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Increased osteoblast and osteoclast indices in individuals with systemic mastocytosis

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Abstract

Summary

Indolent systemic mastocytosis (ISM) can trigger bone loss. However, the clinical relevance of different mast cell infiltration patterns for bone remains to be clarified. Here, we report increased bone turnover in individuals with ISM, and its extent is rather related to the type of mast cell distribution within the bone marrow than to the presence or absence of cutaneous manifestations.

Introduction

It is well established that ISM can trigger osteopenia or osteoporosis. However, neither the clinical relevance of the infiltration pattern of mast cells within the bone marrow nor the impact of the presence or absence of cutaneous mast cell infiltration has been elucidated.

Methods

We retrospectively analysed 300 cases with histologically proven ISM of the bone marrow and performed quantitative histomorphometry for a subgroup of 159 patients that did not receive any treatment before the biopsies were taken. Most importantly, since 66 % of the patients displayed ISM without the characteristic skin lesions, we were able to compare ISM with or without cutaneous manifestation.

Results

We found that both forms of ISM were not only characterized by a decreased trabecular bone mass but also by an increased number of osteoclasts and osteoblasts. Interestingly, when we analysed these data in relation to mast cell distribution, we found that the bone cell numbers in cases with mast cell granulomas were significantly increased compared to cases with diffuse mast cell distribution. Moreover, evidence of increased bone turnover was also found in 16 patients displaying osteosclerosis.

Conclusion

Based on the largest cohort of bone biopsies from patients with ISM analysed so far, we could demonstrate high bone turnover, more specifically increased osteoblast and osteoclast numbers and surface indices, as a cause of the skeletal changes. Moreover, the severity of the bone disease is presumably rather dependent on the amount of mast cells and their distribution within the bone marrow irrespective of the presence or absence of cutaneous involvement.

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Acknowledgements

This work was supported by grants from the Bundesministerium für Bildung und Forschung (BMBF) within the framework of the consortium Osteopath (01EC1006F) to MA.

Conflicts of interest

None.

Author information

Author notes

  1. S. Seitz

    Present address: Department of Orthopaedic Surgery, University Medical Center Hamburg–Eppendorf, Hamburg, Germany

  2. J. Semler

    Present address: Immanuel Women’s Health Center, Immanuel Hospital, Berlin, Germany

  3. H. Minne & M. Pfeiffer

    Present address: Clinic Fürstenhof, Bad Pyrmont, Germany

Authors and Affiliations

  1. Department of Osteology and Biomechanics, University Medical Center Hamburg–Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    S. Seitz, F. Barvencik, T. Koehne, J. Semler, H. Minne, M. Pfeiffer, T. Schinke & M. Amling

  2. Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg–Eppendorf, Hamburg, Germany

    M. Priemel & P. Pogoda

  3. Department of Bone Pathology, University Medical Center Hamburg–Eppendorf, Hamburg, Germany

    J. Zustin

  4. Department of Legal Medicine, University Medical Center Hamburg–Eppendorf, Hamburg, Germany

    K. Püschel

  5. Department of Medical Biometry and Epidemiology, University Medical Center Hamburg–Eppendorf, Hamburg, Germany

    C. Eulenburg

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  1. S. Seitz
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Corresponding author

Correspondence to M. Amling.

Additional information

S.S., F.B. and T.K. contributed equally to this work

Electronic supplementary material

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ESM 1

Comparative histomorphometry of iliac crest biopsies from ISM patients with (Fx+) and without (Fx−) vertebral fractures. a–c Structural histomorphometric parameters (a), cellular parameters (b) as well as mast cell distribution and number (c) were not significantly different with regard to the presence of fractures in patients with ISM. (PDF 22 kb)

ESM 2

Bone serum markers of ISM patients displaying osteosclerosis in comparison with patients with ISM-related bone loss. a–c While serum calcium and inorganic phosphate levels (a, b) were not significantly different between patients with ISM-related bone loss and patients with osteosclerosis, alkaline phosphatase activity was significantly increased in the individuals displaying osteosclerosis (c). All bars represent mean + SD. Asterisks indicate statistically significant differences (p < 0.05) compared to patients with ISM-related bone loss. (PDF 17 kb)

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Seitz, S., Barvencik, F., Koehne, T. et al. Increased osteoblast and osteoclast indices in individuals with systemic mastocytosis. Osteoporos Int 24, 2325–2334 (2013). https://doi.org/10.1007/s00198-013-2305-x

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