Current Osteoporosis Reports

, Volume 15, Issue 4, pp 335–342 | Cite as

Melorheostosis: a Rare Sclerosing Bone Dysplasia

  • Anupam Kotwal
  • Bart L. ClarkeEmail author
Rare Bone Disease (C Langman and E Shore, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Rare Bone Diseases


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.


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.


Melorheostosis Hyperostosis Bone dysplasia Sclerotomal distribution 


Compliance with Ethical Standards

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.


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;20:561–83CrossRefGoogle 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;46:1141–5Google Scholar
  3. 3.
    Murray RO, McCredie J. Melorheostosis and the sclerotomes: a radiological correlation. Skeletal Radiol. 1979;4:57–71CrossRefGoogle 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;67:133–7CrossRefGoogle Scholar
  5. 5.
    Greenspan A, Azouz EM. Bone dysplasia series melorheostosis: review and update. Can Assoc Radiol J. 1999;50:324–30PubMedGoogle Scholar
  6. 6.
    Kessler HB, Recht MP, Dalinka MK. Vascular anomalies in association with osteodystrophies—a spectrum. Skeletal Radiol. 1983;10:95–101CrossRefGoogle 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;45:1191–206CrossRefGoogle Scholar
  8. 8.
    Rhys R, Davies AM, Mangham DC, Grimer RJ. Sclerotome distribution of melorheostosis and multicentric fibromatosis. Skeletal Radiol. 1998;27:633–6CrossRefGoogle 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;26:660–3CrossRefGoogle 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.Google Scholar
  11. 11.
    Ethunandan M, Khosla N, Tilley E, Webb A. Melorheostosis involving the craniofacial skeleton. J Craniofac Surg. 2004;15:1062–5CrossRefGoogle Scholar
  12. 12.
    Williams JW, Monaghan D, Barrington NA. Cranio-facial melorheostosis: case report and review of the literature. Br J Radiol. 1991;64:60–2CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle Scholar
  15. 15.
    Suresh S, Muthukumar T, Saifuddin A. Classical and unusual imaging appearances of melorheostosis. Clin Radiol. 2010;65:593–600CrossRefGoogle Scholar
  16. 16.
    Davis DC, Syklawer R, Cole RL. Melorheostosis on three-phase bone scintigraphy. Case report. Clin Nucl Med. 1992;17:561–4PubMedGoogle Scholar
  17. 17.
    Mahoney J, Achong DM. Demonstration of increased bone metabolism in melorheostosis by multiphase bone scanning. Clin Nucl Med. 1991;16:847–8CrossRefGoogle 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;13:48–50PubMedPubMedCentralGoogle 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;27:290CrossRefGoogle 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;22:243–50CrossRefGoogle 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;10:1423–33CrossRefGoogle 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;36:1213–8CrossRefGoogle 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.CrossRefGoogle Scholar
  24. 24.
    Roger D, Bonnetblanc JM, Leroux-Robert C. Melorheostosis with associated minimal change nephrotic syndrome, mesenteric fibromatosis and capillary haemangiomas. Dermatology. 1994;188:166–8CrossRefGoogle 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;77:169–78Google Scholar
  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;101:145–55CrossRefGoogle 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. AbstractGoogle Scholar
  28. 28.
    Hoshi K, Amizuka N, Kurokawa T, Nakamura K, Shiro R, Ozawa H. Histopathological characterization of melorheostosis. Orthopedics. 2001;24:273–7PubMedGoogle 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;23:310–4CrossRefGoogle 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;96:55–6PubMedGoogle 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;13:27CrossRefGoogle 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.CrossRefGoogle 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: bcr2013009820Google Scholar
  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.CrossRefGoogle 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;302:1055–61CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Mayo ClinicRochesterUSA

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