ObjectiveTo compare magnetic resonance images (MRIs) of the sacroiliac (SI) joints of healthy subjects and individuals with known mechanical strain acting upon the SI joints to those of patients with axial spondyloarthritis (SpA) and patients with chronic back pain.MethodsThree readers who had received standardized training and were blinded with regard to study group randomly scored MRIs of the SI joints of 172 subjects, including 47 healthy individuals without current or past back pain, 47 axial SpA patients from the Spondyloarthritis Caught Early (SPACE) cohort (with a previous MRI confirmed positive for sacroiliitis), 47 controls with chronic back pain (irrespective of MRI results) from the SPACE cohort, 7 women with postpartum back pain, and 24 frequent runners. MRIs were scored according to the Assessment of SpondyloArthritis international Society (ASAS) definition and Spondyloarthritis Research Consortium of Canada (SPARCC) index.ResultsOf the 47 healthy volunteers, 11 (23.4%) had an MRI positive for sacroiliitis, compared to 43 (91.5%) of 47 axial SpA patients and 3 (6.4%) of 47 patients with chronic back pain. Three (12.5%) of the 24 runners and 4 (57.1%) of the 7 women with postpartum back pain had a positive MRI. Using a SPARCC cutoff of ≥2 for positivity, 12 (25.5%) of 47 healthy volunteers, 46 (97.9%) of 47 positive axial SpA patients, 5 (10.6%) of 47 controls with chronic back pain, 4 (16.7%) of 24 runners, and 4 (57.1%) of 7 women with postpartum back pain had positive MRIs. Deep bone marrow edema (BME) lesions were not found in healthy volunteers, patients with chronic back pain, or runners, but were found in 42 (89.4%) of 47 positive axial SpA patients and in 1 (14.3%) of 7 women with postpartum back pain.ConclusionA substantial proportion of healthy individuals without current or past back pain has an MRI positive for sacroiliitis according to the ASAS definition. Deep (extensive) BME lesions are almost exclusively found in axial SpA patients.
Nebulin is a giant filamentous protein that is coextensive with the actin filaments of the skeletal muscle sarcomere. Nebulin mutations are the main cause of nemaline myopathy (NEM), with typical adult patients having low expression of nebulin, yet the roles of nebulin in adult muscle remain poorly understood. To establish nebulin's functional roles in adult muscle, we studied a novel conditional nebulin KO (Neb cKO) mouse model in which nebulin deletion was driven by the muscle creatine kinase (MCK) promotor. Neb cKO mice are born with high nebulin levels in their skeletal muscles, but within weeks after birth nebulin expression rapidly falls to barely detectable levels Surprisingly, a large fraction of the mice survive to adulthood with low nebulin levels (<5% of control), contain nemaline rods and undergo fiber-type switching toward oxidative types. Nebulin deficiency causes a large deficit in specific force, and mechanistic studies provide evidence that a reduced fraction of force-generating cross-bridges and shortened thin filaments contribute to the force deficit. Muscles rich in glycolytic fibers upregulate proteolysis pathways (MuRF-1, Fbxo30/MUSA1, Gadd45a) and undergo hypotrophy with smaller cross-sectional areas (CSAs), worsening their force deficit. Muscles rich in oxidative fibers do not have smaller weights and can even have hypertrophy, offsetting their specific-force deficit. These studies reveal nebulin as critically important for force development and trophicity in adult muscle. The Neb cKO phenocopies important aspects of NEM (muscle weakness, oxidative fiber-type predominance, variable trophicity effects, nemaline rods) and will be highly useful to test therapeutic approaches to ameliorate muscle weakness.
BackgroundInflammation shown on MRI of the sacroiliac joint (MRI-SI) is prevalent in axSpA (±30%) but the specificity is not well known.ObjectivesTo compare MRI of the sacroiliac joints (MRI-SI) of healthy, symptomless individuals and those with known mechanical strain acting upon SI joints to axial spondyloarthritis (axSpA) and chronic back pain (CBP) patients.MethodsThree trained, calibrated and blinded readers randomly scored MRI-SI of 172 subjects: 47 healthy individuals without current/past back pain(;1 47 axSpA patients from the SPondyloArthritis Caught Early (SPACE) cohort (with a previously confirmed positive MRI-SI); 47 CBP controls (irrespective of MRI-SI results) from the SPACE cohort; 7 women with postpartum back pain; and 24 frequent runners. Readers scored according to the ASAS definition and SPARCC score.ResultsOf the 47 healthy volunteers, 11 (23.4%) had a positive MRI-SI, compared to 43 of 47 (91.5%) positive axSpA patients and 3 of 47 (6.4%) CBP patients. Of the runners, 3 of 24 (12.5%) and of the women with postpartum back pain 4 of 7 (57.1%) had a positive MRI-SI. Using a SPARCC cut-off of ≥2 for positivity, 12/47 and healthy volunteers (25.5%), 46/47 positive axSpA patients (97.9%), 5/47 CBP controls (10.6%), 4/24 runners (16.7%) and 4/7 women with postpartum back pain (57.1%) were positive. ‘Deep’ BME-lesions were not found in healthy volunteers, CBP patients and runners, but in 38 of 47 positive axSpA patients (80.9%) and in 1 of 7 women with postpartum back pain (14.3%).ConclusionsA substantial proportion of healthy individuals without current/past back pain has a positive MRI-SI according to the ASAS definition. Deep (extensive) BME lesions are exclusively found in axSpA patients.Reference[1] van Hoeven L, Luime JJ, et al. Bone marrow edema and structural lesions in the sacroiliac joint in a large cohort of patients with axial spondyloarthritis, chronic low back pain and healthy controls. ACR Annu Meet2013;2889.Disclosure of InterestNone declared
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