Abstract
A rare disease afflicts less than 200,000 individuals, according to the National Organization for Rare Diseases (NORD) of the United States. Over 6,000 rare disorders affect approximately 1 in 10 Americans. Rare genetic bone disorders remain the major causes of disability in US patients. These rare bone disorders also represent a therapeutic challenge for clinicians, due to lack of understanding of underlying mechanisms. This systematic review explored current literature on therapeutic directions for the following rare genetic bone disorders: fibrous dysplasia, Gorham-Stout syndrome, fibrodysplasia ossificans progressiva, melorheostosis, multiple hereditary exostosis, osteogenesis imperfecta, craniometaphyseal dysplasia, achondroplasia, and hypophosphatasia. The disease mechanisms of Gorham-Stout disease, melorheostosis, and multiple hereditary exostosis are not fully elucidated. Inhibitors of the ACVR1/ALK2 pathway may serve as possible therapeutic intervention for FOP. The use of bisphosphonates and IL-6 inhibitors has been explored to be useful in the treatment of fibrous dysplasia, but more research is warranted. Cell therapy, bisphosphonate polytherapy, and human growth hormone may avert the pathology in osteogenesis imperfecta, but further studies are needed. There are still no current effective treatments for these bone disorders; however, significant promising advances in therapeutic modalities were developed that will limit patient suffering and treat their skeletal disabilities.
Highlights
In the spectrum of orthopaedic diseases, rare genetic bone disorders are often ignored as major diseases such as osteoporosis generally attract more research funding and attention from the research community
Recent study showed that inactivation of EXT1 in mouse chondrocytes leads to the development of osteochondroma with characteristic bone deformities that is almost identical to human Multiple hereditary exostosis (MHE) [57]
There is yet a large scale of work needed to be done towards the discovery of new therapeutic methods of rare genetic bone disorders
Summary
In the spectrum of orthopaedic diseases, rare genetic bone disorders are often ignored as major diseases such as osteoporosis generally attract more research funding and attention from the research community. Rare bone disorders remain a serious problem in orthopaedics and result in significant morbidity and mortality in patients around the world. In 2006, the gene for fibrodysplasia ossificans progressiva (FOP) was identified by researchers at the University of Pennsylvania, marking a significant milestone in the understanding of this disease. While this does not in and of itself translate to a cure, the discovery provides direction for researchers to investigate possible points of disruption of the basic pathway of FOP. This review summarizes the most current trends in the search for therapeutic interventions for nine rare bone disorders: fibrous dysplasia, Gorham-Stout syndrome, fibrodysplasia ossificans progressiva, melorheostosis, multiple hereditary exostosis, osteogenesis imperfecta, and craniometaphyseal dysplasia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
