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Biomedical subjects

Christian Roux

Publications and source records attributed to Christian Roux.

At least 37 records · Page 2Linked to original sources

Inactivation of the Na-Cl co-transporter (NCC) gene is associated with high BMD through both renal and bone mechanisms: analysis of patients with Gitelman syndrome and Ncc null mice.

UNLABELLED: Chronic thiazide treatment is associated with high BMD. We report that patients and mice with null mutations in the thiazide-sensitive NaCl cotransporter (NCC) have higher renal tubular Ca reabsorption, higher BMD, and lower bone remodeling than controls, as well as abnormalities in Ca metabolism, mainly caused by Mg depletion. INTRODUCTION: Chronic thiazide treatment decreases urinary Ca excretion (UVCa) and increases BMD. To understand the underlying mechanisms, Ca and bone metabolism were studied in two models of genetic inactivation of the thiazide-sensitive NaCl cotransporter (NCC): patients with Gitelman syndrome (GS) and Ncc knockout (Ncc(-/-)) mice. MATERIALS AND METHODS: Ca metabolism was analyzed in GS patients and Ncc(-/-) mice under conditions of low dietary Ca. BMD was measured by DXA in patients and mice, and bone histomorphometry was analyzed in mice. RESULTS: GS patients had low plasma Mg. They exhibited reduced UVCa, but similar serum Ca and GFR as control subjects, suggesting increased renal Ca reabsorption. Blood PTH was lower despite lower serum ionized Ca, and Mg repletion almost corrected both relative hypoparathyroidism and low UVCa. BMD was significantly increased in GS patients at both lumbar (+7%) and femoral (+16%) sites, and osteocalcin was reduced. In Ncc(-/-) mice, serum Ca and GFR were unchanged, but UVCa was reduced and PTH was elevated; Mg repletion largely corrected both abnormalities. Trabecular and cortical BMD were higher than in Ncc(+/+) mice (+4% and +5%, respectively), and despite elevated PTH, were associated with higher cortical thickness and lower endosteal osteoclastic surface. CONCLUSIONS: Higher BMD is observed in GS patients and Ncc(-/-) mice. Relative hypoparathyroidism (human) and bone resistance to PTH (mice), mainly caused by Mg depletion, can explain the low bone remodeling and normal/low serum Ca despite increased renal Ca reabsorption.

Adolescent↗

Benefits of pamidronate in children with osteogenesis imperfecta: an open prospective study.

OBJECTIVES: To study the efficacy of pamidronate in children with osteogenesis imperfecta (OI). PATIENTS AND METHODS: Twenty-nine patients (median age 8.7 years), were given pamidronate in cyclic infusions of 3 days. Patients received 3-13 cycles (median 6), at a dose of 0.5 mg/kg/day in infants (below 2 years of age) and 1 mg/kg/day in children (2 years and older). The interval time between cycles was 2 months in infants and 4 months in children. The median follow-up was 16 months. All patients received daily supplementation of calcium, vitamin D and physical rehabilitation. Assessments were performed at baseline and before each cycle. Fracture rate under treatment was compared to the one in the pre-treatment period. RESULTS: Pain decreased after the first infusion cycle (P < 0.0001). The median of fracture incidence decreased from 15 to 0.5 per year in infants and from 2.0 to 1 per year in children (P = 0.04). Alkaline phosphatase decreased by 31.2% and N-telopeptide collagen cross-links decreased by 61.8% (P < 0.001). Bone mineral density (BMD) of the spine increased by a median of 55.4% (P < 0.001). Z-scores increased from a median of -4.7 to -2.6 (P < 0.001). The femoral neck, BMD increased by a median of 16%. The area of the first four lumbar vertebrae increased by a median of 21.5% (P < 0.001). No adverse effect on growth or on fracture healing was observed. Side effects were symptomatic hypocalcemia in one infant, and the transient acute phase reaction. CONCLUSION: Pamidronate increases BMD, decreases bone remodeling markers, pain and fracture rate in infants and children with OI.

Adolescent↗

[Diagnosis of osteoporosis].

Osteoporosis is the main cause of bone fragility. The diagnosis is suspected in the presence of low-energy traumatic fracture and/or low bone mineral density. Vertebral fractures may be asymptomatic, and they are under-diagnosed. Dual energy X-ray absorptiometry is the gold standard of bone density measurement, at the lumbar spine, and hip. Providing quality control of the device and assessments, the measurements are accurate and precise; BMD is the basis of osteoporosis diagnostic and risk fracture evaluation. Osteoporosis may be related to malignant and metabolic diseases, which must be checked before any treatment.

Female↗

Association of five quantitative ultrasound devices and bone densitometry with osteoporotic vertebral fractures in a population-based sample: the OPUS Study.

UNLABELLED: We compared the performance of five QUS devices with DXA in a population-based sample of 2837 women. All QUS approaches discriminated women with and without osteoporotic vertebral fractures. QUS of the calcaneus performed as well as central DXA. INTRODUCTION: Quantitative ultrasound (QUS) methods have found widespread use for the assessment of bone status in osteoporosis, but their optimal use remains to be established. To determine QUS performance for current devices in direct comparison with central DXA, we initiated a large population-based investigation, the Osteoporosis and Ultrasound Study (OPUS). MATERIALS AND METHODS: A total of 463 women 20-39 years of age and 2374 women 55-79 years of age were measured on five different QUS devices along with DXA of the spine and the proximal femur. Their vertebral fracture status was evaluated radiographically. The association of QUS and DXA with vertebral fracture status was evaluated using logistic regression. RESULTS: All QUS approaches tested discriminated women with and without osteoporotic vertebral fractures (20% height reduction), with age-adjusted standardized odds ratios ranging 1.2-1.3 for amplitude-dependent speed of sound (AD-SOS) at the finger phalanges, 1.2-1.4 for broadband ultrasound attenuation (BUA) at the calcaneus, and 1.4-1.5 for speed of sound (SOS) at the calcaneus, 1.4-1.6 for DXA of the total femur, and 1.5-1.6 for DXA at the spine. For more severe fractures (40% height reduction), age-adjusted standardized odds ratios increased to up to 1.9 for DXA of the spine and 2.3 for SOS of the calcaneus. CONCLUSIONS: In conclusion, all five QUS devices tested showed significant age-adjusted differences between subjects with and without vertebral fracture. When selecting the strongest variable, QUS of the calcaneus worked as well as central DXA for identification of women at high risk for prevalent osteoporotic vertebral fractures. QUS-based case-finding strategies would allow halving the number of radiographs in high-risk populations, and this strategy works increasingly well for women with more severe vertebral fractures. It is likely that the good performance of QUS was in part achieved by rigorous quality assurance measures that should also be used in clinical practice.

Absorptiometry, Photon↗

The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis.

BACKGROUND: Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption. In a phase 2 clinical trial, strontium ranelate, an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption, has been shown to reduce the risk of vertebral fractures and to increase bone mineral density. METHODS: To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial, we randomly assigned 1649 postmenopausal women with osteoporosis (low bone mineral density) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years. We gave calcium and vitamin D supplements to both groups before and during the study. Vertebral radiographs were obtained annually, and measurements of bone mineral density were performed every six months. RESULTS: New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group, with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period (relative risk, 0.59; 95 percent confidence interval, 0.48 to 0.73). Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck (P<0.001 for both comparisons). There were no significant differences between the groups in the incidence of serious adverse events. CONCLUSIONS: Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures.

Administration, Oral↗

Discrimination of osteoporotic patients with quantitative ultrasound using imaging or non-imaging device.

OBJECTIVES: Quantitative ultrasound (QUS) has emerged as a new tool in the assessment of fracture risk. The aim of this study was to compare the clinical utility of QUS parameters measured using imaging and non-imaging devices in the discrimination of osteoporotic patients. METHODS: QUS (Broadband Ultrasound Attenuation, BUA dB/MHz, and Speed of Sound, SOS m/s) were measured and then statistical analyses were performed. RESULTS: The 106 women included were 65 +/- 8 years aged. Using DXA, T score was < or = -2.5 at either lumbar spine or hip in 59% of patients, and 25% had osteoporotic fractures. QUS results were different among devices, and these differences were highly dependent on the measured value. There was a similar effect of age and duration of menopause for all parameters. To obtain 90% of sensitivity for the diagnosis of osteoporosis, the thresholds were 50.80 and 71.70 dB/MHz for BUA and 1544.80 and 1551.50 m/s for SOS, using imaging and non-imaging devices, respectively. Belonging to the highest tertile of QUS had a negative predictive value for osteoporosis ranging from 59% to 65%. In the lowest tertile of QUS, the proportion of osteoporotic women was between 73% and 80%. All QUS parameters, except BUA measured with the non-imaging device, were able to discriminate post-menopausal women with fractures after adjustment for age and hip BMD. CONCLUSIONS: Our data suggest that an imaging system improves the utility of BUA measurement, but not SOS, for post-menopausal osteoporosis assessment.

Absorptiometry, Photon↗

Temporomandibular joint: a methodology of magnetic resonance imaging 3-D reconstruction.

OBJECTIVE: The aim of this study was to develop a new method for the 3-dimensional reconstruction of the temporomandibular joint (TMJ) images by means of magnetic resonance imaging (MRI). In a preliminary study, this modality of 3-D representation was tested to evaluate the joint motion. STUDY DESIGN: Sagittal MRI slices were obtained from a healthy subject. Acquisitions were realized by a spin-echo sequence, with a proton-density weighting and a 2-mm slice thickness. A 3-D reconstruction of the TMJ images was performed. RESULTS: Three-dimensional representations of the temporomandibular joint were obtained. The depiction of the principal anatomical elements of this joint was realized. A study of TMJ dynamics was also carried out. In this case, movements of the right and left disks and condyles were measured. CONCLUSION: This 3-D reconstruction methodology allowed a more understandable anatomical description than 2-D images of the TMJ and offered possibilities for joint functional analysis.

Adult↗

Efficacy of risedronate on clinical vertebral fractures within six months.

OBJECTIVE: Postmenopausal osteoporotic women with pre-existing or new incident vertebral fractures are at high risk for future fracture, so prompt treatment is warranted. Risedronate has been shown to reduce the incidence of radiographically-defined vertebral fractures by approximately two-thirds within 1 year. RESEARCH DESIGN: This study examined the effects of risedronate treatment on the time course of the reduction in the risk of clinical vertebral fractures (i.e., symptomatic fractures), on the risk of moderate-to-severe radiographic vertebral fractures, and on height. RESULTS: In 2442 postmenopausal women with prevalent vertebral fractures from the Vertebral Efficacy with Risedronate Therapy (VERT) studies who received either risedronate 5 mg or placebo, daily risedronate reduced the risk of clinical vertebral fractures within 6 months (RR = 0.08, 95% CI 0.01-0.63), and by 69% at 1 year (RR = 0.31, 95% CI 0.12, 0.78). At 1 year, risedronate also reduced the risk of moderate-to-severe radiographically-defined vertebral fractures by 71% (RR = 0.29 95% CI 0.16, 0.54). Height loss was attenuated with treatment, most notably in patients who experienced new vertebral fractures, with a median difference of 0.73 cm compared with subjects receiving placebo (p = 0.005). CONCLUSION: Risedronate reduces the risk of clinical vertebral fractures in postmenopausal women with osteoporosis within 6 months of commencing treatment.

Body Height↗

Segmentation of quantitative ultrasonographic images of the calcaneus using elastic deformation of the flexible Fourier contour.

OBJECTIVE: This study investigated a new technique for automatic model-based segmentation of broadband ultrasound attenuation (BUA) images of the calcaneus. We determined whether this technique was able to improve osteoporotic fracture discrimination. METHODS: The segmentation process included 2 major steps: a model-building stage and the automatic segmentation of new image data sets via an elastic deformation of contour models. Broadband ultrasound attenuation was then averaged within the final contour (BUAwhole). The results of the segmentation were validated on a database of 256 patients by comparison of the clinical results obtained with the automatic circular region of interest (BUAcirc) currently implemented on a commercially available ultrasonography unit. All patients were selected by the same physician, who assessed that the fractures were caused by bone fragility on the basis of the circumstances under which fractures occurred and radiologic data. RESULTS: Short-term reproducibility assessed in 49 women was 3.5% and 3.98% for BUAcirc and BUAwhole, respectively. Both BUAcirc (age-adjusted T score, -3.78; P < .0005; age-adjusted odds ratio, 1.92; 95% confidence interval, 1.34-2.75; area under the receiver operating characteristic curve, 0.70) and BUAwhole (age-adjusted T score,-2.73; P < .01; age-adjusted odds ratio, 1.57; 95% confidence interval, 1.12-2.21; area under the curve, 0.67) performed equally well in discriminating healthy postmenopausal patients (n = 150) from those with fractures (n = 60). CONCLUSIONS: Fully automatic segmentation by parametrically deformable elastic models for contour using Fourier descriptors can be achieved with reasonable reproducibility and fracture risk prediction. The method is similar to existing methods (automatic circular region of interest); however, the new contour-based region of interest allows more flexible region of interest geometries and placement and potential adaptation to individual anatomy. The method could also possibly be extended to quantitative ultrasonographic imaging at different skeletal sites.

Adult↗

Interest of biochemical markers of bone turnover for long-term prediction of new vertebral fracture in postmenopausal osteoporotic women.

OBJECTIVE: To analyse the interest of baseline levels and short-term (3-months) changes in serum osteocalcin (BGP), serum bone-specific alkaline phosphatase (BALP) and urinary C-telopeptide of type I collagen/creatinine ratio (U-CTX) to predict 3-years changes in bone mineral density (BMD) and spinal deformity index (SDI) in postmenopausal osteoporotic women. METHODS: Data were derived from a cohort of 603 osteoporotic women corresponding to the placebo arm of a 3-years prospective, double-blind study. RESULTS: Baseline values of BALP, BGP and U-CTX were negatively and significantly correlated with baseline spinal BMD. Significant correlations were also observed between the changes in BMD observed after 36 months at the spine and baseline BALP (r=0.20, P=0.0001), BGP (r=0.09, P=0.05) and U-CTX (r=-0.11, P=0.02). At 3 years, 71 women (15.9%) showed an increase in their SDI, corresponding to the occurrence of at least one new vertebral deformity. Baseline values of the four bone turnover markers (BTM) were not significantly related to the occurrence of new vertebral deformities. However, when considering the changes in the BTM observed after 3-months of follow-up, BGP (P=0.003) and U-CTX (P=0.047) were identified as significant predictors of an increase of SDI. The associated odds ratios (95% confidence interval (CI)) were 10.922 (2.218-53.78) for unit changes of log BGP and 1.369 (1.003-1.867) for unit changes of logU-CTX. The relative risk (RR) (IC 95%) of having a new vertebral fracture over 36 months was 0.31 (0.15-0.65) when being in the lowest quartile of 3-months changes in BGP as compared with the highest. CONCLUSION: We conclude that two sequential measurements of BGP and U-CTX performed at 3-months intervals could be of interest to identify postmenopausal osteoporotic women with the highest risk to present new vertebral deformities.

Aged↗

Serum leptin as a determinant of bone resorption in healthy postmenopausal women.

To examine the relationships between serum leptin and bone metabolism, we measured bone mineral density (BMD) at the spine and the hip, fasting serum leptin, and osteocalcin and urinary excretion of C-terminal crosslinking telopeptide of type I collagen (CTX), as markers of bone formation and resorption, respectively, in 121 postmenopausal women aged 54 +/- 5 years. These parameters were also assessed at 6 months and 2 years of treatment with either 2.5 mg tibolone (n = 34), 1.25 mg tibolone (n = 45), or 2 mg estradiol plus 1 mg norethindrone acetate (n = 42). At baseline, serum leptin correlated positively with spine (r = 0.21, P = 0.02) and total hip (r = 0.26, P = 0.0044) BMD and negatively with CTX (r = -0.38, P < 0.0001) and osteocalcin (r = 0.21, P = 0.025). After adjustment for BMI and for fat mass, the association between serum leptin and CTX persisted with a partial correlation coefficient of -0.18 (P = 0.046) and of -0.22 (P = 0.03), respectively. Women in the highest quartile of leptin levels had 11% higher total hip (P = 0.0039) and lumbar spine BMD (P = 0.016), 21% lower osteocalcin (P = 0.01), and 38% lower CTX (P = 0.0005) than women in the lowest quartile (P < 0.05). During treatment, serum leptin levels increased (+14.7 +/- 47.3%, P = 0.019), without significant difference between the groups. This increase correlated with the increase in body weight (r = 0.46, P < 10(-4)). No correlation was found between the changes in leptin and the changes in bone parameters. In conclusion, leptin may play a role as a determinant of bone resorption in healthy, untreated postmenopausal women, but the effect of estradiol or tibolone on bone are not mediated by leptin.

Aged↗

[Non-invasive method for measuring bone mineral density].

Measurement of bone mineral density (BMD) using dual energy X-ray absorptiometry is the basis of the definition of osteoporosis. Accuracy, precision and sensitivity of the method are good enough for clinical use. Prospective studies have shown that there is a gradient of risk between the decrease in BMD, related to age and hormonal insufficiency, and the increase in the incidence of fracture. Thus, therapeutic decision is based on both BMD and clinical risk factors that contribute to fracture risk.

Absorptiometry, Photon↗

Computer-assisted diagnosis system in digestive endoscopy.

The purpose of this paper is to present an intelligent atlas of indexed endoscopic lesions that could be used in computer-assisted diagnosis as reference data. The development of such a system requires a mix of medical and engineering skills for analyzing and reproducing the cognitive processes that underlie the medical decision-making process. The analysis of both endoscopists experience and endoscopic terminologies developed by professional associations shows that diagnostic reasoning in digestive endoscopy uses a scene-object approach. The objects correspond to the endoscopic findings and the medical context of examination and the scene to the endoscopic diagnosis. According to expert assessment, the classes of endoscopic findings and diagnoses, their primitive characteristics (or indices), and their relationships have been listed. Each class describes an endoscopic finding or diagnosis in an intensive way. The retrieval method is based on a similarity metric that estimates the membership value of the case under investigation and the prototype of the class. A simulation test with randomized objects demonstrates a good classification of endoscopic findings. The correct class is the unique response in 68% of the tested objects, the first of multiple responses in 28%. Four descriptors are shown to be of major importance in the classification algorithm: anatomic location, shape, color, and relief. At the present time, the application database contains approximately 150 endoscopic images and is accessible via Internet. Experiments are in progress with endoscopists for the validation of the system and for the understanding of the similarity between images. The next step will integrate the system in a learning tool for junior endoscopists.

Algorithms↗

Bone mineral measurements in mice: comparison of two devices.

Animal models are widely used to explore the pathogenesis and management of osteoporosis. Mice are increasingly being used in animal models. We have evaluated the precision, accuracy, and ability to monitor changes in bone mineral measurements of mice with the Piximus and Hologic QDR 2000 devices. One hundred and twenty-two C57/BL6 mice were used in this study; 70 of them were put on a low calcium diet and followed prospectively for 14 wk. They were measured using both devices at baseline and at wk 14. Using the Piximus, we measured the whole body, the tibia, and two caudal vertebrae. Using the Hologic, we measured the tibia, which we divided into three equal parts. The remaining mice were used to evaluate the precision and accuracy of the measurement. The accuracy, which was determined only for the Hologic device, revealed a mean difference between the in vivo bone mineral content (BMC) and the ash weight of 0.1 mg. The precision, evaluated from the coefficient of variation (%) and the Smallest Detectable Difference (SDD, in absolute values) was good for both devices, confirming their ability to detect small differences in longitudinal studies: as little as 0.004 g for the BMC of the total tibia on both devices, and 0.003 g/cm2 for whole body bone mineral density (BMD) on the Piximus. The BMC found using the two devices was comparable, whereas the BMD obtained on the Hologic device was nearly double that found using the Piximus. The comparison of the results by Bland and Altman's method showed that the difference between the results was not dependent on the magnitude of the measurement. We concluded that bone density and bone-density changes in mice can be measured precisely in vivo using the Hologic and Piximus devices; the latter being able to measure the whole body BMD with good precision.

Absorptiometry, Photon↗

Long-term safety of fluticasone propionate and nedocromil sodium on bone in children with asthma.

OBJECTIVE: Inhaled corticosteroids are recommended as first-line therapy for pediatric asthma. However, few controlled long-term studies have investigated their effect on bone mineral density (BMD) and growth. METHODS: Children who were aged 6 to 14 years and had persistent asthma were randomized to 24 months' treatment with fluticasone propionate (FP) 200 micro g/d or nedocromil sodium (NS) 8 mg/d (if uncontrolled, maximum doses of 400 micro g/d and 16 mg/d, respectively). BMD was assessed blind and analyzed at a central facility on the basis of dual-energy x-ray absorptiometry measurements of the lumbar spine and femoral neck at months 0, 6, 12, and 24. Height was measured at months 0, 12, and 24. Efficacy parameters (lung function, asthma control, occurrence of exacerbations) were measured every 3 months. RESULTS: In total, 174 children were randomized to treatment (87 received FP, and 87 received NS). At month 24, the adjusted mean percentage increase in lumbar spine BMD was 11.6% in the FP group compared with 10.4% in NS-treated children (95% confidence interval for treatment difference: -0.7% to 3.1%). The corresponding increases in femoral neck BMD were 8.9% and 8.5%, respectively. There was no significant difference in growth between the 2 groups: adjusted mean growth rates were 6.1 cm/y with FP and 5.8 cm/y with NS. FP was significantly superior for every efficacy parameter investigated and was similarly well tolerated as NS. CONCLUSIONS: The long-term effects of FP and NS on BMD accrual and growth are similar among children with asthma. The benefit:risk ratio of FP may be considered superior to that of NS.

Administration, Inhalation↗

Effects of tibolone and combined 17beta-estradiol and norethisterone acetate on serum C-reactive protein in healthy post-menopausal women: a randomized trial.

BACKGROUND: Serum C-reactive protein (CRP) is an independent risk factor for the development of cardiovascular diseases in healthy post-menopausal women. Oral unopposed and progestin-combined 17beta-estradiol (E(2)) increase serum CRP in post-menopausal women. The aim of this study was to compare the effects of tibolone, a steroid with estrogenic, androgenic or progestogenic properties, with a combination of E(2) and norethisterone acetate (E(2) + NETA) on serum CRP levels in healthy post-menopausal women. METHODS: A total of 139 post-menopausal women (mean age: 55 years, range 44-48) was randomly assigned to receive tibolone 1.25 mg/day (n = 52), tibolone 2.5 mg/day (n = 39) or E(2) 2 mg/day plus NETA 1 mg/day (n = 48) for 2 years. Serum CRP was measured at baseline and at 6, 12 and 24 months. RESULTS: Both doses of tibolone and E(2) + NETA increased serum CRP by a similar extent as soon as 6 months with a sustained effect over the 24 month treatment period. For example, after 6 months of treatment, serum CRP increased by a median of +106% (P < 0.001), +89% (P < 0.05) and +139% (P < 0.001) for tibolone 1.25 mg/day, tibolone 2.5 mg/day and E(2) + NETA respectively. CONCLUSIONS: Tibolone and E(2) + NETA significantly increase serum CRP levels in healthy post-menopausal women to a comparable extent. Relationships between induced elevated CRP levels with tibolone and E(2) + NETA and cardiovascular events require further studies.

Adult↗

Burst fracture of the spine involving vertebrae presenting no other lesions: the role of vertebroplasty.

We report our experience on percutaneous vertebroplasty performed on five patients who presented with history of trauma to the spine and secondary burst fracture, but with stable fractures, and on whom the medical and orthopedical therapies had been unsuccessful in the relief of the intractable pain and in the treatment of their functional status. Four cases have benefitted from the intervention, with complete disappearance of the symptomatology in two and incomplete in the other two. In one case, the improvement in the persistent painful symptoms was of no significance. Controls by computed tomography (CT). Which were performed after 3 months showed a satisfactory consolidation of the fractured vertebrae.

Adult↗