Osteogenesis imperfecta: clinical assessment and medical treatment

Osteogenesis imperfecta (OI) je fenotipski i molekularno heterogena skupina nasljednih bolesti veziva obilježena smanjenom gustoćom kostiju, čestim lomovima i deformacijama. Većina OI-a nasljeđuje se autosomno dominantno i uzrokovana je mutacijama u genima COL1A1 i COL1A2, što dovodi do kvantitativnog ili kvalitativnog defekta kolagena tip 1. U posljednje vrijeme otkriven je veći broj gena koji su odgovorni za recesivne i dominantne oblike ove bolesti. U ovom kratkom pregledu razmatramo suvremeni pristup kliničkoj dijagnostici i praćenju te farmakološkom liječenju OI-a. Multidisciplinsko praćenje bolesnika uključuje povremeno testiranje sluha i vida, stomatološke preglede, spirometriju ili pletizmografi ju, evaluaciju funkcije srca/valvula, neurološke i psihološke kontrole. Potrebno je redovito pratiti vrijednosti gustoće kostiju (BMD) kako bi se utvrdio uspjeh liječenja i progresija bolesti, a nužne su i rengenske slike kostiju kod postavljanja dijagnoze i kasnije prema indikaciji ortopeda. Svrha liječenja je i da spriječi ili suzbije simptome prisutne kod pojedinog bolesnika, a glavni ciljevi su smanjiti broj lomova, suzbiti bol, poboljšati koštanu masu i mišićnu snagu te osigurati samostalnu pokretnost i rast. To zahtijeva multidisciplinski pristup u liječenju lijekovima, fi zikalnom terapijom, kiruškim ortopedskim zahvatima i odgovarajućom prehranom. Intravenska primjena bisfosfonata je najšire primjenjivan oblik medikamentoznog liječenja. Ona ima očit učinak na BMD slabinske kralježnice, vrata bedrene kosti i kukova djece u rastu, te može dovesti do preoblikovanja kralježaka nakon kompresijskih fraktura, ali nema značajnijeg učinka na rizik pojave lomova kod odraslih osoba. Druge nove obećavajuće terapije uključuju teriparatid, liječenje kombinacijom antiresorptivnih i anaboličih lijekova, denosumab, inhibiciju TGF-β (eng. transforming growth factor beta), sklerostina i kathepsina K te staničnu terapiju, poput transplantacije koštane srži ili mezenimalnih stanica. Genska terapija je još u ranim stadijima ispitivanja.Osteogenesis imperfecta (OI) is a phenotypically and molecularly heterogeneous group of heritable connective tissue disorders characterized by low bone mineral density, recurrent fractures, and bone deformities. Most cases of OI are inherited in an autosomal dominant manner and are caused by mutations in the COL1A1 and COL1A2 genes, leading to quantitative or qualitative defects in type 1 collagen. More recently, a number of other genes responsible for both recessive and dominant forms of this condition have been identifi ed. In this brief review, we discuss current understanding of clinical assessment, follow-up and pharmacological therapies 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 psychological assessment. There is a need for regular assessment of bone mineral density (BMD) to evaluate treatment success and disease progression, and skeletal radiographs at the time of diagnosis and later as indicated by orthopaedists. Treatment of OI is aimed at preventing 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-disciplinary approach, utilizing medical treatment, physical therapy, orthopedic surgery, and nutrition monitoring. Intravenous bisphosphonate therapy is the most widely used medical treatment. It has an evident eff ect on BMD of lumbar spine, femoral neck and total hip in growing children and can lead to vertebral reshaping after compression fractures, but no signifi cant eff ect on the risk of fractures has been observed in adults. Other novel promising therapies include teriparatide, combination therapy with antiresorptive and anabolic drugs, denosumab, transforming growth factor beta, sclerostin and cathepsin K inhibitors, and cell-based therapy, such as bone marrow or mesenchymal stem cell transplantation. Gene targeting approaches are still at early stages of investigation