Eric Lespessailles

Effect of physical training on bone mineral density in prepubertal girls: A comparative study between impact-loading and non-impact-loading sports

Physical activity is known to have an anabolic effect on bone tissue. It has been shown to increase the bone mineral density (BMD) in young adults, as well as in teenagers. But there is little information about the effect of intensive physical activity in childhood, particularly at the prepubertal stage. To examine the influence of an early intensive physical training on BMD, we have studied a group of elite prepubertal girls, at the starting phase of their peak bone mass acquisition. Subjects were engaged either in sport requiring significant impact loading on the skeleton, or in sport without impact loading. Forty-one healthy prepubertal girls took part in this study. The sport group consisted of 10 swimmers (10.5±1.4 years old) and 18 gymnasts (10.4±1.3 years old), who had performed 3 years of high-level sport training (8–12 h per week for swimmers, 10–15 h per week for gymnasts). Thirteen girls (10.7±1 years old) doing less than 3 h per week of physical activity served as a control group. BMD measurements were done using dual-energy X-ray absorptiometry. There was no statistical significant difference between groups as regards age, body height and weight, and body composition. There was no statistical significant difference between swimmers and controls for all the BMD measurements. Mean BMD in gymnasts was statistically higher than in the control group for mid-radius (+15.5%,p<0.001), distal radius (+33%,p<0.001), L2–4 vertebrae (+11%,p<0.05), femoral neck (+15%,p<0.001) and Ward’s triangle (+15%,p<0.01). Moreover, in gymnasts, BMD at radius, trochanter and femoral neck was above normative values. We conclude that physical activity in childhood could be an important factor in bone mineral acquisition in prepubertal girls, but only if the sport can induce bone strains during a long-term program: gymnastics has such characteristics, unlike swimming. Such acquisition could provide protection against risks of osteoporosis in later life, but this remains debatable.

Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor

Objectives Apremilast, an oral phosphodiesterase 4 inhibitor, regulates inflammatory mediators. Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy. Methods In the 24-week, placebo-controlled phase of PALACE 1, patients (N=504) were randomised (1:1:1) to placebo, apremilast 20 mg twice a day (BID) or apremilast 30 mg BID. At week 16, patients without ≥20% reduction in swollen and tender joint counts were required to be re-randomised equally to either apremilast dose if initially randomised to placebo or remained on their initial apremilast dose. Patients on background concurrent DMARDs continued stable doses (methotrexate, leflunomide and/or sulfasalazine). Primary outcome was the proportion of patients achieving 20% improvement in modified American College of Rheumatology response criteria (ACR20) at week 16. Results At week 16, significantly more apremilast 20 mg BID (31%) and 30 mg BID (40%) patients achieved ACR20 versus placebo (19%) (p<0.001). Significant improvements in key secondary measures (physical function, psoriasis) were evident with both apremilast doses versus placebo. Across outcome measures, the 30-mg group generally had higher and more consistent response rates, although statistical comparison was not conducted. The most common adverse events were gastrointestinal and generally occurred early, were self-limiting and infrequently led to discontinuation. No imbalance in major adverse cardiac events, serious or opportunistic infections, malignancies or laboratory abnormalities was observed. Conclusions Apremilast was effective in the treatment of psoriatic arthritis, improving signs and symptoms and physical function. Apremilast demonstrated an acceptable safety profile and was generally well tolerated. Clinical trial registration number NCT01172938.

Fractal analysis of radiographic trabecular bone texture and bone mineral density: two complementary parameters related to osteoporotic fractures.

Trabecular bone microarchitecture and bone mineral density (BMD) are two main factors related to osteoporotic fractures. Currently, however, microarchitecture is not evaluated. We have developed and validated a trabecular bone texture analysis from radiographic images. The objective was to determine if the fractal analysis of texture was able to distinguish osteoporotic fracture groups from control groups, either in vertebrae, hip, or wrist fractures, and to determine if this indicator and BMD were independent and complementary. In this cross‐sectional unicenter case‐control population study in postmenopausal women, 107 fracture cases were enrolled and age‐matched with 197 control cases. This population comprised 40 vertebral fractures (with 70 controls), 30 hip fractures (55 controls), and 37 wrist fractures (62 controls). Hip and lumbar spine BMD were measured by double‐energy X‐ray absorptiometry. Fractal analysis of texture was performed on calcaneus radiographs and the result was expressed as the H parameter (H = 2‐fractal dimension). The H parameter showed a lower value (0.679 ± 0.053 SD) in fracture cases versus control cases (0.696 ± 0.030; p = 0.007), the statistical significance persisting after adjustment for age and for lumbar spine (LS) or hip BMD. This result was confirmed in vertebral fractures (p = 0.0001) and hip fractures (p = 0.003) but not wrist fractures (p = 0.07). We determined the threshold between high and low H values and then the odds ratios (OR) of fracture for low H for BMD ≤ −2.5 SD in T score and for the combinations of both parameters. The OR of fracture for low H was 1.6 (95% CI, 1.1–2.6). For LS BMD ≤ −2.5 SD the OR of 6.1 (3.4–10.8) shifted to 9.0 (4.0–20.4) when we added low H and for hip BMD it shifted from 5.6 (3.3–9.4) to 8.1 (4.0–16.8). In vertebral, hip, and wrist fracture cases the results were also significant. These data have shown that the fractal analysis of texture on calcaneus radiographs can distinguish osteoporotic fracture groups from control groups. This analysis and BMD provide independent and complementary information. These data suggest that we can improve the fracture risk evaluation by adding information related to microarchitecture, derived from analysis of conventional radiographic images.

Fractal Dimension of Trabecular Bone Projection Texture Is Related to Three-Dimensional Microarchitecture

The purpose of this work was to understand how fractal dimension of two‐dimensional (2D) trabecular bone projection images could be related to three‐dimensional (3D) trabecular bone properties such as porosity or connectivity. Two alteration processes were applied to trabecular bone images obtained by magnetic resonance imaging: a trabeculae dilation process and a trabeculae removal process. The trabeculae dilation process was applied from the 3D skeleton graph to the 3D initial structure with constant connectivity. The trabeculae removal process was applied from the initial structure to an altered structure having 99% of porosity, in which both porosity and connectivity were modified during this second process. Gray‐level projection images of each of the altered structures were simply obtained by summation of voxels, and fractal dimension (Df) was calculated. Porosity (φ) and connectivity per unit volume (Cv) were calculated from the 3D structure. Significant relationships were found between Df, φ, and Cv. Df values increased when porosity increased (dilation and removal processes) and when connectivity decreased (only removal process). These variations were in accordance with all previous clinical studies, suggesting that fractal evaluation of trabecular bone projection has real meaning in terms of porosity and connectivity of the 3D architecture. Furthermore, there was a statistically significant linear dependence between Df and Cv when φ remained constant. Porosity is directly related to bone mineral density and fractal dimension can be easily evaluated in clinical routine. These two parameters could be associated to evaluate the connectivity of the structure.

Fractal analysis of trabecular bone texture on radiographs: discriminant value in postmenopausal osteoporosis.

Abstract: Trabecular bone microarchitecture cannot be routinely evaluated. We have developed and validated a fractal analysis of trabecular bone texture on calcaneus radiographs. The aim of this work was to evaluate the ability of the fractal analysis to discriminate a group of 39 postmenopausal women with osteoporotic (OP) vertebral crush fractures (68.0 + 10.8 years) from an age-matched control group of 39 women (68.0 + 10.7 years). The value of the fractal analysis was compared with the value of the femoral neck bone mineral density (FNBMD) and trochanteric bone mineral density (TRBMD). The result is expressed by the parameter Hmean (Hmean= 2 7 fractal dimension). Hmean value was 0.691 + 0.050 in the OP group versus 0.739 + 0.024 in the controls, while FNBMD was 0.598 + 0.113 g/cm2 versus 0.645 + 0.109 g/cm2 and TRBMD was 0.512 + 0.108 g/cm2 versus 0.594 + 0.106 g/cm2 respectively. The statistical significance of the Hmean test (p50.0001) was higher than for FNBMD (p50.05) and for TRBMD (p= 0.0004). We used a receiver operating characteristic (ROC) curve to check this superiority. The area under the ROC curve was 0.824 for Hmean, 0.633 for FNBMD and 0.727 for TRBMD. This superiority of the Hmean ROC curve was statistically significant versus FNBMD, but not versus TRBMD. In a second analysis, we studied the subgroups of OP patients and controls with overlapping FNBMD or TRBMD values to check whether the fractal dimension test could be discriminant in these subgroups. Significant statistical differences were found for Hmean between OP patients and controls in the overlapping subgroup for FNBMD or TRBMD (respectively p= 0.006 and p50.02). These data confirm that the fractal analysis of texture on calcaneus radiographs is able to discriminate OP patients with vertebral crush fracture from controls. This discrimination was stronger than that obtained by FNBMD or TRBMD alone. It was also present when we compared subgroups with overlapping values of FNBMD or TRBMD.

Longterm (52-week) Results of a Phase III Randomized, Controlled Trial of Apremilast in Patients with Psoriatic Arthritis

Objective. To evaluate the efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, over 52 weeks in patients with active psoriatic arthritis (PsA) despite prior treatment. Methods. Patients were randomized to placebo (n = 168), apremilast 20 mg BID (n = 168), or apremilast 30 mg BID (n = 168). Patients whose swollen and tender joint counts had not improved by ≥ 20% at Week 16 were considered nonresponders and were required to be re-randomized (1:1) to apremilast 20 mg BID or 30 mg BID if they were initially randomized to placebo, or continued their initial treatment of apremilast dose. At Week 24, all remaining patients treated with placebo were re-randomized to apremilast 20 mg BID or 30 mg BID. Results. An American College of Rheumatology 20 (ACR20) response at Week 16 was attained by significantly more patients receiving apremilast 20 mg BID (30.4%, p = 0.0166) or 30 mg BID (38.1%, p = 0.0001) than placebo (19.0%). Among patients receiving apremilast continuously for 52 weeks (n = 254), ACR20 response at Week 52 was observed in 63.0% (75/119, 20 mg BID) and 54.6% (71/130, 30 mg BID) of patients. Response was also maintained across secondary outcomes, including measures of PsA signs and symptoms, skin psoriasis severity, and physical function. The nature, incidence, and severity of adverse events were comparable over the 24-week and 52-week periods. The most common adverse events, diarrhea and nausea, generally occurred early and were self-limited. Conclusion. Continuous apremilast treatment resulted in sustained improvements in PsA for up to 52 weeks. Apremilast had an acceptable safety profile and was generally well tolerated. Clinical trial registration: NCT01172938.

Clinical interest of bone texture analysis in osteoporosis: a case control multicenter study

SummaryWe demonstrate the clinical interest of bone texture analysis with a new high resolution X-ray device. We have found that the combination of BMD and texture parameter values provided a better assessment of the fracture risk than that obtainable solely by BMD measurement.IntroductionOsteoporosis is characterized by BMD and trabecular bone microarchitecture. We have developed a new high-resolution X-ray device with direct digitization. The aim of this study was to demonstrate in a multicenter case control study the clinical interest of bone texture analysis with this new device.MethodsIn this cross-sectional multicenter case-control population study in post-menopausal women, 159 osteoporotic fractures were compared with 219 control cases. Images were obtained on calcaneus with a direct digital X-ray device (BMA™, D3A Medical Systems). Co-occurrence, run-length matrices and the fractal parameter Hmean were evaluated. BMD was measured at the lumbar spine (LS), femoral neck (FN) and total hip (TH) by DXA.ResultsThe three texture parameters were significantly lower in osteoporotic fracture cases than in control cases. These differences persisted after adjustment for TH BMD. Receiver operating characteristic curves were used to compare the discriminant capacity of texture parameters and BMD measurements for fracture. The highest areas under curve (AUC) were 0.721 for TH BMD and 0.706 for Hmean (AUC THBMD vs. AUC Hmean, p = NS). We determined the threshold between high and low Hmean parameter values and then the odds ratios (OR) of fracture for low Hmean, for BMD ≤2.5 SD in the T-score and for combinations of both parameters. The OR of fracture for low H was 2.72 (95% CI, 1.36–5.4). For a FN BMD ≤ −2.5 SD, the OR of 4.78 (2.19–10.43) shifted to 14.06 (4.41–44.85) adding H.ConclusionsThese data confirmed the clinical interest of the combination of BMD and texture parameters to improve the assessment of the risk of fracture other that obtainable by the sole BMD measurement.

Bone Texture Analysis on Direct Digital Radiographic Images: Precision Study and Relationship with Bone Mineral Density at the Os Calcis

Assessment of bone microarchitecture in complement to bone mineral density (BMD) exam could improve prediction of osteoporotic fractures. A high-resolution X-ray prototype was developed to assess microarchitecture quality. Images were obtained on os calcis; then, three texture parameters were calculated on the same region of interest (ROI): a fractal parameter, a run-length parameter, and a co-occurrence parameter. This work describes the reproducibility of this method. We also examine the relationship between texture parameters and BMD at a site-matched ROI. Measurements on the left heel were performed on 30 healthy women, on the same day, with repositioning for short-term precision error. An additional measurement was done at 1 week to evaluate mid-term precision error on 14 subjects. Os calcis images from 10 healthy women were used to evaluate both intra- and interobserver reproducibility. Thirty other healthy patients were measured successively on two similar devices for interprototype comparison. BMD and texture analyses of the left heel were obtained from 57 women. Short-term precision errors ranged 1.16–1.24% according to the texture parameter. Mid-term precision error was slightly higher than short-term precision for the mean Hurst exponent parameter. Comparisons of texture parameters and BMD at a site-matched ROI on the os calcis showed no significant relationships. The results also show that the use of this high-resolution digital X-ray device improves the reproducibility of parameter measurement compared to the indirect digitization of radiologic films previously used.

Fractal Analysis of Bone Texture on Os Calcis Radiographs Compared with Trabecular Microarchitecture Analyzed by Histomorphometry

Abstract. Microarchitecture of trabecular bone is an important determinant of bone fragility; to date, its evaluation requires bone biopsy with histomorphometry analysis. Methods of noninvasive characterization of trabecular bone microarchitecture are in development and we have developed and validated a bone texture analysis applied to bone radiographs and based on fractal geometry. The aim of our study was to compare this fractal analysis of trabecular bone texture on radiographs to the trabecular microarchitecture analyzed by bone histomorphometry on os calcis biopsies. Thirty eight ossa calcis from 19 human cadavers were studied. Fractal analysis of the trabecular bone of os calcis radiographs was performed by the maximum likelihood estimator following the fractional brownian motion model. The ossa calcis were dissected, then transcortical biopsy cores focused on the fractal analysis region of interest were obtained. Structural and connectivity parameters were measured with both automatic and semiautomatic analyzers. We have found a significant relationship between the fractal Hmean parameter and structural histomorphometric indices; the best correlation was found with trabecular separation (r =−0.55; P= 0.0004). Based on a stepwise regression analysis, trabecular spacing and trabeculae number together would explain 38% of the variance of the fractal parameter. Although the relationship with connectivity indices was poor, our fractal analysis of os calcis trabecular bone texture on radiographs seemed to partially reflect the trabecular bone microarchitecture.

Prevalence and features of osteoporosis in the French general population: the Instant study.

OBJECTIVES To determine the prevalence of diagnosed osteoporosis, the extent of treatment use and the incidence of fracture in a representative sample of the French general population. METHODS A cross-sectional epidemiological survey of osteoporosis in 2613 women over 45 years in the general population was conducted using a stratified random sampling method and face-to-face interviews. Information was collected on the diagnosis of osteoporosis, fracture history, treatments, clinical and sociodemographic variables. Variables potentially associated with fracture were evaluated using stepwise multivariate logistic regression analysis. RESULTS The overall prevalence of diagnosed osteoporosis was 9.7% [8.6%; 10.9%] and prevalence increased linearly with age. Overall, 155 women (61.0%) received osteoporosis treatment and treatment rates also increased with age. The most frequently prescribed treatments were bisphosphonates, in 50.3% of treated women. The treatment duration was over 2 years for 72.9% of treated women. Overall, 115 (45.3%) reported at least one previous fracture. Vertebral fractures were reported by 101 women (39.8%) and limb fractures by 41 women (16.1%). Multivariate logistic regression analysis identified fracture before the age of 40, menopause before the age of 40, use of sleeping pills, consultation with an eye specialist and history of cardiovascular disease as variables independently associated with fracture. CONCLUSIONS Osteoporosis in France appears to be under-diagnosed and under-treated. Awareness and management of risk factors for osteoporosis and fracture could thus be improved.