The French multicentre elevated bone mass study: prevalence and causes.

The purpose of this multicentric study was to evaluate the prevalence and causes of Elevated Bone Mass (EBM) in patients who underwent DXA scanning over a 10-year period. The prevalence of EBM was 1 in 100. The main causes of EBM were degenerative spine disorders and renal osteodystrophy. INTRODUCTION: Reports of elevated bone mass (EBM) on routine dual energy X-Ray absorptiometry (DXA) scanning are not infrequent. However, epidemiological studies of EBM are few and definition thresholds are variable. The purpose of this French multicentric study was to evaluate the prevalence and causes of EBM in adult patients who underwent DXA scanning over a 10-year period. METHODS: This multicentric, retrospective study was conducted in six French regional bone centres. DXA databases were initially searched for individuals with a bone mineral density (BMD) Z-score ≥ +4 at any site in the lumbar spine or hip from April 1st, 2008 to April 30st, 2018. RESULTS: In all, 72,225 patients with at least one DXA scan were identified. Of these, 909 (322 men and 587 women) had a Z-score ≥ + 4, i.e. a prevalence of 1.26% [1.18-1.34%]. The DXA scan reports and imagery and medical records of the 909 EBM patients were reviewed and 936 causes were found. In 42 patients (4%), no cause could be determined due to unavailability of data. Artefactual causes of EBM were found in 752 patients (80%), in whom the predominant cause was degenerative disease of the spine (613 patients, 65%). Acquired causes of focal EBM-including Paget's disease (n = 7)-were found in 12 patients (1%), and acquired causes of generalized EBM-including renal osteodystrophy (n = 32), haematological disorders (n = 20) and hypoparathyroidism (n = 15)-in 84 patients (9%). Other causes were rare hereditary diseases and unknown EBM in 19 (2%) and 27 (3%) cases respectively. CONCLUSIONS: The prevalence of EBM was approximately 1 in 100. These findings suggest that degenerative disease of the spine is the main cause of EBM, but that acquired or hereditary diseases are also causal factors.

Absence of relationships between depression and anxiety and bone mineral density in patients hospitalized for severe anorexia nervosa.

INTRODUCTION: Low BMD is frequent in anorexia nervosa (AN), depression, and during SSRI treatment but relation between these elements in AN is not established. The aims of this study were to assess the relationships between depression and anxiety, SSRI prescription, and (1) low BMD during inpatient treatment and (2) BMD change 1 year after hospital discharge. METHODS: From 2009 to 2011, 212 women with severe AN have been included in the EVHAN study (EValuation of Hospitalisation for AN). Depression, anxiety and obsessive-compulsive symptoms and comorbidity were evaluated using psychometric scales and CIDI-SF. BMD was measured by dual-energy X-ray absorptiometry. RESULTS: According to the CIDI-SF, 56% of participants (n = 70) had a lifetime major depressive disorder, 27.2% (n = 34) had a lifetime obsessive-compulsive disorder, 32.8% (n = 41) had a lifetime generalized anxiety disorder and 25.6% (n = 32) had a lifetime social phobia disorder. Half of the sample (50.7%; n = 72) had a low BMD (Z score ≤ - 2). In multivariate analysis, lifetime lowest BMI was the only determinant significantly associated with low BMD (OR = 0.56, p = 0.0008) during hospitalization. A long duration of AN (OR = 1.40 (0.003-3.92), p = 0.03), the AN-R subtype (OR = 4.95 (1.11-26.82), p = 0.04), an increase of BMI between the admission and 1 year (OR = 1.69 (1.21-2.60), p = 0.005) and a gain of BMD 1 year after the discharge explained BMD change. CONCLUSION: We did not find any association between depression and anxiety or SSRI treatment and a low BMD or variation of BMD. LEVEL OF EVIDENCE: Level III, cohort study.

Measurement of Trabecular Bone Score of the Spine by Low-Dose Imaging System (EOS®): A Feasibility Study.

Purpose/Introduction: Measurement of trabecular bone score (TBS®) of the lumbar spine on dual energy X-ray absorptiometry (DXA) devices improves fracture risk prediction. We conducted a proof of concept study to assess the feasibility of TBS® measured on the low-dose imaging system EOS®. METHODS: TBS was assessed on both DXA and EOS® in 122 patients aged ≥ 50 yr, receiving no anti-osteoporotic treatment. The TBS® was computed on full-body EOS® images, focusing on the lumbar spine region. The patients were also scanned with a DXA bone densitometer (Hologic) and the spine and hip bone mineral density (g/cm²) were computed. RESULTS: TBS® measurement on EOS® was not possible in 34 patients due to technical problems. It could be measured on both DXA and EOS® in 88 patients (28 with severe low-trauma fracture and 60 without fracture). TBS-EOS values were significantly lower in fractured patients compared to nonfractured patients. TBS-EOS was associated with the presence of fractures as reported by an AUC of 0.70. Odds ratio of TBS-EOS for the presence of severe low-trauma fracture was 2.00 [1.24-3.25], p = 0.005. CONCLUSIONS: This proof of concept study, based on a prototype version of the TBS-EOS, demonstrated the feasibility of the measurement of TBS® on low-dose EOS® imaging devices. Results show that the TBS-EOS was lower in patients with severe low-trauma fractures compared to nonfractured patients independently from bone mineral density. Some technical issues need to be solved before its eventual use in routine clinical settings. Additional prospective studies are still needed to define the actual contribution of this new technique.

Sagittal balance of the spine in patients with osteoporotic vertebral fractures.

UNLABELLED: This study aims to compare the sagittal global spinal balance of patients consulting for osteoporosis, aged above 50 years with and without osteoporotic vertebral fractures (VFs). Global spinal balance is abnormal even in subjects without VFs. VFs and age are determinants of sagittal global balance; however, pelvic parameters play a role in compensatory mechanisms. INTRODUCTION: This study aims to compare the spine curvatures, pelvic parameters, and the sagittal global spinal balance of patients aged above 50 years with and without osteoporotic vertebral fractures. METHODS: Two hundred patients (95 % women) aged 68.3 ± 9.5 years underwent full skeleton radiographs in the standing position, by EOS®, a low dose biplane X-ray imaging system. VFs were evaluated according to Genant's classification. Spinal (thoracic and lumbar Cobb's indices, thoracic and lumbar tilts) and pelvic (pelvic tilt, sacral slope, and pelvic incidence) parameters were measured. Sagittal spinal balance was measured using the C7 plumb line and the spinosacral angle (SSA). We compared these parameters in patients with and without vertebral fracture and assessed the determinants of abnormal sagittal spinal balance. RESULTS: Sixty-nine patients had at least one VF. The sagittal spinal balance was significantly altered in patients with at least one VF, and there was an effect of the number and severity of VFs on parameters. Discriminative value for identification of patients with at least one VF, assessed by Area Under the Curves (AUCs) was 0.652 and 0.706 for C7 plumbline and SSA, respectively. Using multivariate analysis, parameters significantly associated with abnormal spinal balance (SSA) were the presence of at least one VF (OR = 4.96, P < 0.0001), age (OR = 1.07, P = 0.0006), and high pelvic incidence as a protective factor (OR = 0.93, P < 0.0001). CONCLUSIONS: Global spinal balance is abnormal in subjects consulting for osteoporosis, even in subjects without VFs. VFs and age are determinants of abnormal sagittal global balance; however, pelvic parameters play a role in compensatory mechanisms.

Diagnosis of vertebral fractures using a low-dose biplanar imaging system.

UNLABELLED: Vertebral fractures (VFs) are independent risk factors for new fractures. However, spine radiographs cannot be used as a screening method. EOS® has a good diagnostic value for the diagnosis of VF with a better legibility of upper thoracic spine and a higher concordance between readers compared to vertebral fracture assessment (VFA). INTRODUCTION: Vertebral fractures (VFs) are risk factors for new fractures. However, spine radiographs cannot be used as a screening method for both cost and radiation concerns. EOS® X-ray imaging system which allows the acquisition of biplane images in an upright weight-bearing position with low radiation dose was used. The objective of this study was to compare EOS® to VFA for the diagnosis of VF. METHODS: We conducted a cross-sectional study in subjects aged above 50 years with indication for spine imaging. EOS® and VFA of the spine were performed the same day. Sensitivity (Se), specificity (Sp), negative predictive value (NPV), and the interobserver precision of EOS® were compared to VFA for the diagnosis of VF. RESULTS: Two hundred patients (mean age 66.2 years) were included. At the vertebral level, 2.4 and 3.6 % of vertebrae were not legible using EOS® and VFA, respectively (p = 0.0007). The legibility of spine was significantly affected by scoliosis (odds ratio (OR) = 2.8, p < 0.0001, for EOS®, and OR = 1.8, p = 0.0041, for VFA). Sixty-six patients (33.0 %) and 69 (34.5 %) had at least one VF using VFA and EOS®, respectively. At patient level, Se, Sp, and NPV for the diagnosis of VF of EOS® were 79.7, 91.6, and 99 %, respectively. Concordance between both observers was very good for EOS® (kappa-score = 0.89), higher than for VFA (κ = 0.67). CONCLUSIONS: This study shows that EOS® has a good diagnostic value for the diagnosis of VF with a better legibility of upper thoracic spine and a higher concordance between readers compared to VFA.

Added value of trabecular bone score over bone mineral density for identification of vertebral fractures in patients with areal bone mineral density in the non-osteoporotic range.

UNLABELLED: Detection of patients with vertebral fracture is similar for areal bone mineral density (aBMD) and trabecular bone score (TBS) in patients with non-vertebral fracture. In non-osteoporotic patients, TBS adds information to lumbar spine aBMD and is related to an index of spine deterioration. INTRODUCTION: Vertebral fractures (VFs) are more predictive of future fracture than aBMD. The number and severity of VFs are related to microarchitecture deterioration. TBS has been shown to be related to microarchitecture. The study aimed at evaluating TBS in the prediction of the presence and severity of VFs. METHODS: Patients were selected from a Fracture Liaison Service (FLS): aBMD and vertebral fracture assessment (VFA) were assessed after the fracture, using dual-energy X-ray-absorptiometry (DXA). VFs were classified using Genant's semiquantitative method and severity, using the spinal deformity index (SDI). TBS was obtained after analysis of DXA scans. Performance of TBS and aBMD was assessed using areas under the curves (AUCs). RESULTS: A total of 362 patients (77.3% women; mean age 74.3 ± 11.7 years) were analysed. Prevalence of VFs was 36.7%, and 189 patients (52.2%) were osteoporotic. Performance of TBS was similar to lumbar spine (LS) aBMD and hip aBMD for the identification of patients with VFs. In the population with aBMD in the non-osteoporotic range (n = 173), AUC of TBS for the discrimination of VFs was higher than the AUC of LS aBMD (0.670 vs 0.541, p = 0.035) but not of hip aBMD; there was a negative correlation between TBS and SDI (r = -0.31; p < 0.0001). CONCLUSION: Detection of patients with vertebral fracture is similar for aBMD and TBS in patients with non-vertebral fracture. In patients with aBMD in the non-osteoporotic range, TBS adds information to lumbar spine aBMD alone and is related to an index of spine deterioration.

TBS result is not affected by lumbar spine osteoarthritis.

UNLABELLED: The effect of lumbar osteoarthritis on bone density and trabecular bone score (TBS) was evaluated cross-sectionally and prospectively in postmenopausal women. Lumbar spine osteoarthritis was graded according to Kellgren and Lawrence grades. Lumbar osteoarthritis was found to increase lumbar spine bone density, but not TBS. INTRODUCTION: Lumbar osteoarthritis overestimates lumbar bone density (areal bone mineral density (aBMD)). A new texture parameter, the TBS, has been proposed. Calculation of aBMD uses grey level value, while TBS uses grey level variation. Therefore, our hypothesis was that TBS is not influenced by lumbar spine osteoarthritis. METHODS: Menopausal women participating in osteoporosis and ultrasound (OPUS) study were included. They had an aBMD measurement of the spine and hip at baseline and 6-year visit. TBS was calculated on lumbar spine dual-energy X-ray absorptiometry (DXA) scans in an automated manner. The presence of lumbar osteoarthritis was evaluated on baseline radiographs using Kellgren and Lawrence (K&L) classification. Grades range from 0 to 4. In our study, osteoarthritis was defined by at least K&L grade 2. RESULTS: This study included 1,254 menopausal women (66.7 ± 7.1 years). Among them, 727 attended the 6-year follow-up visit. Patients with lumbar osteoarthritis had an aBMD higher than those without lumbar osteoarthritis at the lumbar spine, but not at the hip. However, the aBMD significantly increased in all sites with the grade of K&L. In contrast, spine TBS was not different between patients with and without lumbar osteoarthritis (p = 0.70), and it was not correlated with K&L grade. Spine TBS and aBMD at all sites were negatively correlated with age (p < 0.0001). Body mass index was correlated positively with aBMD and negatively with spine TBS (p < 0.0001). The 6-year change of aBMD was significant in the hip and nonsignificant in the lumbar spine. That of TBS was significant, with a 3.3 % decrease (p < 0.0001), independent of K&L grade (p = 0.28). CONCLUSION: In postmenopausal women, lumbar osteoarthritis leads to an increase in lumbar spine aBMD. In contrast, spine TBS is not affected by lumbar osteoarthritis.

Body fat distribution in HIV-infected patients treated for 96 weeks with darunavir/ritonavir monotherapy versus darunavir/ritonavir plus nucleoside reverse transcriptase inhibitors: the MONOI-ANRS136 substudy.

OBJECTIVES: The aim of the study was to evaluate fat tissue distribution in HIV-infected patients with suppressed viraemia treated with darunavir/ritonavir (darunavir/r) monotherapy versus darunavir/r triple therapy. METHODS: This study was a substudy of the randomized, multicentre, open-label MONOI-ANRS 136 trial. Body fat distribution and metabolic parameters were measured at baseline, week 48 and week 96. RESULTS: In total, 156 patients of the 225 initially enrolled in the MONOI trial participated in this study, 75 in the darunavir/r monotherapy arm and 81 in the darunavir/r triple-therapy arm. The median limb fat increase from baseline was +0.34 kg [interquartile range (IQR) -0.040 to +1.140 kg; P < 0.001] at week 48 and +0.33 kg (IQR -0.14 to +1.26 kg; P = 0.001) at week 96 in the monotherapy arm, while there was no change (-0.02 kg; IQR -0.53 to +0.52 kg) at week 48 and then an increase of +0.23 kg (IQR -0.45 to +0.87 kg; P = 0.046) at week 96 in the triple-therapy arm. The two arms differed significantly at week 48 (P = 0.001) but not at week 96. The median increase in trunk fat was +0.73 kg (IQR -0.24 to +1.60 kg; P < 0.001) and 0.60 kg (IQR -0.41 to +1.49 kg; P = 0.03) at week 48 and +1.16 kg (IQR -0.17 to +2.75 kg; P < 0.001) and +0.90 kg (IQR -0.51 to +2.34 kg; P = 0.001) at week 96 in the monotherapy and triple-therapy arms, respectively, with no difference between arms. At week 96, the only biological change was a glucose level elevation in the monotherapy arm (median +4.0 mg/dL; IQR -4.0 to +7.0 mg/dL) compared with the triple-therapy arm (P = 0.012). CONCLUSIONS: Overall, body fat tissue increased in patients on darunavir/r monotherapy and triple therapy, with no difference between the arms over 96 weeks. The only difference found was a delayed increase in limb fat tissue in the triple-therapy arm compared with the monotherapy arm in the first year.

Prevalence of vertebral fractures in patients with rheumatoid arthritis: revisiting the role of glucocorticoids.

SUMMARY: Vertebral fracture assessment (VFA) is a convenient tool for the diagnosis of vertebral fracture in RA. Optimal control of inflammation may be an effective means to protect against vertebral fractures. INTRODUCTION: The aim of this case-control study was to assess the prevalence of vertebral fractures (VFs) in patients with RA using VFA technology. METHODS: Consecutive women (N = 101, 56.1 ± 14.2 years) with RA (mean disease duration, 14.9 ± 10 years) were recruited in the study. Clinical and biological statuses and treatments including glucocorticoids were assessed. Controls (N = 303), randomly selected from the general population, were individually matched to each case for age. RESULTS: The prevalences of osteoporosis were 55.4% and 10.5% in patients and controls, respectively. Among the subjects, 21.7% and 4.2% had a vertebral fracture in the RA and control groups, respectively. Compared with controls, patients with RA had an increased risk of VFs: odds ratio (OR) (CI 95%) adjusted on body mass index was 6.5 (3.1, 13.9). In a multiple logistic regression analysis, VFs were independently associated with presence of non-vertebral fractures (OR = 9.2 [2.5-33.5]), presence of a fall in the previous year (OR = 4.6 [1.2-18.3]), current use of disease-modifying anti-rheumatic drugs (DMARDs) (OR = 0.05 [0.004, 0.51]) and current use of steroids (OR = 0.17 [0.04, 0.67]). CONCLUSION: Rheumatoid arthritis is a risk factor of VF (OR = 6.5). VFA is a convenient tool for this diagnosis. Presence of VF is inversely related to the use of DMARD and glucocorticoids, enhancing the hypothesis that an appropriate control of the disease may be a protective factor against bone fragility.

Bone texture analysis of human femurs using a new device (BMA™) improves failure load prediction.

UNLABELLED: We measured bone texture parameters of excised human femurs with a new device (BMA™). We also measured bone mineral density by DXA and investigated the performance of these parameters in the prediction of failure load. Our results suggest that bone texture parameters improve failure load prediction when added to bone mineral density. INTRODUCTION: Bone mineral density (BMD) is a strong determinant of bone strength. However, nearly half of the fractures occur in patients with BMD which does not reach the osteoporotic threshold. In order to assess fracture risk properly, other factors are important to be taken into account such as clinical risk factors as well as macro- and microarchitecture of bone. Bone microarchitecture is usually assessed by high-resolution QCT, but this cannot be applied in routine clinical settings due to irradiation, cost and availability concerns. Texture analysis of bone has shown to be correlated to bone strength. METHODS: We used a new device to get digitized X-rays of 12 excised human femurs in order to measure bone texture parameters in three different regions of interest (ROIs). We investigated the performance of these parameters in the prediction of the failure load using biomechanical tests. Texture parameters measured were the fractal dimension (Hmean), the co-occurrence matrix, and the run length matrix. We also measured bone mineral density by DXA in the same ROIs as well as in standard DXA hip regions. RESULTS: The Spearman correlation coefficient between BMD and texture parameters measured in the same ROIs ranged from -0.05 (nonsignificant (NS)) to 0.57 (p = 0.003). There was no correlation between Hmean and co-occurrence matrix nor Hmean and run length matrix in the same ROI (r = -0.04 to 0.52, NS). Co-occurrence matrix and run length matrix in the same ROI were highly correlated (r = 0.90 to 0.99, p < 0.0001). Univariate analysis with the failure load revealed significant correlation only with BMD results, not texture parameters. Multiple regression analysis showed that the best predictors of failure load were BMD, Hmean, and run length matrix at the femoral neck, as well as age and sex, with an adjusted r (2) = 0.88. Added to femoral neck BMD, Hmean and run length matrix at the femoral neck (without the effect of age and sex) improved failure load prediction (compared to femoral neck BMD alone) from adjusted r (2) = 0.67 to adjusted r (2) = 0.84. CONCLUSION: Our results suggest that bone texture measurement improves failure load prediction when added to BMD.

Spinal deformity index (SDI) is a good predictor of incident vertebral fractures.

UNLABELLED: The spinal deformity index is a convenient tool to quantify the number and the severity of prevalent vertebral fractures. It is a predictor of the risk of sustaining incident vertebral fracture. This quantification must be taken into account to improve management of patients. INTRODUCTION: Prevalent fractures are strong risk factors for subsequent fractures. METHODS: The study subjects were women from the placebo groups of two studies of strontium ranelate in postmenopausal osteoporosis (N = 723 and 637 patients, respectively). Three lateral radiographs of the spine were obtained at baseline and annually over 3 years, according to standardized procedures. The semiquantitative visual assessment of each vertebra from T4 to L4 was performed by the same reader throughout the study. A spinal deformity index (SDI) was calculated by summing for each patient the grade of each vertebra from T4 to L4. RESULTS: There was a linear relationship between baseline SDI and the 3-year incidence of vertebral fracture (adjusted R(2) = 0.76). The 3-year incidence of vertebral fractures was different among the tertiles of baseline SDI: 17.3 +/- 3.6%, 25.4 +/- 2.6%, and 47.6 +/- 3.1% from the lowest to the highest, respectively. There was no relationship between SDI and non-vertebral fractures incidence. CONCLUSION: SDI is a good predictor of incident vertebral fractures. Patients with highest SDI should receive highest priority to treatment.

Ultrasound-Based Estimates of Cortical Bone Thickness and Porosity Are Associated With Nontraumatic Fractures in Postmenopausal Women: A Pilot Study.

Recent ultrasound (US) axial transmission techniques exploit the multimode waveguide response of long bones to yield estimates of cortical bone structure characteristics. This pilot cross-sectional study aimed to evaluate the performance at the one-third distal radius of a bidirectional axial transmission technique (BDAT) to discriminate between fractured and nonfractured postmenopausal women. Cortical thickness (Ct.Th) and porosity (Ct.Po) estimates were obtained for 201 postmenopausal women: 109 were nonfractured (62.6 ± 7.8 years), 92 with one or more nontraumatic fractures (68.8 ± 9.2 years), 17 with hip fractures (66.1 ± 10.3 years), 32 with vertebral fractures (72.4 ± 7.9 years), and 17 with wrist fractures (67.8 ± 9.6 years). The areal bone mineral density (aBMD) was obtained using DXA at the femur and spine. Femoral aBMD correlated weakly, but significantly with Ct.Th (R = 0.23, p < 0.001) and Ct.Po (R = -0.15, p < 0.05). Femoral aBMD and both US parameters were significantly different between the subgroup of all nontraumatic fractures combined and the control group (p < 0.05). The main findings were that (1) Ct.Po was discriminant for all nontraumatic fractures combined (OR = 1.39; area under the receiver operating characteristic curve [AUC] equal to 0.71), for vertebral (OR = 1.96; AUC = 0.84) and wrist fractures (OR = 1.80; AUC = 0.71), whereas Ct.Th was discriminant for hip fractures only (OR = 2.01; AUC = 0.72); there was a significant association (2) between increased Ct.Po and vertebral and wrist fractures when these fractures were not associated with any measured aBMD variables; (3) between increased Ct.Po and all nontraumatic fractures combined independently of aBMD neck; and (4) between decreased Ct.Th and hip fractures independently of aBMD femur. BDAT variables showed comparable performance to that of aBMD neck with all types of fractures (OR = 1.48; AUC = 0.72) and that of aBMD femur with hip fractures (OR = 2.21; AUC = 0.70). If these results are confirmed in prospective studies, cortical BDAT measurements may be considered useful for assessing fracture risk in postmenopausal women. © 2019 American Society for Bone and Mineral Research.

Strontium ranelate reduces the risk of vertebral fracture in young postmenopausal women with severe osteoporosis.

OBJECTIVES: Early osteoporotic fractures have a great impact on disease progression, the first fracture being a major risk factor for further fractures. Strontium ranelate efficacy against vertebral fractures is presently assessed in a subset of women aged 50-65 years. METHODS: The Spinal Osteoporosis Therapeutic Intervention (SOTI) was an international, double blind, placebo controlled trial, supporting the efficacy of strontium ranelate 2 g/day in reducing the risk of vertebral fractures in postmenopausal women with osteoporosis and a prevalent vertebral fracture. 353 of these randomly assigned women were included in this analysis. RESULTS: Over 4 years, strontium ranelate significantly reduced the risk of vertebral fracture by 35% (relative risk 0.65; 95% CI 0.42 to 0.99, p<0.05). In the strontium ranelate group, the bone mineral density increased from baseline by 15.8% at lumbar spine and 7.1% at femoral neck. CONCLUSION: These data demonstrate a significant vertebral antifracture efficacy of strontium ranelate in young postmenopausal women aged 50-65 years with severe osteoporosis and confirm the efficacy of this antiosteoporotic treatment to prevent vertebral fractures, whatever the age of the patient.

Effects of strontium ranelate on spinal osteoarthritis progression.

OBJECTIVE: The aim of this study was to determine whether a 3-year treatment with strontium ranelate could delay the progression of spinal osteoarthritis (OA). METHODS: This study was a post-hoc analysis of pooled data from the Spinal Osteoporosis Therapeutic Intervention (SOTI) and TReatment Of Peripheral OSteoporosis (TROPOS) trials performed on 1105 women with osteoporosis and concomitant radiological spinal OA at baseline, and for whom lumbar x-rays were available at baseline and over the 3-year treatment period. The presence and severity of osteophytes, disc space narrowing and sclerosis in the lumbar intervertebral spaces was graded according to a validated method, and an overall OA score was calculated for each intervertebral space. Back pain (measured on a five-point Likert scale only in SOTI) and health-related quality of life (SF-36 questionnaire) were assessed at baseline and after 3 years. Patients who suffered an incident or progressive vertebral fracture during the study were excluded from the analysis. RESULTS: The proportion of patients with worsening overall spinal OA score was reduced by 42% in the strontium ranelate group, compared with placebo (RR, 0.58; 95% CI, 0.42 to 0.79; p = 0.0005). Significantly more patients in the strontium ranelate group experienced an improvement in back pain after 3 years, compared with placebo (p = 0.03), while no significant difference was observed in terms of health-related quality of life between these patient groups. CONCLUSIONS: The results of this post-hoc analysis suggest that strontium ranelate could reduce the progression of the radiographic features of spinal OA and back pain in women with osteoporosis and prevalent spinal OA.

Bone mineral density assessment using the EOS low-dose X-ray device: a feasibility study.

To predict bone strength in the case of osteoporosis, it could be a real benefit to assess the three-dimensional (3D) geometry and the bone mineral density (BMD) with a single low-dose X-ray device, such as the EOS system (Biospace Med, Paris, France). EOS 3D reconstructions of the spine have already been validated. Thus, this study aims at evaluating the accuracy of this low-dose system as a densitometer first ex vivo. The European Spine Phantom (ESP) (number 129) was scanned ten times using both the EOS and a Hologic device (Hologic, Inc., Massachusetts, USA). Accuracy was given by the sum of the systematic error (difference between BMDs assessed and true values given by the phantom manufacturer) and the random error (coefficient of variation). EOS BMDs and Hologic BMDs of 41 ex-vivo vertebrae were calculated and compared. The reproducibility of the method evaluating the EOS BMD was assessed giving the coefficient of variation of three measurements of the 41 vertebrae. The accuracy of the EOS system is below 5.2 per cent, versus 7.2 per cent for the Hologic system in the same conditions. EOS BMDs are significantly higher than Hologic BMDs, but they are strongly correlated. The reproducibility of the method of assessment is equal to 0.95 per cent. The EOS system is accurate for ex-vivo BMD assessments, which is promising regarding the use of this new system to predict vertebral strength.

Adjusting FRAX® on TBS for identification of subjects at high risk of fractures.

The objective of this study was to compare the proportion of patients at high fracture risk according to FRAX® and FRAX® adjusted on TBS in patients hospitalized for a non vertebral fractures. Patients were selected from a Fracture Liaison Service FLS): clinical risk factors, bone mineral density (BMD) and TBS were assessed at the time of the fracture. Without considering the current fracture, we calculated FRAX® and FRAX® adjusted on TBS (TBS-FRAX®), and compared the proportion of patients with a high risk for major osteoporotic fracture (MOF)>20% according to FRAX® and TBS-FRAX®, and the proportion of subjects who should be treated according to current guidelines. Four hundred and thirteen patients were included for a non vertebral fracture (84.5% women, mean age of 73.9±11.7years), Two hundred and eight patients (50.4%) had osteoporosis (T≤-2.5 at least one site) and the mean value of TBS was 1.206 (±0.111). The proportion of patients with a risk of MOF≥20% before the fracture was similar with FRAX® and TBS-FRAX® (24.7% vs 25.4%). The proportion of patients identified with a risk of MOF above the threshold value of therapeutic intervention was higher using TBS-FRAX® than FRAX® for the age categories of 60-70years (38.3% vs 30.9%, p=0.01) and 70-80years (31.2% vs. 26.6%, p=0.04). This study showed that the proportion of patients at high risk of fracture is similar using FRAX® and FRAX® adjusted on TBS in patients hospitalized for a non vertebral fracture in a FLS.

In vitro speed of sound measurement at intact human femur specimens.

Quantitative ultrasound has been recognized as a useful tool for fracture risk prediction. Current measurement techniques are limited to peripheral skeletal sites. Our objective was to demonstrate the in vitro feasibility of ultrasonic velocity measurements on human proximal femur and to investigate the relationship between velocity and bone mineral density (BMD). Sound velocity images were computed from 2-D scans performed on 38 excised human femurs in transmission at 0.5 MHz. Different regions-of-interest were investigated. Dual x-ray absorptiometry scans have been achieved for BMD measurements in site-matched regions. Our study demonstrates the feasibility of ultrasonic velocity measurements at the hip with reasonable precision (coefficient of variation of 0.3%). The best prediction of BMD was reached in the intertrochanter region (r(2) = 0.91, p < 10(-4)), with a residual error of 0.06 g/cm(2) (10%). Because BMD measured at the femur is the best predictor of hip fracture risk, the highly significant correlation and small residual error found in this study suggest that speed of sound measurement at the femur might be a good candidate for hip fracture risk prediction.

Ultrasonic backscatter and transmission parameters at the os calcis in postmenopausal osteoporosis.

Ultrasound technology has emerged as a new tool in the assessment of osteoporosis. Ultrasound parameters usually are measured in transmission; there is a potential for the analysis of backscattered signals to provide information on bone microarchitecture. The aim of this study was to explore a new technological development of the method, adding backscatter coefficient to transmission parameters, and to examine the appropriate thresholds to identify postmenopausal osteoporotic women. We examined 210 postmenopausal women (including 60 with osteoporotic fractures) and 30 healthy premenopausal controls. They had lumbar spine and hip bone mineral density (BMD) measurement and quantitative ultrasound (QUS) evaluation at the os calcis, measured in transmission (broadband ultrasound attenuation [BUA], speed of sound [SOS], ratio of transit time [dt] to BUA [dt/BUA], and "strength" index [STI]) and reflexion (broadband ultrasound backscattering [BUB]). The standardized CVs (sCVs) were between 2.27 % and 3.40 % for QUS measured in transmission and 4.41% for BUB. The odds ratio (OR) for fracture discrimination adjusted for age was 2.77 for hip BMD and between 1.6 and 2.9 for QUS. After adjustment for hip BMD, ORs were still highly significant for SOS, STI, and dt/BUA. According to hip BMD T score, prevalence of osteoporosis in our population was 39%. To detect the same prevalence, T scores ranged between -0.95 and -1.42 for QUS. QUS parameters have adequate ability to discriminate osteoporotic patients from controls. The World Health Organization (WHO) threshold for diagnosis of osteoporosis does not apply to this technology. The clinical utility of BUB at the os calcis, in addition to usual ultrasound parameters, is not yet proven. However, BUB evaluation, which does not require two transducers and may be implemented in conventional reflection mode systems, warrants further studies.

Broadband ultrasound attenuation imaging: a new imaging method in osteoporosis.

The purpose of this study was to evaluate the usefulness in osteoporosis of a new ultrasound imaging device able to create a parametric image of broadband ultrasound attenuation (BUA) at the os calcis. Three regions of interest were located in the great tuberosity of the os calcis. Precision was evaluated in 37 patients. Calcaneal bone mineral density (BMD) and BUA were compared in 33 patients. In 236 patients (including 77 with osteoporotic fractures), BUA and lumbar and femoral BMD measurements were performed. The measurements were compared using correlation coefficients. Their clinical value was estimated by comparisons of the results between patients with fractures and age-matched controls, using comparisons of the means, areas under the ROC curves, and logistic regression. Precision was in a 1.4-3.3% range. Local BUA and BMD were highly correlated (r = 0.88). Significant correlations were found between BUA and lumbar (r = 0.56) and femur (r = 0.66) BMD. In multiple regression, years since menopause and weight were significant predictors of BUA. Patients with fractures had lower BUA and BMD than age-matched controls. BUA showed the largest difference between the two populations (13-16%). Areas under the ROC curves were similar for BUA and BMD. Logistic regression after adjustment for confounding factors showed that BUA discriminated between fracture and nonfracture subjects. Broadband ultrasound attenuation imaging improves the reproducibility of ultrasound measurements. It may be useful in osteoporosis, due to its good discriminating value.