Treatment of fibrous dysplasia: focus on denosumab

Huzum, Bogdan; Antoniu, Sabina A; Dragomir, Raluca

doi:10.1080/14712598.2022.2022118

Cited by 5 publications

(3 citation statements)

References 47 publications

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“…In conjunction with the histological characteristics of clinical FD tissue samples [9,11] and transgenic mouse models [47,48], which both reported overloaded osteoclastogenesis, it is imperative to determine whether PTHrP is associated with excessive osteoclast activity in FD lesions. Recently, medications targeting osteoclasts, such as bisphosphonates and denosumab, have been applied to animal models [48,64] and clinical trials [65][66][67][68], achieving positive results to some extent. We are eager to further investigate the underlying relationship between PTHrP and osteoclasts in FD lesions.…”

Section: Discussionmentioning

confidence: 99%

PTHrP Modulates the Proliferation and Osteogenic Differentiation of Craniofacial Fibrous Dysplasia-Derived BMSCs

Shen

Yang

Chen

et al. 2023

IJMS

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Fibrous dysplasia (FD) is a skeletal stem cell disease caused by mutations in the guanine nucleotide-binding protein, alpha-stimulating activity polypeptide (GNAS) gene, which results in the abnormal accumulation of cyclic adenosine monophosphate (cAMP) and hyperactivation of downstream signaling pathways. Parathyroid hormone-related protein (PTHrP) is secreted by the osteoblast lineage and is involved in various physiological and pathological activities of bone. However, the association between the abnormal expression of PTHrP and FD, as well as its underlying mechanism, remains unclear. In this study, we discovered that FD patient-derived bone marrow stromal cells (FD BMSCs) expressed significantly higher levels of PTHrP during osteogenic differentiation and exhibited greater proliferation capacity but impaired osteogenic ability compared to normal control patient-derived BMSCs (NC BMSCs). Continuous exogenous PTHrP exposure on the NC BMSCs promoted the FD phenotype in both in vitro and in vivo experiments. Through the PTHrP/cAMP/PKA axis, PTHrP could partially influence the proliferation and osteogenesis capacity of FD BMSCs via the overactivation of the Wnt/β-Catenin signaling pathway. Furthermore, PTHrP not only directly modulated cAMP/PKA/CREB transduction but was also demonstrated as a transcriptional target of CREB. This study provides novel insight into the possible pathogenesis involved in the FD phenotype and enhances the understanding of its molecular signaling pathways, offering theoretical evidence for the feasibility of potential therapeutic targets for FD.

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Section: Discussionmentioning

confidence: 99%

PTHrP Modulates the Proliferation and Osteogenic Differentiation of Craniofacial Fibrous Dysplasia-Derived BMSCs

Shen

Yang

Chen

et al. 2023

IJMS

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“…In Germany, Denosumab is approved for the treatment of several conditions affecting bone in adults only. However, it has been used off-label in the treatment of different rare bone diseases worldwide, including fibrous dysplasia in pediatric cases [2][3][4][5][6].…”

Section: Zusammenfassungmentioning

confidence: 99%

Lichen Planus After Denosumab

et al. 2023

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Lichenoid reactions have been described as a side effect of several drugs. Here we describe the development of lichen planus (LP) of the mammilla following off-label use of denosumab in an adolescent patient with mono-ostotic fibrous dysplasia. Lichen planus is considered an autoimmune disorder. Since receptor activator of nuclear factor κΒ ligand (RANKL), the target of denosumab action, has regulatory function in the immune system, it is feasible, that LP may be caused as part of an immunological dysregulation.

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“…Its mechanism of action, which differs from the other antiresorptive agents such as bisphosphonates, is to bind to RANK where it inhibits the development and activity of osteoclasts and decreases bone resorption. In several recent case studies, denosumab was used to treat osteogenesis imperfecta in children and to prevent bone pain in patients with fibrous dysplasia 14 – 16 . Meiss et al 17 achieved favourable outcomes with denosumab in combination with a varus osteotomy to treat Perthes’ disease.…”

Section: Introductionmentioning

confidence: 99%

The efficacy of Denosumab in the treatment of femoral head osteonecrosis: a retrospective comparative study

Moon,

Park,

Yoo

et al. 2024

Sci Rep

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The present study aimed to compare clinical and radiological differences of ONFH patients who were treated with denosumab, and a control group. A total of 178 patients (272 hips) with symptomatic, nontraumatic ONFH were divided into a denosumab group (98 patients, 146 hips) and a control group (80 patients, 126 hips). Patients in the denosumab group received a 60 mg subcutaneous dose of denosumab every 6 months. For the clinical assessments, Harris hip scores (HHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were evaluated. Plain radiographs and MRI were performed before and a minimum of 1 year after administration of denosumab, which were evaluated for radiological results including femoral head collapse (≥ 2 mm) and volume change of necrotic lesion. Femoral head collapse occurred in 36 hips (24.7%) in the denosumab group, and 48 hips (38.1%) in the control group, which was statistically significant (P = 0.012). Twenty-three hips (15.8%) in the denosumab group and 29 hips (23%) in the control group required THA, which showed no significant difference (P = 0.086). At the final follow-up, 71.9% of hips in the denosumab group had a good or excellent HHS compared with 48.9% in the control group, showing a significant difference (P = 0.012). The denosumab group showed a significantly higher rate of necrotic lesion volume reductions compared with the control group (P < 0.001). Denosumab can significantly reduce the volume of necrotic lesions and prevent femoral head collapse in patients with ARCO stage I or II ONFH.

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Treatment of fibrous dysplasia: focus on denosumab

Cited by 5 publications

References 47 publications

PTHrP Modulates the Proliferation and Osteogenic Differentiation of Craniofacial Fibrous Dysplasia-Derived BMSCs

PTHrP Modulates the Proliferation and Osteogenic Differentiation of Craniofacial Fibrous Dysplasia-Derived BMSCs

Lichen Planus After Denosumab

The efficacy of Denosumab in the treatment of femoral head osteonecrosis: a retrospective comparative study

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