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See detailD-hormone analog alfacalcidol: its role in postmenopausal osteoporosis and rheumatoid arthritis management
Richy, Florent; DEROISY, Rita ULg; LECART, Marie-Paule ULg et al

in Osteoporosis International (2005, March), 16(Suppl.3), 105-106

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See detailAn indirect comparison of the efficacies of vitamin D and its hydroxylated analogs in postmenopausal and corticosteroid-induced osteoporosis
Richy, Florent; Schacht, E.; Bruyère, Olivier ULg et al

in Osteoporosis International (2005, March), 16(Suppl.3), 29

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See detailVitamin D analogs versus native vitamin D in preventing bone loss and osteoporosis-related fractures: A comparative meta-analysis
Richy, F.; Schacht, E.; Bruyère, Olivier ULg et al

in Calcified Tissue International (2005), 76(3), 176-186

It has been suggested that early postmenopausal women and patients treated with steroids should receive preventive therapy (calcium, vitamin D, vitamin D analogs, estrogens, or bisphosphonates) to ... [more ▼]

It has been suggested that early postmenopausal women and patients treated with steroids should receive preventive therapy (calcium, vitamin D, vitamin D analogs, estrogens, or bisphosphonates) to preserve their bone mineral density (BMD) and to avoid fragility fractures. We designed the present study to compare the effects of native vitamin D to its hydroxylated analogs alfacalcidol 1-alpha(OH)D and calcitriol 1,25(OH)(2)D. All randomized, controlled, double-blinded trials comparing oral native vitamin D and its analogs, alfacalcidol or calcitriol, to placebo or head-to-head trials in primary or corticosteroids-induced osteoporosis were included in the meta-analysis. Sources included the Cochrane Controlled Trials Register, EMBASE, MEDLINE, and a hand search of abstracts and references lists. The study period January 1985 to January 2003. Data were abstracted by two investigators, and methodological quality was assessed in a similar manner. Heterogeneity was extensively investigated. Results were expressed as effect-size (ES) for bone loss and as rate difference (RD) for fracture while allocated to active treatment or control. Publication bias was investigated. Fourteen studies of native vitamin D, nine of alfacalcidol, and ten of calcitriol fit the inclusion criteria. The two vitamin D analogs appeared to exert a higher preventive effect on bone loss and fracture rates in patients not exposed to glucocorticoids. With respect to BMD, vitamin D analogs versus placebo studies had an ES of 0.36 (P < 0.0001), whereas native vitamin D versus placebo had an ES of 0.17 (P = 0.0005), the interclass difference being highly significant (ANOVA-1, P < 0.05). When restricted to the lumbar spine, this intertreatment difference remained significant: ES = 0.43 (P = 0.0002) for vitamin D analogs and ES = 0.21 (P = 0.001) for native vitamin D (analysis of variance [ANOVA-1], P = 0.047). There were no significant differences regarding their efficacies on other measurement sites (ANOVA-1, P = 0.36). When comparing the adjusted global relative risks for fracture when allocated to vitamin D analogs or native vitamin D, alfacalcidol and calcitriol provided a more marked preventive efficacy against fractures: RD = 10% (95% Confidence interval [CI-2] to 17) compared to RD = 2% (95% CI, 1 to 2), respectively. The analysis of the spinal and nonspinal showed that fracture rates differed between the two classes, thereby confirming the benefits of vitamin D analogs, with significant 13.4% (95% CI 7.7 to 19.8) and. 6% (95% CI 1 to 12) lower fracture rates for vitamin D analogs, respectively. In patients receiving corticosteroid therapy, both treatments provided similar global ESs for BMD: ES = 0.38 for vitamin D analogs and ES = 0.41 for native vitamin D (ANOVA-1, P = 0.88). When restriced to spinal BMD, D analogs provided significant effects, whereas native vitamin D did not: ES = 0.43 (P < 0.0001) and ES = 0.33 (P = 0.21), respectively. The intertreatment difference was nonsignificant (ANOVA-1, P = 0.52). Neither D analogs for native vitamin D significantly prevented fractures in this subcategory of patients: RD = 2.6 (95%CI, -9.5 to 4.3) and RD = 6.4 (95%CI, -2.3 to 10), respectively. In head-to-head studies comparing D analogs and native vitamin D in patients receiving corticosteroids, significant effects favoring D analogs were found for femoral neck BMD: ES = 0.31 at P = 0.02 and spinal fractures: RD = 15% (95%CI, 6.5 to 25). Publication bias was not significant. Our analysis demonstrates a superiority of the D analogs atfacalcidol and calcitriol in preventing bone loss and spinal fractures in primary osteoporosis, including postmenopausal women. In corticosteroid-induced osteoporosis, the efficacy of D analogs differed depending on the comparative approach: indirect comparisons led to nonsignificant differences, whereas direct comparison did provide significant differences. In this setting, D analogs seem to prevent spinal fractures to a greater extent than do native vitamin D, but this assumption should be confirmed on a comprehensive basis in multiarm studies including an inactive comparator. [less ▲]

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See detailThe therapeutic effects of alfacalcidol on bone strength, muscle metabolism and prevention of falls and fractures.
Schacht, E.; Richy, F.; Reginster, Jean-Yves ULg

in Journal of Musculoskeletal & Neuronal Interactions (2005), 5(3), 273-84

Established osteoporosis in older patients of both sexes is characterized by decoupled bone remodelling induced by sex hormone deficits and by somatopause, but also by lack of vitamin D and reduced ... [more ▼]

Established osteoporosis in older patients of both sexes is characterized by decoupled bone remodelling induced by sex hormone deficits and by somatopause, but also by lack of vitamin D and reduced synthesis of the D-Hormone (calcitriol; 1.25 (OH)2D) in the kidneys and bone, as well as from lack of receptors and/or receptor affinity for D-Hormone in the target organs. Parallel to the decreased bone strength a loss of muscle power occurs, together with an increase in balance disorders and an increasing risk of "intrinsic", nonsyncopal locomotoric falls. In alfacalcidol therapy, D-Hormone is provided to the body in circumvention of its own regulation, by means of which higher hormone concentrations can be achieved in the target tissues than by administration of plain vitamin D. In vitro and in vivo experiments have provided growing evidence that D-Hormone analogs tend to normalize PTH, lead to an increase in the number and activity of osteoblasts, reduce the activity of osteoclasts, and might thus normalize the "high bone turnover" in elderly osteoporotic patients ("supercoupling"). In addition, it has been shown that D-Hormone analogs are able to increase muscle power and walking distance in elderly D-Hormone deficient patients. Besides the known effect on the vertebral fracture rate, new clinical data confirm that D-Hormone analogs might reduce peripheral fractures by reducing falls. The expanded understanding of the pathogenesis of glucocorticoid- induced osteoporosis with its disturbed calcium homeostasis and the pharmacological effects of alfacalcidol, which counteract such iatrogenic bone loss, contribute to the understanding of its clinical efficacy in this most frequent form of secondary osteoporosis. Due to its recently discovered immunomodulating properties, alfacalcidol might find a slot in the management of bone loss caused by chronic inflammatory diseases or by organ transplantations. Alfacalcidol has multifactorial effects, among which the best known are its anti-bone loss and anti-fracture efficacies in postmenopausal osteoporosis. This demonstrated efficacy is related to its involvement in bone remodelling, leading to an improved bone strength. Its mode of action on muscle power, which reduces falls, is unique, differentiating this form of therapy from all other anti-osteoporotic drugs, none having demonstrated any influence on falls. [less ▲]

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See detailSynthesis and Inverse Emulsion Polymerization of Aminated Acrylamidodextran
Daubresse, Catherine; Grandfils, Christian ULg; Jérôme, Robert ULg et al

in Journal of Pharmacy & Pharmacology (1993), 45

A chemically modified form of dextran was prepared; having a polymerizable moiety (acrylamide) and a reactive functional group (primary amine). Dextran was activated with 4-nitrophenylchloroformate (24 ... [more ▼]

A chemically modified form of dextran was prepared; having a polymerizable moiety (acrylamide) and a reactive functional group (primary amine). Dextran was activated with 4-nitrophenylchloroformate (24 mol per polysaccharide, 9,8 mol per 100 glucose residues); 9,8% glucose residues were converted to aliphatic carbonates and 5,2% were converted to cyclic carbonates. The activated dextran was coupled with trityldiaminoethane (8 mol per 100 glucose residues), reactivated with 4-nitrophenylchloroformate, then coupled with acryloamidodiaminohexane (6,8 mol per 100 glucose residues). The trityl group was removed by hydrolysis with trifluoroacetic acid to yield the required aminated acryloamidodextran. The modified dextran was shown to be polymerizable by inverse emulsion polymerization. Submicron particules were successfully prepared, containing functional amine groups suitable for preparing drug conjugates or for modifying the surface properties of thisbiomaterial. [less ▲]

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See detailSynthesis and inverse emulsion polymerization of aminated acrylamidodextran
Daubresse, C; Grandfils, Christian ULg; Jérôme, Robert ULg et al

Conference (1992, September 13)

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