Understanding Coupling between Bone Resorption and Formation
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Reversal cells express osteoblast lineage cell markers Runx2, ALP, and Col3, but not TRAcP or CatK.
“Indeed, the reversal cells express osteoblast lineage cell markers such as Runx2, ALP, and Col3, but not TRAcP or CatK.265”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [265]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
PARFITT, A. M., Drezner, M. K., Glorieux, F. H., Kanis, J. А., Malluche, H. H., Meunier, P. J., Ott, S. M., & Recker, R. R. (1987) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650020617 · Cited by 5,015 · see citing works
Nakashima, K., Zhou, X., Kunkel, G., Zhang, Z., Deng, J. M., Behringer, R. R., & de Crombrugghe, B. (2002) · Cell · doi:10.1016/s0092-8674(01)00622-5 · Cited by 3,608 · see citing works
Pathogenesis of osteoporosis: concepts, conflicts, and prospects
Raisz, L. G. (2005) · Journal of Clinical Investigation · doi:10.1172/jci27071 · Cited by 1,779 · see citing works
Cellular and molecular mechanisms of bone remodeling
Raggatt, L. J., & Partridge, N. C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.r109.041087 · Cited by 1,402 · see citing works
Manolagas, S. C. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0024 · Cited by 1,210 · see citing works
TGF-β1–induced migration of bone mesenchymal stem cells couples bone resorption with formation
Tang, Y., Wu, X., Lei, W., Pang, L., Wan, C., Shi, Z., Zhao, L., Nagy, T. R., Peng, X., Hu, J., et al. (2009) · Nature Medicine · doi:10.1038/nm.1979 · Cited by 1,165 · see citing works
Bone histomorphometry : techniques and interpretation
Recker, R. R. (1983) · CRC Press eBooks · Cited by 1,160 · see citing works
DETRE, S. I., Jotti, G. S., & Dowsett, M. (1995) · Journal of Clinical Pathology · doi:10.1136/jcp.48.9.876 · Cited by 884 · see citing works
Silverberg, S. J., Lewiecki, E. M., Mosekilde, L., Peacock, M., & Rubin, M. R. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1760 · Cited by 683 · see citing works
Osteoclast-derived activity in the coupling of bone formation to resorption
Martin, T. J., & Sims, N. A. (2005) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2004.12.004 · Cited by 659 · see citing works
Regulatory mechanisms of osteoblast and osteoclast differentiation.
Katagiri, T., & Takahashi, N. (2002) · Oral Diseases · doi:10.1034/j.1601-0825.2002.01829.x · Cited by 640 · see citing works
ERIKSEN, E. F. (1986) · Endocrine Reviews · doi:10.1210/edrv-7-4-379 · Cited by 601 · see citing works
Pederson, L., Ruan, M., Westendorf, J. J., Khosla, S., & Oursler, M. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805133106 · Cited by 556 · see citing works
The Bone Lining Cell: Its Role in Cleaning Howship's Lacunae and Initiating Bone Formation
Everts, V., Delaissé, J. M., Korper, W., Jansen, D. C., Tigchelaar-Gutter, W., Saftig, P., & Beertsen, W. (2002) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2002.17.1.77 · Cited by 411 · see citing works
Parfitt, A. M. (1984) · Calcified Tissue International · doi:10.1007/bf02406132 · Cited by 406 · see citing works
Glucocorticoid-Induced Osteoporosis
Baylink, D. J. (1983) · New England Journal of Medicine · doi:10.1056/nejm198308043090509 · Cited by 398 · see citing works
PARFITT, A. M. (1982) · Metabolic Bone Disease and Related Research · doi:10.1016/0221-8747(82)90002-9 · Cited by 396 · see citing works
Matrix metalloproteinases (MMP) and cathepsin K contribute differently to osteoclastic activities
Delaissé, J., Andersen, T. L., Engsig, M. T., Henriksen, K., Troen, T., & Blavier, L. (2003) · Microscopy Research and Technique · doi:10.1002/jemt.10374 · Cited by 341 · see citing works
Self-citationA Physical Mechanism for Coupling Bone Resorption and Formation in Adult Human Bone
Andersen, T. L., Sondergaard, T. E., Skorzynska, K. E., Dagnaes-Hansen, F., Plesner, T. L., Hauge, E. M., Plesner, T., & Delaisse, J.-M. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.080627 · Cited by 325 · see citing works
Self-citationAre Nonresorbing Osteoclasts Sources of Bone Anabolic Activity?
Karsdal, M. A., Martin, T. J., Bollerslev, J., Christiansen, C., & Henriksen, K. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.070109 · Cited by 242 · see citing works
Self-citationOsteoporosis: Recent Advances in Pathogenesis and Treatment
Barbieri, E. B. (1984) · Journal of Gerontological Nursing · doi:10.3928/0098-9134-19840801-16 · Cited by 238 · see citing works
Mosekilde, L. (1990) · Bone and Mineral · doi:10.1016/0169-6009(90)90046-i · Cited by 237 · see citing works
Osteoporosis: recent advances in pathogenesis and treatment
Cooper, C. C., & Aihie, A. (1994) · QJM · doi:10.1093/oxfordjournals.qjmed.a068917 · Cited by 233 · see citing works
Senescence‐associated intrinsic mechanisms of osteoblast dysfunctions
Kassem, M., & Marie, P. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00669.x · Cited by 228 · see citing works
Eriksen, E. F., Gundersen, H. J. G., Melsen, F., & Mosekilde, L. (1984) · Metabolic Bone Disease and Related Research · doi:10.1016/0221-8747(84)90066-3 · Cited by 191 · see citing works
Glucocorticoid-Induced Osteoporosis
Weinstein, R. S. (2001) · Reviews in Endocrine and Metabolic Disorders · doi:10.1023/a:1010007108155 · Cited by 189 · see citing works
Use of an alpha-smooth muscle actin GFP reporter to identify an osteoprogenitor population
Kalajzić, Ž., Li, H., Wang, L., Jiang, X., Lamothe, K., Adams, D. J., Aguila, H. L., Rowe, D. W., & Kalajzić, I. (2008) · Bone · doi:10.1016/j.bone.2008.04.023 · Cited by 167 · see citing works
Cellular kinetics of the bone remodeling sequence in the rat
Van, P. T., Vignery, A., & Baron, R. (1982) · The Anatomical Record · doi:10.1002/ar.1092020403 · Cited by 158 · see citing works
Andersen, T. L., del Carmen Ovejero, M., Kirkegaard, T., Lenhard, T., Foged, N. T., & Delaissé, J.-M. (2004) · Bone · doi:10.1016/j.bone.2004.06.019 · Cited by 145 · see citing works
Self-citationKassem, M. S., Ankersen, L., Eriksen, E. F., Clark, B. F. C., & Rattan, S. I. S. (1997) · Osteoporosis International · doi:10.1007/bf02652556 · Cited by 131 · see citing works
Osteopontin and the Bone Remodeling Sequence
McKee, M. D., & Nanci, A. (1995) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1995.tb44629.x · Cited by 121 · see citing works
An electron-microscopic study of the bone-remodeling sequence in the rat
Tran, P. V., Vignery, A., & Baron, R. (1982) · Cell and Tissue Research · doi:10.1007/bf00214682 · Cited by 118 · see citing works
Increased presence of capillaries next to remodeling sites in adult human cancellous bone
Kristensen, H. B., Andersen, T. L., Marcussen, N., Rolighed, L., & Delaisse, J.-M. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1760 · Cited by 97 · see citing works
Self-citationMulari, M. T. K., Qu, Q., H�rk�nen, P. L., & V��n�nen, H. K. (2004) · Calcified Tissue International · doi:10.1007/s00223-004-0172-3 · Cited by 93 · see citing works
Jansen, I. D. C., Vermeer, J. A. F., Bloemen, V., Stap, J., & Everts, V. E. (2012) · Calcified Tissue International · doi:10.1007/s00223-012-9600-y · Cited by 88 · see citing works
Complementary Roles of Intracellular and Pericellular Collagen Degradation Pathways In Vivo
Wagenaar-Miller, R. A., Engelholm, L. H., Gavard, J., Yamada, S. S., Gutkind, J. S., Behrendt, N., Bugge, T. H., & Holmbeck, K. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00291-07 · Cited by 85 · see citing works
Tartrate-resistant acid phosphatase activity in rat osteoblasts and osteocytes
Bianco, P., Ballanti, P., & BONUCCI, E. (1988) · Calcified Tissue International · doi:10.1007/bf02571315 · Cited by 84 · see citing works
Matsuo, K. (2009) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0b013e32832b75f1 · Cited by 79 · see citing works
Baron, R., & Vignery, A. (1981) · Metabolic Bone Disease and Related Research · doi:10.1016/0221-8747(81)90020-5 · Cited by 74 · see citing works
(Pre-)Osteoclasts Induce Retraction of Osteoblasts Before Their Fusion to Osteoclasts
Perez-Amodio, S., Beertsen, W., & Everts, V (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.040509 · Cited by 70 · see citing works
Histomorphometric assessment of trabecular bone remodelling in osteoporosis
Compston, J. E., & Croucher, P. I. (1991) · Bone and Mineral · doi:10.1016/0169-6009(91)90086-f · Cited by 69 · see citing works
Lee, Y., & Chuong, C. (1992) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650071211 · Cited by 60 · see citing works
Primary hyperparathyroidism: lessons from bone histomorphometry.
Eriksen, E. F. (2002) · PubMed · Cited by 59 · see citing works
Solari, F., Domenget, C., Gire, V., et al. (1995) · Journal of Cell Science · doi:10.1242/jcs.108.10.3233 · Cited by 56 · see citing works
Transitional structures in lamellar bone
Ziv, V., Sabanay, I., Arad, T., Traub, W., & Weiner, S. (1996) · Microscopy Research and Technique · doi:10.1002/(sici)1097-0029(19960201)33:2 · Cited by 55 · see citing works
Deposition of cement at reversal lines in rat femoral bone
Zhou, H. Y., Chernecky, R., & Davies, J. E. (1994) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650090311 · Cited by 55 · see citing works
Jensen, P. R., Andersen, T. L., Søe, K., Hauge, E., Bollerslev, J., Amling, M., Barvencik, F., & Delaissé, J. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1490 · Cited by 37 · see citing works
Self-citationReconstruction of the formative site in trabecular bone by a new, quick, and easy method
Steiniche, T., Eriksen, E. F., Kudsk, H., Mosekilde, L., & Melsen, F. (1992) · Bone · doi:10.1016/8756-3282(92)90004-g · Cited by 34 · see citing works
Bianco, P., & BONUCCI, E. (1991) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/bf01605077 · Cited by 31 · see citing works
Mocetti, P., Ballanti, P., Zalzal, S., Silvestrini, G., BONUCCI, E., & Nanci, A. (2000) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540004800804 · Cited by 30 · see citing works
Baron, R., & Jl, S. (1977) · Calcified Tissue International · doi:10.1007/bf02010365 · Cited by 26 · see citing works
Organic Extracellular Matrix Components at the Bone Cell/Substratum Interface
Shen, X., Roberts, E. W., Peel, S. A. F., et al. (1993) · Digital Commons - USU (Utah State University) · Cited by 22 · see citing works
Oguro, I., & Ozawa, H. (1989) · Journal of Bone and Mineral Metabolism · doi:10.1007/bf02377581 · Cited by 20 · see citing works
Domon, T., Suzuki, R., Takata, K., et al. (2001) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/s0940-9602(01)80027-3 · Cited by 18 · see citing works
Structural aspects of the reversal phase of alveolar bone remodelling.
Kang, Y., Ko, J. S., & Hwang, S. (1994) · PubMed · Cited by 12 · see citing works
Arrest of the reversal phase in postmenopausal and glucocorticoid-induced osteoporosis
Jensen, P. R., Andersen, T. L., Abdelgawad, M. E., et al. (2011) · University of Southern Denmark Research Portal (University of Southern Denmark) · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Andersen TL, Hauge E, Bollerslev J, Kjaersgaard-Andersen P, Delaisse JM: Absence of bone remodeling compartment canopies correlates with an arrested reversal phase and dificient bone formation in post-menopausal osteoporosis. J Bone Miner Res 2010, 25:S102
Cited by
Sorted by citations
Coupling of bone resorption and formation by RANKL reverse signalling
Ikebuchi, Y., Aoki, S., Honma, M., Hayashi, M., Sugamori, Y., Khan, M., Kariya, Y., Kato, G., Tabata, Y., Penninger, J. M., et al. (2018) · Nature · doi:10.1038/s41586-018-0482-7 · Cited by 557 · see citing works
Bone remodeling: an operational process ensuring survival and bone mechanical competence
Bolamperti, S., Villa, I., & Rubinacci, A. (2022) · Bone Research · doi:10.1038/s41413-022-00219-8 · Cited by 482 · see citing works
Quiescent Bone Lining Cells Are a Major Source of Osteoblasts During Adulthood
Matic, I., Matthews, B. G., Wang, X., Dyment, N. A., Worthley, D. L., Rowe, D. W., Grcevic, D., & Kalajzic, I. (2016) · Stem Cells · doi:10.1002/stem.2474 · Cited by 195 · see citing works
Sims, N. A., & Martin, T. J. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00041 · Cited by 184 · see citing works
Lassen, N. E., Andersen, T. L., Pløen, G. G., Søe, K., Hauge, E. M., Harving, S., Eschen, G. E. T., & Delaisse, J.-M. (2017) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3091 · Cited by 152 · see citing works
Self-citationRe-thinking the bone remodeling cycle mechanism and the origin of bone loss
Delaisse, J.-M., Andersen, T. L., Kristensen, H. B., Jensen, P. R., Andreasen, C. M., & Søe, K. (2020) · Bone · doi:10.1016/j.bone.2020.115628 · Cited by 152 · see citing works
Self-citationCoupling factors involved in preserving bone balance
Kim, B.-J., & Koh, J.-M. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2981-y · Cited by 111 · see citing works
Abdelgawad, M. E., Delaisse, J.-M., Hinge, M., Jensen, P. R., Alnaimi, R. W., Rolighed, L., Engelholm, L. H., Marcussen, N., & Andersen, T. L. (2016) · Histochemistry and Cell Biology · doi:10.1007/s00418-016-1414-y · Cited by 76 · see citing works
Self-citation
- Authors
- Andersen, T. L., Abdelgawad, M. E., Kristensen, H. B., Hauge, E. M., Rolighed, L., Bollerslev, J., Kjærsgaard-Andersen, P., & Delaisse, J.-M.
- Affiliations
- University of Southern Denmark (DK)
- Aarhus University Hospital (DK)
- Oslo University Hospital (NO)
- Corresponding author
- Andersen, Thomas L.
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 183
- Issue
- 1
- Pages
- 235-246
- ISSN
- 0002-9440 (ISSN-L)
- OpenAlex
- W117344629
- Cited by
- 137
- References
- 56
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 7 · 2023: 15 · 2022: 12 · 2021: 12 · 2020: 17 · 2019: 11 · 2018: 9 · 2017: 10 · 2016: 6 · 2015: 6 · 2014: 10 · 2013: 4
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
- Keywords
- bone remodeling, bone resorption, bone formation, osteoclasts, osteoblasts, postmenopausal osteoporosis, primary hyperparathyroidism, trabecular bone volume, bone loss
- MeSH terms
- Aged, Bone Resorption, Female, Humans, Ilium, Immunohistochemistry, Male, Middle Aged, Osteogenesis, Biomarkers, Osteoporosis, Postmenopausal, Case-Control Studies, Hyperparathyroidism, Primary
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
