Clinical improvement in a patient with monostotic melorheostosis after treatment with denosumab: a case report

Byberg, Sarah; Abrahamsen, Bo; Kassem, Moustapha; Ralston, Stuart H.; Schwarz, Peter

doi:10.1186/s13256-018-1820-y

Cited by 11 publications

(8 citation statements)

References 16 publications

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“…A significant clinical improvement in symptomatology was presented by Byberg S. et al in a case report of a patient with monostatic melorheostosis following the administration of denosumab [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Melorheostosis: A Review of the Literature and a Case Report

et al. 2023

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Background and Objectives: Melorheostosis, also referred to in the literature as Leri’s disease, is an unusual mesenchymal dysplasia with the clinical appearance of benign sclerosing bone dysplasia; it frequently occurs in late adolescence. Any bone in the skeletal system can be affected by this disease, though the long bones of the lower extremities are the most common, at any age. Melorheostosis has a chronic evolution, and symptoms are usually absent in the early stages. The etiopathogenesis is still unknown, however, numerous theories have been proposed that could explain the appearance of this lesion formation. An association with other benign or malignant bone lesions is also possible, and associations with osteosarcoma, malignant fibrous histiocytoma, or Buschke–Ollendorff syndrome have also been reported. There have also been reported cases of the malignant transformation of a pre-existing melorheostosis lesion into malignant fibrous histiocytoma or osteosarcoma. The diagnosis of melorheostosis can be made only based on radiological images, but, due to its polymorphism, additional imaging investigations are often necessary and sometimes only a biopsy can establish a definite diagnosis. Because there are currently no guidelines for treatment based on scientific evidence, due to the low number of cases diagnosed worldwide, our objective was to highlight the early recognition and specific surgical treatments for better prognosis and outcomes. Materials and Methods: We conducted a review of the literature consisting of original papers, case reports, and case series and presented the clinical and paraclinical characteristics of melorheostosis. We aimed to synthesize the treatment methods available in the literature as well as determine possible future directions related to the treatment of melorheostosis. Furthermore, we presented the results of a case of femoral melorheostosis admitted to the orthopedics department of the University Emergency Hospital of Bucharest in a 46-year-old female patient with severe pain in the left thigh and limitation of joint mobility. Following the clinical examination, the patient complained of pain in the middle third of the left thigh in the antero-medial compartment; the pain appeared spontaneously and was aggravated during physical activity. The pain started about two years prior, but the patient experienced complete pain relief after the administration of non-steroidal anti-inflammatory drugs. In the last six months, the patient presented an increase in pain intensity without significant improvement following the administration of non-steroidal anti-inflammatory drugs. The patient’s symptoms were mainly determined by the increase in the volume of the tumor and the mass effect on the adjacent tissues, especially on the vessels and the femoral nerve. The CT examination and bone scintigraphy showed a unique lesion in the middle third of the left femur and no oncological changes in the thoracic, abdominal, and pelvic regions; however, at the level of the femoral shaft, there was a localized cortical and pericortical bone lesion formation that surrounded approximately 180 degrees of the femoral shaft (anterior, medial, and lateral). It had a predominantly sclerotic structure but was associated with lytic areas with thickening of the bone cortex and areas of periosteal reaction. The next therapeutic gesture was to perform an incisional biopsy using a lateral approach at the level of the thigh. The histopathological result supported the diagnosis of melorheostosis. Additionally, immunohistochemical tests completed the data obtained after the microscopic examination through the classic histopathological technique The patient was discharged and included in a full medical recovery program for eight weeks in a specialized medical center, during which she also received analgesic treatment in maximum doses, but without improvement regarding her symptoms. Taking into account the chronic evolution of the pain, the complete lack of response to conservative treatment after eight weeks, and the lack of treatment guidelines in the case of melorheostosis, a surgical approach needed to be considered. The surgical option in this case, considering the circumferential location of the lesion at the level of the femoral diaphysis, was a radical resection. The surgical approach consisted of segmental resection to healthy bone tissue and reconstruction of the remaining defect with a modular tumoral prosthesis. At the 45-day postoperative control, the patient no longer complained of pain in the operated-on limb and was mobile with full support without gait difficulties. The follow-up period was one year, and the patient presented complete pain relief and a very good functional outcome. Results: In the case of asymptomatic patients, conservative treatment seems to be a good option with optimal results. However, for benign tumors, it remains unclear whether radical surgery is a viable option. Conclusions: Melorheostosis remains an incompletely understood disease, given the limited number of cases worldwide, and thus, there is a lack of clinical guidelines regarding specialized treatment.

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Section: Discussionmentioning

confidence: 99%

Melorheostosis: A Review of the Literature and a Case Report

et al. 2023

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“…Given the high prevalence of nerve entrapment from melorheostotic bone expansion, drugs such as pregabalin and gabapentin may be considered for management of neuropathic pain. The finding of markedly increased ratio of RANKL/OPG transcripts in osteoblasts from affected bone in patients with MAP2K1 ‐positive melorheostosis raises the possibility of using RANKL inhibitors in these patients, although it is possible that the increased ratio of RANKL/OPG transcripts is actually a compensatory mechanism for the dense bone. Case reports describing the use of bisphosphonates resulting in symptomatic and scintigraphic improvement of melorheostosis have also been published .…”

Section: Discussionmentioning

confidence: 99%

Clinical Evaluation of Melorheostosis in the Context of a Natural History Clinical Study

et al. 2019

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Melorheostosis is a rare dysostosis involving cortical bone overgrowth that affects the appendicular skeleton. Patients present with pain, deformities, contractures, range of motion limitation(s), and limb swelling. It has been described in children as well as adults. We recently identified somatic mosaicism for gain‐of‐function mutations in MAP2K1 in patients with melorheostosis. Despite these advances in genetic understanding, there are no effective therapies or clinical guidelines to help clinicians and patients in disease management. In a study to better characterize the clinical and genetic aspects of the disease, we recruited 30 adults with a radiographic appearance of melorheostosis and corresponding increased uptake on 18 F‐NaF positron emission tomography (PET)/CT. Patients underwent physical exam, imaging studies, and laboratory assessment. All patients underwent nerve conduction studies and ultrasound imaging of the nerve in the anatomic distribution of melorheostosis. We found sensory deficits in approximately 77% of patients, with evidence of focal nerve entrapment in five patients. All patients reported pain; 53% of patients had changes in skin overlying the affected bone. No significant laboratory abnormalities were noted. Our findings suggest that patients with melorheostosis may benefit from a multidisciplinary team of dermatologists, neurologists, orthopedic surgeons, pain and palliative care specialists, and physical medicine and rehabilitation specialists. Future studies focused on disease management are needed. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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“…In one case, zoledronate not only improved pain but also reduced bone turnover as judged by scintigraphy; these authors also nicely review the evidence for positive results from etidronate and pamidronate [60]. In a more recent case, the efficacy of bisphosphonates is reviewed and the successful use of denosumab after failure of zoledronate is reported [61]. However, there are potential pitfalls to the excessive use of bisphosphonates in this condition.…”

Section: Managementmentioning

confidence: 97%

Melorheostosis and Osteopoikilosis: A Review of Clinical Features and Pathogenesis

Wordsworth

Chan

2019

Calcif Tissue Int

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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.

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Clinical improvement in a patient with monostotic melorheostosis after treatment with denosumab: a case report

Cited by 11 publications

References 16 publications

Melorheostosis: A Review of the Literature and a Case Report

Melorheostosis: A Review of the Literature and a Case Report

Clinical Evaluation of Melorheostosis in the Context of a Natural History Clinical Study

Melorheostosis and Osteopoikilosis: A Review of Clinical Features and Pathogenesis

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