Current and Emerging Therapeutic Options for the Management of Rare Skeletal Diseases

Increasing knowledge in the field of rare diseases has led to new therapeutic approaches in the last decade. Treatment strategies have been developed after elucidation of the underlying genetic alterations and pathophysiology of certain diseases (e.g., in osteogenesis imperfecta, achondroplasia, hypophosphatemic rickets, hypophosphatasia and fibrodysplasia ossificans progressiva). Most of the drugs developed are specifically designed agents interacting with the disease-specific cascade of enzymes and proteins involved. While some are approved (asfotase alfa, burosumab), others are currently being investigated in phase III trials (denosumab, vosoritide, palovarotene). To offer a multi-disciplinary therapeutic approach, it is recommended that patients with rare skeletal disorders are treated and monitored in highly specialized centers. This guarantees the greatest safety for the individual patient and offers the possibility of collecting data to further improve treatment strategies for these rare conditions. Additionally, new therapeutic options could be achieved through increased awareness, not only in the field of pediatrics but also in prenatal and obstetric specialties. Presenting new therapeutic options might influence families in their decision of whether or not to terminate a pregnancy with a child with a skeletal disease.