Penna Sara, Capo Valentina, Palagano Eleonora, Sobacchi Cristina, Villa Anna
San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), San Raffaele Hospital, Milan, Italy.
Translational and Molecular Medicine (DIMET), University of Milano-Bicocca, Monza, Italy.
Front Endocrinol (Lausanne). 2019 Feb 19;10:85. doi: 10.3389/fendo.2019.00085. eCollection 2019.
Osteopetrosis is a condition characterized by increased bone mass due to defects in osteoclast function or formation. In the last decades, the molecular dissection of osteopetrosis has unveiled a plethora of molecular players responsible for different forms of the disease, some of which present also primary neurodegeneration that severely limits the therapy. Hematopoietic stem cell transplantation can cure the majority of them when performed in the first months of life, highlighting the relevance of an early molecular diagnosis. However, clinical management of these patients is constrained by the severity of the disease and lack of a bone marrow niche that may delay immune reconstitution. Based on osteopetrosis genetic heterogeneity and disease severity, personalized therapies are required for patients that are not candidate to bone marrow transplantation. This review briefly describes the genetics of osteopetrosis, its clinical heterogeneity, current therapy and innovative approaches undergoing preclinical evaluation.
骨质石化症是一种由于破骨细胞功能或形成缺陷导致骨量增加的病症。在过去几十年中，对骨质石化症的分子剖析揭示了众多导致不同形式该疾病的分子因素，其中一些还伴有原发性神经退行性变，这严重限制了治疗。造血干细胞移植在生命的最初几个月进行时可治愈大多数患者，凸显了早期分子诊断的重要性。然而，这些患者的临床管理受到疾病严重程度以及可能延迟免疫重建的骨髓微环境缺乏的限制。基于骨质石化症的遗传异质性和疾病严重程度，对于不适合进行骨髓移植的患者需要个性化治疗。本综述简要描述了骨质石化症的遗传学、其临床异质性、当前治疗方法以及正在进行临床前评估的创新方法。
