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Functional Heterogeneity Within Osteoclast Populations—a Critical Review of Four Key Publications that May Change the Paradigm of Osteoclasts

Abstract

Purpose of Review

In this review, we critically evaluate the literature for osteoclast heterogeneity, including heterogeneity in osteoclast behavior, which has hitherto been unstudied and has only recently come to attention. We give a critical review centered on four recent high-impact papers on this topic and aim to shed light on the elusive biology of osteoclasts and focus on the variant features of osteoclasts that diverge from the classical viewpoint.

Recent Findings

Osteoclasts originate from the myeloid lineage and are best known for their unique ability to resorb bone. For decades, osteoclasts have been defined simply as multinucleated cells positive for tartrate-resistant acid phosphatase activity and quantified relative to the bone perimeter or surface in histomorphometric analyses. However, several recent, high-profile studies have demonstrated the existence of heterogeneous osteoclast populations, with variable origins and functions depending on the microenvironment. This includes long-term persisting osteoclasts, inflammatory osteoclasts, recycling osteoclasts (osteomorphs), and bone resorption modes. Most of these findings have been revealed through murine studies and have helped identify new targets for human studies. These studies have also uncovered distinct sets of behavioral patterns in heterogeneous osteoclast cultures.

Summary

The underlying osteoclast heterogeneity likely drives differences in bone remodeling, altering patient risk for osteoporosis and fracture. Thus, identifying the underlying key features of osteoclast heterogeneity may help in better targeting bone diseases.

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Fig. 1

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Acknowledgements

We wish to thank Jean-Marie Delaissé for critical reading and commenting on our manuscript.

Funding

Neha Sharma, Megan Weivoda, and Kent Søe are all supported by the National Institutes of Health (R01AR077538-01A1), while Megan Weivoda is also financed by NIH-U01 AG075227, R61 AR078073, P30 AR069620, AFAR Junior Faculty Award, and the Mayo Clinic. Kent Søe is funded by the University of Southern Denmark. Megan Weivoda has received honoraria from Amgen Europe for lectures.

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Sharma, N., Weivoda, M.M. & Søe, K. Functional Heterogeneity Within Osteoclast Populations—a Critical Review of Four Key Publications that May Change the Paradigm of Osteoclasts. Curr Osteoporos Rep (2022). https://doi.org/10.1007/s11914-022-00738-7

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  • Published:

  • DOI: https://doi.org/10.1007/s11914-022-00738-7

Keywords

  • Osteoclast
  • Inflammatory osteoclasts
  • Osteomorphs
  • Erythromyeloid
  • Longevity
  • Bone resorption