Loss of RANKL in osteocytes dramatically increases cancellous bone mass in the osteogenesis imperfecta mouse (oim)

Osteogenesis imperfecta (OI) is characterized by osteopenia and bone fragility, and OI patients during growth often exhibit high bone turnover with the net result of low bone mass. Recent evidence shows that osteocytes significantly affect bone remodeling under physiological and pathological conditions through production of osteoclastogenic cytokines. The receptor activator of nuclear factor kappa-B ligand (RANKL) produced by osteocytes for example, is a critical mediator of bone loss caused by ovariectomy, low-calcium diet, unloading and glucocorticoid treatment. Because OI bone has increased density of osteocytes and these cells are embedded in matrix with abnormal type I collagen, we hypothesized that osteocyte-derived RANKL contributes to the OI bone phenotype. In this study, the conditional loss of RANKL in osteocytes in oim/oim mice (oim-RANKL-cKO) resulted in dramatically increased cancellous bone mass in both the femur and lumbar spine compared to oim/oim mice. Bone cortical thickness increased significantly only in spine but ultimate bone strength in the long bone and spine was minimally improved in oim-RANKL-cKO mice compared to oim/oim mice. Furthermore, unlike previous findings, we report that oim/oim mice do not exhibit high bone turnover suggesting that their low bone mass is likely due to defective bone formation and not increased bone resorption. The loss of osteocyte-derived RANKL further diminished parameters of formation in oim-RANKL-cKO. Our results indicate that osteocytes contribute significantly to the low bone mass observed in OI and the effect of loss of RANKL from these cells is similar to its systemic inhibition. Keywords: Osteocyte, RANKL, Osteogenesis imperfecta, Bone fragilit

Predictors of No-Show in Neurology Clinics

In this study, we aim to identify predictors of a no-show in neurology clinics at our institution. We conducted a retrospective review of neurology clinics from July 2013 through September 2018. We compared odds ratio of patients who missed appointments (no-show) to those who were present at appointments (show) in terms of age, lead-time, subspecialty, race, gender, quarter of the year, insurance type, and distance from hospital. There were 60,012 (84%) show and 11,166 (16%) no-show patients. With each day increase in lead time, odds of no-show increased by a factor of 1.0019 (p p ≤ 0.0001, OR = 0.49) compared to older (age ≥ 60) patients and in women (p p p = 0.03, OR = 0.6871) and American Indian/Alaskan Native (p = 0.055, OR = 0.6318) as compared to White/Caucasian. Patients with Medicare (p p < 0.0001, OR = 1.3354) had higher odds of no-show compared to other insurance. Young age, female, Black/African American, long lead time to clinic appointments, Medicaid/Medicare insurance, and certain subspecialties (resident and stroke clinics) are associated with high odds of no show. Possible suggested interventions include better communication and flexible appointments for the high-risk groups as well as utilizing telemedicine

Inter-Rater Reliability of Clinical Testing for Laxity After Knee Arthroplasty

Background: The clinical examination for laxity has been considered a mainstay in evaluation of the painful knee arthroplasty, especially for the diagnosis of instability. More than 10 mm of anterior-posterior (AP) translation in flexion has been described as important in the diagnosis of flexion instability. The inter-observer reliability of varus/valgus and AP laxity testing has not been tested. Methods: Ten subjects with prior to total knee arthroplasty (TKA) were examined by 4 fellowship-trained orthopedic knee arthroplasty surgeons. Each surgeon evaluated each subject in random order and was blinded to the results of the other surgeons. Each surgeon performed an anterior drawer test at 30 and 90 degrees of flexion and graded the instability as 0-5 mm, 5-10 mm or \u3e10 mm. Varus-valgus testing was also graded. Motion capture was used during the examination to determine the joint position and estimate joint reaction force during the examination. Results: Inter-rater reliability (IRR) was poor at 30 and 90 degrees for both the subjective rater score and the measured AP laxity in flexion (k = 018-0.22). Varus-valgus testing similarly had poor reliability. Force applied by the rater also had poor IRR. Conclusion: Clinical testing of knee laxity after TKA has poor reliability between surgeons using motion analysis. It is unclear if this is from differences in examiner technique or from differences in pain or quadriceps function of the subjects. Instability after TKA should not be diagnosed strictly by clinical testing and should involve a complete clinical assessment of the patient