Sirolimus Therapy as Perioperative Treatment of Gorham-Stout Disease in the Thoracic Spine

Mo, Andrew Z.; Trenor, Cameron C.; Hedequist, Daniel

doi:10.2106/jbjs.cc.17.00287

Cited by 18 publications

(18 citation statements)

References 27 publications

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“…Emerging therapies include the mammalian target of rapamycin (mTOR) inhibitor (Sirolimus) in combination with bisphosphonates to treat the dual face of the disease 30,31 …”

Section: Discussionmentioning

confidence: 99%

Dysregulated miRNAs in bone cells of patients with Gorham‐Stout disease

et al. 2021

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Gorham‐Stout disease (GSD) is a very rare disease characterized by increased bone erosion with angiomatous proliferation. The mechanisms underlying this disorder have not been deeply investigated. Due to its rarity, no guidelines are currently available for treatment and management of GSD. We recently evaluated the cellular alterations of the bone remodeling in patients showing that osteoclast precursors displayed increased ability to differentiate into osteoclasts and that affected osteoclasts resorb bone more actively than control cells. Moreover, osteoblasts isolated from a patient showed a defective ability to form mineralized nodules. In this paper, we investigated the molecular pathways involved in the cellular defects of GSD bone cells. For this study, we recruited nine patients and performed miRNome analysis of bone cells. Between the 178 miRNAs robustly expressed in GSD osteoclasts, significant modulation of three miRNAs (miR‐1246, miR‐1‐3p, and miR‐137‐3p) involved in the regulation of osteoclast formation and activity or in the angiomatous proliferation was found in patients' cells. Interestingly, miR‐1246 was also up‐regulated in serum exosomes from patients. Analysis of miRNAs from patient osteoblasts suggested alteration of miR‐204a‐5p, miR‐615‐3p and miR‐378a‐3p regulating osteoblast function and differentiation. The resulting miRNA pattern may help to understand better the mechanisms involved in GSD and to identify new potential therapeutic targets for this rare disease.

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“…Emerging therapies include the mammalian target of rapamycin (mTOR) inhibitor (Sirolimus) in combination with bisphosphonates to treat the dual face of the disease 30,31 …”

Section: Discussionmentioning

confidence: 99%

Dysregulated miRNAs in bone cells of patients with Gorham‐Stout disease

et al. 2021

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“…In 2016, Triana et al reported a large study on the use of sirolimus on various vascular anomalies: Authors observed an overall successful response in 33 out of 41 patients (80.4%) and specifically 6/7 of the patients affected by GSD responded well (106). Since its first use, sirolimus has been used many other times with good results; in some cases, a decrease of more than a half of the size of the lesion has been observed (107,108,109,110,111).…”

Section: Radiotherapy and Medical Treatmentsmentioning

confidence: 99%

Current concepts from diagnosis to management in Gorham–Stout disease: a systematic narrative review of about 350 cases

et al. 2022

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Patients with Gorham–Stout disease (GSD) present progressive destruction and resorption of bone. Typical bone-related symptoms include swelling, pain and functional impairment in the region involved. The three aspects of GSD etiopathology are osteoclasts, angiogenesis/lymphangiogenesis and osteoblast function. Multi-targeted pharmacological approach includes innovative options and represent milestones of treatment, sometimes associated with radiotherapy. Surgery is mainly used to treat complications: pathologic/impending fractures, spinal instability or deformities and chylothorax. In this narrative review, we highlight current standards in diagnosis, clinical management and therapeutic strategies.

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“…The growth factors VEGF-A and VEGF-C, but also plateletderived growth factor-BB, play a role in the invasion of lymphatic vessels (26). These growth factors signal through the same pathway which ends in the mammalian target of rapamycin (mTor) (27)(28)(29). mTor is an important kinase in the progression of the cell cycle and a key regulator of immune responses.…”

Section: Pathogenesismentioning

confidence: 99%

“…Pharmacological agents that have been reported are bisphosphonates, interferon-a 2b, mTor inhibitors, vitamin D, calcium, calcitonin, anti-VEGF antibodies, bevacizumab, bleomycin, thalidomide, somatostatin, androgens, propranolol, low-molecular-weight heparin, and glucocorticosteroids (3). Patients have been treated with monotherapy, but frequently a combination of drugs has been used, such as bisphosphonates with sirolimus (27) or bisphosphonates with interferon-a-2b (31). Pharmacological treatment is also frequently combined with surgery.…”

Section: Treatmentmentioning

confidence: 99%

A Large Skull Defect Due to Gorham-Stout Disease: Case Report and Literature Review on Pathogenesis, Diagnosis, and Treatment

et al. 2020

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A 24-year old man was referred to the Erasmus MC Bone Center because of an asymptomatic increasing skull defect of the left parietal bone. The defect was first noticed at the age of six, and gradually increased over the years. His medical history was unremarkable, without any known trauma and a negative family history for bone diseases. Laboratory tests showed a low vitamin D level without other abnormalities. Particularly, there was no increase in markers of inflammation or bone turnover. CT-scans of the skull showed an osteolytic region of the parietal skull bone, with a two-centimeter increase in diameter over 9 years. Contrast enhanced MRI showed lymphangiogenic invasion, which was compatible with our suspicion of Gorham-Stout disease. The patient was referred to the neurosurgeon for treatment with a bone graft while considering additional drug treatment. Gorham-Stout or vanishing bone disease is a rare entity characterized by progressive osteolysis with lymphangiogenic bone invasion. Although already reported in 1838, currently the diagnosis and treatment of Gorham-Stout disease is still challenging. The underlying pathophysiology is not clarified yet and several theories exist. The disease usually affects persons younger than 40 years and the majority present with bone disease of the maxillofacial region, the upper extremities or the torso. The clinical presentation includes most frequently pain, swelling, and functional impairment of the affected region, but the disease can also be asymptomatic. Laboratory investigations are usually normal, and diagnosis is based upon imaging and sometimes pathology examination of affected bone tissue. Treatment is experimental and there is no general consensus about the best option due to lack of randomized controlled trials. Case reports showed patients treated with bisphosphonates, interferon-alpha, anti-VEGF therapy, mTOR inhibitors, and radiotherapy. There are some reports of surgery with prosthetic or bone grafts but no long-term follow-up data exist. This paper describes a unique case of Gorham-Stout disease of the parietal skull bone and discusses the current state of knowledge about this rare bone disease.

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Sirolimus Therapy as Perioperative Treatment of Gorham-Stout Disease in the Thoracic Spine

Cited by 18 publications

References 27 publications

Dysregulated miRNAs in bone cells of patients with Gorham‐Stout disease

Dysregulated miRNAs in bone cells of patients with Gorham‐Stout disease

Current concepts from diagnosis to management in Gorham–Stout disease: a systematic narrative review of about 350 cases

A Large Skull Defect Due to Gorham-Stout Disease: Case Report and Literature Review on Pathogenesis, Diagnosis, and Treatment

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