Osteogenesis imperfecta in adults: phenotypic characteristics and response to treatment in an Irish cohort.

BACKGROUND: Osteogenesis imperfecta (OI) is a heritable disorder of variable phenotype that is characterised by bone fragility and frequent fractures, with deformities and short stature in more severe cases. AIMS: We sought to review the response to treatment in a cohort of adult patients with OI. METHODS: Charts of 16 patients with OI attending a metabolic bone disease clinic were reviewed, particularly with respect to the response to treatment using bisphosphonates and recombinant human parathyroid hormone (rhPTH). The response to treatment was assessed by monitoring bone mineral density (BMD) and bone turnover markers (BTMs). RESULTS: In response to bisphosphonate therapy, median (range) BMD increased at the spine by 15.1(6.9-43.7) %. In response to rhPTH in 2 cases, spinal BMD increased by 40.3 and 27.2 %. CONCLUSION: OI is debilitating disorder, but the course of the disease may be altered by treatment that increases BMD such as bisphosphonates and rhPTH. Both serial BMD and BTM aid in assessing response to intervention. Further study is needed with regard to fracture prevention.

Rat islet cell aggregates are superior to islets for transplantation in microcapsules.

AIMS/HYPOTHESIS: Islet transplantation is a promising treatment for type 1 diabetes but is hampered by a shortage of donor human tissue and early failure. Research on islet cell transplantation includes finding new sources of cells and immunoisolation to protect from immune assault and tumourigenic potential. Small islet cell aggregates were studied to determine if their survival and function were superior to intact islets within microcapsules because of reduced oxygen transport limitation and inflammatory mediators. METHODS: Islet cell aggregates were generated by dispersing rat islets into single cells and allowing them to re-aggregate in culture. Rat islets and islet cell aggregates were encapsulated in barium alginate capsules and studied when cultured in low (0.5% or 2%) or normal (20%) oxygen, or transplanted into mice. RESULTS: Encapsulated islet cell aggregates were able to survive and function better than intact islets in terms of oxygen-consumption rate, nuclei counts, insulin-to-DNA ratio and glucose-stimulated insulin secretion. They also had reduced expression of pro-inflammatory genes. Islet cell aggregates showed reduced tissue necrosis in an immunodeficient transplant model and a much greater proportion of diabetic xenogeneic transplant recipients receiving islet cell aggregates (tissue volume of only 85 islet equivalents) had reversal of hyperglycaemia than recipients receiving intact islets. CONCLUSIONS/INTERPRETATION: These aggregates were superior to intact islets in terms of survival and function in low-oxygen culture and during transplantation and are likely to provide more efficient utilisation of islet tissue, a finding of importance for the future of cell therapy for diabetes.