Regression of fibrous dysplasia in response to denosumab therapy: A report of two cases.
Ontology highlight
ABSTRACT:
SUBMITTER: Meier ME
PROVIDER: S-EPMC8066421 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Fibrous dysplasia (FD) is a skeletal disease caused by somatic activating mutations of the cyclic adenosine monophosphate (cAMP)-regulating protein, α-subunit of the Gs stimulatory protein (G(s) α). These mutations lead to replacement of normal bone by proliferative osteogenic precursors, resulting in deformity, fracture, and pain. Medical treatment has been ineffective in altering the disease course. Receptor activator of NF-κB ligand (RANKL) is a cell-surface protein involved in many cellular processes, including osteoclastogenesis, and is reported to be overexpressed in FD-like bone cells. Denosumab is a humanized monoclonal antibody to RANKL approved for treatment of osteoporosis and prevention of skeletal-related events from bone metastases. We present the case of a 9-year-old boy with severe FD who was treated with denosumab for a rapidly expanding femoral lesion. Immunohistochemical staining on a pretreatment bone biopsy specimen revealed marked RANKL expression. He was started on monthly denosumab, with an initial starting dose of 1 mg/kg and planned 0.25 mg/kg dose escalations every 3 months. Over 7 months of treatment he showed marked reduction in pain, bone turnover markers (BTMs), and tumor growth rate. Denosumab did not appear to impair healing of a femoral fracture that occurred while on treatment. With initiation of treatment he developed hypophosphatemia and secondary hyperparathyroidism, necessitating supplementation with phosphorus, calcium, and calcitriol. BTMs showed rapid and sustained suppression. With discontinuation there was rapid and dramatic rebound of BTMs with cross-linked C-telopeptide (reflecting osteoclast activity) exceeding pretreatment levels, accompanied by severe hypercalcemia. In this child, denosumab lead to dramatic reduction of FD expansion and FD-related bone pain. Denosumab was associated with clinically significant disturbances of mineral metabolism both while on treatment and after discontinuation. Denosumab treatment of FD warrants further study to confirm efficacy and determine potential morbidity, as well as to determine the mechanism of RANKL in the pathogenesis of FD and related bone marrow stromal cell diseases.
| S-EPMC3377825 | biostudies-literature
Project description:Fibrous dysplasia (FD) is a relatively rare osseous disease of unknown etiology, wherein the normal bone is replaced by collagen-rich tissue, comprising of fibroblasts and variably abundant immature woven bone. Clinically, it may involve a single bone or multiple bones. It commonly arises in the jaw bone, skull, rib, and proximal femur. Those arising in the skull and the jaw are together termed "craniofacial fibrous dysplasia." The differential diagnosis at this location includes meningioma and metastatic carcinoma. In this report, we highlight two diagnostically challenging cases presenting with orbital swelling and headache as the main complaints. Our first case was misinterpreted as meningioma on intraoperative squash smear, and paraffin sections revealed characteristic features of FD. The second case highlights the morphological feature of non-specific cystic degeneration occurring in FD. Radiographs in such cases show cystic swelling, which is indicative of a secondary aneurysmal bone cyst.
| S-EPMC6561353 | biostudies-other
Project description: Not available
| S-EPMC7497813 | biostudies-literature
Project description:RationaleFibrous dysplasia is a rare disorder that results in fractures, pain, and disability and can affect any bone in the body. The treatment of symptomatic fibrous dysplasia is determined based on the affected bones. Although some lesions are often too extensive for surgical procedures, there are currently no effective or recommended medical treatments available for them.Patient concernsA 27-year-old woman developed right buttock pain and was diagnosed with a bone tumor in the right ilium. Clinical images revealed an expansive osteolytic lesion with thinning of the cortex and cystic change from the acetabulum to the sacroiliac joint.DiagnosisAn incisional biopsy was performed, and the lesion was diagnosed as cystic fibrous dysplasia. Occasional osteoclast-like giant cells and woven bone were observed. The patient had no evidence of polyostotic lesions or findings of McCune-Albright syndrome. Biochemical blood test results showed no obvious abnormal values, except for an increase in serum tartrate-resistant acid phosphatase 5b to 459 mU/dL.InterventionsSince surgical treatment appeared to be challenging, she was treated with denosumab with decreased dose-intensity schedules.OutcomesThe administration of denosumab caused osteosclerosis within the lesion, resulting in the elimination of bone pain. The patient received denosumab treatment for 18 months. Pain relief and lesion radiodensity were maintained for 9 months after denosumab discontinuation. The serum level of tartrate-resistant acid phosphatase 5b was measured to monitor the response to denosumab, which was suppressed during denosumab treatment.LessonsWe described successful denosumab treatment in a patient with cystic fibrous dysplasia (FD) who maintained efficacy for 9 months after treatment. Although the use of denosumab in fibrous dysplasia is currently off-label, our experience with this patient supports the potential of denosumab therapy for patients for whom surgical treatment is challenging.
| S-EPMC8663861 | biostudies-literature
Project description:As aberrant Notch signaling has been linked to cancerous growth, Notch inhibitors represent a novel category of targeted oncological therapy. Notch pathways in tumor cells may contribute to proliferation or limit apoptosis and differentiation. Healthy skin differentiation and homeostasis are reliant on normal Notch expression, and disruption of this signaling has been implicated in dermatological conditions such as hidradenitis suppurativa, psoriasis, atopic dermatitis, and lichen planus. Here, we describe two cases of patients with cutaneous side effects from Notch inhibitor treatment for adenoid cyst carcinoma (ACC) and review the role of Notch signaling in skin disease. By illuminating connections between medication side effects and disease pathogenesis, our goal is to increase awareness of the cutaneous side effects of Notch inhibitor treatment.
| S-EPMC7352146 | biostudies-literature
Project description:BackgroundIn Indonesia, 175 cases resulted in death in children from March to December 2020. Studies regarding Convalescent Plasma Therapy's (CPT) safety and efficacy in children are scarce. Our case report was the first to write CPT in Indonesian children.Case presentationIn our case, two obese children with progressive shortness of breath, worsening cough, and high fever, the findings met severe COVID-19 criteria. We performed CPT for these patients and the patient's condition was improved and able to be discharged.DiscussionSevere COVID-19 with or without comorbid was the indication of CPT which had been approved by the U.S. FDA and Indonesian Pediatrics Society. The key factors associated with CPT efficacy were the donor's titer antibody, the treatment time point, and the patient's comorbidities. The clinical impact showed an improvement by the combination therapy of CPT and remdesivir.ConclusionWe noted that CPT might be well tolerated, could improve the clinical impact of severe COVID-19 in adolescents, and have no adverse events as well. CPT for severe COVID-19 cases in children had the potential to be developed in studies with better designs and stronger levels of evidence.
| S-EPMC8598255 | biostudies-literature
Project description:Denosumab is an antiresorptive drug targeting RANK ligand, currently licensed for postmenopausal and male osteoporosis, bone loss associated with hormone ablation in men with prostate cancer and with systemic glucocorticoid treatment, and also used in oncology for the treatment of bone metastases and unresectable giant cell tumour of bone. When used for the treatment of osteoporosis or bone loss the drug is usually well-tolerated with non-specific musculoskeletal pain being the most common side effect. However denosumab has been associated with some dermatological manifestations including dermatitis, eczema, pruritus and, less commonly, cellulitis. All these side effects are generally mild and self-limiting. We hereby report the first documented case of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome following denosumab administration. DRESS syndrome is an extremely rare but potentially life-threatening hypersensitivity reaction. The syndrome should be considered in patients who present with new rash, eosinophilia and systemic organ dysfunction, especially when associated with new medications. Notably it has been previously reported in patients with osteoporosis treated with strontium ranelate but it has never been linked to any other antiosteoporotic drugs. Since the clinical manifestations of DRESS syndrome can span over a period of several months the diagnosis can frequently be quite difficult and it can become even more challenging in people taking denosumab and other drugs given in period doses, as both clinicians and patients are less likely to link the symptoms to the medication. Better recognition of DRESS syndrome is therefore needed, as well as awareness of the possibility of this reaction to occur in patients taking denosumab.
| S-EPMC6933223 | biostudies-literature
Project description:Although voriconazole, a triazole antifungal, is a safe drug, treatment with this agent is associated with certain adverse events such as hepatic, neurologic, and visual disturbances. The current report presents two cases, one a 9-year-old boy and the other a 17-year-old girl, who experienced neurologic side effects associated with voriconazole therapy. Our aim is to remind readers of the side effects of voriconazole therapy in order to prevent unnecessary investigations especially for psychological and ophthalmologic problems. The first case was a 9-year-old boy with cystic fibrosis and invasive aspergillosis that developed photophobia, altered color sensation, and fearful visual hallucination. The second case was a 17-year-old girl with cystic fibrosis and allergic bronchopulmonary aspergillosis, and she experienced photophobia, fatigue, impaired concentration, and insomnia, when the dose of voriconazole therapy was increased from 12 mg/kg/day to 16 mg/kg/day. The complaints of the two patients disappeared after discontinuation of voriconazole therapy. Our experience in these patients reminded us of the importance of being aware of the neurologic adverse events associated with voriconazole therapy in establishing early diagnosis and initiating prompt treatment. In addition, although serum voriconazole concentration was not measured in the present cases, therapeutic drug monitoring for voriconazole seems to be critically important in preventing neurologic side effects in pediatric patients.
| S-EPMC4895037 | biostudies-other
Project description:BackgroundPolyostotic fibrous dysplasia (PFD) is an uncommon developmental bone disease in which normal bone and marrow are replaced by pseudotumoral tissue. The etiology of PFD is unclear, but it is generally thought to be caused by sporadic, post-zygotic mutations in the GNAS gene. Herein, we report the case of a young female with bone pain and lesions consistent with PFD, unique physical findings, and gene mutations.Case summaryA 27-year-old female presented with unbearable bone pain in her left foot for 4 years. Multiple bone lesions were detected by radiographic examinations, and a diagnosis of PFD was made after a biopsy of her left calcaneus with symptoms including pre-axial polydactyly on her left hand and severe ophthalmological problems such as high myopia, vitreous opacity, and choroidal atrophy. Her serum cortisol level was high, consistent with Cushing syndrome. Due to consanguineous marriage of her grandparents, boosted whole exome screening was performed to identify gene mutations. The results revealed mutations in HSPG2 and RIMS1, which may be contributing factors to her unique findings.ConclusionThe unique findings in this patient with PFD may be related to mutations in the HSPG2 and RIMS1 genes.
| S-EPMC7723713 | biostudies-literature
Project description:McCune-Albright syndrome is a rare sporadic disease characterized by bone fibrous dysplasia, café-au-lait skin spots and a variable association of hyperfunctional endocrine disorders. Fibrous dysplasia (FD), which can involve the craniofacial, axial, and appendicular skeleton, may range from an isolated, asymptomatic monostotic lesion to a severe disabling polyostotic disease involving the entire skeleton. A twenty-five-year old male patient presented to our clinic with recently developed heart palpitations. He had also been feeling pain in the right femur since he was younger, without any trauma history, leading to difficulties of ambulation and limping occasionally. His physical examination revealed café-au-lait spots with irregular borders and right testicular agenesis. Laboratory findings identified hyperthyroidism with hyperparathyroidism. Radiographs of the pelvis revealed multiple lytic lesions of the right femur and magnetic resonance imaging (MRI) characterized these lesions as specific to fibrous dysplasia of the bone, without any insufficiency fracture at this level. The association of café-au-lait skin spots with bone fibrous dysplasia, and hyperthyroidism in this patient suggested the diagnosis of McCune - Albright syndrome.
| S-EPMC5111499 | biostudies-literature