Osteoarthritis in osteogenesis imperfecta: A nationwide register-based cohort study.

BACKGROUND: Osteogenesis Imperfecta (OI) is a genetic disease characterized by skeletal fragility. Collagen type 1 is found in many tissues and collagen abnormalities may result in organ specific symptomatology. Musculoskeletal pain is a known issue for patients with OI, osteoarthritis (OA) can be a likely cause. Only few studies have investigated the relationship between OI and OA but demonstrated a greater propensity in OI patients to develop rapidly progressing OA. Therefore, we wanted to investigate if OA is more frequent in patients with OI compared to the general population. OBJECTIVE: To evaluate the risk of osteoarthritis in patients with OI. DESIGN: A Danish nationwide, population-based and register-based longitudinal open cohort study. PARTICIPANTS: From 1977 to 2019, all patients registered with an OI diagnosis and a reference population matched on age and sex 5:1. MEASUREMENTS: Sub-hazard ratios for any, hip, and knee osteoarthritis comparing the OI cohort to the reference population. RESULTS: We identified 907 patients with OI (493 women) and included 4535 patients in the reference population (2465 women). The Sub Hazard Ratio was 2.20 [95% CI 1.73-2.79] for any osteoarthritis with 11.4% of the OI population and 5.4% of the reference population being registered. We found lower incidences of upper extremity joint OA compared to lower joint OA, but upper extremity joint OA was significantly more frequent in the OI population 2.1% vs 0.6%, SHR 3.19 [95% CI 1.78-5.70]. CONCLUSION: Patients with OI have a higher risk of OA than the reference population. MINIABSTRACT: Osteogenesis Imperfecta (OI) is a hereditary connective tissue disorder with skeletal fragility and extraskeletal manifestations. Osteoarthritis is a frequent joint disease and the incidence increases with age. In a population-register-based study, the risk of osteoarthritis was higher in patients with OI at an earlier age compared to a reference population.

Treatment of Osteoporosis: Unmet Needs and Emerging Solutions.

Efficient therapies are available for the treatment of osteoporosis, however, there are still unmet needs. Anti-resorptive therapies only increase bone mineral density to a certain extent and reduce the risk of non-vertebral fractures by 20%, only one anabolic option is available in most parts of the world-the effect of which levels off over time, and the evidence for combination therapy targeting both resorption and formation is limited. In addition, identification and treatment of patients with high and imminent fracture risk following a recent fracture and long-term adherence to treatment are 2 other very prominent challenges to the management of osteoporosis. The current review will focus on emerging osteoporosis treatments and optimized use of the existing treatments that may help overcome the currently unmet needs in the management of osteoporosis.

Chronic ischemic mitral regurgitation induced in pigs by catheter-based coronary artery occlusion.

BACKGROUND AND AIM OF THE STUDY: Ischemic mitral regurgitation (IMR) appears in 20-50% of patients after acute myocardial infarction, and entails an increased long-term mortality. In order to compensate for the diversified pathology in humans, this disease entity has been developed in pigs in order to allow investigations of therapeutic options against IMR. METHODS: The left circumflex coronary artery was occluded using catheter-based intracoronary coil deployment in 24 female pigs (body weight 50 kg). This was followed by a rapid pacing protocol. The left ventricular (LV) volumes at end-diastole and end-systole were assessed with multi-slice, short-axis cardiovascular magnetic resonance imaging. From these image sequences the mitral regurgitant volume (MRV) was quantified by subtracting the aortic flow volume from the LV stroke volume. The extension of myocardial infarction was quantified using a delayed contrast (gadolinium) enhancement technique. Five pigs served as controls. RESULTS: During the procedure, seven animals died due to intractable ventricular fibrillation and technical problems. Eleven of the remaining 17 pigs fitted with coils survived the six-week follow up period. Of these animals, nine had a transmural inferior-lateral LV wall infarction and significant IMR (MRV = 10.5 +/- 6.3 ml). None of the control pigs had IMR. There was a positive correlation between the size of the myocardial infarction and the mitral regurgitant volume. CONCLUSION: A catheter-based porcine model has been established for chronic IMR which balances between an adequate infarct size and acceptable mortality. The model provides a platform for further investigations of the geometric and hemodynamic features of chronic IMR in order to identify potential geometric targets of the disease. The model also allows the evaluation of innovative surgical approaches to reverse LV remodeling.