PubMed Health⌕ Search

Biomedical subjects

Thierry Thomas

Publications and source records attributed to Thierry Thomas.

At least 19 recordsLinked to original sources
PubMed2006

How long should patients take medications for postmenopausal osteoporosis?

Several medications have proved effective in reducing the fracture risk in postmenopausal women with osteoporosis. The optimal duration of use of these medications remains to be established, however. Gains in bone mineral density (BMD) persisted throughout 10 years of treatment with alendronate or 7 years with risedronate. However, proof of long-term protection against fractures was obtained only for shorter treatment periods, 4 years with alendronate and 5 years with risedronate. The persistence of treatment effects after drug discontinuation varies across medications, and further studies are needed before this point can be incorporated into treatment decisions. With raloxifene, the BMD effect observed after 3 and 4 years persisted when the drug was given for 8 years, and the fracture risk reduction was similar after 4 years and after 3 years. The long-term safety profile also was similar, with a significant decrease in the incidence of invasive estrogen-receptor-positive breast cancer and a persistent increase in the risk of deep vein thrombosis. However, a sharp drop in BMD occurred upon raloxifene discontinuation. Thus, 4 years may be appropriate for anti-resorptive drug therapy. However, the optimal treatment duration should be determined on a case-by-case basis according to the results of regular fracture-risk evaluations.

Aged↗
PubMed2006

[Non-traumatic pathology of the shoulder: medical treatment].

Recently published meta-analyses emphasized weak methodology of clinical research evaluating medical treatment of non-traumatic shoulder pathology. Experts recommend medical treatment as the first step in the management of rotator cuff tendinopathies, the focus of this review. This step precedes surgical treatment of rotator cuff tear with the objective of recovering passive motion of the shoulder. It can be the unique therapeutic phase of rotator cuff tear or simple tendinopathy when clinical results match functional needs of the patient. Therefore, the physician prior treatment has to establish a lesion diagnostic, which is necessary to propose an appropriate strategy. Medical treatment includes NSAID, local injections of corticosteroids and physiotherapy with the double objective of a painless shoulder and normal range of motion. In case rotator cuff calcifying tendinitis, medical treatment is specific with first NSAID and local injections of cortico-steroïds, second needle aspiration and third arthroscopic removal, which remains the gold-standard procedure when other treatments failed.

Adrenal Cortex Hormones↗
PubMed2006

Intermittent parathyroid hormone therapy to increase bone formation.

Clinical data suggested that parathyroid hormone (PTH) might be effective in improving bone mass in patients with osteoporosis, providing its resorptive effects, which are particularly marked at cortical sites, were kept under control. We reviewed the evidence that intermittent PTH therapy is a valid treatment option whose predominant effect is bone anabolism. In cell culture studies, PTH affected both bone formation and bone resorption, suggesting that the net result of PTH therapy may be either bone gain or bone loss depending on the dosage, mode of administration, bone site, and animal species. Histological studies established that intermittent PTH therapy was associated with an increase in trabecular bone and, importantly, with improvements in trabecular and cortical microarchitectural parameters that have not been reported with antiresorptive drugs. This anabolic effect of intermittent PTH therapy translates into increased biomechanical strength, despite the increase in endocortical porosity seen in humans and nonhuman primates. The biochemical response profile to intermittent PTH therapy in clinical trials indicated a phase of isolated anabolism followed by an overall increase in bone remodeling that predominantly affected bone formation, the result being a large increase in spinal bone mineral density as early as the first treatment year. Thus, intermittent PTH therapy exerts predominantly anabolic effects on bone.

Animals↗
PubMed2006

[Osteoporosis: Optimizing treatment strategy].

Selection of patients for treatment is based on the assessment of their absolute fracture risk over 10 years. Assessment of fracture risk includes not only DXA measurement and age, the two principal risk factors, but also other clinical risk factors. The main goal of postmenopausal osteoporosis treatment is to reduce the risk of fragility fractures. Choice of treatment is based on drug properties, demonstrated in clinical trials, and patients' specific fracture risks. The minimum duration of treatment is 4-5 years, after which individual fracture risk must be reevaluated. Combinations of available drugs are not recommended for treatment of postmenopausal osteoporosis.

Age Factors↗
PubMed2006

Leptin increases proliferation of human steosarcoma cells through activation of PI(3)-K and MAPK pathways.

BACKGROUND: Serum leptin levels are strongly and directly related to fat body mass (FBM). Bone mineral density (BMD) increases with FBM, and obesity has a protective effect against osteoporosis. We have previously demonstrated that leptin therapy has a significant effect in preventing ovariectomy-induced bone loss in rats and leptin also exerts direct osteogenic effects in vitro. To obtain a better understanding of the physiology and pharmacology of leptin in bone metabolism, we evaluated the leptin-induced signal transduction pathways and proliferative response in the human osteosarcoma cell line Saos-2. MATERIAL/METHODS: Saos-2 cell lines were used. Leptin receptor common form (OB-Ra) and long form (OB-Rb) were detected by RT-PCR and immunocytochemistry. PI(3)-K activity was immunoprecipitated using antibodies directed against tyrosine-phosphorylated proteins and IRS-1. The activated form of p42/p44 MAPK was investigated in cytosolic extracts of confluent Saos-2 in response to leptin. RESULTS: In this study, we tested the hypothesis that leptin might be a mediator linking obesity and bone cell proliferation. We found that Saos-2 cells expressed OB-Ra and OB-Rb. Leptin (10 nmol/L - 2 umol/L) caused a significant increase in the activation of PI (3)-K that was accompanied by an increase in cell proliferation dose dependently based on the [3H]-thymidine incorporation. The specific PI (3)-K inhibitors LY294002 and wortmannin blocked leptin-induced cell proliferation. Interestingly, leptin activated MAPK and the specific MAPK-inhibitor PD98059 blocked DNA synthesis induced by leptin. CONCLUSIONS: Our data support the hypothesis that leptin may increase bone mass by stimulating osteoblast proliferation through activation of the P1 (3)-K and MAPK signaling pathways.

Bone and Bones↗
PubMed2005

The rheumatoid shoulder: current consensus on diagnosis and treatment.

Shoulder involvement is usually inconspicuous in patients with rheumatoid arthritis, and the clinical manifestations are nonspecific. Nevertheless, shoulder involvement should be sought routinely and detected early. Range of motion at the shoulder should be evaluated. Although normal radiographic findings do not rule out shoulder involvement, radiographs are crucial for detecting micro- and macro-geodes during follow-up. The development of glenohumeral joint space narrowing is a turning point that indicates a risk of rapid joint destruction. Magnetic resonance imaging is useful for assessing the lesions and guiding the treatment strategy. Stepwise use of local interventions as indicated by imaging findings is recommended. Joint replacement should not be left too late, and surgical procedures on the shoulder should be built into the overall treatment plan.

Arthritis, Rheumatoid↗
PubMed2005

Leptin modulates both resorption and formation while preventing disuse-induced bone loss in tail-suspended female rats.

In vitro studies have demonstrated leptin-positive effects on the osteoblast lineage and negative effects on osteoclastogenesis. Therefore, we tested the hypothesis that leptin may prevent tail-suspension-induced bone loss characterized by an uncoupling pattern of bone remodeling, through both mechanisms. Female rats were randomly tail-suspended or not and treated either with ip administration of leptin or vehicle for 3, 7, and 14 d. As measured by dual energy x-ray absorptiometry, tail-suspension induced a progressive decrease in tibia-metaphysis bone mineral density, which was prevented by leptin. Histomorphometry showed that this was related to the prevention of the transient increase in osteoclast number observed with suspension at d 7. These effects could be mediated by the receptor activator of nuclear factor kappaB-ligand (RANKL)/osteoprotegerin (OPG) pathway since we observed using direct RT-PCR, a suspension-induced increase in RANKL gene expression in proximal tibia at d 3, which was counterbalanced by leptin administration with a similar 3-fold increase in OPG expression and a RANKL to OPG ratio close to nonsuspended conditions. In addition, leptin prevented the decrease in bone formation rate induced by tail-suspension at d 14. The latter could be related to the role of leptin in mediating the reciprocal differentiation between adipocytes and osteoblasts, because leptin concurrently blunted the disuse-induced increase in bone marrow adipogenesis. In summary, these data suggest that peripheral administration of leptin could prevent disuse-induced bone loss through, first, a major inhibitory effect on bone resorption and, second, a delayed effect preventing the decrease in bone formation.

Animals↗
PubMed2005

Recommendations for monitoring antiresorptive therapies in postmenopausal osteoporosis.

Antiresorptive agents are effective in preventing and treating postmenopausal osteoporosis, provided they are taken as directed. Regular physical examinations including height measurements may fail to ensure optimal compliance. Bone mineral density (BMD) measurement is indispensable for determining whether treatment is warranted. The measurement can be repeated after 2 years at least, provided quality-control procedures are adequate. BMD changes over time should be compared to the least significant change calculated from the in vivo BMD reproducibility at the measurement center. However, BMD changes are not correlated with the fracture risk reduction induced by antiresorptive treatment. Biochemical markers for bone turnover can be monitored after only 3-6 months provided steps are taken to control for intraindividual variability. They are useful when patient compliance is poor or the treatment response inadequate.

Biomarkers↗
PubMed2004

Interactions between estrogen and mechanical strain effects on U2OS human osteosarcoma cells are not influenced by estrogen receptor type.

Estrogens (E) and mechanical strain (MS) exert direct effects on osteoblast activity, with good evidence of interactions between their respective effects. Osteoblasts express both forms of estrogen receptors (ER) ERalpha and ERbeta, and previous studies have suggested a specific role for each receptor. Therefore, our working hypothesis was that the interactions between E and MS on osteoblast activity vary depending on which ER is preferentially activated. Using human osteosarcoma cells U2OS stably transfected either with ERalpha or ERbeta, we evaluated the effects of cyclical cell loading on a F-3000 Flexercell Strain Unit (1.5% elongation, 10 min/day) in presence of estradiol (E2) 10(-8) M or not. The original U2OS cell line, which does not express ER, was characterized by low alkaline phosphatase (AP) activity. In both U2OS-ERalpha and U2OS-ERbeta cell lines, MS induced similar increases in AP activity and gene expression as measured by real-time quantitative RT-PCR, and a decrease in type I collagen gene expression. MS and E2 had a synergistic effect on AP activity as compared to each stimulus alone. No change in proliferation rate was observed. Neither proliferation nor differentiation of the original U2OS cell line was altered by strain or E2. In summary, our data showing differences in response to MS between the U2OS with no ER expression and the U2OS-ERalpha or -ERbeta cell lines provide additional evidence that ER plays a critical role in mechanotransduction. However, we were not able to demonstrate that interactions between E and MS were dependent on ER type in U2OS osteosarcoma cells.

Alkaline Phosphatase↗
PubMed2004

The complex effects of leptin on bone metabolism through multiple pathways.

Leptin has recently emerged as a mediator of the protective effects of fat on bone tissue. However, it remains difficult to draw a clear picture of how leptin effects bone metabolism. From conflicting or apparently contradictory data, it is tempting to hypothesize that leptin exerts dual effects depending on bone tissue, skeletal maturity and/or signaling pathway. Early in life, leptin might stimulate bone growth and bone size through direct angiogenic and chondro-osteogenic effects. Later, it may decrease bone remodeling in the mature skeleton, when trabecular bone turnover is high, by stimulating the osteoprotegerin-RANK-ligand pathway. Leptin also exerts negative effects on bone formation through a hypothalamic pathway mediated downstream by the sympathetic nervous system. The two pathways could counterbalance each other, with the peripheral and positive effects being predominant when leptin central resistance occurs with obesity onset.

Animals↗
PubMed2003

Leptin: a potential mediator for protective effects of fat mass on bone tissue.

Body weight is among the most powerful predictors of bone status, and adipose tissue plays a substantial role in weight-related protective effects on bone. An understanding of the mechanisms underlying the relation between adipose tissue and bone may open up new perspectives for treatment. Leptin, which is known to regulate appetite and energy expenditures, may also contribute to mediate the effects of fat mass on bone. Although reported data are somewhat conflicting, there is some evidence that leptin may decrease bone formation via a central nervous effect and may stimulate both bone formation and bone resorption via direct peripheral effects on stromal precursor cells. The net result of these central and peripheral effects may depend on serum leptin levels and blood-brain barrier permeability, of which the first increase and the second decrease as obesity develops. Further work is needed to improve our understanding of these effects.

Adipose Tissue↗
PubMed2003

Glucocorticoid-induced osteoporosis: pathophysiological data and recent treatments.

Long-term glucocorticoid therapy promptly induces osteoporosis, whose severity depends on the dose and duration of the treatment. Recent data suggest that there is no safety threshold for adverse effects on bone. Glucocorticoid therapy impairs calcium intestinal absorption, dramatically suppresses osteoblastic formation, and stimulates osteocyte apoptosis. In contrast, the contribution of secondary hyperparathyroidism and increased bone resorption, although frequently mentioned, is now a focus of controversy. Beneficial effects on bone have been obtained with calcium and vitamin D supplementation, as well as with hormone replacement therapy (HRT) in postmenopausal women. Bisphosphonates are clearly effective in preventing and treating glucocorticoid-induced osteoporosis, although their mechanism of action in this condition remains poorly understood. Parathyroid hormone (PTH) is being evaluated as a potential therapeutic agent for glucocorticoid-induced osteoporosis.

Animals↗
PubMed2003

Bone mineral density directly correlates with elevated serum leptin in haemodialysis patients.

BACKGROUND: Experimentally, leptin has a positive effect on bone mass when infused intravenously, but a negative one after intracerebroventricular administration. Renal failure increases its serum level above the concentration beyond which its transport to the brain may be saturated. Thus, we tested, in a chronic haemodialysis population, the hypothesis of a positive relationship between serum leptin and bone mineral density (BMD) when serum levels are above this threshold. METHODS: Serum leptin (using a two-site RIA), and BMD at the femoral neck, midshaft, and ultradistal radius, as measured by DEXA, were assessed in 17 female and 16 male chronic dialysis patients, with comparable calcium and phosphate metabolism, age and dialysis duration. RESULTS: Polynomial regression analysis showed a U-shaped correlation between BMD Z-score, with an inflexion point, which may correspond to the concentration threshold at which leptin blood-brain carrier is saturated. Linear regression analysis showed no correlation between BMD and serum leptin levels below these points but a significant positive correlation between BMD at the two radius sites and leptin levels above these points. The correlation remained significant after adjustment for BMI, serum PTH and duration of dialysis. Leptin levels were twice as high in female patients and associated with higher BMD Z-scores close to zero. CONCLUSIONS: This study suggests a bone-sparing effect of serum leptin in haemodialysis patients only when the serum levels of leptin were higher than the presumed threshold of blood-brain transport saturation. Higher leptin levels in post-menopausal female haemodialysis patients than in male patients may account for their slower bone loss with ageing.

Aged↗
PubMed2003

Tail suspension induces bone loss in skeletally mature mice in the C57BL/6J strain but not in the C3H/HeJ strain.

We assessed the effects of tail-suspension in two skeletal genetic backgrounds, the high C3H/HeJ (C3H) and low C57BL/6J (B6) bone masses inbred mice (male, 4-months old). Cancellous bone mass and structural parameters were evaluated in distal femoral metaphysis by three dimensional microcomputed tomography. Bone cellular activities were evaluated by histomorphometry and measurements of alkaline phosphatase activity (ALP) and osteocalcin in blood and deoxypyridinoline (D-pyr) in urine. In C3H mice, 2- and 3-week unloading experiments were performed. After an early and transient decrease in body weight, a 2-week suspension period resulted in stimulation of both bone formation rate by 45% and active osteoclastic surfaces by 19%. D-pyr did not change, but ALP and osteocalcin levels increased by 18% and 72%, respectively, in 2-week suspended mice, and osteocalcin remained elevated by 30% in the 3-week suspended mice. Such cellular modifications allowed the C3H mice to maintain their initial bone mass and trabecular structural parameters even after a 3-week suspension period. In B6 mice, 1- and 2-week unloading experiments were performed. Tail suspension resulted in decreased body weight during the first days followed by an incomplete recovery during the second week of unloading. The resorption activity was unaffected by any suspension time period, whereas a decrease of 42.5% in bone formation rate and of 21.5% in ALP were seen by the end of the first week of suspension, both values being restored after a 2-week suspension period. At this latter time, trabeculae were thinner, leading to a 24.5% cancellous bone loss. Trabecular number and connectivity, rod-plate index, and degree of anisotropy were not modified. We concluded that C3H mice constituted a unique model in which genetic background overwhelmed the usual effects of reduced biomechanical usage in bone, whereas B6 mice, compared with the standardized rat model, offered an alternative model of bone loss in a mature skeleton.

Animals↗