Bone Abstracts

Objectives: A common feature of nearly all forms of osteogenesis imperfecta (OI) is a hypermineralized bone matrix. Null mutations in SERPINF1, encoding the potent antiangiogenic factor PEDF, lead to type VI OI with excessive osteoid formation, abnormal osteoblast-osteocyte development and increased matrix mineralization. Recently, atypical type VI OI has been delineated, caused by a loss-of-function mutation (p.S40L) in IFITM5 the causative gene for type V OI. The 6 cases rep...

Objectives: To elucidate the incidence and risk factors of skeletal toxicity in children with ALL treated with the dexamethasone-based DCOG-ALL9 protocol.Methods: Prospectively, the cumulative incidence of fractures was assessed in 672 patients and compared between different subgroups using the log-rank test. Serial measurements of bone mineral density of the lumbar spine (BMDLS) were performed in 399 ALL patients using dual energy X-ray absor...

The development of optimally performing biomaterials mimicking the natural physiological processes underlying bone repair is essential for non-healing large bone lesions. We sought to develop scaffolds that fill the lesions and improve bone healing. We tested three scaffolds comprised of varying percentages of lactide (LA), caprolactone (CL), and methacrylate produced by two-photon photopolymerization; LCM 3 (8:2; 85%), 4 (9:1; 90%), and 6 (9:1; 40%). We hypothesized that the ...

Non-healing fractures caused by trauma, disease or tumour resection demand the use of bone grafts to support and stimulate the healing process. We sought to develop and evaluate the effect of a novel bioactive biodegradable biomaterial designed to fill large bone lesions and to improve bone healing. We used two-photon polymerised synthetic polymer scaffolds composed of lactide (LA), caprolactone (CL), and methacrylate (MA) with varying LA: CL ratio and percentage of methacryla...

Objectives: We sought to identify the disease-causing mutations in two unrelated girls with a clinical diagnosis of osteogenesis imperfecta type IV.Methods: Whole-exome sequencing and cellular studies in skin fibroblasts were conducted.Results: We identified two homozygous variants in SPARC (NM_003118.3; c.497G>A (p.Arg166His) in individual 1; c.787G>A (p.Glu263Lys) in individual 2). Secreted protein, acidic, cyste...

The transplantation of autologous bone graft represents the ‘gold standard’ treatment for large bone defects, despite the harvesting co-morbidity and limited availability. An alternative scaffold-based approach is presented. Our aim was to investigate to what degree structured scaffolds alone, or in combination with biological stimuli, allow guiding tissue regeneration. Scaffolds consisting of medical-grade polycaprolactone and tricalcium phosphate microparticles, co...

Introduction: Parathyroid hormone (PTH) measurement is of use in i) differential diagnosis of hypercalcaemia and ii) patients with renal impairment at risk of bone disease. PTH immunoassays are complicated by cross-reactivity with truncated (inactive) variant forms, which accumulate in patients with renal impairment. PTH assay variability is a critical governance issue in renal medicine, suggesting an MS-based reference method is required.Aim: To develop...

Aim: Evaluate the differences with densitometry after 2-year treatment in patients with breast cancer and LBMD.Materials and methods: A 2 year duration longitudinal study was done in patients diagnosed with breast cancer sent to the Rheumatology Osteoporosis Unit in Hospital d’Ontinyent, who required supplements of calcium and vitamin D+bisphosphonates after a risk fracture study. Socio-demographic data, breast tumor characteristics, risk f...

Denosumab (DMAb) has a unique profile of bone resorption inhibition: CTX decreases rapidly by 3 days and inhibition is released at the end of the 6-month dosing interval, when DMAb serum levels decrease (McClung NEJM 2006). The dynamic CTX inhibition profile is not curtailed by continued treatment. In the 3-year FREEDOM study, CTX values at 6 months were influenced by baseline CTX values and days since the 1st injection (Eastell JBMR 2011). With 3 additional ...

BA058 is being developed as an anabolic therapy for the treatment of osteoporosis. Daily BA058 SC injection has produced promising safety and efficacy results in early clinical studies, and is currently enrolling in a Phase 3 fracture prevention study. There is, however, a significant need for an alternative to injection that improves patient convenience and compliance. We have investigated the use of a solid Microstructured Transdermal System (3M) for transdermal (TD) deliver...