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Acta Reumatologica Portuguesa 2020
Topics: Humans; Male; Melorheostosis; Middle Aged; Trigger Finger Disorder
PubMed: 32578577
DOI: No ID Found -
Revista Brasileira de Ortopedia 2013Melorheostosis is a rare disease (0.9/million habitants), characterized by linear hyperostosis along the cortex bone. It can affect any bone, being more frequent in long... (Review)
Review
Melorheostosis is a rare disease (0.9/million habitants), characterized by linear hyperostosis along the cortex bone. It can affect any bone, being more frequent in long bones. The lesions tend to be segmental and unilateral. The etiology remains unknown although several theories proposed over the past year (vascular, inflammatory processes, embryonic defects or genetic). Show no significant difference between sexes or heredity. Clinical manifestations are mainly pain, deformity and joint stiffness. The diagnosis is obtained by combining the clinical findings with imaging studies (mainly radiography with typical image in "candle wax"). There is no definitive or specific treatment, being always palliative. We describe a case of a patient of twenty-four years, followed in Orthopedic consultation since age eight, with a deformity of the right side of the body. X-rays showed hyperostosis of the bones of the limbs in the right side of the body (image in "candle wax"). The patient is in physical therapy program and has a positive response to analgesia with ibuprofen.
PubMed: 31214547
DOI: 10.1016/j.rboe.2012.07.007 -
The Pan African Medical Journal 2014
Topics: Adult; Female; Humans; Knee Joint; Melorheostosis; Pain
PubMed: 25883741
DOI: 10.11604/pamj.2014.19.314.5328 -
Journal of Bone and Mineral Research :... Dec 2023Patients with classical melorheostosis exhibit exuberant bone overgrowth in the appendicular skeleton, resulting in pain and deformity with no known treatment. Most...
Patients with classical melorheostosis exhibit exuberant bone overgrowth in the appendicular skeleton, resulting in pain and deformity with no known treatment. Most patients have somatic, mosaic mutations in MAP2K1 (encoding the MEK1 protein) in osteoblasts and overlying skin. As with most rare bone diseases, lack of affected tissue has limited the opportunity to understand how the mutation results in excess bone formation. The aim of this study was to create a cellular model to study melorheostosis. We obtained patient skin cells bearing the MAP2K1 mutation (affected cells), and along with isogenic control normal fibroblasts reprogrammed them using the Sendai virus method into induced pluripotent stem cells (iPSCs). Pluripotency was validated by marker staining and embryoid body formation. iPSCs were then differentiated to mesenchymal stem cells (iMSCs) and validated by flow cytometry. We confirmed retention of the MAP2K1 mutation in iMSCs with polymerase chain reaction (PCR) and confirmed elevated MEK1 activity by immunofluorescence staining. Mutation-bearing iMSCs showed significantly elevated vascular endothelial growth factor (VEGF) secretion, proliferation and collagen I and IV secretion. iMSCs were then differentiated into osteoblasts, which showed increased mineralization at 21 days and increased VEGF secretion at 14 and 21 days of differentiation. Administration of VEGF to unaffected iMSCs during osteogenic differentiation was sufficient to increase mineralization. Blockade of VEGF by bevacizumab reduced mineralization in iMSC-derived affected osteoblasts and in affected primary patient-derived osteoblasts. These data indicate that patient-derived induced pluripotent stem cells recreate the elevated MEK1 activity, increased mineralization, and increased proliferation seen in melorheostosis patients. The increased bone formation is driven, in part, by abundant VEGF secretion. Modifying the activity of VEGF (a known stimulator of osteoblastogenesis) represents a promising treatment pathway to explore. iPSCs may have wide applications to other rare bone diseases. © 2023 American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Bone and Bones; Cell Differentiation; MAP Kinase Kinase 1; Melorheostosis; Osteogenesis; Vascular Endothelial Growth Factor A
PubMed: 37737377
DOI: 10.1002/jbmr.4915 -
Radiology Case Reports Nov 2020Melorheostosis is a rare sclerosing bone dysplasia that most commonly affects the lower extremity long bones in a sclerotomal distribution. Melorheostosis of the spine...
Melorheostosis is a rare sclerosing bone dysplasia that most commonly affects the lower extremity long bones in a sclerotomal distribution. Melorheostosis of the spine is a particularly rare manifestation of this disease. In the appendicular skeleton, melorheostosis has a pathognomonic imaging appearance of flowing hyperostosis resembling melted candle wax flowing down the margins of a candlestick. In the spine, it can have a variety of imaging manifestations from unilateral focal sclerotic lesions resembling enostoses, to more bulky and deformative hyperostosis that span and fuse multiple adjacent spinal segments. This combination of nonaggressive radiologic features makes melorheostosis a particularly important diagnosis for radiologists to understand so that they may spare their patients unnecessary biopsy. Here we present the clinical features and computed tomography findings in a 33-year-old male with spinal melorheostosis involving the first and second cervical vertebrae.
PubMed: 32994853
DOI: 10.1016/j.radcr.2020.09.028 -
Proceedings of the Royal Society of... Jan 1951
Topics: Bones of Lower Extremity; Humans; Leg; Melorheostosis; Tibia
PubMed: 14808238
DOI: No ID Found -
Journal of Bone and Mineral Research :... Jan 2019Melorheostosis is a rare hyperostotic disease of the long bones classically characterized by a "dripping candle-wax" radiographic appearance. We recently described... (Clinical Trial)
Clinical Trial
Melorheostosis is a rare hyperostotic disease of the long bones classically characterized by a "dripping candle-wax" radiographic appearance. We recently described somatic activating mutations in MAP2K1 as a cause of melorheostosis. Here, we report distinguishing characteristics of patients with MAP2K1-positive melorheostosis. Fifteen unrelated patients with radiographic appearance of melorheostosis underwent paired biopsies of affected and unaffected bone for whole-exome sequencing, histology, and cell culture. Eight patients with mutations in MAP2K1 in affected bone were compared to the seven MAP2K1-negative patients to identify distinguishing characteristics. Patients with MAP2K1-positive melorheostosis had a distinct phenotype with classic "dripping candle-wax" appearance on radiographs (p = 0.01), characteristic vascular lesions on skin overlying affected bone (p = 0.01), and higher prevalence of extraosseous mineralization and joint involvement (p = 0.04 for both). Melorheostotic bone from both MAP2K1-positive and MAP2K1-negative patients showed two zones of distinct morphology-an outer segment of parallel layers of primary lamellar bone and a deeper zone of intensely remodeled highly porous osteonal-like bone. Affected bone from MAP2K1-positive patients showed excessive osteoid (p = 0.0012), increased number of osteoblasts (p = 0.012) and osteoclasts (p = 0.04), and increased vascularity on histology in comparison to paired unaffected bone which was not seen in affected bone in most MAP2K1-negative patients. The identification of a distinct phenotype of patients with MAP2K1-positive melorheostosis demonstrates clinical and genetic heterogeneity among patients with the disease. Further studies are needed to better understand the underlying pathophysiology and associated skin findings. © 2018 American Society for Bone and Mineral Research.
Topics: Adult; Aged; Bone and Bones; Female; Humans; MAP Kinase Kinase 1; Male; Melorheostosis; Middle Aged; Mutation; Osteoblasts; Skin; Exome Sequencing
PubMed: 30138550
DOI: 10.1002/jbmr.3577 -
BioMed Research International 2014A rare disease afflicts less than 200,000 individuals, according to the National Organization for Rare Diseases (NORD) of the United States. Over 6,000 rare disorders... (Review)
Review
A rare disease afflicts less than 200,000 individuals, according to the National Organization for Rare Diseases (NORD) of the United States. Over 6,000 rare disorders affect approximately 1 in 10 Americans. Rare genetic bone disorders remain the major causes of disability in US patients. These rare bone disorders also represent a therapeutic challenge for clinicians, due to lack of understanding of underlying mechanisms. This systematic review explored current literature on therapeutic directions for the following rare genetic bone disorders: fibrous dysplasia, Gorham-Stout syndrome, fibrodysplasia ossificans progressiva, melorheostosis, multiple hereditary exostosis, osteogenesis imperfecta, craniometaphyseal dysplasia, achondroplasia, and hypophosphatasia. The disease mechanisms of Gorham-Stout disease, melorheostosis, and multiple hereditary exostosis are not fully elucidated. Inhibitors of the ACVR1/ALK2 pathway may serve as possible therapeutic intervention for FOP. The use of bisphosphonates and IL-6 inhibitors has been explored to be useful in the treatment of fibrous dysplasia, but more research is warranted. Cell therapy, bisphosphonate polytherapy, and human growth hormone may avert the pathology in osteogenesis imperfecta, but further studies are needed. There are still no current effective treatments for these bone disorders; however, significant promising advances in therapeutic modalities were developed that will limit patient suffering and treat their skeletal disabilities.
Topics: Bone Diseases; Bone and Bones; Humans; Osteogenesis; Rare Diseases
PubMed: 25530967
DOI: 10.1155/2014/670842 -
Cureus Jun 2020Melorheostosis is a very rare bone dysplasia, especially in the hand. Most cases were diagnosed incidentally, with the lower limbs being the most affected. This is the...
Melorheostosis is a very rare bone dysplasia, especially in the hand. Most cases were diagnosed incidentally, with the lower limbs being the most affected. This is the first Saudi woman with hand melorheostosis. A 33-year-old Saudi female had mild to moderate right-hand pain that started six years ago. Hand examination showed a full range of motion and full hand grip, and there was no tenderness upon palpation. Plain X-ray, unenhanced CT scan, and MRI of the hand showed an appearance resembling dripping candle wax as melorheostosis. The bone scan showed a nonvascular and nonacute lesion. An unenhanced CT scan demonstrated cortical and endosteal hyperostosis involving the proximal, middle, and distal third and fourth phalanges. Multi-sequential MRI of the hand demonstrated cortical hyperostosis involving the ulnar and radial aspect of the right fourth proximal, middle, and distal phalanges. Features in the X-ray, CT scan, bone scan, and MRI confirmed a diagnosis of melorheostosis with associated flexor tenosynovitis.
PubMed: 32626632
DOI: 10.7759/cureus.8877 -
Annals of Saudi Medicine 2014Melorheostosis is an uncommon, sporadic, sclerosing bone lesion that may affect the adjacent soft tissues. It has been associated with many entities such as...
Melorheostosis is an uncommon, sporadic, sclerosing bone lesion that may affect the adjacent soft tissues. It has been associated with many entities such as osteopoikilosis, soft tissue vascular malformations, bone and soft tissue tumors, nephrotic syndrome, segmental limb contractures, osteosarcoma, desmoid tumor, and mesenteric fibromatosis. Synovial osteochondromatosis is a benign neoplasia of the hyaline cartilage presenting as nodules in the subsynovial tissue of a joint or tendon sheath. The intra-articular extension of melorheostosis mimicking synovial osteochondromatosis has not been reported before. In this article, the authors describe an unusual case mimicking synovial chondromatosis arising as a result of melorheostosis and their characteristic imaging findings.
Topics: Chondromatosis, Synovial; Diagnosis, Differential; Female; Humans; Knee Joint; Magnetic Resonance Imaging; Melorheostosis; Middle Aged
PubMed: 25971832
DOI: 10.5144/0256-4947.2014.547