increase in low mineralized bone area were not observed. Additionally, we found no influence of treatment with ALN or TPTD or combination thereof on Ca_DL2, Ca_DL1, or Ca_int. Pooling the information from all groups, Ca_DL1 was +5.9% (p<0.001) higher compared to Ca_DL2, corresponding to a mineralization rate of 0.18 wt% Ca per week during the early secondary mineralization process.Our data suggest that the patients in the ALN-Rx arm had more highly mineralized bone matrix than those without ALN due to their lower bone turnover. The reason for the unexpected BMDD findings in the TPTD treated remain unknown and cannot be attributed to altered mineralization kinetics as no differences in the time course of early secondary mineralization were observed between the treatment groups.
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spelling doaj.art-12da4b5886e64aa1ace6afbbd87694092022-12-22T02:42:50ZengElsevierBone Reports2352-18722020-06-0112100253No evidence for alteration in early secondary mineralization by either alendronate, teriparatide or combination of both in transiliac bone biopsy samples from postmenopausal osteoporotic patientsBarbara M. Misof0Paul Roschger1Hua Zhou2Jeri W. Nieves3Mathias Bostrom4Felicia Cosman5Robert Lindsay6Klaus Klaushofer7David W. Dempster8Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Med. Dept. Hanusch Hospital, Vienna, Austria; Corresponding author at: Ludwig Boltzmann Institute of Osteology, UKH Meidling, Kundratstr. 37, A-1120 Vienna, Austria.Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Med. Dept. Hanusch Hospital, Vienna, AustriaRegional Bone Center and Clinical Research Center, Helen Hayes Hospital, West Haverstraw, NY, USADepartment of Epidemiology, Columbia University, New York, NY, USA; Hospital for Special Surgery, New York, NY, USARegional Bone Center and Clinical Research Center, Helen Hayes Hospital, West Haverstraw, NY, USA; Hospital for Special Surgery, New York, NY, USADepartment of Medicine, Columbia University, New York, NY, USARegional Bone Center and Clinical Research Center, Helen Hayes Hospital, West Haverstraw, NY, USA; Department of Medicine, Columbia University, New York, NY, USALudwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Med. Dept. Hanusch Hospital, Vienna, AustriaRegional Bone Center and Clinical Research Center, Helen Hayes Hospital, West Haverstraw, NY, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY, USAThe influence of treatment with alendronate (ALN), teriparatide (TPTD) or concurrent treatment with both on the human bone matrix mineralization has not yet been fully elucidated. For this purpose we analyzed quadruple fluorochrome labelled transiliac bone biopsy samples (n = 66) from postmenopausal osteoporotic women with prior and ongoing ALN (ALN-Rx arm) or without ALN (Rx-Naïve arm) after 7 months treatment with cyclic or daily TPTD or without TPTD using quantitative backscattered electron imaging and confocal scanning laser microscopy. Additionally to the bone mineralization density distribution (BMDD) of entire cancellous and cortical compartments, we measured the mineralization kinetics, i.e. the calcium concentration between the younger (Ca_DL2) and older double labels (Ca_DL1), and in interstitial bone (Ca_int) in a subset of the biopsy cohort.We found the BMDD from the patients with prior and ongoing ALN generally shifted to higher calcium concentrations compared to those without ALN (average degree of mineralization in cancellous bone Cn.CaMean + 3.1%, p<0.001). The typical BMDD changes expected by cyclic or daily TPTD treatment due to the increased bone turnover/formation, e.g. an increase in low mineralized bone area were not observed. Additionally, we found no influence of treatment with ALN or TPTD or combination thereof on Ca_DL2, Ca_DL1, or Ca_int. Pooling the information from all groups, Ca_DL1 was +5.9% (p<0.001) higher compared to Ca_DL2, corresponding to a mineralization rate of 0.18 wt% Ca per week during the early secondary mineralization process.Our data suggest that the patients in the ALN-Rx arm had more highly mineralized bone matrix than those without ALN due to their lower bone turnover. The reason for the unexpected BMDD findings in the TPTD treated remain unknown and cannot be attributed to altered mineralization kinetics as no differences in the time course of early secondary mineralization were observed between the treatment groups.http://www.sciencedirect.com/science/article/pii/S2352187220300139Bone matrix mineralizationCombined therapy with alendronate and teriparatideQuadruple labellingSecondary mineralizationTransiliac bone biopsy
spellingShingle Barbara M. Misof
Paul Roschger
Hua Zhou
Jeri W. Nieves
Mathias Bostrom
Felicia Cosman
Robert Lindsay
Klaus Klaushofer
David W. Dempster
No evidence for alteration in early secondary mineralization by either alendronate, teriparatide or combination of both in transiliac bone biopsy samples from postmenopausal osteoporotic patients
Bone Reports
Bone matrix mineralization
Combined therapy with alendronate and teriparatide
Quadruple labelling
Secondary mineralization
Transiliac bone biopsy
title No evidence for alteration in early secondary mineralization by either alendronate, teriparatide or combination of both in transiliac bone biopsy samples from postmenopausal osteoporotic patients
title_full No evidence for alteration in early secondary mineralization by either alendronate, teriparatide or combination of both in transiliac bone biopsy samples from postmenopausal osteoporotic patients
title_fullStr No evidence for alteration in early secondary mineralization by either alendronate, teriparatide or combination of both in transiliac bone biopsy samples from postmenopausal osteoporotic patients
title_full_unstemmed No evidence for alteration in early secondary mineralization by either alendronate, teriparatide or combination of both in transiliac bone biopsy samples from postmenopausal osteoporotic patients
title_short No evidence for alteration in early secondary mineralization by either alendronate, teriparatide or combination of both in transiliac bone biopsy samples from postmenopausal osteoporotic patients
title_sort no evidence for alteration in early secondary mineralization by either alendronate teriparatide or combination of both in transiliac bone biopsy samples from postmenopausal osteoporotic patients
topic Bone matrix mineralization
Combined therapy with alendronate and teriparatide
Quadruple labelling
Secondary mineralization
Transiliac bone biopsy
url http://www.sciencedirect.com/science/article/pii/S2352187220300139
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