Diffuse, fracturing systemic skeletal histiocytosis of unknown type: a novel metabolic bone disease

Abstract

We describe a novel disease of diffuse skeletal histiocytosis associated with multiple fragility fractures and high osteoclast activity. Clinical, radiographic, biochemical, genetic, and histopathological investigations were performed to characterize the diagnosis of an Asian man who presented with hip fracture and diffuse skeletal lytic lesions. After excluding malignancy and other common metabolic bone diseases, open bone biopsy yielded several pathological samples all showing extensive skeletal histiocytosis likely to explain the diffuse axial and appendicular lytic lesions. Rare disorders such as Langerhans histiocytosis, Erdheim-Chester disease, and diffuse cystic skeletal angiomatosis were excluded through careful pathological examination and lack of CD1a and S-100 staining. Whole exome sequencing did not yield diagnostic findings to explain this likely acquired disease. High markers of osteoclast activity suggested excessive focal bone resorption but normalized after zoledronic acid treatment. A novel disease of skeletal histiocytosis with high bone turnover is differentiated from other histiocytic and lytic skeletal diseases.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  1. 1.

    Ferraz-de-Souza B, Correa PH (2013) Diagnosis and treatment of Paget's disease of bone: a mini-review. Arq Bras Endocrinol Metabol 57(8):577–582

    Article  PubMed  Google Scholar 

  2. 2.

    Stull MA, Kransdorf MJ, Devaney KO (1992) Langerhans cell histiocytosis of bone. Radiographics 12:801–823

    Article  CAS  PubMed  Google Scholar 

  3. 3.

    Levey DS, MacCormack LM, Sartoris DJ, Haghighi P, Resnick D, Thorne R (1996) Cystic angiomatosis: case report and review of the literature. Skelet Radiol 25(3):287–293

    Article  CAS  Google Scholar 

  4. 4.

    Hutter C, Minkov M (2016) Insights into the pathogenesis of Langerhans cell histiocytosis: the development of targeted therapies. Immunotargets Ther 12(5):81–91 eCollection 2016

    Article  Google Scholar 

  5. 5.

    Dougall WC (2007) RANKL signaling in bone physiology and cancer. Curr Opin Support Palliat Care 1(4):317–322

    Article  PubMed  Google Scholar 

  6. 6.

    Stoppacciaro A, Ferrarini M, Salmaggi C, Colarossi C, Praderio L, Tresoldi M, Beretta AA, Sabbadini MG (2006) Immunohistochemical evidence of a cytokine and chemokine network in three patients with Erdheim-Chester disease: implications for pathogenesis. Arthritis Rheum 54(12):4018–4022

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to G. A. Kline.

Ethics declarations

Conflict of interest

None.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Saini, R., DiFrancesco, L.M., Johnston, K. et al. Diffuse, fracturing systemic skeletal histiocytosis of unknown type: a novel metabolic bone disease. Osteoporos Int 30, 1893–1896 (2019). https://doi.org/10.1007/s00198-019-05021-7

Download citation

Keywords

  • Histiocytosis
  • Lytic lesions
  • Metabolic bone disease
  • Osteoporosis