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Cited by 152Bone Metabolism and DiseasesBone health and osteoporosis researchBone and Dental Protein Studies

Re-thinking the bone remodeling cycle mechanism and the origin of bone loss

Open access
Delaisse, Jean-Marie, Andersen, Thomas Levin, Kristensen, Helene Bjoerg, Jensen, Pia Rosgaard, Andreasen, Christina Møller, Søe, Kent·2020·Bone
DOI 10.1016/j.bone.2020.115628
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Abstract

Proper bone remodeling necessarily requires that osteoblasts reconstruct the bone that osteoclasts have resorbed. However, the cellular events connecting resorption to reconstruction have remained poorly known. The consequence is a fragmentary understanding of the remodeling cycle where only the resorption and formation steps are taken into account. New tools have recently made possible to elucidate how resorption shifts to formation, thereby allowing to comprehend the remodeling cycle as a whole. This new knowledge is reviewed herein. It shows how teams of osteoclasts and osteoblast lineage cells are progressively established and how they are subjected therein to reciprocal interactions. Contrary to the common view, osteoclasts and osteoprogenitors are intermingled on the eroded surfaces. The analysis of the resorption and cell population dynamics shows that osteoprogenitor cell expansion and resorption proceed as an integrated mechanism; that a threshold cell density of osteoprogenitors on the eroded surface is mandatory for onset of bone formation; that the cell initiating osteoprogenitor cell expansion is the osteoclast; and that the osteoclast therefore triggers putative osteoprogenitor reservoirs positioned at proximity of the eroded bone surface (bone lining cells, canopy cells, pericytes). The interplay between magnitude of resorption and rate of cell expansion governs how soon bone reconstruction is initiated and may determine uncoupling and permanent bone loss if a threshold cell density is not reached. The clinical perspectives opened by these findings are discussed.

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  • BLCs are covered by a thin layer of mesenchyme-derived cells called bone marrow envelope (BME) cells that morphologically resemble BLCs and, similar to BLCs, are considered osteoprogenitors.

    “BLCs are covered by a thin layer of mesenchyme-derived cells called bone marrow envelope (BME) cells that morphologically resemble BLCs and, similar to BLCs, are considered osteoprogenitors.2”

    From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [2]

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Research works printed but not linked: 4

  1. A.M. Parfitt, The physiolgic and clinical significance of bone histomorphometric data, in: R.R. Recker (Ed.), Bone Histomorphometry Tech. Interpret, CRC Press, Boca Raton, 1983, pp. 143-223.
  2. R. Baron, A. Vignery, R. Lang, Reversal phase and osteopenia: Defective coupling of resorption to formation in the pathogenesis of osteoporosis, in: H.F. Deluca, H.M. Frost, W.S.S. Jee, C.C. Johnston, A.M. Parfitt (Eds.), Osteoporos. Recent Adv. Pathog. Treat, University Park Press, Baltimore, MD, 1980, pp. 311-320.
  3. R. Baron, Importance of the intermediate phases between resorption and forma- tion in the measurement and understanding of the bone remodeling sequence, in: P.J. Meunier (Ed.), Bone Histomorphometry Second Int. Work, Armour Montagu, Paris, 1977, pp. 179-183.
  4. V. Everts, J.M. Delaisse, W. Korper, W. Beertsen, Involvement of matrix metallo- proteinases and cysteine proteinases in degradation of bone matrix, in: Z. Davidovitch (Ed.), Biol. Mech. Tooth Eruption, Resorption, Replace. by Implant, Harvard Society for the Advancement of Orthodontics, Boston, 1994, pp. 85-97.

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Authors
Delaisse, J.-M., Andersen, T. L., Kristensen, H. B., Jensen, P. R., Andreasen, C. M., & Søe, K.
Affiliations
University of Southern Denmark (DK)
ORCID
Venue
Bone
Publisher
Elsevier BV
Published
2020-12
Volume
141
Pages
115628
ISSN
  • 1873-2763 (ISSN-L)
  • 8756-3282
DOI
10.1016/j.bone.2020.115628
OpenAlex
W3083261547
Cited by
152
References
170
Citations by year
2026: 20 · 2025: 29 · 2024: 29 · 2023: 30 · 2022: 29 · 2021: 10 · 2020: 5
FWCI
1.79
Type
journal article
Language
en
Open access
Licence
Locations
  • Bone (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, cc-by-nc-nd)
Funders
Velux Stiftung (34368)
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 › Rheumatology › Bone and Dental Protein Studies
Keywords
osteoclasts, osteoblasts, osteoprogenitor cells, bone resorption, bone formation, bone loss, osteoblast-osteoclast interaction, bone lining cells, pericytes
MeSH terms
Bone and Bones, Bone Resorption, Humans, Osteoblasts, Osteoclasts, Osteogenesis, Bone Remodeling

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