Melorheostosis: a Rare Sclerosing Bone Dysplasia

Abstract

Purpose of Review

Melorheostosis is a rare sclerosing bone dysplasia that affects both cortical bone and adjacent soft tissue structures in a sclerotomal distribution. In this review, we describe the natural history, radiological features, proposed pathogenesis, and management options for this debilitating condition.

Recent Findings

Since its first description in 1922, about 400 cases of melorheostosis have been reported, either as single reports or in small case series. Melorheostosis affects the appendicular skeleton more commonly than the axial skeleton and usually presents with lower limb deformity. Diagnosis is based on a combination of clinical and radiological features that help differentiate this condition from other sclerosing bone dysplasias. LEM domain-containing protein 3 (LEMD3) gene mutations have been demonstrated in several familial cases, but these have been more strongly correlated with other hereditary dysplasias, such as osteopoikilosis, and are not thought to be the causative gene for melorheostosis. The exact etiology of classic sporadically occurring melorheostosis remains unknown, with possible causes being somatic LEMD3 mutations, somatic mutations in the bone morphogenetic protein/transforming growth factor-beta pathway, mutations in multiple genes, or other non-genetic causes. Management in recent years has involved nitrogen-containing bisphosphonates in addition to traditional orthopedic surgical approaches and physical therapy.

Summary

Melorheostosis may present as mixed or atypical osseous involvement in addition to the classically described “dripping candle wax” appearance of hyperostosis. Some patients may have overlap with osteopoikilosis or Buschke–Ollendorff syndrome. In the future, better characterization of genetic and developmental factors predisposing to melorheostosis may lead to the development of targeted therapy for this condition, as well as for more commonly encountered skeletal abnormalities.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

References

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

  1. 1.

    Greenspan A. Sclerosing bone dysplasias—a target-site approach. Skeletal Radiol. 1991;20:561–83

    CAS  Article  Google Scholar 

  2. 2.

    Léri A, Joanny J. Une affection non décrite des os: hyperostose “en coulée” sur toute la longueur d’un membre ou “mélorhéostose”. Bull Mem Soc Med Hosp Paris. 1922;46:1141–5

    Google Scholar 

  3. 3.

    Murray RO, McCredie J. Melorheostosis and the sclerotomes: a radiological correlation. Skeletal Radiol. 1979;4:57–71

    CAS  Article  Google Scholar 

  4. 4.

    Wynne-Davies R, Gormley J. The prevalence of skeletal dysplasias. An estimate of their minimum frequency and the number of patients requiring orthopaedic care. J Bone Joint Surg Br. 1985;67:133–7

    CAS  Article  Google Scholar 

  5. 5.

    Greenspan A, Azouz EM. Bone dysplasia series melorheostosis: review and update. Can Assoc Radiol J. 1999;50:324–30

    CAS  PubMed  Google Scholar 

  6. 6.

    Kessler HB, Recht MP, Dalinka MK. Vascular anomalies in association with osteodystrophies—a spectrum. Skeletal Radiol. 1983;10:95–101

    CAS  Article  Google Scholar 

  7. 7.

    Morris JM, Samilson RL, Corley CL. Melorheostosis. Review of the literature and report of an interesting case with a nineteen-year follow-up. J Bone Joint Surg Am. 1963;45:1191–206

    CAS  Article  Google Scholar 

  8. 8.

    Rhys R, Davies AM, Mangham DC, Grimer RJ. Sclerotome distribution of melorheostosis and multicentric fibromatosis. Skeletal Radiol. 1998;27:633–6

    CAS  Article  Google Scholar 

  9. 9.

    Woolridge B, Stone NC, Denic N. Melorheostosis isolated to the calcaneus: a case report and review of the literature. Foot Ankle Int. 2005;26:660–3

    Article  Google Scholar 

  10. 10.

    • Smith GC, Pingree MJ, Freeman LA, Matsumoto JM, Howe BM, Kannas SN, et al. Melorheostosis: A retrospective clinical analysis of 24 patients at the Mayo Clinic. PM&R. 2016;30:30813–9. This is the largest available case series reporting that the most common radiological finding in melorheostosis patients is a mixed pattern consisting of different forms of hyperostosis.

  11. 11.

    Ethunandan M, Khosla N, Tilley E, Webb A. Melorheostosis involving the craniofacial skeleton. J Craniofac Surg. 2004;15:1062–5

    Article  Google Scholar 

  12. 12.

    Williams JW, Monaghan D, Barrington NA. Cranio-facial melorheostosis: case report and review of the literature. Br J Radiol. 1991;64:60–2

    CAS  Article  Google Scholar 

  13. 13.

    • Ihde LL, Forrester DM, Gottsegen CJ, Masih S, Patel DB, Vachon LA, et al. Sclerosing bone dysplasias: review and differentiation from other causes of osteosclerosis. RadioGraphics. 2011;31:1865–82. This review describes the various sclerosing bone dysplasias, differentiating between hereditary and non-hereditary conditions, and discusses each condition briefly.

    Article  Google Scholar 

  14. 14.

    • Freyschmidt J. Melorheostosis: a review of 23 cases. Eur Radiol. 2001;11:474–9. This article describes patterns of melorheostosis other than the classically described “dripping candle wax” pattern.

    CAS  Article  Google Scholar 

  15. 15.

    Suresh S, Muthukumar T, Saifuddin A. Classical and unusual imaging appearances of melorheostosis. Clin Radiol. 2010;65:593–600

    CAS  Article  Google Scholar 

  16. 16.

    Davis DC, Syklawer R, Cole RL. Melorheostosis on three-phase bone scintigraphy. Case report. Clin Nucl Med. 1992;17:561–4

    CAS  PubMed  Google Scholar 

  17. 17.

    Mahoney J, Achong DM. Demonstration of increased bone metabolism in melorheostosis by multiphase bone scanning. Clin Nucl Med. 1991;16:847–8

    CAS  Article  Google Scholar 

  18. 18.

    Hassan A, Khalid M, Khawar S. Detection of melorheostosis in a young lady with upper limb pain on Three Phase Bone Scintigram/SPECT-CT. Clin Cases Miner Bone Metab. 2016;13:48–50

    PubMed  PubMed Central  Google Scholar 

  19. 19.

    Hellemans J, Debeer P, Wright M, Janecke A, Kjaer KW, Verdonk PC, et al. Germline LEMD3 mutations are rare in sporadic patients with isolated melorheostosis. Hum Mut. 2006;27:290

    Article  Google Scholar 

  20. 20.

    Mumm S, Wenkert D, Zhang X, McAlister WH, Mier RJ, Whyte MP. Deactivating germline mutations in LEMD3 cause osteopoikilosis and Buschke–Ollendorff syndrome, but not sporadic melorheostosis. J Bone Miner Res. 2007;22:243–50

    CAS  Article  Google Scholar 

  21. 21.

    Vanhoenacker FM, De Beuckeleer LH, Van Hul W, Balemans W, Tan GJ, Hill SC, et al. Sclerosing bone dysplasias: genetic and radioclinical features. Eur Radiol. 2000;10:1423–33

    CAS  Article  Google Scholar 

  22. 22.

    Hellemans J, Preobrazhenska O, Willaert A, Debeer P, Verdonk PC, Costa T, et al. Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke–Ollendorff syndrome and melorheostosis. Nat Genet. 2004;36:1213–8

    CAS  Article  Google Scholar 

  23. 23.

    Campbell CJ, Papademetriou T, Bonfiglio M. Melorheostosis. A report of the clinical, roentgenographic, and pathological findings in fourteen cases. J Bone Joint Surg Am. 1968;50:1281–304.

    CAS  Article  Google Scholar 

  24. 24.

    Roger D, Bonnetblanc JM, Leroux-Robert C. Melorheostosis with associated minimal change nephrotic syndrome, mesenteric fibromatosis and capillary haemangiomas. Dermatology. 1994;188:166–8

    CAS  Article  Google Scholar 

  25. 25.

    Kim JE, Kim EH, Han EH, Park RW, Park IH, Jun SH, et al. A TGF-beta-inducible cell adhesion molecule, betaig-h3, is downregulated in melorheostosis and involved in osteogenesis. J Cell Biochem. 2000;77:169–78

  26. 26.

    Whyte MP, Griffith M, Trani L, Mumm S, Gottesman GS, McAlister WH, et al. Melorheostosis: Exome sequencing of an associated dermatosis implicates postzygotic mosaicism of mutated KRAS. Bone. 2017;101:145–55

    CAS  Article  Google Scholar 

  27. 27.

    Jha S, Papadakis G, Kim L, Malayeri A, Cowen EW, Lehky T, et al. Melorheostosis: clinical experience of 23 cases. Endocrine Society 2017. Orlando, FL. 2017. Abstract

  28. 28.

    Hoshi K, Amizuka N, Kurokawa T, Nakamura K, Shiro R, Ozawa H. Histopathological characterization of melorheostosis. Orthopedics. 2001;24:273–7

    CAS  PubMed  Google Scholar 

  29. 29.

    Baer SC, Ayala AG, Ro JY, Yasko AW, Raymond AK, Edeiken J. Case report 843. Malignant fibrous histiocytoma of the femur arising in melorheostosis. Skeletal Radiol. 1994;23:310–4

    CAS  Article  Google Scholar 

  30. 30.

    Murphy M, Kearns S, Cavanagh M, O’Connell D, Hurson B. Occurrence of osteosarcoma in a melorheostotic femur. Ir Med J. 2003;96:55–6

    CAS  PubMed  Google Scholar 

  31. 31.

    Saxena A, Neelakantan A, Jampana R, Sangra M. Melorheostosis causing lumbar radiculopathy: a case report and a review of the literature. Spine J. 2013;13:27

    Article  Google Scholar 

  32. 32.

    Donáth J, Poór G, Kiss C, Fornet B, Genant H. Atypical form of active melorheostosis and its treatment with bisphosphonate. Skeletal Radiol. 2002;31:709–13.

    Article  Google Scholar 

  33. 33.

    Slimani S, Nezzar A, Makhloufi H. Successful treatment of pain in melorheostosis with zoledronate, with improvement on bone scintigraphy. BMJ Case Rep. 2013; 2013:pii: bcr2013009820

  34. 34.

    • Theriault RL. Zoledronic acid (Zometa) use in bone disease. Expert Rev Anticancer Ther. 2003;3:157–66. This case demonstrated radiological and clinical improvement following intravenous zoledronic acid.

    CAS  Article  Google Scholar 

  35. 35.

    Wood J, Bonjean K, Ruetz S, Bellahcène A, Devy L, Foidart JM, et al. Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther. 2002;302:1055–61

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Bart L. Clarke.

Ethics declarations

Conflict of Interest

Bart Clarke and Anupam Kotwal declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Rare Bone Disease

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kotwal, A., Clarke, B.L. Melorheostosis: a Rare Sclerosing Bone Dysplasia. Curr Osteoporos Rep 15, 335–342 (2017). https://doi.org/10.1007/s11914-017-0375-y

Download citation

Keywords

  • Melorheostosis
  • Hyperostosis
  • Bone dysplasia
  • Sclerotomal distribution