| 1. |
- Kayan, K, et al.
(author)
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Can fall risk be incorporated into fracture risk assessment algorithms: a pilot study of responsiveness to clodronate
- 2009
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In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965.
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Journal article (peer-reviewed)abstract
- Fall risk does not significantly impact on the efficacy of the bisphosphonate clodronate in reducing the incidence of fracture. INTRODUCTION: The debate about the efficacy of skeletal therapies on fracture risk in women at increased risk of falling continues. We determined whether fall risk impeded the efficacy of clodronate to reduce osteoporotic fracture incidence. METHODS: This is a post hoc analysis of a 3-year placebo-controlled study of bisphosphonate clodronate involving 5,212 women aged 75 years or more. At entry, self-reported multiple falls in the previous month and ability to rise from a chair were documented. Their interaction with treatment efficacy was examined using Poisson regression. RESULTS: Oral doses of clodronate at 800 mg daily reduced osteoporotic fracture incidence by 24% (hazard ration (HR) 0.76, 95% confidence interval 0.63-0.93). The efficacy was similar in women with recent multiple falls compared to those without (HR 0.61 vs. 0.77, p value for interaction >0.30) or impaired ability in rising compared to those with no impairment (HR 0.79 vs. 0.74, respectively; p value > 0.30). CONCLUSION: Fall risk does not significantly impact on the anti-fracture efficacy of clodronate. If confirmed with other agents, fall risk may be incorporated into risk assessment tools designed to target skeletal therapies.
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| 2. |
- McCloskey, E V, et al.
(author)
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Ten-year fracture probability identifies women who will benefit from clodronate therapy--additional results from a double-blind, placebo-controlled randomised study
- 2009
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In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 20:5, s. 811-7
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Journal article (peer-reviewed)abstract
- Fracture risk prediction can be enhanced by the concurrent assessment of other clinical risk factors. This study demonstrates that the estimation of an individual's 10-year probability of fracture by the FRAX algorithm identifies patients at high risk of fracture who will respond to bisphosphonate therapy. INTRODUCTION: Treatments for osteoporosis are targeted largely to patients with low bone density (BMD) or a prior fragility fracture. Fracture risk prediction can be enhanced by the concurrent assessment of other clinical risk factors, but it is important to determine whether the risk so identified can be reduced by intervention. We determined the effect of a bisphosphonate on fracture rates when risk was calculated using a new risk algorithm (FRAX). METHODS: Women aged 75 years or more were recruited to a randomised, double-blind controlled trial of 800 mg oral clodronate (Bonefos) daily over 3 years. Baseline clinical risk factors were entered in the FRAX model to compute the 10-year probability of major osteoporotic fractures with or without input of femoral neck BMD. The interaction between fracture probability and treatment efficacy was examined by Poisson regression. RESULTS: In 3,974 women, the interaction between fracture probability and treatment efficacy was significant when probability was assessed without BMD (p = 0.043), but not when BMD was included (p = 0.10). Efficacy was more evident in those deemed at highest risk. For example women lying at the 75th percentile of fracture probability in the absence of BMD (10-year probability 24%) treatment reduced fracture risk by 27% (HR 0.73, 95%CI 0.58-0.92). In those with a fracture probability of 30% (90th percentile), the fracture risk reduction was 38% (HR 0.62, 0.46-0.84). CONCLUSIONS: The estimation of an individual's 10-year probability of fracture by the FRAX algorithm identifies patients at high risk of fracture who will respond to bisphosphonate therapy.
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| 3. |
- Upadhayaya, Shankar, et al.
(author)
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Design, synthesis and biological evaluation of novel triazole, urea and thiourea derivatives of quinoline against Mycobacterium tuberculosis
- 2009
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In: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 17:13, s. 4681-4692
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Journal article (peer-reviewed)abstract
- A new series of 20 quinoline derivatives possessing triazolo, ureido and thioureido substituents have been synthesized and their antimycobacterial properties have been evaluated. Compounds 10, 22 and 24 inhibited Mycobacterium tuberculosis H37Rv up to 96%, 98% and 94% respectively, at a fixed concentration of 6.25 mu g/mL. Minimum inhibitory concentration of 3.125 mu g/mL was obtained for compound 10 and 24, while for compound 22 it was 6.25 mu g/mL. Molecular docking calculations suggest critical hydrogen bonding and electrostatic interactions between polar functional groups (such as quinoline-nitrogen, urea-carbonyl and hydroxyl) of anti-mycobacterial (anti-TB) compounds and amino acids (Arg186 and Glu61) of ATP-synthase of M. tuberculosis, could be the probable reason for observed anti-mycobacterial action. (C) 2009 Elsevier Ltd. All rights reserved.
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