Bisphosphonate Use and Risk of Atypical Femoral Fractures: A Danish Case Cohort Study with Blinded Radiographic Review.

CONTEXT: Prolonged bisphosphonate (BP) treatment for osteoporosis prevents hip and other fractures but causes atypical femoral fractures (AFF). OBJECTIVE: To establish the relationship between patterns of BP use and the risk of AFF and hip fractures. Other potential risk factors for AFF were also examined. DESIGN: Population-based case-cohort study. SETTING: The Danish National Healthcare system maintains longitudinal records of medication use, healthcare utilization, and x-ray images. PARTICIPANTS: Among all 1.9 million Danish adults ≥50, those with subtrochanteric or femoral shaft fractures between 2010-2015 (n = 4,973) were identified and compared to a random sample (n = 37,021). PREDICTORS: Bisphosphonate use was collected from 1995-2015. MAIN OUTCOME MEASURES: Fracture radiographs (n = 4,769) were reviewed by blinded study radiologists to identify AFFs (n = 181) using established criteria. Traditional hip fractures in the random sample (n = 691) were identified by ICD-10. RESULTS: Compared to <1 year of BP use, 5-7 years of use was associated with a 7-fold increase in AFF [adjusted HR = 7.29 (CI: 3.07,17.30)]; the risk of AFF fell quickly after discontinuation. The 5-year number-needed-to-harm for one AFF was 1,424, while the 5-year number-needed-to-treat to prevent one hip fracture was 56. Glucocorticoid and proton pump inhibitor use were independently associated with increased AFF risk. Thirty-one percent of those with AFF had no BP exposure. CONCLUSIONS: The risk of AFF increases with duration of BP use but the beneficial effects of BP therapy in adults ≥50 dramatically exceed this increased risk. Nearly one-third of those with AFF have no BP exposure.

Diffusion-weighted MR imaging in chronic non-bacterial osteitis: Proof-of-concept of the apparent diffusion coefficient as an outcome measure.

BACKGROUND: The apparent diffusion coefficient (ADC), as determined by whole-body diffusion-weighted MRI, may be useful as an outcome measure for monitoring response to treatment in chronic non-bacterial osteitis. PURPOSE: To test and demonstrate the feasibility of ADC-measurement methods for use as outcome measure in chronic non-bacterial osteitis. MATERIALS AND METHODS: Using data from a randomized pilot study, feasibility of change-score ADC between baseline and second MRI (ΔADC12) and third MRI (ΔADC13) as outcome measure was assessed in three settings: "whole-lesion," "single-slice per lesion," and "index-lesion per patient". Bone marrow edema lesions were depicted on short tau inversion recovery sequence at baseline and copied to ADC maps at the three time-points. Correlations between the three settings were measured as were analysis of variances. Discriminant validity was assessed as inter- and intra-observer reproducibility and smallest detectable change. RESULTS: 12 subjects were enrolled, and MRI was performed at baseline and weeks 12 and 36. Pearson correlation was high (r > 0.86; p ≤ 0.01) for ΔADC between single-slice-whole-lesion and whole-lesion-index-lesion and tended to be significant for single-slice-index-lesion settings (p = 0.06). For ΔADC12 and ΔADC13, Bland-Altman plots showed small differences (0.02, 0.03) and narrow 95% limits-of-agreement (-0.13-0.09, -0.07-0.05 µm2/s) between whole-lesion and single-slice ROI settings. Inter-observer reproducibility measured by intra-class correlation coefficient was poor-to-fair (range: 0.09-0.31), whereas intra-observer reproducibility was good-to-excellent (range: 0.67-0.90). Smallest detectable changes were between 0.21-0.28 µm2/s. CONCLUSION: ADC change-score as outcome measure was feasible, and the single-slice per lesion ROI setting performed almost equally to whole-lesion setting resulting in reduced assessment time.

What Level of Inflammation Leads to Structural Damage in the Sacroiliac Joints? A Four-Year Magnetic Resonance Imaging Follow-Up Study of Low Back Pain Patients.

OBJECTIVE: Sacroiliac (SI) joint bone marrow edema (BME) is considered to be pivotal in the detection of early spondyloarthritis. However, the link between BME and development of spondyloarthritis-related bone remodeling remains unclear. This study was undertaken to investigate the evolution of BME and structural lesions in the SI joints over time. METHODS: Baseline and 4-year follow-up magnetic resonance imaging scans were conducted in 604 patients ages 18-40 years who were referred with low back pain to an outpatient spine clinic. Eight SI joint regions were scored for BME and categorized as absent, limited (<25% of subcortical bone region), intermediate (25-50%), or extensive (>50%). Structural lesions including erosions and fat lesions were scored as absent or present. RESULTS: SI joint BME was seen at either time point (baseline or at 4 years) in 41% of participants but was persistent at both time points in only 16% of participants. Structural SI joint lesions developed according to the extent of BME at baseline: limited, intermediate, and extensive BME (as compared to absent BME) were independently associated with erosion at follow-up with odds ratios (ORs) of 3, 5, and 46, respectively, and with fat lesions (ORs 3, 7, and 33, respectively). In regions with limited and intermediate BME at baseline, 60% and 50% had resolved by follow-up, respectively, while only 2% and 7% had evolved into extensive BME by follow-up. CONCLUSION: While extensive SI joint BME was a strong independent predictor of development of structural lesions, limited and intermediate BME were mostly transient and only rarely evolved into extensive BME or structural lesions. These findings enhance our understanding of the natural development of SI joint lesions and indicate different progression patterns for limited/intermediate versus extensive BME, possibly due to different etiologies.

Imaging Methodology for Hip Preservation: Techniques, Parameters, and Thresholds.

The concept of hip impingement and hip-preserving surgery has been appreciated in more detail since 2001 when a new surgical approach was reported and a hypothesis linking femoroacetabular impingement (FAI) with osteoarthritis was presented. Paralleling the introduction of hip arthroscopy, these events led to an increasing interest in the hip, and the number of publications has risen rapidly over the past 15 years, despite limited evidence levels and inconsistent methodology. Accordingly, etiology, diagnosis, prognosis, and the effects of treatment for FAI are still elusive due to a number of uncertainties and a lack of clear diagnostic criteria.Future research must focus on developing high-quality scientific studies, so thorough and reproducible methodology is needed. This review provides researchers, radiologists, and clinicians with a comprehensive approach to hip imaging with a focus on strategies to help guide the clinical diagnosis. Using evidence from current literature and knowledge from experienced clinicians, some of the imaging methodology challenges are deciphered.

Association Between Inflammatory Back Pain Characteristics and Magnetic Resonance Imaging Findings in the Spine and Sacroiliac Joints.

OBJECTIVE: To investigate the association between magnetic resonance imaging (MRI) findings at the sacroiliac (SI) joints and vertebral endplates and pain characteristics assumed to be indicative of axial inflammation. METHODS: Patients ages 18-40 years with persistent low back pain referred to an outpatient spine clinic participated, including an unknown proportion of axial spondyloarthritis patients. Data included MRI of the spine and SI joints and self-reported responses to questions covering the Calin, Berlin, Assessment of Spondyloarthritis International Society, and Bailly inflammatory back pain (IBP) definitions. RESULTS: In the 1,020 included patients, 53% were women, and the median age was 33 years. Positive associations were found between the SI joint MRI findings and pain characteristics, odds ratios ranging from 1.4 to 2.7. SI joint bone marrow edema (BME) was associated with morning stiffness >60 minutes, and SI joint erosions with the Calin, Berlin, and Bailly IBP definitions, alternating buttock pain, and good response to nonsteroidal antiinflammatory drugs. SI joint fatty marrow deposition (FMD) was associated with insidious onset, and SI joint sclerosis with pain at night. In addition, the spinal MRI changes were associated with IBP, odds ratios ranging from 1.4 to 2.0; vertebral endplate BME was associated with morning stiffness, and vertebral endplate FMD with the Calin and Bailly IBP definitions, improvement with exercise, morning stiffness >30 minutes, and pain worst in the morning. CONCLUSION: The identified associations between inflammatory MRI findings and pain characteristics indicate that axial inflammation to some degree induces a specific pain pattern. Thus, the results add to knowledge of axial inflammatory processes. However, all identified associations were weak, which compromises the use of IBP as a marker of axial inflammation.

Prevalence of degenerative and spondyloarthritis-related magnetic resonance imaging findings in the spine and sacroiliac joints in patients with persistent low back pain.

OBJECTIVE: To estimate the prevalence of degenerative and spondyloarthritis (SpA)-related magnetic resonance imaging (MRI) findings in the spine and sacroiliac joints (SIJs) and analyse their association with gender and age in persistent low back pain (LBP) patients. METHODS: Degenerative and SpA-related MRI findings in the whole spine and SIJs were evaluated in Spine Centre patients aged 18-40 years with LBP. RESULTS: Among the 1,037 patients, the prevalence of disc degeneration, disc contour changes and vertebral endplate signal (Modic) changes were 87 % (±SEM 1.1), 82 % (±1.2) and 48 % (±1.6). All degenerative spinal findings were most frequent in men and patients aged 30-40 years. Spinal SpA-related MRI findings were rare. In the SIJs, 28 % (±1.4) had at least one MRI finding, with bone marrow oedema being the most common (21 % (±1.3)). SIJ erosions were most prevalent in patients aged 18-29 years and bone marrow oedema in patients aged 30-40 years. SIJ sclerosis and fatty marrow deposition were most common in women. SIJ bone marrow oedema, sclerosis and erosions were most frequent in women indicating pregnancy-related LBP. CONCLUSION: The high prevalence of SIJ MRI findings associated with age, gender, and pregnancy-related LBP need further investigation of their clinical importance in LBP patients. KEY POINTS: • The location of vertebral endplate signal changes supports a mechanical aetiology. • Several sacroiliac joint findings were associated with female gender and pregnancy-related back pain. • Sacroiliac joint bone marrow oedema was frequent and age-associated, indicating a possible degenerative aetiology. • More knowledge of the clinical importance of sacroiliac joint MRI findings is needed.

Decreased plasma levels of soluble CD18 link leukocyte infiltration with disease activity in spondyloarthritis.

INTRODUCTION: Spondyloarthritis (SpA) comprises a group of diseases often associated with HLA-B27 and characterized by inflammation of the entheses and joints of the axial skeleton. The inflammatory process in SpA is presumably driven by innate immune cells but is still poorly understood. Thus, new tools for monitoring and treating inflammation are needed. The family of CD18 integrins is pivotal in guiding leukocytes to sites of inflammation, and CD18 hypomorphic mice develop a disease resembling SpA. Previously, we demonstrated that altered soluble CD18 (sCD18) complexes in the blood and synovial fluid of patients with arthritis have anti-inflammatory functions. Here, we study the mechanisms for these alterations and their association with SpA disease activity. METHODS: Plasma levels of sCD18 in a study population with 84 patients with SpA and matched healthy controls were analyzed with a time-resolved immunoflourometric assay (TRIFMA). Binding of sCD18 to endothelial cells and fibroblast-like synoviocytes (FLSs) was studied with confocal microscopy. Shedding of CD18 from peripheral blood mononuclear cells (PBMCs) was studied with flow cytometry and TRIFMA. RESULTS: Plasma levels of sCD18 were decreased in patients with SpA compared with healthy volunteers (P <0.001), and the lowest levels were in the HLA-B27-positive subgroup (P <0.05). In a multiple regression model, the sCD18 levels exhibited an inverse correlation with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (P <0.05), the level of morning stiffness (P <0.05), the Bath Ankylosing Spondilitis Metrology Index (P <0.05), the physician global assessment score (P <0.01), and the sacroiliac magnetic resonance imaging activity score (P <0.05). The mechanisms for these changes could be simulated in vitro. First, sCD18 in plasma adhered to inflammation-induced intercellular adhesion molecule 1 (ICAM-1) on endothelial cells and FLS, indicating increased consumption. Second, CD18 shedding from SpA PBMCs correlated inversely with the BASDAI (P <0.05), suggesting insufficient generation. CD18 was shed primarily from intermediate CD14⁺⁺ CD16⁺ monocytes, supporting the view that alterations in innate immunity can regulate the inflammatory processes in SpA. CONCLUSIONS: Taken together, the failure of patients with SpA to maintain adequate sCD18 levels may reflect insufficient CD18 shedding from monocytes to counterbalance the capture of sCD18 complexes to inflammation-induced ICAM-1. This could increase the availability of ICAM-1 molecules on the endothelium and in the synovium, facilitating leukocyte migration to the entheses and joints and aggregating disease activity.

Anterior chest wall inflammation by whole-body magnetic resonance imaging in patients with spondyloarthritis: lack of association between clinical and imaging findings in a cross-sectional study.

INTRODUCTION: Inflammatory involvement of the anterior chest wall (ACW) affects the quality of life of patients with spondyloarthritis (SpA), although involvement of the ACW is often neglected on clinical and imaging evaluation. Whole-body (WB) MRI is an imaging method used to assess the ACW in addition to the sacroiliac joints and spine without inconvenience for patients. Our goals in this study were to describe the distribution of ACW inflammation by WB MRI in both early and established SpA and associations between clinical and imaging findings indicative of inflammation. METHODS: The ACWs of 122 consecutive SpA patients (95 with ankylosing spondylitis (AS) and 27 with nonradiographic SpA (nrSpA)) and 75 healthy controls were scanned by sagittal and coronal WB MRI. The MRI scans were scored independently in random order by seven readers blinded to patient identifiers. Active and structural inflammatory lesions of the ACW were recorded on a web-based data entry form. ACW pain by patient self-report, ACW tenderness on physical examination according to the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) and lesions detected by MRI were analyzed descriptively. κ statistics served to assess the agreement between clinical and imaging findings. RESULTS: ACW pain or tenderness was present in 26% of patients, with little difference between AS and nrSpA patients. Bone marrow edema (BME), erosion and fat infiltration were recorded in 44.3%, 34.4% and 27.0% of SpA patients and in 9.3%, 12.0% and 5.3% of controls, respectively. Lesions found by MRI occurred more frequently in AS patients (BME, erosion and fat infiltration in 49.5%, 36.8% and 33.7%, respectively) than in nrSpA patients (25.9%, 25.9% and 3.7%, respectively). The joint most frequently affected by lesions found on MRI scans was the manubriosternal joint. The κ values between clinical assessments and MRI inflammation ranged from -0.10 to only 0.33 for both AS and nrSpA patients. CONCLUSIONS: Among SpA patients, 26% had clinical involvement of the ACW. WB MRI signs of ACW inflammation were found in a substantial proportion of patients with AS (49.5%) and nrSpA (25.9%). There was no association between clinical assessments of ACW, including the MASES, and MRI features.

Assessment of active spinal inflammatory changes in patients with axial spondyloarthritis: validation of whole body MRI against conventional MRI.

OBJECTIVE: To evaluate the performance of whole body (WB) MRI versus conventional (CON) MRI in assessing active inflammatory lesions of the entire spine in patients with established and clinically active axial spondyloarthritis (SpA) using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index. METHODS: 32 consecutive patients with SpA fulfilling the modified New York criteria and with clinically active disease (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score > or =4) were scanned by sagittal WB and CON MRI of the spine. The MR images were scored independently in random order by three readers blinded to patient identifiers. Active inflammatory lesions of the spine were recorded on a web-based scoring form. Pearson correlation coefficients were used to compare scores for WB MRI and CON MRI for each rater and intraclass correlation coefficients (ICC) were used to assess interobserver reliability. RESULTS: The median percentage of inflammatory lesions recorded concordantly for both WB MRI and CON MRI ranged from 83% to 91% for the three readers; 4-9% were only recorded by WB MRI and 4-9% were recorded by CON MRI only. The Pearson correlation coefficients between WB and CON MRI per rater were 0.79, 0.89 and 0.81, respectively. The ICC(2, 1) were 0.75, 0.80 and 0.68 for CON MRI and 0.82, 0.83 and 0.93 for WB MRI for the three possible reader pairs. CONCLUSION: WB MRI and CON MRI scores showed a high correlation and comparable high reliability for the detection of active inflammatory lesions in the spine of patients with clinically active SpA.

Validation of whole-body against conventional magnetic resonance imaging for scoring acute inflammatory lesions in the sacroiliac joints of patients with spondylarthritis.

OBJECTIVE: To compare the performance of whole-body magnetic resonance imaging (MRI) versus conventional MRI in assessing acute inflammatory lesions of the sacroiliac (SI) joints in patients with established and active spondylarthritis (SpA) using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index. This study is validating whole-body MRI against the current MRI standard for assessing active inflammatory lesions of the SI joints in patients with SpA. METHODS: Thirty-two SpA patients with clinically active disease (Bath Ankylosing Spondylitis Disease Activity Index score >/=4) fulfilling the modified New York criteria were scanned by whole-body and conventional MRI of the SI joints. The MRIs were scored independently in random order by 3 readers blinded to patient identity. Active inflammatory lesions of the SI joints were recorded on a Web-based SPARCC index. Pearson's correlation coefficients were used to compare scores for whole-body and conventional MRI for each reader, whereas intraclass correlation coefficients (ICCs) were used to compare interobserver reliability. RESULTS: The Pearson's correlation coefficients between whole-body and conventional MRI per rater were 0.94, 0.87, and 0.93. The mean sum scores for conventional versus whole-body MRI were statistically significantly higher for all 3 readers, although all patients showing inflammatory lesions on conventional MRI also demonstrated them on whole-body MRI. The ICCs(2,1) were 0.69, 0.78, and 0.95 for conventional MRI, and 0.79, 0.85, and 0.96 for whole-body MRI for the 3 possible reader pairs. CONCLUSION: Whole-body and conventional MRI scores show a strong correlation and comparable reliability for the detection of inflammatory lesions of the SI joints.