François Duboeuf

Bone Fragility: Failure of Periosteal Apposition to Compensate for Increased Endocortical Resorption in Postmenopausal Women

The increase in bone fragility after menopause results from reduced periosteal bone formation and increased endocortical resorption. Women with highest remodeling had greatest loss of bone mass and estimated bone strength, whereas those with low remodeling lost less bone and maintained estimated bone strength.

Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis.

Bone sialoprotein (BSP) and osteopontin (OPN) are both highly expressed in bone, but their functional specificities are unknown. OPN knockout (−/−) mice do not lose bone in a model of hindlimb disuse (tail suspension), showing the importance of OPN in bone remodeling. We report that BSP−/− mice are viable and breed normally, but their weight and size are lower than wild-type (WT) mice. Bone is undermineralized in fetuses and young adults, but not in older (≥12 mo) BSP−/− mice. At 4 mo, BSP−/− mice display thinner cortical bones than WT, but greater trabecular bone volume with very low bone formation rate, which indicates reduced resorption, as confirmed by lower osteoclast surfaces. Although the frequency of total colonies and committed osteoblast colonies is the same, fewer mineralized colonies expressing decreased levels of osteoblast markers form in BSP−/− versus WT bone marrow stromal cultures. BSP−/− hematopoietic progenitors form fewer osteoclasts, but their resorptive activity on dentin is normal. Tail-suspended BSP−/− mice lose bone in hindlimbs, as expected. In conclusion, BSP deficiency impairs bone growth and mineralization, concomitant with dramatically reduced bone formation. It does not, however, prevent the bone loss resulting from loss of mechanical stimulation, a phenotype that is clearly different from OPN−/− mice.

Hyperpolarized 3He MR for Sensitive Imaging of Ventilation Function and Treatment Efficiency in Young Cystic Fibrosis Patients with Normal Lung Function

PURPOSE To assess the sensitivity of hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging for the detection of peripheral airway obstruction in younger cystic fibrosis (CF) patients showing normal spirometric results (mean forced expiratory volume in 1 second [FEV(1)], 112% +/- 14.5 [standard deviation]) and to observe the immediate effects of a single chest physical therapy (CPT) session, thereby comparing two image quantification techniques. MATERIALS AND METHODS Ten pediatric CF patients (age range, 8-16 years) with normal spirometric results were included in this study after approval from the local research ethics committee. Spirometry followed by proton and hyperpolarized (3)He three-dimensional lung imaging were performed with a 1.5-T MR unit before and after 20 minutes of CPT. The number of ventilation defects per image (VDI) and the ventilated lung fraction (VF), defined as the ratio of ventilated lung volume divided by total lung volume, were quantified. RESULTS Ventilation defects were found in all patients (mean VDI, 5.1 +/- 1.9; mean global VF, 78.5% +/- 12.3; and mean peripheral VF, 75.5% +/- 17.1) despite normal spirometric results. After CPT, disparate changes in the distribution of ventilation defects were observed but the average VDI and VF did not change significantly (mean VDI, 5.1 +/- 1.1; mean global VF, 83.5% +/- 12.2; and mean peripheral VF, 80.3% +/- 12.2). There was no correlation between FEV(1) and VDI (rho = -0.041, P = .863) or global VF (rho = -0.196, P = .408) values but peripheral VF and VDI were correlated (rho = -0.563, P = .011). CONCLUSION Although spirometric results indicate normal lung function, the mean VDI in patients (5.1) found in this study is well above the VDI in healthy subjects (1.6) reported in the literature. A single CPT session induces disparate changes in the distribution and extent of ventilation defects.

Characterization of hepatocellular carcinoma and colorectal liver metastasis by means of perfusion MRI.

To characterize and compare hepatocellular carcinoma and liver metastases of colorectal metastatic cancer (CMC) by means of quantitative liver perfusion MRI.

Bone Microarchitecture Assessed by HR-pQCT as Predictor of Fracture Risk in Postmenopausal Women: The OFELY Study

Several cross‐sectional studies have shown that impairment of bone microarchitecture contributes to skeletal fragility. The aim of this study was to prospectively investigate the prediction of fracture (Fx) by bone microarchitecture assessed by high‐resolution peripheral computed tomography (HR‐ pQCT) in postmenopausal women. We measured microarchitecture at the distal radius and tibia with HR‐pQCT in the OFELY study, in addition to areal BMD with dual‐energy X‐ray absorptiometry (DXA) in 589 women, mean ± SD age 68 ± 9 years. During a median [IQ] 9.4 [1.0] years of follow‐up, 135 women sustained an incident fragility Fx, including 81 women with a major osteoporotic Fx (MOP Fx). After adjustment for age, women who sustained Fx had significantly lower total and trabecular volumetric densities (vBMD) at both sites, cortical parameters (area and thickness at the radius, vBMD at the tibia), trabecular number (Tb.N), connectivity density (Conn.D), stiffness, and estimated failure load at both sites, compared with control women. After adjustment for age, current smoking, falls, prior Fx, use of osteoporosis‐related drugs, and total hip BMD, each quartile decrease of several baseline values of bone microarchitecture at the radius was associated with significant change of the risk of Fx (HR of 1.39 for Tb.BMD [p = 0.001], 1.32 for Tb.N [p = 0.01], 0.76 for Tb.Sp.SD [p = 0.01], 1.49 [p = 0.01] for Conn.D, and 1.27 for stiffness [p = 0.02]). At the tibia, the association remained significant for stiffness and failure load in the multivariate model for all fragility Fx and for Tt.BMD, stiffness, and failure load for MOP Fx. We conclude that impairment of bone microarchitecture—essentially in the trabecular compartment of the radius—predict the occurrence of incident fracture in postmenopausal women. This assessment may play an important role in identifying women at high risk of fracture who could not be adequately detected by BMD measurement alone, to benefit from a therapeutic intervention.

Evaluation and Development of Automatic Two-Dimensional Measurements of Histomorphometric Parameters Reflecting Trabecular Bone Connectivity: Correlations with Dual-Energy X-Ray Absorptiometry and Quantitative Ultrasound in Human Calcaneum

In osteoporosis, bone fragility results from both bone loss and changes in trabecular microarchitecture, which can be quantified by bone histomorphometric parameters. Twenty human calcaneum were collected after necropsy. All measurements were performed at the same anatomical location. Bone histomorphometric parameters were measured on histological slides with an automatic image analyzer. The aims of our study were (1) to develop automatic measurements of four additional parameters reflecting trabecular network connectivity and complexity, i.e., trabecular bone pattern factor (TBPf), Euler number/tissue volume (Euler) according to the three definitions previously reported and to a fourth one established in the laboratory (Eulerstrut.cavity), marrow star volume, and interconnectivity index, and to determine their usefulness in microarchitecture characterization; and (2) to validate these parameters by evaluating their relationship with dual-energy X-ray absorptiometry and quantitative ultrasound (QUS) measurements performed on the same samples. The statistical analysis showed that TBPf and Eulerstrut.cavity appeared to be the most significant connectivity parameters, independently of bone quantity (bone mineral density, apparent density, cancellous bone volume). For QUS, after adjustment for bone quantity, only speed of sound (SOS) was significantly and negatively correlated to Eulerstrut.cavity. Broadband ultrasound attenuation depends only on bone quantity. In conclusion, TBPf (a strut analysis parameter extrapolable in three dimensions) and Eulerstrut.cavity (the only bone connectivity parameter reflecting SOS) are two valid bone microarchitecture parameters. These new parameters were significantly correlated to the established trabecular structure parameters: trabecular thickness or trabecular spacing, being weakly correlated with SOS.

Euler strut.cavity , a New Histomorphometric Parameter of Connectivity Reflects Bone Strength and Speed of Sound in Trabecular Bone from Human Os Calcis

The amount of bone and the trabecular microarchitecture are two determinants of bone strength which can be quantified by bone histomorphometry. Among the parameters of bone microarchitecture, the Euler number developed in our laboratory (Estrut.cavity) and trabecular bone pattern factor (TBPf) evaluate the connectivity and complexity independently of the bone quantity, and the speed of sound (SOS) measured by quantitative ultrasound (QUS) corroborates Estrut.cavity. The aim of the present study was to validate Estrut.cavity, TBPf, and SOS as parameters of bone microarchitecture and their contribution to bone strength. We examined 20 right os calcis taken after necropsy in 11 males and 9 females, aged 52–95 years. At the same anatomic location, we measured SOS and broadband ultrasound attenuation (BUA) using a Hologic Sahara device and bone mineral density (BMD) using a Hologic QDR 1000W. At this site a transcortical cylinder was cut for both apparent density measurement (Ap.Dens) and biomechanical tests (maximum compressive stress (σmax) and Young’s modulus (E)), and histomorphometry was performed with an automatic image analyzer (Visiolab, Explora Nova, France). E and σmax were significantly correlated with the parameters of bone quantity, microarchitecture, and QUS. However, after adjustment for the bone quantity, E correlated only with Estrut.cavity, TBPf, and SOS, and σmax with BUA. In conclusion, the bone connectivity and complexity evaluated by Estrut.cavity and TBPf contribute to bone strength, independently of the bone quantity. The bone mechanical properties may be assessed, in os calcis, in the elastic domain by SOS and in the plastic domain by BUA.

Muscle mass is associated with incident fracture in postmenopausal women: The OFELY study

The relationships between body composition and bone mineral density are well established but the contribution of body composition to the risk of fracture (Fx) has rarely been evaluated prospectively. We analyzed the risk of Fx by body composition in 595 postmenopausal women (mean age 66±8years) from a longitudinal cohort study (Os des Femmes de Lyon). We assessed the risk of the first incident fragility Fx according to body composition obtained from whole-body DXA: abdominal visceral (VFAT) and subcutaneous fat mass (SFAT), total body fat mass (FM), lean mass index (LMI) and appendicular skeletal muscle mass index (ASMI). During a median [IQ] follow-up of 13.1years [1.9], 138 women sustained a first incident Fx, including 85 women with a major osteoporotic Fx (MOP Fx: hip, clinical spine, humerus or wrist). After adjustment for age, women who sustained Fx had lower BMI (-4%, p=0.01), LMI (-6%, p=0.002) and ASMI (-3%, p=0.003), compared with women without Fx. After adjustment for age, prevalent Fx, physical activity, incident falls and FN BMD, each SD increase of baseline values of LMI and ASMI was associated with decreased Fx risk with adjusted hazard ratios of 0.76 for both of p≤0.02. Those associations were similar after accounting for the competing risk of death. VFAT and SFAT were associated with Fx risk in the multivariate model only for MOP Fx and the association did not persist after consideration of competing mortality. We conclude that lean mass and appendicular muscle mass indexes are associated with the risk of fracture in postmenopausal women independently of BMD and clinical risk factors.

Texture analysis of ultrasound liver images with contrast agent to characterize the fibrosis stage

The present work proposes to identify the liver fibrosis stage from a characterization of the perfusion using ultrasound images. A liver disease leads to changes in the organ perfusion that can be emphasized on ultrasound images by injecting contrast agent. In the evolution of the disease, 5 stages are usually defined and a visual evaluation of these stages is often difficult. We propose to characterize the evolution of the perfusion when the contrast agent is injected from image texture analysis and ultrasound tissue characterization techniques. To validate this approach, a set of 18 sequences of liver images at different pathological stages is used. The sequences represent at the beginning the liver without contrast agent and about 20 s later the contrast agent is fully distributed in the tissue. A window of homogeneous tissue is extracted each second for processing. 38 features were involved in the statistical analysis. The results show that the texture analysis of images corresponding to the fully distributed contrast agent is more relevant to identify the stage of fibrosis than the features characterizing the evolution of the texture. In particular, a classification of the samples in two classes (the 2 highest pathological grades versus the 3 lowest) exhibits a sensitivity of about 80 % and a specificity of about 60 %. The statistical significance was set to p<0.05.

Age-Related Changes in Fat Mass and Distribution in Men—the Cross-Sectional STRAMBO Study

Data on age-related differences in fat mass and distribution in men are scarce. We performed a cross-sectional analysis of age-related differences in fat distribution in men. In a cohort of 1133 men aged 20-87 yr, body composition was assessed using a Hologic Discovery A device. We assessed fat mass (FM) and FM indices adjusted for height. Interindividual variability was calculated as standard deviation, interquartile range, and difference between the 95th and 5th percentiles in 5-yr age groups. After adjustment for lifestyle factors, the FM and FM index of appendicular, gynoid, central, android, and subcutaneous abdominal compartments increased with age. Their variability did not vary with age. Visceral FM was 181% higher in men aged >80 yr compared to men aged 20-30 yr, and the variability increased with age. FM in the central, android, subcutaneous abdominal, and visceral compartments correlated with age significantly more strongly before the age of 70 than after this age. The relative differences between the elderly and younger men were greater for visceral FM than for subcutaneous (abdominal and appendicular) fat. The interindividual variability in visceral FM is higher in elderly men. The association between visceral FM and age is stronger before the age of 70.