Denosumab Versus Zoledronic Acid in Thalassemia-Induced Osteoporosis
Palabras clave
Abstracto
Descripción
Despite the significant improvements in the therapeutic management of beta thalassemia major (BTM) over the past few decades, osteoporosis is still a common finding, even in optimally treated patients. The relationships between bone mineral densities (BMD) and several clinical characteristics or hematological markers have been described. Chronic anemia, bone marrow expansion due to ineffective erythropoiesis, iron toxicity, calcium and zinc deficiencies, low vitamin D levels and endocrine complications have been suggested to contribute to the etiology of bone diseases in BTM. Nevertheless, the complex etiological mechanisms of this heterogeneous osteopathy remain incompletely clarified. A complex mechanism controls bone remodeling in human. This mechanism includes the receptor activator of nuclear factor kappa B ligand (RANKL), its natural receptor (RANK) and osteoprotegerin (OPG). The RANK/RANKL pathway is an essential to promote osteoclast formation and activation and prolongs osteoclast survival.
OPG acts as a decoy receptor for RANKL and prevents its interaction with RANK thereby inhibiting osteoclast formation, function, and survival. Alteration of the RANK/RANKL/OPG system for increased osteoclastic activity and enhanced osteoblastic dysfunction is proposed as an important mechanism in the etiology of osteoporosis in BTM. Hypogonadism, a common finding in BTM, is associated with enhanced RANKL activity. The sex steroid hormones, androgen, and estrogens, via their respective nuclear receptors, regulate BMD in humans and mice. Testosterone is likely to have direct and indirect inhibitory effects on human osteoclast formation and bone resorption. Animal model and cell culture studies suggest a direct inhibitory effect of androgens on the OPG/RANKL cytokines system. In human osteoblastic cells, testosterone and 5‑dihydrotestosterone mediate an androgen receptor‑induced specific inhibition of OPG messenger ribonucleic acid (mRNA) expression. Androgens have also been shown to block RANKL‑induced osteoclastic formation while RANKL expression was found to be up‑regulated in osteoblastic cells from androgen receptor‑deficient mice. The effect of oestradiol (E2) on osteoclast precursors and osteoclasts seems to be mediated by osteoblastic cells. Inhibitory effect of E2 is associated with the stimulated secretion of OPG by osteoblasts. Previous studies have focused on the characteristics of thalassemic patients with osteoporosis and their response to therapy with bisphosphonate. Because RANK‑RANKL and OPG play a significant role in bone resorption and seem to be the principal implicated mechanism for the development of osteoporosis in BTM, we will conduct this prospective study to evaluate the anti‑RANKL denosumab versus zoledronic acid on TM‑induced osteoporosis.
fechas
| Verificado por última vez: | 04/30/2018 |
| Primero enviado: | 01/21/2017 |
| Inscripción estimada enviada: | 01/30/2017 |
| Publicado por primera vez: | 02/01/2017 |
| Última actualización enviada: | 12/09/2019 |
| Última actualización publicada: | 12/11/2019 |
| Fecha de inicio real del estudio: | 05/13/2018 |
| Fecha estimada de finalización primaria: | 04/07/2019 |
| Fecha estimada de finalización del estudio: | 04/07/2019 |
Condición o enfermedad
Intervención / tratamiento
Drug: Denosumab
Drug: Zoledronic Acid
Fase
Grupos de brazos
| Brazo | Intervención / tratamiento |
|---|---|
| Active Comparator: Denosumab Denosumab 60 MG/ML Prefilled Syringe
Denosumab Dose: 60 milligrams, subcutaneous injection, every 6 months (twice a year) | Drug: Denosumab Denosumab 60 MG/ML will be administered to 20 patients with b-thalassemia major |
| Active Comparator: Zoledronic Acid Zoledronic Acid 5Mg/Bag 100Ml Inj
Zoledronic acid will be 5 milligrams, Intravenous injection, once a year | Drug: Zoledronic Acid Zoledronic Acid 5Mg/Bag 100Ml Inj will be administered to 20 patients with b-thalassemia major |
Criterio de elegibilidad
| Edades elegibles para estudiar | 18 Years A 18 Years |
| Sexos elegibles para estudiar | All |
| Acepta voluntarios saludables | si |
| Criterios | Inclusion Criteria: - Willing to participate in the study - Age 18 years old or older - Eastern Cooperative Oncology Group Performance Status less than or equal 2 Exclusion Criteria: - Age less than 18 years old - Not willing to participate in the study - Vulnerable subjects or Eastern Cooperative Oncology Group Performance Status 3 or 4 |
Salir
Medidas de resultado primarias
1. Number of patients with a 50 percent or greater reduction in type-1 collagen carboxy telopeptide from the baseline [12 months]
Medidas de resultado secundarias
1. Number of patients with a 50 percent or greater improvement in Dual-energy X-ray absorptiometry scan from the baseline [12 months]
2. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [12 months]
