Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Workshop: Osteogenesis Imperfecta in Adults Malachi J McKenna & Susan van der Kamp DXA Unit & Department of Endocrinology St. Vincent’s University Hospital Dublin, Ireland Disclosures • No disclosures or conflicts of interest Learning Objectives •Overview of osteogenesis imperfecta in adults –Classification of OI –Bone health in adulthood •Investigation of OI –Role of DXA –Role of bone turnover markers •Medication options •Case Studies Learning Objectives • Overview of osteogenesis imperfecta in adults – Classification of OI – Bone health in adulthood • Investigation of OI – Role of DXA – Role of bone turnover markers • Medication options • Case Studies OI Phenotypes Nosology of Osteogenesis Imperfecta Type Classical Sillence types I: Mild II: Perinatal lethal III: Severely deforming Affected gene Mode of inheritance COL1A1 AD COL1A1 or COL1A2 COL1A1 or COL1A2 AD IV: Moderately deforming COL1A1 or COL1A2 AD AD Phenotype Normal stature, few fractures, blue sclera, hearing loss in 50% Severe, multiple fractures, blue or grey sclerae, soft cranium Severe, short stature, scoliosis with vertebral fractures, triangular face, multiple fractures, blue or grey sclera, frequent hearing loss, platybasia, dentinogenesis imperfecta Moderately short stature, mild to moderate scoliosis, white or grey sclerae Distinctive histology V: Moderately deforming IFITM5 AD Mild to moderate short stature, dislocation of radial head, hyperplastic callus, white sclerae Mineralisation defect VI: Severe SERPINF1 AR Moderately short, scoliosis, fish-scale pattern of bone lamellation, white sclera 3-hydroxylation defects VII: Severe CRTAP AR VIII: Severe LEPRE1 AR Rhizomelia, short stature, white sclera, undertubulated long bones Rhizomelia, white sclera, undertubulated long bones, seen in Irish Travellers IX: Severe PPIB AR Similar to type VII & VIII but no rhizomelia Modified from Forlino A, Cabral WA, Barnes AM, Marini JC. New perspectives on osteogenesis imperfecta. Nat Rev Endocrinol 2011;7:540-57 Critical steps in collagen type I biosynthesis and indication of genes known to be involved in OI. Type I collagen is the major structural protein in bone, tendon, ligament, skin & cornea Mechanism of disease in OI type I Mechanism of disease in OI type III & IV Abnormal folding of collagen molecule Approach to Genetic Testing Bone Health in Adulthood • OI type I – Low or low-normal BMD – Stable BMD – Normal or high-normal bone turnover – Fragility fractures • Variable prevalence • Less frequent than childhood Bone Health in Adulthood • OI type III & IV – Low BMD – Stable BMD – High-normal or high bone turnover – Fractures • Fragility fractures are common but variable prevalence • Stress fractures may occur easily – Problems related to bone deformity • Wheelchair-bound • Platybasia Learning Objectives • Overview of osteogenesis imperfecta in adults – Classification of OI – Bone health in adulthood • Investigation of OI – Role of DXA – Role of bone turnover markers • Medication options • Case Studies Challenges of DXA in OI Type I Challenges of DXA in OI Type III Panel of Bone Turnover Markers Resorption Formation sCTX Procollagen I aminopropeptide urNTX Bone specific alkaline phosphatase sTRAP5b Osteocalcin Collagen-based Markers of Bone Remodelling Origin of Collagen Cross Links N-TELOPEPTIDE REGION HELICAL REGION C-TELOPEPTIDE REGION CTx NTx Pyr Dpd Watts, N. B. Clin Chem 1999 45:1359-68, with permission. Learning Objectives • Overview of osteogenesis imperfecta in adults – Classification of OI – Bone health in adulthood • Investigation of OI – Role of DXA – Role of bone turnover markers • Medication options • Case Studies Medications for OI (off-label use of medications) • Bisphosphonates – Alendronate – Risedronate – Ibandronate – Zoledronate • Parathyroid hormone – rhPTH1-34 • RANKL inhibitor – Denosumab Cochrane Review on Bisphosphonates in OI Dwan K, Phillipi CA, Steiner RD, Basel D. The Cochrane Library 2014, Issue 7 • Current evidence demonstrates that oral or intravenous bisphosphonates increase bone mineral density in children and adults • These were not shown to be different in their ability to increase bone mineral density. • It is unclear whether treatment consistently decreases fractures, though multiple studies report this independently and no studies report an increased fracture rate. • The studies did not show bisphosphonates conclusively improve clinical status (reduce pain; improve growth and functional mobility) in people with osteogenesis imperfecta. • Given their current widespread and expected continued use, the optimal method, duration of therapy and long-term safety of bisphosphonate therapy require further investigation. • In addition, attention should be given to long-term fracture reduction and improvement in quality of life indicators. Study of Teriparatide in Adults with OI • Evaluation of teriparatide treatment in adults with osteogenesis imperfecta. Eric S. Orwoll, Jay Shapiro, Sandra Veith, Ying Wang, Jodi Lapidus, Chaim Vanek, Jan L. Reeder, Tony M. Keaveny, David C. Lee, Mary A. Mullins, Sandesh C.S. Nagamani, and Brendan Lee • Oregon Health and Science University, Portland, Oregon, USA. Kennedy Krieger Institute, Baltimore, Maryland, USA. ON Diagnostics, Berkeley, California, USA. Departments of Mechanical Engineering and Bioengineering, UC Berkeley, Berkeley, California, USA. Baylor College of Medicine, Houston, Texas, USA. Howard Hughes Medical Institute, Houston, Texas, USA. • J Clin Invest. 2014;124(2):491–498. doi:10.1172/JCI71101 Study of Teriparatide in Adults with OI BMD Response to Teriparatide BTM Response to Teriparatide Bone Strength Response to Teriparatide Learning Objectives • Overview of osteogenesis imperfecta in adults – Classification of OI – Bone health in adulthood • Investigation of OI – Role of DXA – Role of bone turnover markers • Medication options • Case Studies