S. Kolta

Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleoside reverse transcriptase inhibitor regimens in HIV-1 infected naive patients.

OBJECTIVEnTo evaluate the change in bone mineral density (BMD) at specific sites in patients initiating antiretroviral therapy in a substudy of the ANRS 121 trial.nnnMETHODSnAntiretroviral-naive patients were randomized (2: 1: 1) into three treatment strategy arms: a nonnucleoside reverse transcriptase inhibitor (NNRTI) and a boosted protease inhibitor (PI/r), a PI/r and two nucleoside reverse transcriptase inhibitors (NRTIs) or an NNRTI and NRTIs. Hip and lumbar spine standardized BMD were evaluated at baseline and week 48 by dual X-ray absorptiometry by a central reading laboratory.nnnRESULTSnSeventy-one patients were enrolled: 36 in the PI/r and NNRTI, 19 in the PI/r and NRTIs and 16 in the NNRTI and NRTIs arms. Baseline characteristics were [median (interquartile range)]: male (77%), age 40 years (33-49), 69% white, 58% smokers, BMI 23 kg/m2 (21-24), CD4 cell count 219 cells/microl (144-285). In the arms with NRTIs, 86% of patients received zidovudine/lamivudine. At baseline, 31% had osteopenia and 3% had osteoporosis. At week 48, there was a mean change in BMD of -4.1 +/- 3.9% at lumbar spine and -2.8 +/- 4.7% at hip (both P< or = 0.001). The decrease of BMD at lumbar spine was significantly worse in the PI/r and NNRTI arm (-4.4 +/- 3.4%) and in the PI/r and NRTIs arm (-5.8 +/- 4.5%) compared with the NNRTI and NRTIs arm (-1.5 +/- 2.9%), P = 0.007 and P = 0.001, respectively.nnnCONCLUSIONnBMD was impaired in 34% of patients, before starting any antiretrovirals. After 1 year, the decrease in lumbar spine BMD was more pronounced in patients receiving either PI/r-containing regimen compared with NNRTI and NRTIs. BMD at specific sites should be monitored during lifelong antiretroviral therapy.

Mild prevalent and incident vertebral fractures are risk factors for new fractures

SummaryThis prospective four-year study indicates that post-menopausal osteoporotic women with mild prevalent and incident vertebral fractures have an increased risk of incident fractures.IntroductionMild vertebral fractures are under diagnosed as there is disagreement about their clinical significance. Our aim was to assess the risk of subsequent fractures induced by both prevalent and incident mild vertebral fractures in osteoporotic post-menopausal women.Patients and methodsThree thousand three hundred and fifty-eight patients, aged 74u2009±u20096xa0years, with post-menopausal osteoporosis included in the placebo groups of two clinical trials of strontium ranelate were followed for 4xa0years. A Cox regression model adjusted on age, body mass index and bone mineral density was used to calculate the relative risk (RR) of fracture in subjects with only mild fractures as compared to patients without fracture, and to patients with at least one grade ≥ 2 fracture. These calculations were made for prevalent and then incident fractures.ResultsThe RR of vertebral fracture in 4xa0years was 1.8 (1.3–2.4) pu2009<u20090.001, and 2.7 (2.3–3.3) pu2009<u20090.001 for patients having only mild vertebral fractures and at least one grade ≥ 2 fracture at baseline respectively. The RR of vertebral fracture in the 3rd and 4th years of follow-up was 1.7 (1.1–2.6) pu2009=u20090.01, and 1.9 (1.3–2.6) pu2009<u20090.001 for patients having during the first 2xa0years incident mild fractures only, and for patients having at least one grade ≥ 2 incident fracture respectively. The RR of non-vertebral fracture in 4xa0years was 1.3 (0.9–1.9) pu2009=u20090.15 and 1.7 (1.4–2.1) pu2009<u20090.001 for patients having only mild or at least one grade ≥ 2 vertebral fracture at baseline respectively. For patients aged more than 70xa0years, these RR were 1.45 (0.99–2.11) (pu2009=u20090.06), and 1.72 (1.36–2.18) pu2009<u20090.001 respectively. The RR of non-vertebral fracture in the 3rd and 4th years was 1.68 (1.36–2.09) pu2009<u20090.001 for patients having at least one grade ≥ 2 incident fracture during the 2 first years of follow-up.ConclusionMild vertebral fractures are a risk factor for subsequent vertebral and non-vertebral fracture in postmenopausal women with osteoporosis; 1 out of 4 patients with an incident mild vertebral fracture in 2xa0years will fracture again within the 2 next years.

Radiographic methods for evaluating osteoporotic vertebral fractures

UNLABELLEDnReproducible methods for the radiological assessment of osteoporotic vertebral fractures, defined based on accurate criteria, are needed in everyday practice and in therapeutic trials and epidemiological studies.nnnOBJECTIVESnTo describe and to evaluate methods for osteoporotic vertebral fracture assessment based on standard radiographs or dual-energy X-ray absorptiometry (DXA) and to determine the role for each method in clinical practice, therapeutic trials, and epidemiological studies.nnnMETHODSnA review written by a rheumatologist based on his clinical experience and on a literature review was submitted to four experts. Studies in English or French published between 1975 and February 2008 were retrieved from Medline using the keywords vertebral fracture, osteoporosis, vertebral deformity, and vertebral fracture assessment.nnnRESULTSnOne hundred forty-nine articles were selected and read in their full-text version. There was no consensus regarding the definition of osteoporotic vertebral fractures. The following methods were evaluated: visual assessment, Genants semi-quantitative assessment, Jiangs algorithm-based qualitative method, morphometric radiography, and DXA of the spine. In everyday practice, Genants semi-quantitative assessment on standard radiographs may provide useful information on the severity and prognosis of osteoporosis. DXA done for bone mineral density measurement may detect vertebral fractures in asymptomatic patients. Assessment of standard radiographs remains the reference standard for diagnosing vertebral fractures in patients with suggestive symptoms (e.g., pain in the thoracic or lumbar spine, height loss, or thoracic kyphosis). For therapeutic trials and epidemiological studies, Genants semi-quantitative assessment used by a trained and experienced observer is the preferred method, based on its good reproducibility and ability to differentiate fractures from other deformities. However, thousands of radiographs may be needed, making routine interpretation by an expert impractical. A visual semi-quantitative method may be used to separate normal radiographs from radiographs showing possible or obvious fractures, which can then be read by an expert. Alternatively, radiomorphometric indices can be determined on digitized radiographs in combination with a semi-quantitative assessment, with discordant cases being reviewed by an expert. We do not recommend Jiangs method at present, as it is still undergoing validation.

Vertebral dimensions as risk factor of vertebral fracture in osteoporotic patients: a systematic literature review

SummaryThis systematic literature review studied the potential association between vertebral fracture risk and vertebral dimensions. Analysis showed that patients with vertebral fractures have smaller non-fractured vertebrae than patients without fractures. Vertebral size is an independent risk factor of vertebral fractures.IntroductionBiomechanical factors such as vertebral dimensions may be a risk factor for vertebral fractures beside bone mineral density (BMD). The objective of this study was to evaluate potential association of vertebral size and shape with osteoporotic fracture risk through a systematic literature review.MethodsSystematic analysis of published reports comparing vertebral dimensions of patients with and without osteoporotic fractures was performed. Data sources were electronic databases. Data extraction included methods, site, reproducibility and results of vertebral measurement, study population characteristics. It was noted if populations were matched or data were adjusted for age, height, weight and BMD.ResultsOf 634 reports identified by the literature search, the final review included 13 reports studying 4,428 women and 508 men; median age 64.2xa0years [range 51.7%–73.0%]. Measurements were performed with computed tomography scan, X-ray, or dual energy X-ray absorptiometry. Vertebral body height, width, depth, area, cross-sectional area (CSA), and volume were 5.5% to 9.5% smaller in fractured group than control group. After adjustment for confounding factors, area, CSA and volume were, respectively, 10.2% [range 7.1%–13.3%], 7.7% [range 1.2%–14.2%] and 9.5% [8.5%–10.5%] smaller in fractured group.ConclusionsVertebral size should be considered as a potential independent vertebral fracture risk factor.

Accuracy and precision of 62 bone densitometers using a European Spine Phantom.

Abstract: Dual-energy absorptiometry (DXA) is widely used for bone mineral density measurements. Different types of devices are available. Differences between devices from either the same manufacturer or different manufacturers can lead to difficulties in clinical practice when patients are followed on different machines. We calculated the accuracy and precision of 62 DXA devices from two manufacturers (51 Hologic, 11 Lunar) using a European Spine Phantom (ESP, semi-anthropomorphic). The ESP was measured 5 times on each device without repositioning. Accuracy was assessed by comparing bone mineral density (BMD, g/cm2) values measured on each device with the actual value of the phantom. Precision was assessed by the coefficient of variation (CVsd), using the root mean square average. The limits of agreement were estimated from the differences between each replicate measurement of BMD and the estimated true value for a particular manufacturer, according to Bland and Altman. The results confirm the difference between devices from different manufacturers (18.5%). Mean CVsd values were 0.57% and 0.64% for Hologic and Lunar respectively. The limits of agreement among devices from the same manufacturer were 0.026 g/cm2 and 0.025 g/cm2 for Hologic and Lunar respectively. Differences in extreme results between devices from the same manufacturer were on average 5.4% and 3.6% for Hologic and Lunar respectively. Results of different devices from the same manufacturer are highly comparable, although unpredictable differences exist that may be clinically relevant.

Follow-up of individual patients on two DXA scanners of the same manufacturer.

Abstract: Measuring and monitoring changes in bone mineral density (BMD) is usually done by dual-energy X-ray absorptiometry (DXA). Replacement of old devices is becoming increasingly frequent. To cross-calibrate two Hologic devices, a QDR 1000 and a QDR 4500A, we measured three phantoms – a Hologic spine phantom, a Hologic block phantom (without and with subregions analysis) and a European Spine Phantom – 20 times each without repositioning on both devices. The mean difference between BMD obtained on the two devices was 0.003, 0.033, 0.051 and −0.045 g/cm2 respectively. We also measured the spine and hip of 60 women aged 19–78 years twice on the same day on both devices. Another group of 30 women aged 52–83 years were measured twice on the QDR 4500 A device (15 days apart). We analyzed the data using Pearson’s correlation coefficient, and Bland and Altman’s method, and calculated the smallest detectable difference (SDD). Results on the two devices were highly correlated: r2= 0.99, 0.95, 0.96 for spine, femoral neck and total hip BMD respectively. SDD was higher for scans done on different devices than for those done twice on the same device: the SDDs were 0.048, 0.046 and 0.047 g/cm2 for spine, femoral neck and total hip BMD respectively measured on two different devices, while the equivalent values were 0.034, 0.036 and 0.027 g/cm2 using a single device. The difference in BMD results was not dependent on BMD. Our results suggest that, although devices are properly cross-calibrated, differences among them great enough to be clinically relevant can be observed in vivo.

Vertebral fracture assessment by dual X-ray absorptiometry

Dear Editor, We have readwith a real attention the interesting paper of Rud B. et al. [1], which is a great contribution in the field, showing that vertebral fracture assessment (VFA) by dual X-ray absorptiometry could be an important help for the vertebral fracture diagnosis. Vertebral fractures (VFs) are the most common osteoporosisrelated fractures. VFs have, in men and women, well-known consequences in terms of mortality and morbidity. At any given bone density, prevalent VFs are a strong risk factor for sustaining a new vertebral or nonvertebral fracture. In postmenopausal women, only one out of three VFs comes to clinical attention. Spine radiographs are the gold standard for the diagnosis of VFs, but routine osteoporosis assessment could not include spinal radiographs. VFA by DXA gives a great help as a test due to its low radiation. VFA has been evaluated for many years, but its use and positioning in clinical practice is still debated. In the paper of Rud B. et al. [1], BAmong patients not referred for spinal radiographs 10% to 18 % would have one or more grade II-III VFs that was overlooked by VFA.^ Considering also grade I VFs, these results became 33 to 45%. Even at the patient level, it would be difficult to accept that about one out of seven patients having grades II-III VFs, and two out of five patients having a VF of any grade would be considered without any VF. These Bundiagnosed^ VFs would have consequences on incident VF, morbidity, and even mortality. Discrepancy between the results of different trained technicians participating in the study has been pointed out, even if the unit of analysis is the patient and not the vertebra. The DXA technicians performed heterogeneously and the percentage of patients with at least one VF varied significantly between the participating technicians. This influences directly the number of VFA to be seen by the radiologist and influences the number of possible false negative results. In this paper, there was no information about the agreement between radiologists or the number of discrepancies that justified reevaluation. In the MrOs study, Cawthon et al. [2] found acceptable results for triage, by technicians on X-rays. Thus, are these discrepancies due to a technician effect or to the inferiority of VFA compared to radiographs, as recently suggested by Deleskog et al. [3], especially in the upper spine? The authors suggest measuring the vertebral heights. Because there is no gold standard for defining a morphometric VF, there are variable true and false-positive rates of different morphometric definitions of VFs. In fact, wide discrepancies have been found [4] in results among studies using different morphometric definitions, ranging from 33 to 85%. Morphometric assessment will add another source of discrepancy to the diagnosis of VF and therefore is not useful in routine practice. This paper confirms that a great caution is necessary for VF diagnosis. VFA can be used as triage to select patients for spinal radiographs, in the slightest diagnostic doubt, thanks to its very important negative predictive value for the diagnosis of VF [5]. A reply to these comments can be found at doi: 10.1007/s00198-016-3856-4.

THU0414 Trabecular Bone Score: A Tool for Identification of Severe Spinal Osteoporosis

Background Vertebral fractures (VFs) are the hallmark of osteoporosis and are more predictive of future fracture than areal Bone Mineral Density (BMD). Number and severity of VFs are related to bone microarchitecture deterioration. Trabecular Bone Score (TBS), derived from the texture of the DXA image, has been shown to be related to bone microarchitecture and fracture risk. Our hypothesis is that TBS measurement could be related to the severity of VFs. Objectives to evaluate performance of TBS, alone or added to aBMD, in the prediction of the presence of VFs and of the severity of these fractures. Methods Patients were selected from the Fracture Liaison Service (FLS) of our department, aiming at providing assessment of osteoporosis to patients over the age of 50 years who had sustained low trauma fractures and who are hospitalized in the Orthopaedic surgery department. aBMD and Vertebral Fracture Assessment (VFA) were performed one week to 3 months after the fracture using DXA. VFs were classified using the Genant’s semiquantitative evaluation and severity was assessed using the spinal deformity index (SDI), i.e. the sum of number and grades of VFs. TBS was obtained after re-analysis of DXA lumbar spine (L2-L4) scans. Performance of TBS, BMD and their combination was assessed using Receiver operator characteristic (ROC) and areas under receiver operating characteristics curves (AUCs). Results Data from 528 patients over 50 years with a non vertebral fragility fracture were examined between February 2009 and October 2012. VFA and TBS were not performed in 166 of them due to technical reasons. 362 patients (77.3% women; mean age 74.3±11.7 years) were analysed; 182 (50.3%) had hip fractures and 49 (13.5%) received an anti-osteoporotic treatment. Prevalence of VFs by VFA was 36.7%; 189 (52.2%) patients were osteoporotic (T score≤-2.5 at at least one site). TBS was lower in the patients with VFs than in patients without VFs in the whole population (1.16 ±0.11 vs 1.23±0.11, p<0.0001) and in non osteoporotic patients (1.19 ±0.12 vs 1.25±0.10, p=0.001). In the whole population, performance of TBS (AUC=0.677) was similar to lumbar spine (LS) BMD (AUC= 0.669) and hip BMD (AUC= 0.692) for the identification of VFs. However combination of TBS and LS BMD improves the discrimination as compared to LS BMD alone (AUC=0.707, p=0.043). In the non osteoporotic population (n=173), AUC of TBS for the discrimination of VFs was higher than AUC of LS BMD (0.67 0vs 0.541, p=0.035). There was a negative correlation between TBS and SDI: r= -0.31 (p<0.0001). Conclusions Our study suggests that about 40% of patients with a non vertebral fracture have vertebral fractures that were not previously diagnosed. TBS is able to discriminate patients with vertebral fractures, and adds information on LS aBMD. TBS is correlated to the number and severity of vertebral fractures evaluated by SDI. TBS measurement may be useful to identify subjects with non vertebral fracture requiring spine imaging. Disclosure of Interest None Declared

FRI0111 Body mass index (BMI) is not a surrogate of rheumatoid cachexia

Background Rheumatoid cachexia (RC) is a metabolic abnormality defined by a low fat-free mass with a normal or high fat mass in patients with Rheumatoid Arthritis (RA). It is predictor of poor health outcomes in RA. Objectives The objectives of this study were to determine the prevalence of rheumatoid cachexia and its determinants in RA patients, and, during a 6-year retrolective follow-up, the body composition changes and its determinants. Data were compared with those of the body mass index (BMI, kg/m²). Methods 133 patients with RA (115 women and 18 men) with a mean age 56.9±12.7 years, who consulted in a tertiary Department of Rheumatology were included; 91 of the patients (75 women and 16 men) were retrolectively followed during 6.3±2.0 years. Demographic data, disease duration, RA activity and severity, RA therapies were collected. Dual Energy X ray Absorptiometry (DXA) was performed for body composition measurement (fat free and fat mass index). We defined RC as fat-free mass index below the 10th percentile together with fat mass index above the 25th percentile (1). Results 106(76.7%), 66(49.6%) and 86(64.7%) of the 133 patients were treated by DMARDs, corticosteroids and biological therapies, respectively at the time of the body composition assessment. Prevalence of rheumatoid cachexia was 45.1% (n=60), higher in men (66.7%) than in women (41.7%) (p=0.048). None of the patients with body mass index (BMI) below 19kg/m2 had RC while prevalence of RC was high (82.4%) in overweight patients (25<BMI≤30). Univariate analysis showed that disease duration and activity disease, use of biological treatments and corticosteroids were not associated with presence of RC. In the retrolective follow-up, 55 patients (59.8%) received continuously biological therapies, 27 (29.3%) intermittently and 9 never received biological therapies. BMI significantly decreased over follow-up (2.8% (±10.3), (p= 0.005). Fat mass index significantly increased from baseline of 7.5% (±21.3) (p= 0.001) in whole population, in patients with continuous biological treatments (8.0 % (±20.4), p=0.005) and a trend was observed in patients without biological treatment (13.1% ±14.3, p=0.055) without any difference between groups. Fat free mass index did not significantly change from baseline. Body composition changes during the retrolective follow-up did not significantly change prevalence of RC. Conclusions This study suggests that rheumatoid cachexia is frequent in RA patients even treated with biological therapies. Fat mass increase in RA can be observed in patients with biological therapies or without. In RA, Body Mass Index (BMI) cannot be used to identify patients with rheumatoid cachexia. References Elkan AC, et al. Rheumatoid cachexia, central obesity and malnutrition in patients with low-active rheumatoid arthritis: feasibility of anthropometry, Mini Nutritional Assessment and body composition techniques. Eur J Nutr 2009; 48:315-22. Disclosure of Interest None Declared

SAT0083 Abdominal Aortic Calcifications are Associated with Cardiovascular Diseases and Vertebral Fractures in Patients with Rheumatoid Arthritis.

Background Cardiovascular disease and osteoporosis are two major causes of morbidity in rheumatoid arthritis (RA) patients. Vertebral fracture assessment (VFA) by dual-energy X ray absorptiometry (DXA) is a validated tool for the diagnosis of vertebral fracture. Studies show that lateral VFA image is an accurate method for the diagnosis of abdominal aortic calcifications (AAC), which is a relevant risk factor for cardiovascular disease. Studies in postmenopausal women are conflicting about the association between AAC and presence of vertebral fractures (VFs) and there is no study in RA. Objectives The aim of the study was to assess the prevalence of AAC in RA patients and the relationships between AAC, cardiovascular diseases and bone status (osteoporosis, VFs). Methods This study was performed in 132 patients who consulted for a bone mineral density (BMD) measurement in a tertiary department of Rheumatology. Demographic data, disease duration, activity and severity, RA therapies, cardiovascular risk factors and diseases, low trauma fractures and presence of osteoporosis (T score≤-2.5 at either lumbar spine and/or hip) were assessed. Diagnosis of VF was performed using the Genant semiquantitative analysis on VFA and severity of VF was quantified from grades 1 to 3. AAC were assessed on lateral VFA images of spine by two readers experts in this field, using a 24 and 8 point scale for scored AAC (1) with a good Inter-observer reliability (ICC) (0.845 (95% CI 0.702-0.923) and 0.882 (95% CI 0.769-0.942) for the 24 and 8-AAC scores, respectively). Univariate and multivariate analyses were performed to investigate associations between presence of AAC and disease-related factors. The accuracy of the multivariate model was measured by the area under the curve (AUC). Results 132 RA patients (114 women, mean age of 56.6±12.7) with a mean duration of RA of 15.1±9.1 years were included in the study. 107 (83.0%), 66 (51.2%) and 85 (64.4%) received DMARDs, corticosteroids and biological therapies respectively. Presence of AAC was observed in 32 (24.2%) patients. AAC were significantly associated with the presence of hypertension (p=0.043) and coronaropathy (p=0.0045). 35 patients (26.5%) were osteoporotic and 20 (15.2%) had at least one VF. There was a significant association between presence of AAC and osteoporosis (p=0.003), and between AAC and prevalent VF (p=0.019). Severity of AAC is correlated with VF severity (r= 0.27, p=0.003 and r= 0.23, p=0.011, for the 24 and 8-AAC scores, respectively) Age, male gender, menopause, calcium intake were significantly associated with presence of AAC in univariate analysis (p≤0.05). In multivariate analysis, age was the single variable associated with the presence of AAC (OR=1.24, CI 95% 1.1-1.4, p=0.0004) and calcium intake had a protective effect (0R=0.02, IC 95%0.0001-0.33, p=0.007) (AUC= 0.915). Conclusions This study conducted in severe RA patients suggests that presence of AAC is associated with cardiovascular diseases and vertebral fractures. RA patients with VF should have a systematic cardiovascular assessment. References Schousboe JT, et Al. Detection of aortic calcification during vertebral fracture assessment (VFA) compared to digital radiography. PLoS One.2007;2:e715 Disclosure of Interest None Declared