Understanding coupling between bone resorption and formation: are reversal cells the missing link?

Thomas Levin Andersen, Mohamed E Abdelgawad, Helene B Kristensen, Ellen Margrethe Hauge, Lars Rolighed, Jens Bollerslev, Per Kjærsgaard-Andersen, Jean-Marie Delaisse

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Resumé

Bone remodeling requires bone resorption by osteoclasts, bone formation by osteoblasts, and a poorly investigated reversal phase coupling resorption to formation. Likely players of the reversal phase are the cells recruited into the lacunae vacated by the osteoclasts and presumably preparing these lacunae for bone formation. These cells, called herein reversal cells, cover >80% of the eroded surfaces, but their nature is not identified, and it is not known whether malfunction of these cells may contribute to bone loss in diseases such as postmenopausal osteoporosis. Herein, we combined histomorphometry and IHC on human iliac biopsy specimens, and showed that reversal cells are immunoreactive for factors typically expressed by osteoblasts, but not for monocytic markers. Furthermore, a subpopulation of reversal cells showed several distinctive characteristics suggestive of an arrested physiological status. Their prevalence correlated with decreased trabecular bone volume and osteoid and osteoblast surfaces in postmenopausal osteoporosis. They were, however, virtually absent in primary hyperparathyroidism, in which the transition between bone resorption and formation occurs optimally. Collectively, our observations suggest that arrested reversal cells reflect aborted remodeling cycles that did not progress to the bone formation step. We, therefore, propose that bone loss in postmenopausal osteoporosis does not only result from a failure of the bone formation step, as commonly believed, but also from a failure at the reversal step.
OriginalsprogEngelsk
TidsskriftAmerican Journal of Pathology
Vol/bind183
Udgave nummer1
Sider (fra-til)235-46
ISSN0002-9440
DOI
StatusUdgivet - jul. 2013

Fingeraftryk

Osteogenesis
Postmenopausal Osteoporosis
Osteoblasts
Osteoclasts
Primary Hyperparathyroidism

Citer dette

Levin Andersen, Thomas ; Abdelgawad, Mohamed E ; Kristensen, Helene B ; Hauge, Ellen Margrethe ; Rolighed, Lars ; Bollerslev, Jens ; Kjærsgaard-Andersen, Per ; Delaisse, Jean-Marie. / Understanding coupling between bone resorption and formation : are reversal cells the missing link?. I: American Journal of Pathology. 2013 ; Bind 183, Nr. 1. s. 235-46.
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title = "Understanding coupling between bone resorption and formation: are reversal cells the missing link?",
abstract = "Bone remodeling requires bone resorption by osteoclasts, bone formation by osteoblasts, and a poorly investigated reversal phase coupling resorption to formation. Likely players of the reversal phase are the cells recruited into the lacunae vacated by the osteoclasts and presumably preparing these lacunae for bone formation. These cells, called herein reversal cells, cover >80{\%} of the eroded surfaces, but their nature is not identified, and it is not known whether malfunction of these cells may contribute to bone loss in diseases such as postmenopausal osteoporosis. Herein, we combined histomorphometry and IHC on human iliac biopsy specimens, and showed that reversal cells are immunoreactive for factors typically expressed by osteoblasts, but not for monocytic markers. Furthermore, a subpopulation of reversal cells showed several distinctive characteristics suggestive of an arrested physiological status. Their prevalence correlated with decreased trabecular bone volume and osteoid and osteoblast surfaces in postmenopausal osteoporosis. They were, however, virtually absent in primary hyperparathyroidism, in which the transition between bone resorption and formation occurs optimally. Collectively, our observations suggest that arrested reversal cells reflect aborted remodeling cycles that did not progress to the bone formation step. We, therefore, propose that bone loss in postmenopausal osteoporosis does not only result from a failure of the bone formation step, as commonly believed, but also from a failure at the reversal step.",
author = "{Levin Andersen}, Thomas and Abdelgawad, {Mohamed E} and Kristensen, {Helene B} and Hauge, {Ellen Margrethe} and Lars Rolighed and Jens Bollerslev and Per Kj{\ae}rsgaard-Andersen and Jean-Marie Delaisse",
note = "Copyright {\circledC} 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.",
year = "2013",
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Understanding coupling between bone resorption and formation : are reversal cells the missing link? / Levin Andersen, Thomas; Abdelgawad, Mohamed E; Kristensen, Helene B; Hauge, Ellen Margrethe; Rolighed, Lars; Bollerslev, Jens; Kjærsgaard-Andersen, Per; Delaisse, Jean-Marie.

I: American Journal of Pathology, Bind 183, Nr. 1, 07.2013, s. 235-46.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Understanding coupling between bone resorption and formation

T2 - are reversal cells the missing link?

AU - Levin Andersen, Thomas

AU - Abdelgawad, Mohamed E

AU - Kristensen, Helene B

AU - Hauge, Ellen Margrethe

AU - Rolighed, Lars

AU - Bollerslev, Jens

AU - Kjærsgaard-Andersen, Per

AU - Delaisse, Jean-Marie

N1 - Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

PY - 2013/7

Y1 - 2013/7

N2 - Bone remodeling requires bone resorption by osteoclasts, bone formation by osteoblasts, and a poorly investigated reversal phase coupling resorption to formation. Likely players of the reversal phase are the cells recruited into the lacunae vacated by the osteoclasts and presumably preparing these lacunae for bone formation. These cells, called herein reversal cells, cover >80% of the eroded surfaces, but their nature is not identified, and it is not known whether malfunction of these cells may contribute to bone loss in diseases such as postmenopausal osteoporosis. Herein, we combined histomorphometry and IHC on human iliac biopsy specimens, and showed that reversal cells are immunoreactive for factors typically expressed by osteoblasts, but not for monocytic markers. Furthermore, a subpopulation of reversal cells showed several distinctive characteristics suggestive of an arrested physiological status. Their prevalence correlated with decreased trabecular bone volume and osteoid and osteoblast surfaces in postmenopausal osteoporosis. They were, however, virtually absent in primary hyperparathyroidism, in which the transition between bone resorption and formation occurs optimally. Collectively, our observations suggest that arrested reversal cells reflect aborted remodeling cycles that did not progress to the bone formation step. We, therefore, propose that bone loss in postmenopausal osteoporosis does not only result from a failure of the bone formation step, as commonly believed, but also from a failure at the reversal step.

AB - Bone remodeling requires bone resorption by osteoclasts, bone formation by osteoblasts, and a poorly investigated reversal phase coupling resorption to formation. Likely players of the reversal phase are the cells recruited into the lacunae vacated by the osteoclasts and presumably preparing these lacunae for bone formation. These cells, called herein reversal cells, cover >80% of the eroded surfaces, but their nature is not identified, and it is not known whether malfunction of these cells may contribute to bone loss in diseases such as postmenopausal osteoporosis. Herein, we combined histomorphometry and IHC on human iliac biopsy specimens, and showed that reversal cells are immunoreactive for factors typically expressed by osteoblasts, but not for monocytic markers. Furthermore, a subpopulation of reversal cells showed several distinctive characteristics suggestive of an arrested physiological status. Their prevalence correlated with decreased trabecular bone volume and osteoid and osteoblast surfaces in postmenopausal osteoporosis. They were, however, virtually absent in primary hyperparathyroidism, in which the transition between bone resorption and formation occurs optimally. Collectively, our observations suggest that arrested reversal cells reflect aborted remodeling cycles that did not progress to the bone formation step. We, therefore, propose that bone loss in postmenopausal osteoporosis does not only result from a failure of the bone formation step, as commonly believed, but also from a failure at the reversal step.

U2 - 10.1016/j.ajpath.2013.03.006

DO - 10.1016/j.ajpath.2013.03.006

M3 - Journal article

C2 - 23747107

VL - 183

SP - 235

EP - 246

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 1

ER -