Disease relevance of Risedronate sodium

• Meta-analyses of therapies for postmenopausal osteoporosis. III. Meta-analysis of risedronate for the treatment of postmenopausal osteoporosis [1].
• RESULTS: Gastric ulcers were observed during the treatment period in 9 of 221 (4.1%) evaluable subjects in the risedronate group compared with 30 of 227 (13.2%) in the alendronate group (P < 0.001) [2].
• Esophageal ulcers were noted in 3 evaluable subjects in the alendronate group, compared with none in the risedronate group, and duodenal ulcers were noted in 1 evaluable subject in the alendronate group and 2 in the risedronate group [2].
• We examined the effects of the third generation bisphosphonate, risedronate, which is a specific inhibitor of osteoclastic bone resorption, in a bone metastasis model in nude mice in which intracardiac injection of the human breast cancer cell line MDA-231 leads to osteolytic bone metastases [3].
• In contrast, the growth of metastatic breast cancer in soft tissues surrounding bones was not affected by risedronate [3].

Psychiatry related information on Risedronate sodium

• When the actual data from two risedronate studies were analyzed, the meta-regression based on summary statistics demonstrated a stronger correlation between BMD change and fracture risk reduction than the results based on the IPD analysis [4].
• Effects of risedronate on bone density in anorexia nervosa [5].

High impact information on Risedronate sodium

• BACKGROUND: Risedronate increases bone mineral density in elderly women, but whether it prevents hip fracture is not known [6].
• This section summarizes the results of the seven systematic reviews of osteoporosis therapies published in this series [calcium, vitamin D, hormone replacement therapy (HRT), alendronate, risedronate, raloxifene, and calcitonin] and systematic reviews of etidronate and fluoride we have published elsewhere [7].
• Furthermore, a large reduction of non-vertebral fractures has been shown for alendronate, risedronate, and the 1-34 fragment of parathyroid hormone [8].
• This study compared the incidence of gastric ulcers after treatment with risedronate, a pyridinyl bisphosphonate, and alendronate, a primary amino bisphosphonate [2].
• We report here high-resolution x-ray structures of the human enzyme in complexes with risedronate and zoledronate, two of the leading N-BPs in clinical use [9].

Chemical compound and disease context of Risedronate sodium

• Urinary deoxypyridinoline, a bone resorption marker, decreased by 58.7% in the risedronate group and by 37.2% in the placebo group [10].
• Risedronate (15 mg/kg) and zoledronate (0.5 mg/kg) inhibited the growth of s.c. tumors and increased the median survival of mice with i.p. mesothelioma tumors in vivo [11].
• In animal models, ibandronate was more potent than etidronate, clodronate, pamidronate and alendronate and equivalent in potency or more potent than risedronate in inhibiting induced hypercalcaemia and bone resorption [12].
• In vitro studies indicate that the clinically used nitrogen-containing bisphosphonates (N-BPs) such as alendronate (ALN), risedronate (RIS) and ibandronate (IBA) suppress bone resorption via inhibition of the mevalonate pathway enzyme farnesyl diphosphate (FPP) synthase in osteoclasts (Ocs) [13].
• The aim of this study was to evaluate the efficacy and safety of risedronate and pamidronate in 30 patients (mean age = 57.86 +/- 8.90 years) with severe Paget's disease of bone (PDB), showing acquired resistance to intravenous (IV) clodronate treatment [14].

Biological context of Risedronate sodium

• Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer: a double-blind, placebo-controlled study [15].
• Moreover, risedronate had no effects on the local growth of s.c. implanted MDA-231 breast cancers in nude mice or on MDA-231 cell proliferation in culture [3].
• The order of potency for four BPs in inhibiting tumor cell adhesion to extracellular matrices was found to be: ibandronate > NE-10244 (antiresorptive active pyridinium analogue of risedronate) > pamidronate > clodronate [16].
• Using purified osteoclasts, we examined the effects of alendronate, risedronate, pamidronate, etidronate, and clodronate on apoptosis and signaling kinases [17].
• Effects of 3- and 5-year treatment with risedronate on bone mineralization density distribution in triple biopsies of the iliac crest in postmenopausal women [18].

Anatomical context of Risedronate sodium

• Myeloma cells or monocytes pulsed with risedronate and then washed rendered these target cells sensitive to lysis by a Vgamma2Vdelta2 T-cell clone or cell line [19].
• In contrast to risedronate, NE10790 inhibited bone resorption in vitro without markedly affecting osteoclast number or the F-actin "ring" structure in polarized osteoclasts [20].
• The mean differences in BMD between the 5-mg risedronate and the placebo groups were 3.8 +/- 0.8% at the lumbar spine (P < 0.001), 4.1 +/- 1.0% at the femoral neck (P < 0.001), and 4.6 +/- 0.8% at the femoral trochanter (P < 0.001) [21].
• The study showed that risedronate preserved trabecular architecture in the vertebra of OVX minipigs, and that bone strength is tightly coupled to bone mass and architecture [22].
• CONCLUSIONS: Long-term treatment with risedronate affects the homogeneity and degree of mineralization without inducing hypermineralization of the bone matrix [18].

Associations of Risedronate sodium with other chemical compounds

• Risedronate was active in vivo against T. brucei infection in mice (giving a 60% survival rate), but pamidronate was not effective [23].
• Consistent with their inhibition of the mevalonate pathway, apoptosis and cleavage of Mst1 kinase induced by alendronate, risedronate, and lovastatin, but not clodronate, are blocked by geranylgeraniol, a precursor of geranylgeranyl diphosphate [17].
• The remaining OVX rats were then treated for 10 weeks with vehicle, antiresorptive agents alone (estrogen, the bisphosphonate risedronate, or calcitonin) or PTH alone [24].
• The prevention of hip fracture with risedronate and ergocalciferol plus calcium supplementation in elderly women with Alzheimer disease: a randomized controlled trial [25].
• This was a multicenter, double-blind study in which 290 ambulatory men and women receiving high-dose oral corticosteroid therapy (prednisone > or = 7.5 mg/day or equivalent) for 6 or more months were randomized to receive placebo, risedronate 2.5 mg/day, or risedronate 5 mg/day for 12 months [26].

Gene context of Risedronate sodium

• We examined whether bone formation is coupled with bone resorption in OPG-deficient (OPG-/-) mice using risedronate, an inhibitor of bone resorption [27].
• The purpose of this study was to determine how sequential treatment of ovariectomized (OVXed) mice with bFGF followed by risedronate would restore trabecular microarchitecture and improve bone strength through alterations in bone mineralization [28].
• However, the -511 CC genotype of the IL1B gene was associated with a higher percentage of resistance to BSP (49% vs. 20%; P = 0.00 for all BSP, 60% vs. 39%, P = 0.17 for etidronate, 50% vs. 37% P = 0.53 for clodronate, 48 vs. 34% P = 0.05 for tiludronate and 50% vs. 4% P = 0.01 for risedronate) [29].
• Pyrophosphate and bisphosphonates (alendronate and risedronate) were ineffective in blocking synovial fluid MMP-9 autoactivation [30].
• Accordingly, risedronate suppressed the phosphorylation of ERK 1/2, a downstream survival signaling kinase of Ras, affected the intracellular distribution of Bcl-xL, and induced the mitochondrial membrane depolarization, cytochrome c release, activated caspase cascade and DNA fragmentation [31].

Analytical, diagnostic and therapeutic context of Risedronate sodium

• Mean gastric endoscopy scores for the risedronate group were lower than those for the alendronate group at days 8 and 15 (P </= 0.001) [2].
• Unexpectedly, there was also a marked decrease in tumor burden in bone in risedronate-treated animals [3].
• METHODS: Data were obtained from 2 randomized clinical trials (prevention and treatment trials of risedronate) using similar methods, but different inclusion criteria were applied with regard to prior exposure to GCs [32].
• Safety and efficacy of risedronate in patients with age-related reduced renal function as estimated by the Cockcroft and Gault method: a pooled analysis of nine clinical trials [33].
• During the study period, bone mineral density in the risedronate group increased by 4.1% and decreased by 0.9% in the control group [25].

References