New Perspectives of Therapies in Osteogenesis Imperfecta-A Literature Review.
Alexandru DinulescuAlexandru-Sorin PăsăricăMădălina CarpAndrei DușcăIrina DijmărescuMirela Luminița PavelescuDaniela PăcurarAlexandru UliciPublished in: Journal of clinical medicine (2024)
(1) Background: Osteogenesis imperfecta (OI) is a rare skeletal dysplasia characterized as a heterogeneous disorder group with well-defined phenotypic and genetic features that share uncommon bone fragility. The current treatment options, medical and orthopedic, are limited and not efficient enough to improve the low bone density, bone fragility, growth, and mobility of the affected individuals, creating the need for alternative therapeutic agents. (2) Methods: We searched the medical database to find papers regarding treatments for OI other than conventional ones. We included 45 publications. (3) Results: In reviewing the literature, eight new potential therapies for OI were identified, proving promising results in cells and animal models or in human practice, but further research is still needed. Bone marrow transplantation is a promising therapy in mice, adults, and children, decreasing the fracture rate with a beneficial effect on structural bone proprieties. Anti-RANKL antibodies generated controversial results related to the therapy schedule, from no change in the fracture rate to improvement in the bone mineral density resorption markers and bone formation, but with adverse effects related to hypercalcemia. Sclerostin inhibitors in murine models demonstrated an increase in the bone formation rate and trabecular cortical bone mass, and a few human studies showed an increase in biomarkers and BMD and the downregulation of resorption markers. Recombinant human parathormone and TGF-β generated good results in human studies by increasing BMD, depending on the type of OI. Gene therapy, 4-phenylbutiric acid, and inhibition of eIF2α phosphatase enzymes have only been studied in cell cultures and animal models, with promising results. (4) Conclusions: This paper focuses on eight potential therapies for OI, but there is not yet enough data for a new, generally accepted treatment. Most of them showed promising results, but further research is needed, especially in the pediatric field.
Keyphrases
- bone mineral density
- postmenopausal women
- body composition
- endothelial cells
- bone loss
- bone marrow
- bone regeneration
- healthcare
- gene therapy
- induced pluripotent stem cells
- pluripotent stem cells
- soft tissue
- systematic review
- cell therapy
- primary care
- stem cells
- case report
- machine learning
- metabolic syndrome
- cell proliferation
- type diabetes
- copy number
- adipose tissue
- nuclear factor
- drug induced
- inflammatory response
- oxidative stress
- case control