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Melorheostosis is a rare type of bone dysplasia, presumably induced by gene mutations but non-hereditary. Due to characteristic findings on plain radiographic images, melorheostosis is also called candle bone disease.


Symptom onset often occurs in childhood or adolescence and complaints typically aggravate over time. Eventually, patients may seek medical attention for pain, diminished motion ranges of affected joints, and/or deformities. MRO usually affects hands or feet; more proximal parts of the limbs are the second most commonly affected anatomical structures. However, MRO has also been described in bones forming parts of the axial skeleton, namely the vertebral column, sternum, ribs and pelvis [9]. In some patients, one single bone shows pathological alterations. In other cases, symptoms are more diffuse and arise from lesions of multiple bones. Unilateral complaints are more frequently registered than bilateral MRO.

Pain may be persistent or intermittent, dull or sharp, and is often the first symptom noted. It may worsen with exercise. Compromised joints become increasingly stiff, may swell, and contractures of the respective tendons, ligaments and muscles may occur. Deformities develop slowly and may be striking. Patients may present with limbs of distinct length, twisted hands, feet, fingers or toes. Additionally, physical examination may reveal scleroderma and edema, whereby the latter results from either primary or secondary vascular anomalies. Affected skin may be hyperpigmented. Structural alterations of adjacent soft tissues may not only interfere with vessel function but can also compress nerves. This occurs rarely but may cause severe complications. In the United Kingdom, a case of disabling radiculopathy due to nerve root compression has been described [10].

  • It may be asymptomatic, but pain and limb deformity may occur and can be very debilitating. Different reports have indicated efficacy of bisphosphonates (pamidronate and etidronate) on symptoms.[ncbi.nlm.nih.gov]
  • […] families with osteopoikilosis and that is characterized by a variable presentation of limb pain and deformities.EpidemiologyLess than 5 families have been reported in the literature to date.Clinical descriptionAs osteopoikilosis is a benign, usually asymptomatic[malacards.org]
Renal Artery Stenosis
  • This unusual condition can also be associated with nephrotic syndrome, carpal tunnel syndrome and renal artery stenosis ( Roger et al. 1994 ; Igiesias et al. 1994 ).[doi.org]
  • Renal artery stenosis associated with melorheostosis. Pediatr Nephrol. 1994; 8(4):441-443. Murphy M, Kearns S, Cavanagh M, O’Connell D, Hurson B. Occurrence of osteosarcoma in a melorheostotic femur. Ir Med J. 2003; 96(2):55-56.[healio.com]
  • Gaudio, Teresa Mattina, Fiorella Gurrieri, Antonio Percesepe, Iria Neri, Annalucia Virdi, Morena Tremosini, Annamaria Milanesi, Evelise Brizola, Elena Pedrini and Luca Sangiorgi, Melorheostosis and Osteopoikilosis Clinical and Molecular Description of an Italian[doi.org]
Respiratory Insufficiency
  • She ultimately died of global respiratory insufficiency. In patients with melorheostosis, involvement of the soft tissue can result in distinctive morbidity, and whenever possible, treatment should be conservative.[ncbi.nlm.nih.gov]
Pleural Effusion
  • This resulted in a clear reduction of pleural effusions, but her medical condition subsequently worsened due to progressive parenchymatous infiltrates, and increased interlobal pleural effusions.[ncbi.nlm.nih.gov]
Abnormal Gait
  • The second patient presented with abnormal gait but no pain. Radiographs demonstrated endosteal hyperostosis, which were consistent with a mixed picture of melorheostosis and osteopoikilois.[ncbi.nlm.nih.gov]


Plain radiography is the technique of choice to diagnose MRO. Characteristic findings are undulating bone surfaces, cortical hyperostosis and general deformities resulting from growth defects. Cortical bone typically resembles a candle marked by numerous wax droplets and this appearance has lead to alternative designations like candle bone disease or melting wax syndrome. Contrary to an ordinary candle, MRO-associated cortical defects are generally one-sided and segmental. Furthermore and as has been indicated above, unilateral MRO is much more common than bilateral bone dysplasia. In fact, the distribution pattern of sclerotic bone lesions generally corresponds to a single sclerotome. Of note, retrospective analyses have shown that only minor shares of patients show the classical, candle wax-like appearance on radiographic images [3]. In other cases, anomalies rather reminded those of osteoma, osteopathia striata or myositis ossificans. Mixed patterns were also observed. Moreover, calcifications of the overlying soft tissue are frequently seen in plain radiography.

Magnetic resonance imaging and computed tomography scans may be conducted but provide little additional information unless MRO affects the spine. Here, precise localization of MRO lesions can be much more easily achieved with those techniques than with plain radiography. Magnetic resonance imaging may also be helpful if patients present extensive soft tissue lesions. If bone scintigraphy is carried out, focal accumulation of technetium-99m has to be expected.

Laboratory analyses of blood samples, i.e., measurement of calcium, phosphorus and alkaline phosphatase, has been proven little helpful in MRO diagnosis. Those parameters are usually within reference ranges. However, more specific parameters like transforming growth factor β, osteonectin, fibronectin and fibroblast growth factor-23 may be altered [11]. This may be partially explained by the fact that MRO patients carry a LEMD3 gene which encodes for a defective protein that is unable to adequately regulate transforming growth factor β and bone morphogenic protein signaling.

Alkaline Phosphatase Decreased
  • Following treatment with bisphosphonate (30 mg/day of pamidronate for 6 days) infusion, the pain and swelling of his right foot showed improvement and his elevated serum alkaline phosphatase decreased.[ncbi.nlm.nih.gov]
Pleural Effusion
  • This resulted in a clear reduction of pleural effusions, but her medical condition subsequently worsened due to progressive parenchymatous infiltrates, and increased interlobal pleural effusions.[ncbi.nlm.nih.gov]


Specific treatment for MRO is not available, but patients may benefit considerably from symptomatic therapy. Only general recommendations can be given to this end since MRO patients may report very different complaints. These largely depend on the affected bone(s), compromised joints and soft tissues, and on the overall severity of the disease.

  • Most patients require analgesics, at least during episodes of intense pain. Non-steroidal anti-inflammatory drugs are most commonly prescribed, but tend to lose efficacy over time. Steroids and opioid analgesics may constitute alternatives, but possible side effects should be considered before resorting to these compounds. In the case of intractable pain, nerve blocks or sympathectomy may become necessary [12]. The need for amputation because of MRO-induced pain has been described.
  • Physiotherapy is probably helpful in all cases; it may not be sufficient if people suffer from severe MRO, though. This measure aims at improving joint motion ranges and long-term therapeutic approaches may even reduce contractures.
  • In the case of severe lesions, more invasive interventions may be required. This applies particularly to patients who present with shortened limbs, deformities or contractures. Surgery may considerably improve life quality and prevent from a progression of secondary orthopedic issues like joint disorders.
  • Casts, braces, and other orthopedic devices are recommended if needed.


In most cases, MRO-associated symptoms worsen over time. Causative treatment is not available. Nevertheless, medical and surgical care, physiotherapy and use of orthopedic devices usually cause symptomatic relieve and improve life quality. Despite considerable morbidity, MRO does not diminish life expectancy. Osteosarcoma and malignant fibrous histiocytoma have been reported to develop in melorheostotic bones, but due to low case numbers, a mere coincidence cannot be ruled out. Fatal outcomes have been reported very rarely. The death of a young woman diagnosed with MRO occurred after respiratory failure [8]. This patient did suffer from multiple additional pathologies, though.


Retrospective analysis of reported MRO cases revealed that most patients suffer from unilateral bone lesions that are typically restricted to a particular segment of the appendicular or axial skeleton - namely to determined sclerotomes. A sclerotome comprises those parts of a bone that are innervated by a single spinal nerve [2]. If a patient suffers from more extensive lesions, these may correspond to an involvement of multiple, generally neighboring sclerotomes. These observations imply developmental defects to account for MRO. To date, it is not known why such defects are restricted to determined sclerotomes. Mosaicism and nerve infection during embryonic development have been proposed as possible triggers [3]. These events may be related to defective intramembranous or endochondral ossification or vascular malformations. The fact that MRO patients may suffer from edema due to vascular function impairment argues for the latter hypothesis.

More recently, mutations in the LEMD3 gene have been associated with MRO. This gene encodes for an eponymous protein which fulfills regulatory functions. In detail, the LEMD3 protein is located at the inner surface of the nuclear membrane and affects transforming growth factor β, bone morphogenic protein and subsequent SMAD protein signaling [4]. These pathways regulate gene expression and thus influence cell growth, differentiation, and proliferation as well as apoptosis. Of note, LEMD3 gene mutations have also been related to other sclerosing dysplasias such as osteopoikilosis and Buschke-Ollendorff syndrome [5]. Either of those diseases may co-occur with MRO. It has to be noted though that the same authors that first described LEMD3 mutations in MRO patients refuted their own theory in a later study. The vast majority of cases is sporadic and LEMD3 mutations could no be detected in 12 unrelated patients suffering from MRO; LEMD3 germline mutations have been identified only in patients diagnosed with concurrent MRO and Buschke-Ollendorff syndrome [6].


Despite an estimated annual incidence of 0.9 per 1,000,000 inhabitants [7], only a few hundred cases have been reported to date. This apparent contradiction cannot be explained by a large share of asymptomatic patients since according to current knowledge, about 50% of affected individuals manifest symptoms during their first two decades of life.

No gender predilection has been reported.

Sex distribution
Age distribution


MRO is a type of sclerosing bone dysplasia that additionally affects adjacent soft tissues. According to the above-described hypothesis, transforming growth factor β and bone morphogenic protein signaling are dysregulated due to a defective LEMD3 protein. In general, transforming growth factor β favors differentiation over proliferation and has a proapoptotic effect. Bone morphogenic proteins play important roles in embryonic skeletal formation. These facts seem to agree with a potential modification of intramembranous and endochondral ossification, but according to latest findings, LEMD3 mutations only play a minor role in MRO pathogenesis [6]. Disturbed signaling pathways are apparently not restricted to osseous tissues, and MRO patients may present considerable vascular and dermatological lesions. Unfortunately, this still leaves massive room for speculation about signaling cascades implied in MRO pathogenesis. Histopathological analyses have been conducted and may narrow down the possibilities. Respective studies revealed increases in both bone formation and bone resorption. There is abundant non-mineralized osteoid in MRO bone specimens, but osteoclast counts are also incremented. Further target-oriented research regarding MRO pathophysiology is largely dependent on the identification of the causative factors of the disease.


No specific measures can be recommended to prevent MRO.


Melorheostosis (MRO) is a rare type of bone dysplasia. Only a few hundred cases have been described so far, with first reports dating back to the early 20th century. French neurologist André Léri and his colleague Joanny published their description of a "flowing hyperostosis comprising the whole length of a member" and suggested the name that's still used today [1].

Pathologic alterations in bone structure are the most characteristic signs of MRO. Cortical thickening and superficial irregularities that remind of dripping candle wax are most typical. However, MRO does also affect the overlying soft tissues, namely tendons, muscles, vessels, loose connective tissue, and skin. Bones of hands and feet are most frequently affected and lesions generally span joints. In fact, MRO typically shows a sclerotomal distribution pattern, i.e., only parts of the skeleton innervated by a single, sensory spinal nerve show the above-described lesions.

Affected individuals suffer from muscle and joint contractures, deformities of the respective parts of the skeleton and consequent orthopedic problems and disability. Circumscribed or linear scleroderma and hyperpigmentation are also readily palpable and observable. Such signs may be noted in infants, as early as during the first few days of life, but generally manifest during childhood or adolescence. In some cases, symptom onset does not occur until adulthood.

The etiology of the disease is still unclear. The aforementioned sclerotomal distribution pattern indicates a developmental defect restricted to an individual spinal nerve. Distinct hypotheses regarding possible triggers have been proposed and recently, MRO has been related to a gene defect. However, MRO is a non-hereditary disease and if gene mutations contribute to MRO pathogenesis, they are most likely not germline mutations.

Causative treatment is not available. Depending on the severity of the disease, patients may receive analgesics, may be referred to physiotherapy or surgery. Orthopedic measures may be indicated.

Patient Information

Melorheostosis (MRO) is a rare type of bone dysplasia. Its precise causes are unknown, but disturbances in embryonic development are assumed to contribute to osseous lesions.

Symptom onset typically occurs during childhood or adolescence but may be observed at any age. In detail, affected individuals may claim persistent or intermittent chronic pain as well as decreased mobility of compromised joints. In more severe cases, these processes result in considerable deformities like an unequal length of limbs. These complaints result from pathological alterations of determined bones and overlying soft tissue. With regards to the latter, tendon and muscle contractures, hardening of the skin and hyperpigmentation are frequently observed.

The limbs are most frequently affected, but MRO may also account for lesions of the axial skeleton, namely the vertebral column, sternum, ribs, and pelvis. In most cases, MRO patients present unilateral symptoms that are restricted to a well-defined part of the arm or leg.

MRO diagnosis is based on plain radiography. In fact, affected bones may resemble a candle marked by numerous wax droplets - a very characteristic finding that led to the alternative denomination candle bone disease.

Treatment is symptomatic and has to be adjusted to the needs of each individual patient. In general, medication may be prescribed to relieve pain, surgery may be necessary to correct deformities. Most patients will be referred to physiotherapy in order to improve joint motion ranges.



  1. Léri A, Joanny J. Une affection non decrite des os: hyperostose “en coulee” sur toute la longueur d’un membre ou “melorheostose”. Bull Mem Soc Med Hosp Paris. 1922; 46:1141-1145.
  2. Murray RO, McCredie J. Melorheostosis and the sclerotomes: a radiological correlation. Skeletal Radiol. 1979; 4(2):57-71.
  3. Freyschmidt J. Melorheostosis: a review of 23 cases. Eur Radiol. 2001; 11(3):474-479.
  4. Lin F, Morrison JM, Wu W, Worman HJ. MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and Smad3 and antagonizes transforming growth factor-beta signaling. Hum Mol Genet. 2005; 14(3):437-445.
  5. Hellemans J, Preobrazhenska O, Willaert A, et al. Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. Nat Genet. 2004; 36(11):1213-1218.
  6. Hellemans J, Debeer P, Wright M, et al. Germline LEMD3 mutations are rare in sporadic patients with isolated melorheostosis. Hum Mutat. 2006; 27(3):290.
  7. Suresh S, Muthukumar T, Saifuddin A. Classical and unusual imaging appearances of melorheostosis. Clin Radiol. 2010; 65(8):593-600.
  8. Kalbermatten NT, Vock P, Rufenacht D, Anderson SE. Progressive melorheostosis in the peripheral and axial skeleton with associated vascular malformations: imaging findings over three decades. Skeletal Radiol. 2001; 30(1):48-52.
  9. Motimaya AM, Meyers SP. Melorheostosis involving the cervical and upper thoracic spine: radiographic, CT, and MR imaging findings. AJNR Am J Neuroradiol. 2006; 27(6):1198-1200.
  10. 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(8):e27-29.
  11. Kerkeni S, Chapurlat R. Melorheostosis and FGF-23: is there a relationship? Joint Bone Spine. 2008; 75(4):486-488.
  12. Meyr AJ, Diprimio R. Lower-extremity sclerotomes: clinical applications and the modified mayo block. J Am Podiatr Med Assoc. 2009; 99(3):232-235.

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Last updated: 2019-07-11 22:02