Osteogenesis imperfecta: clinical assessment and medical treatment

Osteogenesis imperfecta (OI) is a phenotypically and molecularly heterogeneous group of heritable connective tissue disorderscharacterized by low bone mineral density, recurrent fractures, and bone deformities. Most cases of OI are inherited in an autosomaldominant manner and are caused by mutations in the COL1A1 and COL1A2 genes, leading to quantitative or qualitative defects intype 1 collagen. More recently, a number of other genes responsible for both recessive and dominant forms of this condition havebeen identifi ed. In this brief review, we discuss current understanding of clinical assessment, follow-up and pharmacologicaltherapies for the treatment of OI. The multidisciplinary surveillance in patients with OI includes periodical hearing and vision testing,dental examination, spirometry or body plethysmography, evaluation of heart/valvular function, and neurological and psychologicalassessment. There is a need for regular assessment of bone mineral density (BMD) to evaluate treatment success and diseaseprogression, and skeletal radiographs at the time of diagnosis and later as indicated by orthopaedists. Treatment of OI is aimed atpreventing or controlling the symptoms present in individual patient with the main goals to decrease fracture rate, relieve bone pain,and provide suffi cient bone mass and good muscle strength promoting self-mobility and growth. This requires a multi-disciplinaryapproach, utilizing medical treatment, physical therapy, orthopedic surgery, and nutrition monitoring. Intravenous bisphosphonatetherapy is the most widely used medical treatment. It has an evident eff ect on BMD of lumbar spine, femoral neck and total hip ingrowing children and can lead to vertebral reshaping after compression fractures, but no signifi cant eff ect on the risk of fractures hasbeen observed in adults. Other novel promising therapies include teriparatide, combination therapy with antiresorptive and anabolicdrugs, denosumab, transforming growth factor beta, sclerostin and cathepsin K inhibitors, and cell-based therapy, such as bonemarrow or mesenchymal stem cell transplantation. Gene targeting approaches are still at early stages of investigation.Key words: children, fractures, osteogenesis imperfecta, bone mineral density, bisphosphonates, denosumab, teriparatide,mesenchymal stem cell, transforming growth factor beta, sclerostin antibody, growth hormone

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