A single infusion of zoledronic acid produces more rapid, more complete, and more sustained responses in Paget's disease than does daily treatment with risedronate.

ObjectivesTo investigate baricitinib (LY3009104, formerly INCB028050), a novel, oral inhibitor of JAK1/JAK2 in patients with moderate to severe rheumatoid arthritis (RA) despite treatment with methotrexate.MethodsIn this phase IIb study, 301 patients were randomised 2:1:1:1:1 to receive once daily doses of placebo or 1, 2, 4 or 8 mg baricitinib for 12 weeks. Patients assigned to 2, 4 and 8 mg baricitinib continued blinded treatment for an additional 12 weeks. Patients assigned to placebo or 1 mg baricitinib were reassigned to 2 mg twice daily or 4 mg once daily baricitinib between weeks 12–24. The primary endpoint was the proportion of patients in the combined 4 and 8 mg groups achieving an American College of Rheumatology 20% (ACR20) response versus placebo at week 12.ResultsSignificantly more patients in the combined baricitinib 4 and 8 mg groups compared with placebo achieved an ACR20 response at week 12 (76% vs 41%, p<0.001). At week 12, significant differences versus placebo were also observed in patients achieving ACR50, ACR70 and remission as measured by Disease Activity Score for 28-joint counts, Clinical Disease Activity Index and Simplified Disease Activity Index. Patients receiving 2, 4, or 8 mg baricitinib maintained or improved in all measures through 24 weeks. Similar proportions of patients experienced at least one adverse event in the placebo and baricitinib groups. Serious infections developed in three patients receiving baricitinib. No cases of tuberculosis, herpes zoster, opportunistic infections or deaths were reported. Dose-dependent decreases in haemoglobin were observed with baricitinib.ConclusionsBaricitinib improved the signs and symptoms of RA in methotrexate inadequate responders with active disease. Baricitinib was well tolerated with no unexpected safety findings through week 24.Trial registration numberNCT01185353.

Objective-The performance characteristics of hyaline articular cartilage measurement on magnetic resonance imaging (MRI) need to be accurately delineated before widespread application of this technology. Our objective was to assess the rate of natural disease progression of cartilage morphometry measures from baseline to 1 year in knees with osteoarthritis (OA) from a subset of participants from the Osteoarthritis Initiative (OAI).Methods-Subjects included for this exploratory analysis are a subset of the approximately 4700 participants in the OAI Study. Bilateral radiographs and 3T MRI (Siemans Trio) of the knees and clinical data were obtained at baseline and annually in all participants. 160 subjects from the OAI Progression subcohort all of whom had both frequent symptoms and, in the same knee, radiographic OA based on a screening reading done at the OAI clinics were eligible for this exploratory analysis. One knee from each subject was selected for analysis. 150 participants were included. Using sagittal 3D DESSwe (double echo, steady-state sequence with water excitation) MR images from the baseline and 12 follow-up month visit, a segmentation algorithm was applied to the cartilage plates of the index knee to compute the cartilage volume, normalised cartilage volume (volume normalised to bone surface interface area), and percentage denuded area (total cartilage bone interface area denuded of cartilage).Results-Summary statistics of the changes (absolute and percentage) from baseline at 1 year and the standardised response mean (SRM), ie, mean change divided by the SD change were calculated. On average the subjects were 60.9 years of age and obese, with a mean body mass index of 30. Despite being extraordinarily prevalent OA remains a condition that is poorly understood, and a condition for which available effective therapeutic options are limited to symptomatic treatment. The development of therapies aimed at joint preservation in OA is constrained by the slow progress of the condition, its heterogeneous clinical manifestations and the need for long-term follow-up to observe changes in structure. NIH Public AccessNew technologies may improve the assessment of early disease development, and progression, and could greatly facilitate measurement of structural outcomes in OA clinical trials. Foremost among these is magnetic resonance imaging (MRI), a sensitive non-invasive method for assessing joint morphology. 5 6 MRI is ideally suited for imaging arthritic joints as: (1) it is free of ionising radiation; (2) it defines both calcified as well as soft tissue joint components; and (3) its tomographic viewing perspective obviates morphological distortion, magnification and superimposition. MRI of the knee can directly visualise hyaline articular cartilage and cover the whole joint in one examination, meaning that the cartilage defects in the joint can be visualised directly regardless of their location. 5Although yet to be formally accepted by regulatory authorities, many experts now agree that MRI may b...

Objective. Magnetic resonance imaging (MRI) and radiography are established imaging modalities for the assessment of knee osteoarthritis (OA). The objective of our study was to compare the responsiveness of radiographic joint space width (JSW) with MRI-derived measures of cartilage morphometry for OA progression in participants from the Osteoarthritis Initiative (OAI). Methods. This study examined the baseline and 12-month visits of a subset of 150 subjects from the OAI. Measurement of radiographic JSW was facilitated by the use of automated software that delineated the femoral and tibial margins of the joint. Measures of medial compartment minimum JSW and JSW at fixed locations were compared with cartilage morphometry measures derived from MRI. The results were stratified by Kellgren/Lawrence (K/L) scale grade and by tibiofemoral anatomic axis angle. In order to examine the relative responsiveness of various techniques, we calculated the standardized response mean (SRM) between the 2 visits. Results. The SRM for radiographic JSW measured at the optimal location was ؊0.32 compared with ؊0.39 for the most responsive MRI measure. For the subgroup with a K/L scale grade of 2 or 3, the most responsive SRM values were ؊0.34 for radiographic JSW and ؊0.42 for MRI. Conclusion. Our study demonstrates that new measures using a software analysis of digital knee radiographic images are comparable with MRI in detecting OA progression, and potentially superior when considering the cost-effectiveness of the 2 imaging modalities.