-
Medicina 2023
Topics: Humans; Melorheostosis; Diagnosis, Differential
PubMed: 37870352
DOI: No ID Found -
Journal of Clinical Imaging Science 2022Melorheostosis is a rare bone dysplasia of unknown etiology with an incidence of 0.9 cases per million. It typically affects the upper or lower limbs and can cause...
Melorheostosis is a rare bone dysplasia of unknown etiology with an incidence of 0.9 cases per million. It typically affects the upper or lower limbs and can cause severe deformity and functional impairment. Diagnosis is radiological and is often described as a "flowing candle wax" appearance on the radiograph. Treatment is individualized depending on the site and severity of symptoms. We report a rare case of spinal melorheostosis. We demonstrate the imaging features of melorheostosis on CT and MRI. We discuss the classification, genetics, and management of this condition.
PubMed: 35251764
DOI: 10.25259/JCIS_202_2021 -
Bone May 2020Etidronate is a non-nitrogen-containing bisphosphonate. Because it binds with calcium and inhibits crystal formation and dissolution, it was considered by Procter &...
Etidronate is a non-nitrogen-containing bisphosphonate. Because it binds with calcium and inhibits crystal formation and dissolution, it was considered by Procter & Gamble as an additive to toothpaste (to prevent build-up of tartar) and detergent (to bind calcium and increase sudsing in "hard" water). The first clinical use (1968) was for fibrodysplasia ossificans progressiva. The first approved clinical use (1977) was for treatment of Paget's disease of bone. Other approved indications are hypercalcemia of malignancy and heterotopic ossification, with a host of off-label uses (including fibrous dysplasia, periodontal disease, multiple myeloma, neuropathic arthropathy, pulmonary microlithiasis, diabetic retinopathy, bone metastases, melorheostosis, urinary stone disease, periodontal disease, etc.). Unique among bisphosphonates, etidronate (oral therapy) results in hyperphosphatemia, increased tubular reabsorption of phosphorus and increased levels of 1,25-dihydroxyvitamin D. The dose that reduces bone resorption is close to the dose that impairs mineralization; prolonged high-dose use can result in osteomalacia and bone fractures. Intermittent cyclic etidronate for osteoporosis resulted in favorable changes in bone density and histomorphometry (no mineralization defect) as well as a decrease in vertebral fracture rates in postmenopausal women with osteoporosis. Later studies showed similar effects in men with osteoporosis and patients with glucocorticoid-induced osteoporosis. Although its use for osteoporosis has given way to newer bisphosphonates and other agents, because of its unique properties, it remains the bisphosphonate of choice for treatment of heterotopic ossification.
Topics: Bone Density; Bone Density Conservation Agents; Diphosphonates; Etidronic Acid; Female; History, 20th Century; History, 21st Century; Humans; Male; Osteitis Deformans; Osteoporosis; Osteoporosis, Postmenopausal
PubMed: 31911206
DOI: 10.1016/j.bone.2020.115222 -
Calcified Tissue International May 2019Melorheostosis is an exceptionally rare sclerosing hyperostosis that typically affects the appendicular skeleton in a limited segmental fashion. It occasionally occurs... (Review)
Review
Melorheostosis is an exceptionally rare sclerosing hyperostosis that typically affects the appendicular skeleton in a limited segmental fashion. It occasionally occurs on a background of another benign generalised sclerosing bone condition, known as osteopoikilosis caused by germline mutations in LEMD3, encoding the inner nuclear membrane protein MAN1, which modulates TGFβ/bone morphogenetic protein signalling. Recent studies of melorheostosis lesional tissue indicate that most cases arise from somatic MAP2K1 mutations although a small number may arise from other genes in related pathways, such as KRAS. Those cases associated with MAP2K1 mutations are more likely to have the classic "dripping candle wax" appearance on radiographs. The relationship between these somatic mutations and those found in a variety of malignant conditions is discussed. There are also similar germline mutations involved in a group of genetic disorders known as the RASopathies (including Noonan syndrome, Costello syndrome and various cardiofaciocutaneous syndromes), successful treatments for which could be applied to melorheostosis. The diagnosis and management of melorheostosis are discussed; there are 4 distinct radiographic patterns of melorheostosis and substantial overlap with mixed sclerosing bone dysplasia. Medical treatments include bisphosphonates, but definitive guidance on their use is lacking given the small number of patients that have been studied. Surgical intervention may be required for those with large bone growths, nerve entrapments, joint impingement syndromes or major limb deformities. Bone regrowth is uncommon after surgery, but recurrent contractures represent a major issue in those with extensive associated soft tissue involvement.
Topics: Bone Morphogenetic Proteins; Bone and Bones; DNA-Binding Proteins; Diagnosis, Differential; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; MAP Kinase Kinase 1; Melorheostosis; Membrane Proteins; Osteopoikilosis; Proto-Oncogene Proteins p21(ras); Signal Transduction; Transforming Growth Factor beta
PubMed: 30989250
DOI: 10.1007/s00223-019-00543-y -
Current Osteoporosis Reports Aug 2017Melorheostosis is a rare sclerosing bone dysplasia that affects both cortical bone and adjacent soft tissue structures in a sclerotomal distribution. In this review, we... (Review)
Review
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.
Topics: Bone and Bones; DNA-Binding Proteins; Humans; Joint Capsule Release; Melorheostosis; Membrane Proteins; Mutation; Nuclear Proteins; Osteotomy; Pain Management; Radiography; Rare Diseases; Tenotomy
PubMed: 28676968
DOI: 10.1007/s11914-017-0375-y -
Foot (Edinburgh, Scotland) Jun 2017
Review
Topics: Ankle; Conservative Treatment; Disease Progression; Foot; Foot Deformities, Acquired; Humans; Male; Melorheostosis; Middle Aged; Radiography; Risk Assessment; Severity of Illness Index
PubMed: 28544914
DOI: 10.1016/j.foot.2017.02.004 -
Case Reports in Oncology 2023Melorheostosis is a rare benign bone pathology involving bone dysplasia and hyperostosis. The disease can be recognized with a characteristic radiographic feature of...
Melorheostosis is a rare benign bone pathology involving bone dysplasia and hyperostosis. The disease can be recognized with a characteristic radiographic feature of radiopaque lesions dripping along a long bone's diaphysis. The aberrant bone formation and development manifests mainly as pain, edema, and paresthesia of the affected limb. Severe cases may report limb deformity as well as limited range of motion. Until now, there have been approximately 300 cases reported about melorheostosis worldwide and its diverse clinical picture and age distribution. In Vietnam, there is only one known case of melorheostosis discovered incidentally via radiography. The scarcity of cases presents a challenge within the medical community in recognizing and diagnosing the condition, and a delayed diagnosis can lead to severe contracture and compromised limb motility. In this article, we reported an 82-year-old case of polyostotic melorheostosis with late onset and predominant edema, affecting the sternum, the ribs, and multiple bones of the right extremities and presented our clinical approach for a geriatric patient with chronic limb edema. Our case is distinctive in terms of anatomical location as well as the predominant 20-year non-pitting edema. A prompt diagnosis was made upon the classic dripping candle wax radiographic features emphasizing the role of plain X-ray in establishing the diagnosis without extraneous utilization of other modalities and invasive procedures. Exclusion of other causes of chronic edema such as lymphadenopathy, malignancy as well as parasitic infection is of clinical importance.
PubMed: 38130895
DOI: 10.1159/000534241 -
PM & R : the Journal of Injury,... May 2023Melorheostosis is a rare bone disorder with limited literature that describes the effect of this disease on functional and motor abilities. As part of a natural history... (Observational Study)
Observational Study
INTRODUCTION
Melorheostosis is a rare bone disorder with limited literature that describes the effect of this disease on functional and motor abilities. As part of a natural history study, four outcome measures were administered to better understand the burden this disease has on a person's ability to engage in basic and instrumental activities of daily living.
OBJECTIVE
To investigate the relationship between functional engagement, fatigue, and motor ability in patients with melorheostosis.
DESIGN
Cross-sectional data gathered from a longitudinal natural history observational study.
SETTING
Rehabilitation department within a single institution.
PARTICIPANTS
Forty-seven adult volunteers with melorheostosis were enrolled. Two participants were removed for failure to meet diagnosis eligibility. Thirty patients had lower extremity (LE) osteosclerotic bone lesions, 14 had upper extremity (UE) lesions, and one had lesions in both UEs and LEs.
INTERVENTIONS
Not applicable.
MAIN OUTCOME MEASURES
Activity Card Sort, Second Edition (ACS); Multi-Dimensional Fatigue Inventory; Lower Extremity Functional Scale; Upper Extremity Functional Index.
RESULTS
On the ACS, high-demand leisure (HDL) activities were the least retained (p < .001). Of the activities rated most important, HDL activities were the most likely to have been given up (27%). General fatigue (μ = 11.8) and physical fatigue (μ = 11.0) were the two most limiting fatigue constructs. There were moderate negative correlations with HDL activities compared to physical fatigue (r = -0.524, p < .001) and reduced activity fatigue (r = -0.58, p = .001). LE lesions had a large effect on completing LE tasks (d = 0.95) and UE lesions had a medium effect on completing tasks involving the UE (d = 0.69).
CONCLUSIONS
Patients with melorheostosis experience fatigue and low engagement in HDL activities. The results of this study underscore the importance of acknowledging activity domain, fatigue constructs, and lesion location to support and provide targeted evidence-based rehabilitative therapy.
CLINICAL TRIAL REGISTRATION NUMBER
NCT02504879.
Topics: Adult; Humans; Activities of Daily Living; Cross-Sectional Studies; Fatigue; Lower Extremity; Melorheostosis; Upper Extremity
PubMed: 35403375
DOI: 10.1002/pmrj.12817 -
Radiologia Brasileira 2015
PubMed: 25798011
DOI: 10.1590/0100-3984.2013.0019 -
International Journal of Molecular... Jul 2021A review of the available literature was performed in order to summarize the existing evidence between osteoblast dysfunction and clinical features in non-hereditary... (Review)
Review
A review of the available literature was performed in order to summarize the existing evidence between osteoblast dysfunction and clinical features in non-hereditary sclerosing bone diseases. It has been known that proliferation and migration of osteoblasts are concerted by soluble factors such as fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF), bone morphogenetic protein (BMP) but also by signal transduction cascades such as Wnt signaling pathway. Protein kinases play also a leading role in triggering the activation of osteoblasts in this group of diseases. Post-zygotic changes in mitogen-activated protein kinase (MAPK) have been shown to be associated with sporadic cases of Melorheostosis. Serum levels of FGF and PDGF have been shown to be increased in myelofibrosis, although studies focusing on Sphingosine-1-phosphate receptor was shown to be strongly expressed in Paget disease of the bone, which may partially explain the osteoblastic hyperactivity during this condition. Pathophysiological mechanisms of osteoblasts in osteoblastic metastases have been studied much more thoroughly than in rare sclerosing syndromes: striking cellular mechanisms such as osteomimicry or complex intercellular signaling alterations have been described. Further research is needed to describe pathological mechanisms by which rare sclerosing non hereditary diseases lead to osteoblast dysfunction.
Topics: Animals; Bone Morphogenetic Proteins; Fibroblast Growth Factors; Humans; MAP Kinase Signaling System; Melorheostosis; Osteoblasts; Platelet-Derived Growth Factor; Sphingosine-1-Phosphate Receptors
PubMed: 34360745
DOI: 10.3390/ijms22157980