Lepton flavor violating Higgs boson decays from massive seesaw neutrinos

Lepton flavor violating Higgs boson decays are studied within the context of seesaw models with Majorana massive neutrinos. Two models are considered: The SM-seesaw, with the Standard Model Particle content plus three right handed neutrinos, and the MSSM-seesaw, with the Minimal Supersymmetric Standard Model particle content plus three right handed neutrinos and their supersymmetric partners. The widths for these decays are derived from a full one-loop diagrammatic computation in both models, and they are analyzed numerically in terms of the seesaw parameters, namely, the Dirac and Majorana mass matrices. Several possible scenarios for these mass matrices that are compatible with neutrino data are considered. In the SM-seesaw case, very small branching ratios are found for all studied scenarios. These ratios are explained as a consequence of the decoupling behaviour of the heavy right handed neutrinos. In contrast, in the MSSM-seesaw case, sizeable branching ratios are found for some of the leptonic flavor violating decays of the MSSM neutral Higgs bosons and for some choices of the seesaw matrices and MSSM parameters. The relevance of the two competing sources of lepton flavor changing interactions in the MSSM-seesaw case is also discussed. The non-decoupling behaviour of the supersymmetric particles contributing in the loop-diagrams is finally shown.Comment: 44pgs. Version to appear in Phys.Rev.

SUSY-electroweak one-loop contributions to Flavour-Changing Higgs-Boson Decays

The SUSY-EW one-loop quantum contributions to flavour-changing MSSM Higgs-boson decays into $b \bar s$ and $s \bar b$ are computed and discussed. We use the full diagrammatic approach that is valid for all $\tan \beta$ values and do not rely on the mass-insertion approximation for the characteristic flavour-changing parameter. We analyze in full detail the dependence of these flavour-changing partial widths on all the relevant MSSM parameters and also study the non-decoupling behaviour of these widths with the SUSY mass parameters. We find that these contributions are sizable as compared to the SM ones, and together with the SUSY-QCD contributions they can be very efficient as an indirect method in the future search for Supersymmetry.Comment: LaTeX, 25 pages, 12 figures. Text improved and References added. Version to appear in Phys.Rev.

Il percorso ideale nella gestione del paziente con osteoporosi severa:dalla valutazione del rischio all'approccio multidisciplinare

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Flavour Changing Neutral Higgs Boson Decays from Squark - Gluino Loops

We study the flavour changing neutral Higgs boson decays that can be induced from genuine supersymmetric particles at the one-loop level and within the context of the Minimal Supersymmetric Standard Model. We consider all the possible flavour changing decay channels of the three neutral Higgs bosons into second and third generation quarks, and focus on the Supersymmetric-QCD corrections from squark-gluino loops which are expected to provide the dominant contributions. We assume here the more general hypothesis for flavour mixing, where there is misalignment between the quark and squark sectors, leading to a flavour non-diagonal squark mass matrix. The form factors involved, and the corresponding Higgs partial decay widths and branching ratios, are computed both analytically and numerically, and their behaviour with the parameters of the Minimal Supersymmetric Standard Model and with the squark mass mixing are analyzed in full detail. The large rates found, are explained in terms of the non-decoupling behaviour of these squark-gluino loop corrections in the scenario with very large supersymmetric mass parameters. Our results show that if these decays are seen in future colliders they could provide clear indirect signals of supersymmetry.Comment: 32 Pages and 12 PostScript Level 2 Figures. Some references adde

Efficacy and safety of strontium ranelate in the treatment of osteoporosis in men

CONTEXT: Strontium ranelate reduces vertebral and nonvertebral fracture risk in postmenopausal osteoporosis. OBJECTIVE: The objective of this study was to determine the efficacy and safety of strontium ranelate in osteoporosis in men over 2 years (main analysis after 1 year). DESIGN: This was an international, unbalanced (2:1), double-blind, randomized placebo-controlled trial (MALEO [MALE Osteoporosis]). SETTING: This international study included 54 centers in 14 countries. PARTICIPANTS: PARTICIPANTS were 261 white men with primary osteoporosis. INTERVENTION: Strontium ranelate at 2 g/d (n = 174) or placebo (n = 87) was administered. MAIN OUTCOME MEASURES: Lumbar spine (L2-L4), femoral neck, and total hip bone mineral density (BMD), biochemical bone markers, and safety were measured. RESULTS: Baseline characteristics were similar in both groups in the whole population (age, 72.9 ± 6.0 years; lumbar spine BMD T-score, -2.7 ± 1.0; femoral neck BMD T-score, -2.3 ± 0.7). Men who received strontium ranelate over 2 years had greater increases in lumbar spine BMD than those who received placebo (relative change from baseline to end, 9.7% ± 7.5% vs 2.0% ± 5.5%; between-group difference estimate (SE), 7.7% (0.9%); 95% confidence interval, 5.9%-9.5%; P < .001). There were also significant between-group differences in relative changes in femoral neck BMD (P < .001) and total hip BMD (P < .001). At the end of treatment, mean levels of serum cross-linked telopeptides of type I collagen, a marker of bone resorption, were increased in both the strontium ranelate group (10.7% ± 58.0%; P = .022) and the placebo group (34.9% ± 65.8%; P < .001). The corresponding mean changes of bone alkaline phosphatase, a marker of bone formation, were 6.4% ± 28.5% (P = .005) and 1.9% ± 25.4% (P = .505), respectively. After 2 years, the blood strontium level (129 ± 66 μmol/L) was similar to that in trials of postmenopausal osteoporosis. Strontium ranelate was generally well tolerated. CONCLUSIONS: The effects of strontium ranelate on BMD in osteoporotic men were similar to those in postmenopausal osteoporotic women, supporting its use in the treatment of osteoporosis in men

An experience- and preference-based EQ-5D-3L value set derived using 18 months of longitudinal data in patients who sustained a fracture: results from the ICUROS

Introduction EQ-5D-3L preference-based value sets are predominately based on hypothetical health states and derived in cross-sectional settings. Therefore, we derived an experience-based value set from a prospective observational study. Methods The International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) was a multinational study on fragility fractures, prospectively collecting EQ-5D-3L and Time trade-off (TTO) within two weeks after fracture (including pre-fracture recall), and at 4, 12, and 18 months thereafter. We derived an EQ-5D-3L value set by regressing the TTO values on the ten impairment levels in the EQ-5D-3L. We explored the potential for response shift and whether preferences for domains vary systematically with prior impairment in that domain. Finally, we compared the value set to 25 other EQ-5D-3L preference-based value sets. Results TTO data were available for 12,954 EQ-5D-3L health states in 4683 patients. All coefficients in the value set had the expected sign, were statistically significant, and increased monotonically with severity of impairment. We found evidence for response shift in mobility, self-care, and usual activities. The value set had good agreement with the only other experience- and preference-based value set, but poor agreement with all hypothetical value sets. Conclusions We present an experience- and preference-based value set with high face validity. The study indicates that response shift may be important to account for when deriving value sets. Furthermore, the study suggests that perspective (experienced versus hypothetical) is more important than country setting or demographics for valuation of EQ-5D-3L health states

Maintenance of antifracture efficacy over 10 years with strontium ranelate in postmenopausal osteoporosis

In an open-label extension study, BMD increased continuously with strontium ranelate over 10 years in osteoporotic women (P < 0.01). Vertebral and nonvertebral fracture incidence was lower between 5 and 10 years than in a matched placebo group over 5 years (P < 0.05). Strontium ranelate's antifracture efficacy appears to be maintained long term. INTRODUCTION: Strontium ranelate has proven efficacy against vertebral and nonvertebral fractures, including hip, over 5 years in postmenopausal osteoporosis. We explored long-term efficacy and safety of strontium ranelate over 10 years. METHODS: Postmenopausal osteoporotic women participating in the double-blind, placebo-controlled phase 3 studies SOTI and TROPOS to 5 years were invited to enter a 5-year open-label extension, during which they received strontium ranelate 2 g/day (n = 237, 10-year population). Bone mineral density (BMD) and fracture incidence were recorded, and FRAX(R) scores were calculated. The effect of strontium ranelate on fracture incidence was evaluated by comparison with a FRAX(R)-matched placebo group identified in the TROPOS placebo arm. RESULTS: The patients in the 10-year population had baseline characteristics comparable to those of the total SOTI/TROPOS population. Over 10 years, lumbar BMD increased continuously and significantly (P < 0.01 versus previous year) with 34.5 +/- 20.2% relative change from baseline to 10 years. The incidence of vertebral and nonvertebral fracture with strontium ranelate in the 10-year population in years 6 to 10 was comparable to the incidence between years 0 and 5, but was significantly lower than the incidence observed in the FRAX(R)-matched placebo group over 5 years (P < 0.05); relative risk reductions for vertebral and nonvertebral fractures were 35% and 38%, respectively. Strontium ranelate was safe and well tolerated over 10 years. CONCLUSIONS: Long-term treatment with strontium ranelate is associated with sustained increases in BMD over 10 years, with a good safety profile. Our results also support the maintenance of antifracture efficacy over 10 years with strontium ranelate

Vertebral anti-fracture efficacy of strontium ranelate according to pre-treatment bone turnover

Osteoporotic post-menopausal women patients in two randomised trials comparing the anti-fracture efficacy of strontium ranelate with placebo were separated into tertiles according to their baseline levels of biochemical markers of bone formation and resorption. The vertebral anti-fracture efficacy of strontium ranelate was shown to be independent of baseline bone turnover levels. INTRODUCTION: Bone turnover (BTO) levels vary among women at risk of osteoporotic fracture. Strontium ranelate is an anti-osteoporotic treatment increasing bone formation and reducing bone resorption. It was hypothesised that its anti-fracture efficacy would be independent of baseline BTO levels. METHODS: Post-menopausal women with osteoporosis from two pooled studies were stratified in tertiles according to baseline levels of two BTO markers: bone-specific alkaline phosphatase (b-ALP, n = 4995) and serum C-telopeptide cross-links (sCTX, n = 4891). Vertebral fracture risk was assessed over 3 years with strontium ranelate 2 g/day or placebo. RESULTS: In the placebo group, relative risk of vertebral fractures increased with BTO tertiles by 32% and 24% for patients in the highest tertile for b-ALP and CTX, respectively, compared to those in the lowest tertile. In the strontium ranelate group, incidences of vertebral fracture did not differ significantly across BTO tertiles. Significant reductions in vertebral fractures with strontium ranelate were seen in all tertiles of both markers, with relative risk reductions of 31% to 47% relative to placebo. Risk reduction did not differ among tertiles (b-ALP: p = 0.513; sCTX: p = 0.290). CONCLUSION: The vertebral anti-fracture efficacy of strontium ranelate was independent of baseline BTO levels. Strontium ranelate offers clinical benefits to women across a wide range of metabolic states