Atypical form of active melorheostosis and its treatment with bisphosphonate

Donáth, Judit; Poór, Gyula; Kiss, Csaba; Fornet, B; Genant, Harry K.

doi:10.1007/s00256-002-0576-y

Cited by 41 publications

(24 citation statements)

References 13 publications

(18 reference statements)

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“…OPK/BOS‐associated MEL is especially rare, but understandably reported because of its intriguing nature. There may be differences between classic, sporadic MEL, sporadic MEL occurring in mixed‐sclerosing‐bone‐ dystrophy, OPK/BOS‐associated MEL, and MEL occurring in other unusual presentations (31–34) . The etiology of any form of MEL remains unknown (35)…”

Section: Discussionmentioning

confidence: 99%

Deactivating Germline Mutations in LEMD3 Cause Osteopoikilosis and Buschke-Ollendorff Syndrome, but Not Sporadic Melorheostosis

Mumm

Wenkert

Zhang

et al. 2007

Journal of Bone and Mineral Research

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Autosomal dominant OPK and BOS feature widespread foci of osteosclerotic trabeculae without or with skin lesions, respectively. Occasionally, a larger area of dense bone in OPK or BOS resembles MEL, a sporadic sclerosing disorder primarily involving cortical bone. Others, finding deactivating germline LEMD3 mutations in OPK or BOS, concluded such defects explain all three conditions. We found germline LEMD3 mutations in OPK and BOS but not in sporadic MEL. Introduction:In 2004, others discovered that heterozygous, loss-of-function, germline mutations in the LEMD3 gene (LEMD3 or MAN1) cause both osteopoikilosis (OPK) and Buschke-Ollendorff syndrome (BOS). OPK is an autosomal dominant, usually benign, skeletal dysplasia featuring multiple, small, especially metaphyseal, oval or round, dense trabecular foci distributed symmetrically throughout the skeleton. BOS combines OPK with connective tissue nevi comprised of collagen and elastin. In some OPK and BOS families, an individual may have relatively large, asymmetric areas of dense cortical bone interpreted as melorheostosis (MEL). MEL, however, classically refers to a sporadic, troublesome skeletal dysostosis featuring large, asymmetric, "flowing hyperostosis" of long bone cortices often with overlying, constricting soft tissue abnormalities. However, a heterozygous germline mutation in LEMD3 was offered to explain MEL. Materials and Methods: We studied 11 unrelated individuals with sclerosing bone disorders where LEMD3 mutation was a potential etiology: familial OPK (1), familial BOS (2), previously reported familial OPK with MEL (1), sporadic MEL (3), sporadic MEL with mixed-sclerosing-bone dystrophy (1), and patients with other unusual sclerosing bone disorders (3). All coding exons and adjacent mRNA splice sites for LEMD3 were amplified by PCR and sequenced using genomic DNA from leukocytes. We did not study lesional tissue from bone or skin. Results: In the OPK family, a heterozygous nonsense mutation (c.1433T>A, p.L478X) was discovered in exon 1. In the two BOS families, a heterozygous nonsense mutation (exon 1, c.1323C>A, p.Y441X) and a heterozygous frame-shift mutation (exon 1, c.332_333insTC) were identified. In the individual with MEL and familial OPK, a heterozygous nonsense mutation (c.1963C>T, p.R655X) was detected in exon 7. However, no LEMD3 mutation was found for any other patient, including all four with sporadic MEL. Conclusions: We confirm that OPK and BOS individuals, including those with MEL-like lesions, have heterozygous, deactivating, germline LEMD3 mutations. However, MEL remains of unknown etiology.

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Section: Discussionmentioning

confidence: 99%

Deactivating Germline Mutations in LEMD3 Cause Osteopoikilosis and Buschke-Ollendorff Syndrome, but Not Sporadic Melorheostosis

Mumm

Wenkert

Zhang

et al. 2007

Journal of Bone and Mineral Research

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“…Donath et al described a case of melorheostosis with extensive bilateral disease and elevated alkaline phosphatase where the patient was treated with 30 mg of pamidronate daily for 6 days which resulted in a rapid improvement in symptoms. 23 It is recognised that osteonecrosis of jaw is common, although still very rare, with bisphosphonate treatment. Therefore it is important to ensure good dental hygiene and adequate 25-hydroxy vitamin D levels prior to administering intravenous bisphosphonates due to the increased risk of osteonecrosis of the jaw.…”

Section: -4mentioning

confidence: 99%

Localised melorheostosis

Agarwal¹,

Khanna²,

Varghese³

et al. 2017

Int J Res Orthop

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<p class="abstract"><span lang="EN-IN">Melorheostosis is a sclerosing bone dysplasia of unknown aetiology. Diagnosis is mainly based on a combination of clinical and imaging studies. The classical dripping candle wax picture on plain radiograph is diagnostic. We report a case of localized melorheostosis of a 14 year old boy on daily analgesics for two years for pain relief. Radiographs showed endosteal bone formation like dripping candle wax. Biopsy and decompression of the hyperostosis was done. However biopsy did not relieve his symptoms. Based on literature survey he was given a single infusion of zoledronic acid. This gave dramatic relief in pain.</span></p>

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“…Treatment options have remained rather limited and include surgical interventions such as tendon lengthening, excision of soft tissue masses, release of joint contractures and occasionally amputation. There have been a few case reports documenting the use of bisphosphonates7 – 9 but we report for the first time the successful and prolonged benefit of intravenous zoledronic acid in the symptomatic treatment of melorheostosis.…”

Section: Introductionmentioning

confidence: 78%

Melorheostosis and its treatment with intravenous zoledronic acid

Hollick¹,

Black

Reid

2010

Case Reports

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We report a case of melorheostosis, a rare bone disorder characterised by mesodermal dysplasia, and its successful and prolonged treatment with the intravenous bisphosphonate zoledronic acid. The middle-aged man presented with pain and swelling of his tibia, which was diagnosed by imaging and bone biopsy as being due to melorheostosis. There was early symptom control after a single infusion of intravenous zoledronic acid. Prolonged symptom relief was accompanied by long-term suppression of the bone resorption marker β cross-laps. We suggest that melorheostosis can be treated with intravenous zoledronic acid and that treatment can be monitored by the use of a specific bone resorption marker.

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Atypical form of active melorheostosis and its treatment with bisphosphonate

Cited by 41 publications

References 13 publications

Deactivating Germline Mutations in LEMD3 Cause Osteopoikilosis and Buschke-Ollendorff Syndrome, but Not Sporadic Melorheostosis

Deactivating Germline Mutations in LEMD3 Cause Osteopoikilosis and Buschke-Ollendorff Syndrome, but Not Sporadic Melorheostosis

Localised melorheostosis

Melorheostosis and its treatment with intravenous zoledronic acid

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