P. Geusens

Ankylosing spondylitis and the risk of fracture: results from a large primary care-based nested case-control study

Background and aims: Ankylosing spondylitis (AS) is associated with bone loss in the vertebrae and an increased prevalence of vertebral fractures, but literature about the magnitude of the risk of fracturing is limited. One retrospective cohort study provided evidence of an increased risk of clinical vertebral fractures but not of non-vertebral fractures. This study further explores the risk of clinical vertebral and non-vertebral fractures in a large population database. Methods: In a primary care-based nested case-control study, 231u2009778 patients with fracture and 231u2009778 age- and sex-matched controls were recruited. A history of AS was assessed from the medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated after adjustment for medication, other illnesses, smoking and body mass index when known. Results: AS was diagnosed in 758 subjects. The prevalence of AS was 0.18% in patients with fracture and 0.15% in controls. Patients with AS had an increased risk of clinical vertebral fracture (OR 3.26; 95% CI 1.51 to 7.02). The risk of fractures of the forearm and hip was not significantly increased (OR 1.21; 95% CI 0.87 to 1.69 and OR 0.77; 95% CI 0.43 to 1.37, respectively). The risk of any clinical fracture was increased in patients with AS with a history of inflammatory bowel disease (OR 2.79; 95% CI 1.10 to 7.08), whereas it was decreased in patients with AS taking non-steroidal anti-inflammatory drugs (OR 0.65; 95% CI 0.50 to 0.84). The risk was not associated with recent back pain, psoriasis, joint replacement therapy and use of sulfasalazine. Conclusions: Patients with AS have an increased risk of clinical vertebral fracture but not of non-vertebral fractures, while the risk of any clinical fracture is increased in patients with concomitant inflammatory bowel disease. The mechanism by which non-steroidal anti-inflammatory drugs reduce the risk of any clinical fracture warrants further research.

Early Changes in Bone Density, Microarchitecture, Bone Resorption, and Inflammation Predict the Clinical Outcome 12 Weeks After Conservatively Treated Distal Radius Fractures: An Exploratory Study

Fracture healing is an active process with early changes in bone and inflammation. We performed an exploratory study evaluating the association between early changes in densitometric, structural, biomechanical, and biochemical bone parameters during the first weeks of fracture healing and wrist‐specific pain and disability at 12 weeks in postmenopausal women with a conservatively treated distal radius fracture. Eighteen patients (aged 64u2009±u20098 years) were evaluated at 1 to 2 and 3 to 4 weeks postfracture, using high‐resolution peripheral quantitative computed tomography (HR‐pQCT), micro‐finite element analysis, serum procollagen type‐I N‐terminal propeptide (P1NP), carboxy‐terminal telopeptide of type I collagen (ICTP), and high‐sensitive C‐reactive protein (hsCRP). After 12 weeks, patients rated their pain and disability using Patient Rated Wrist Evaluation (PRWE) questionnaire. Additionally, Quick Disability of the Arm Shoulder and Hand (QuickDASH) questionnaire and active wrist range of motion was evaluated. Linear regression models were used to study the relationship between changes in bone parameters and in hsCRP from visit 1 to 2 and PRWE score after 12 weeks. A lower PRWE outcome, indicating better outcome, was significantly related to an early increase in trabecular bone mineral density (BMD) (β −0.96 [95% CI −1.75 to −0.16], R2u2009=u20090.37), in torsional stiffness (−0.14 [−0.28 to −0.004], R2u2009=u20090.31), and to an early decrease in trabecular separation (209 [15 to 402], R2u2009=u20090.33) and in ICTP (12.1 [0.0 to 24.1], R2u2009=u20090.34). Similar results were found for QuickDASH. Higher total dorsal and palmar flexion range of motion was significantly related to early increase in hsCRP (9.62 [3.90 to 15.34], R2u2009=u20090.52). This exploratory study indicates that the assessment of early changes in trabecular BMD, trabecular separation, calculated torsional stiffness, bone resorption marker ICTP, and hsCRP after a distal radius fracture provides valuable information regarding the 12‐week clinical outcome in terms of pain, disability, and range of motion and validates its use in studies on the process of early fracture healing.

Visual detection of cortical breaks in hand joints : reliability and validity of high-resolution peripheral quantitative CT compared to microCT

BackgroundTo study the reliability and validity of high-resolution peripheral quantitative CT (HR-pQCT) with microCT (μCT) as gold standard in the visual detection of cortical breaks in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints.MethodsTen cadaveric fingers (10 MCP and 9 PIP joints) were imaged by HR-pQCT and μCT and visually analyzed by two independent readers. Intra- and interreader reliability were evaluated for the presence (yes/no, kappa statistics) and the total number (intraclass correlation coefficient, ICC) of cortical breaks. Sensitivity, specificity, positive and negative predictive value (PPV respectively NPV) of HR-pQCT in detecting cortical breaks were calculated.ResultsWith HR-pQCT, mean 149 cortical breaks were identified and with μCT mean 129 (pu2009<u20090.05). Intrareader reliability for the presence of a cortical break per quadrant was 0.52 (95xa0% CI 0.48–0.56) and 0.71 (95xa0% CI 0.67–0.75) for HR-pQCT and μCT, respectively, and for the total number of cortical breaks 0.61 (95xa0% CI 0.49–0.70) and 0.75 (95xa0% CI 0.68–0.82). Interreader reliability for the presence of a cortical break per quadrant was 0.37 (95xa0% CI 0.33–0.41) and 0.45 (95xa0% CI 0.41–0.49) for HR-pQCT and μCT, respectively, and for the number of cortical breaks 0.55 (95xa0% CI 0.43–0.65) and 0.54 (95xa0% CI 0.35–0.67). Sensitivity, specificity, PPV and NPV of HR-pQCT were 81.6, 64.0, 81.6, and 64xa0% respectively.ConclusionCortical breaks were commonly visualized in MCP and PIP joints with HR-pQCT and μCT. Reliability of both HR-pQCT and μCT was fair to moderate. HR-pQCT was highly sensitive to detect cortical breaks with μCT as gold standard.

Feasibility of rigid 3D image registration of high-resolution peripheral quantitative computed tomography images of healing distal radius fractures

For accurate analysis of bone formation and resorption during fracture healing, correct registration of follow-up onto baseline image is required. A per-fragment approach could improve alignment compared to standard registration based on the whole fractured region. In this exploratory study, we tested the effect of fragment size and displacement on a per-fragment registration, and compared the results of this per-fragment registration to the results of the standard registration in two stable fractures and one unstable fracture. To test the effect of fragment size and displacement, high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of three unfractured radii were divided into subvolumes. Different displacements in x-, y, or z-direction or rotations around each axis were applied, and each subvolume was registered onto the initial volume to realign it. Next, registration of follow-up onto baseline scan was performed in two stable and one unstable fracture. After coarsely aligning the follow-up onto the baseline scan, a more accurate registration was performed of the whole fracture, i.e. the standard registration, and of each fracture fragment separately, i.e. per-fragment registration. Alignment was checked using overlay images showing baseline, follow-up and overlap between these scans, and by comparing correlation coefficients between the standard and per-fragment registration. Generally, subvolumes as small as 300 mm3 that were displaced up to 0.82 mm in x- or y-, or up to 1.64 mm in z-direction could be realigned correctly. For the fragments of all fractures, correlation coefficients were higher after per-fragment registration compared to standard registration. Most improvement was found in the unstable fracture and one fragment of the unstable fracture did not align correctly. This exploratory study showed that image registration of individual subvolumes, such as fracture fragments, is feasible in both stable and unstable fractures, and leads to better alignment of these fragments compared to an approach that is based on registration using the whole fractured region. This result is promising for additional analysis of bone formation and resorption in HR-pQCT studies on fracture healing.

SAT0165 Cortical Breaks and Bone Erosions in the Hand Joints: A Cadaver Study Comparing Conventional Radiography with High-Resolution and Micro-Computed Tomography

Background Conventional radiography (CR) is considered the gold standard for diagnosing bone erosions in rheumatic diseases. However, High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT) and microCT (μCT) allow analysis of bone erosions in finger joints at micro level. Objectives To evaluate cortical breaks and erosions in 16 hand joints imaged by CR, HR-pQCT and μCT. Methods Eight female human cadaveric index fingers with unknown medical history were scanned by HR-pQCT (82 μm, XtremeCT, Scanco Medical AG, Switzerland) and μCT (18μm, μCT 80, Scanco Medical AG, Switzerland). Also radiographs were taken. A modified SPECTRA (Study grouP for xtrEme Computed Tomography in Rheumatoid Arthritis) algorithm was used by one reader to assess all cortical breaks and all erosions. A cortical break was defined as an interruption of cortical bone on two consecutive slices on two orthogonal planes on HR-pQCT, and similarly, but on eight consecutive slices, for the μCT. Erosion was defined as a definite cortical break, with irregular shape, and loss of underlying trabecular bone on two consecutive slices on two orthogonal planes for HR-pQCT, and eight consecutive slices on two orthogonal planes for μCT. CRs were independently scored for erosions by two rheumatologists. Descriptives and intraclass correlation coefficients (ICC) were calculated. Results In total, eight metacarpal phalangeal (MCP), four proximal interphalangeal (PIP) and four distal interphalangeal joints of 16 cadaveric index fingers (mean ± SD age 82.6±9.1 years) were imaged by HR-pQCT and μCT. In total, 123 cortical breaks were detected on HR-pQCT (7.0±2.7 per joint) and 237 on μCT (14.5±5.0 per joint). A total of 24 erosions were detected on HR-pQCT (1.3±1.0 per joint) and 72 on μCT (4.0±2.6 per joint). The ICC for total number of cortical breaks was 0.399 (p=0.056), and for number of erosions -0.142 (p=0.706). On CR, twelve joints, eight MCPs and four PIPs, were scored. The total number of erosions scored on CR was four by Reader 1, and two by Reader 2. On the same joints, 16 and 45 erosions were scored on HR-pQCT and μCT, respectively. Conclusions HR-pQCT detected four times more erosions than CR. The μCT detected even three times more erosions than HR-pQCT. Furthermore, almost twice the number of cortical breaks was scored on μCT than HR-pQCT. These results indicate that further research, such as histological and longitudinal studies, will be necessary to reveal the prevalence, incidence and significance of cortical breaks and erosions as found by HR-pQCT and μCT of hand joints. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1851

Structural damage and inflammation on radiographs or magnetic resonance imaging are associated with cortical interruptions on high-resolution peripheral quantitative computed tomography: a study in finger joints of patients with rheumatoid arthritis and healthy subjects.

Objectives: To study the relationship between structural damage and inflammatory features on magnetic resonance imaging (MRI) or radiography and other risk factors [anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) seropositivity, hand dominance, disease duration] and the presence or number of cortical interruptions in finger joints on high-resolution peripheral quantitative computed tomography (HR-pQCT). Method: Finger joints of 38 healthy subjects and 39 patients with rheumatoid arthritis (RA) were examined through radiographs, MRI, and HR-pQCT. Radiographs were scored according to the Sharp/van der Heijde (SvH) method; MRI for the presence of cortical interruptions, bone marrow oedema (BMO), and synovitis; and HR-pQCT images for cortical interruptions. Descriptive statistics were calculated and associations examined using generalized estimating equations. Results: Cortical interruptions were found in healthy subjects and patients with RA on HR-pQCT (mean ± sd 0.33 ± 0.63 vs 0.38 ± 0.64 per joint quadrant, respectively, p < 0.01). Structural damage on MRI (cortical interruptions) or radiographs (SvH ≥ 1) was associated with the presence of cortical interruptions on HR-pQCT [odds ratio (OR) 12.4, 95% confidence interval (CI) 7.5–21.4, p < 0.01 and OR 4.8, 95% CI 1.9–11.7, respectively, p < 0.01]. The presence of BMO or synovitis was associated with more cortical interruptions on HR-pQCT (β 0.47, 95% CI 0.4–0.6, p < 0.01 and β 1.9, 95% CI 0.6–3.1, p < 0.01). In patients with RA, ACPA, and/or RF seropositivity, hand dominance and disease duration were not associated with more cortical interruptions on HR-pQCT. Conclusion: Structural damage and inflammatory features on MRI and radiographs are associated with cortical interruptions on HR-pQCT. No association between other risk factors and cortical interruptions was demonstrated.

Diagnosis of vertebral deformities on chest CT and DXA compared to routine lateral thoracic spine X-ray

SummaryX-ray, CT and DXA enable diagnosis of vertebral deformities. For this study, level of agreement of vertebral deformity diagnosis was analysed. We showed that especially on subject level, these imaging techniques could be used for opportunistic screening of vertebral deformities in COPD patients.IntroductionX-ray and CT are frequently used for pulmonary evaluation in patients with chronic obstructive pulmonary disease (COPD) and also enable to diagnose vertebral deformities together with dual-energy X-ray absorptiometry (DXA) imaging. The aim of this research was to study the level of agreement of these imaging modalities for diagnosis of vertebral deformities from T4 to L1.MethodsEighty-seven subjects (mean age of 65; 50 males; 57 COPD patients) who had X-ray, chest CT (CCT) and DXA were included. Evaluable vertebrae were scored twice using SpineAnalyzer™ software. ICCs and kappas were calculated to examine intra-observer variability. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AUROC) were calculated to compare vertebral deformities diagnosed on the different imaging modalities.ResultsICCs for height measurements were excellent (>u20090.94). Kappas were good to excellent (0.64–0.77). At vertebral level, the AUROC was 0.85 for CCT vs. X-ray, 0.74 for DXA vs. X-ray and 0.77 for DXA vs. CCT. Sensitivity (51%–73%) and PPV (57%–70%) were fair to good; specificity and NPV were excellent (≥u200996%). At subject level, the AUROC values were comparable.ConclusionsReproducibility of height measurements of vertebrae is excellent with all three imaging modalities. On subject level, diagnostic performance of CT (PPV 79–82%; NPV 90–93%), and to a slightly lesser extend of DXA (PPV 73–77%; NPV 80–89%), indicates that these imaging techniques could be used for opportunistic screening of vertebral deformities in COPD patients.

The impact of GI events on persistence and adherence to osteoporosis treatment: 3-, 6-, and 12-month findings in the MUSIC-OS study

SummaryThe goal of this multinational, prospective, observational study was to examine the relationship between gastrointestinal (GI) events and self-reported levels of medication adherence and persistence in postmenopausal women. A total of 73.9% of patients remained on their osteoporosis (OP) therapy at month 12, although the presence of a GI event at baseline, month 3, and month 6 significantly reduced month 12 persistence among new users. The odds of a month-12 ADEOS score ≥ 20 were significantly lower among patients who experienced a GI event between baseline and month 6. The occurrence of GI events was observed to be associated with a lower likelihood of patient adherence and persistence to OP medication.IntroductionThis study examines the relationship between gastrointestinal (GI) events and self-reported adherence and persistence with initial osteoporosis (OP) therapy over the course of the first 12xa0months of treatment.MethodsThe Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study was a multinational, prospective, observational study examining the impact of GI events on OP management in postmenopausal women. Information regarding GI events was collected at the time of enrollment and at months 3, 6, and 12 of follow-up. Patients reported GI events and medication persistence and completed the 12-item Adherence Evaluation of Osteoporosis treatment (ADEOS) questionnaire. Multivariate logistic and general linear models examined the association between GI events at various time points and persistence and adherence at month 12.ResultsThe study enrolled 2943 women; 22.8% were classified as new users of OP therapy and the remainder were considered experienced users. Across all patients, 68.1% reported GI events at baseline; by month 12, over 80% of subjects who completed follow-up reported at least one GI problem. The majority of patients (86.7%) were treated only with bisphosphonates at baseline. At month 12, 73.9% of patients remained on therapy; logistic regression revealed that those with GI problems by month 6 were significantly less likely to persist with treatment, after adjusting for other factors. The odds of a month 12 ADEOS score ≥xa020 (considered predictive of adherence) were significantly lower among patients who experienced a GI event between baseline and month 6.ConclusionsThe occurrence of GI events was associated with a lower likelihood of patient adherence to and persistence with OP medication.

FRI0662 Assessment of bone density, structure, and cortical interruptions of finger joints in patients with rheumatoid arthritis using high-resolution peripheral quantitative ct

Background Rheumatoid arthritis (RA) is characterized by peri-articular bone loss. In patients with RA, lower bone density and structural integrity, and an increased number of erosions compared to healthy controls (HCs) has been demonstrated using High-Resolution peripheral Quantitative CT (HR-pQCT) (1,2). To further characterize RA-related changes, we recently introduced a method for quantifying small cortical interruptions in finger joints (3). Objectives To investigate the cortical and trabecular bone density, structure, and cortical interruptions in MCP joints in early and late RA patients compared to HCs using HR-pQCT imaging. Methods The 2nd and 3rd MCP joint of 70 subjects (mean age 53.1 (SD 9.2) years) were evaluated by HR-pQCT (82μm isotropic voxel size): 38 HCs, 10 early RA (diagnosis ≤2 years ago) and 22 late RA (diagnosis ≥10 years ago). Images were analyzed for cortical interruptions, and for cortical and trabecular bone density and structure. Descriptives were analyzed per joint by one-way ANOVA with Bonferroni post-hoc testing or Kruskal-Wallis with Mann-Whitney post-hoc testing, as appropriate. Results Significant differences with respect to all parameters were found across the groups (Table 1). In early and late RA, the percentage of joints with at least 1 interruption was higher, and number of trabeculae, cortical thickness, total density and cortical density were lower than in HC. In addition, in late RA, number of interruptions, interruption volume and trabecular separation were higher, and trabecular density was lower than in HC. Bone loss at the cortical and trabecular bone was primarily observed at the rim of the joint (Figure 1, arrows).Table 1. Comparison of cortical interruptions, and bone density and structure parameters across early RA patients, late RA patients and HCs HC Early RA Late RA p-value Cortical interruption parameters n=82 n=39 n=73 u2003Percentage of joints ≥1 interruption, % 69.5 89.7 * 82.2 0.025 u2003Number of interruptions 1.50 (1.49) 2.64 (2.95) 5.22* (6.32) <0.001 u2003Interruption volume, mm3 1.49 (5.16) 2.05 (6.76) 39.31* (78.51) <0.001 Bone density parameters n=50 n=31 n=68 u2003Total vBMD, mg HA/cm3 327.3 (35.3) 295.8* (38.9) 286.4* (65.1) <0.001 u2003Trabecular vBMD, mg HA/cm3 202.1 (20.6) 185.0 (21.6) 177.3* (42.0) <0.001 u2003Cortical vBMD, mg HA/cm3 685.8 (42.8) 643.7* (58.2) 634.0* (73.3) <0.001 Bone structure parameters n=50 n=31 n=68 u2003Trabecular number, mm1 1.68 (0.31) 1.45* (0.29) 1.52* (0.37) 0.004 u2003Trabecular thickness, μm 102.3 (15.3) 109.1 (17.8) 98.6 (14.7) 0.009 u2003Trabecular separation, μm 513.9 (116.9) 608.4 (132.3) 611.4* (220.6) 0.007 u2003Distribution of trabecular separation, μm 550.6 (287.0) 728.5 (306.1) 689.4 (368.8) 0.029 u2003Cortical thickness, μm 440.0 (99.2) 363.2* (90.2) 357.5* (132.8) <0.001 Values are displayed as mean (SD) or otherwise described. *Significantly different from HC, p<0.05. 1p-value obtained across the groups. vBMD, volumetric bone mineral density. Conclusions Bone density and structural integrity were impaired in early and late RA patients compared to HCs whereas the number of cortical interruptions is increased. The assessment of such parameters using HR-pQCT is, therefore, a promising tool for the follow-up of bone involvement in MCP joints in patients with RA. References Fouque-Aubert et al., ARD 2010. Stach et al., A&R 2010. Peters et al., ACR2016 (abstract). Disclosure of Interest M. Peters: None declared, A. Scharmga: None declared, A. van Tubergen: None declared, D. Loeffen: None declared, R. Weijers: None declared, B. van Rietbergen Consultant for: Scanco Medical AG, P. Geusens: None declared, J. van den Bergh: None declared

SAT0531 Can Histologically Defined Peri-Articular Vascular Channels Be Identified on High-Resolution Computed Tomography? A Study in Cadaveric Finger Joints

Background Several studies have indicated that High Resolution peripheral CT (HR-pQCT) scanning is more sensitive than radiography in detecting cortical breaks in destructive joint diseases like rheumatoid arthritis (RA)[1–3]. Cortical breaks are also seen in healthy controls, but the exact nature of these breaks is not known, and might represent vascular channels (VCs). No previous study has compared histology to HR-pQCT images in finger joints. We hypothesized that VCs seen on histology can also be detected by HR-pQCT imaging. Objectives To identify histologically defined VCs in cadaveric hand joints on HR-pQCT imaging. Methods Based on HR-pQCT, three regions in metacarpophalangeal joints from female cadavers with an unknown medical history (mean age 84.7, SD 5.5 years) were selected. These regions were extracted, embedded undecalcified in methylmetacrylate and histologically sectioned (thickness 15μm) parallel to the axial plane. Every second section (n=450) was stained with Goldner Trichrome. VCs were identified as a cortical break in one histological section which contained one or more vessels. HR-pQCT images (thickness 82μm) were independently scored by two trained readers for the presence of cortical breaks and if applicable categorized as VC. A break on HR-pQCT was defined as an interruption of the cortex seen on 2 consecutive slices in at least 2 orthogonal planes. A VC was defined as a break that is linear in shape with parallel lining. Finally, the histological sections were matched visually to corresponding axial HR-pQCT images. Results A total of 56 VCs were identified on histology. On HR-pQCT 20 breaks were identified, of which 7 were categorized as VC. Only 3 VCs matched with VCs on histology. Of the remaining 53 histologically identified VCs, 34 could be detected on HR-pQCT, but the interruption of the cortex was not seen on 2 consecutive slices therefore they were not classified as a break. Eight histologically VCs fulfilled the definition of a break on HR-pQCT, but were not categorized as a VC. Eleven histologically VCs could not be identified on HR-pQCT. Figure 1 demonstrates histology and HR-pQCT images. Conclusions VCs were frequently seen on histology. Only a minority of histologically defined VCs is interpreted as VC using a pre-specified definition on HR-pQCT images. Small histological VCs were often identified as an interruption but rarely considered a break according to the current definition of a VC on HR-pQCT. Therefore, additional criteria in order to diagnose the presence of VCs on HR-pQCT are warranted. References Stach CM, A&R.2010 Feb; 62(2):330–339. Srikhum W, JRheum.2013 Apr; 40(4):408–416. Fouque-Aubert A, ARD.2010 Sep; 69(9):1671–1676. Disclosure of Interest A. Scharmga: None declared, K. Keller: None declared, M. Peters: None declared, A. van Tubergen: None declared, J. van den Bergh: None declared, B. van Rietbergen Consultant for: Scanco Medical AG, R. Weijers: None declared, D. Loeffen: None declared, E. M. Hauge: None declared, P. Geusens: None declared