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Medical research on risedronate
Clin Ther. 2008 May; 30(5): 834-44
Perkins AC, Blackshaw PE, Hay PD, Lawes SC, Atherton CT, Dansereau RJ, Wagner LK, Schnell DJ, Spiller RC
Background: Delayed esophageal transit or disintegration of oral bisphosphonate tablets before they enter the stomach may be of concern with respect to iatrogenic complications among patients receiving longterm treatment. Different formulations of generic bisphosphonate tablets meeting regulatory requirements may have substantial differences in pharmaceutical attributes from the branded product that may result in different characteristics during esophageal transit. Objective: The primary objective of this study was to evaluate and compare esophageal transit times and in vivo disintegration of 3 bisphosphonate formulations, one branded and the others generic, that are commercially available in Canada and the United Kingdom. Methods: This was a single-center, randomized, singleblind, 6-period crossover study in healthy postmenopausal women aged >50 years. Each subject received a single oral dose of a branded risedronate sodium 35-mg tablet and 2 generic formulations of alendronic acid 70-mg tablets (Novopharm Limited, Toronto, Canada, and Teva UK Limited, Morley, United Kingdom) in both the erect and semisupine (45 degrees ) positions. Although the products are labeled to be taken in the erect position, the semisupine position was included to simulate dosing in bedridden patients. Subjects took tablets with 30 mL of water in the morning after an overnight fast. The tablets were radiolabeled with technetium-99m ion-exchange resins to enable visualization and measurement of esophageal transit time and disintegration using a gamma camera. Dynamic scintigraphic images were obtained for a total of 10 minutes: 2 images per second for the first 30 seconds and 1 image every 15 seconds for 9.5 minutes. This was a mechanistic study and tolerability was not assessed. Results: The study was conducted in 20 healthy white female subjects with a mean age of 62 years (range, 51-77 years). The effect of body position was statistically significant (P = 0.043), with the estimated hazard ratio (HR) of 0.74 indicating longer transit time in the semisupine position relative to the erect position. There was a statistically significant difference in transit time among the 3 types of tablets (P = 0.007), with the Novopharm tablet (HR = 0.59; P < 0.001) and Teva tablet (HR = 0.71; P = 0.042) having longer transit times compared with the risedronate tablet. In 4 instances, the Novopharm tablet disintegrated and dispersed in the esophagus, once in the erect position and 3 times in the semisupine position. Conclusions: In these healthy female subjects, esophageal transit was delayed when the tablets were given in the semisupine position. The branded risedronate tablet had a significantly faster transit time than the 2 generic formulations of alendronate tested.
Changes of the quality-of-life under the treatment of severe senile osteoporosis with teriparatide.
Arch Gerontol Geriatr. 2008 Jun 12;
Maugeri D, Russo E, Luca S, Carmelo L, Mamazza G, Sorace R, Rizzotto M, Manuele S, Fiore V, Taverna G, Biagio C, Calitro M
Despite being treated with antiresorptive drugs, the severe osteoporosis (SO) is being considered as a condition in which patients are still subject to one or more vertebral or femoral fractures, or non-vertebral or non-femoral fractures, i.e., of other parts of the body such as the wrist, shoulder, tibia, ribs or hip. These patients are defined as non-responders (NRs) to the antiresorptive therapy, and recent research has shown that they represent 10-25% of all SO patients. During the last almost 3 years a new drug has become available in Italy, called teriparatide (rh-PTH-1-34), produced in Escherichia coli using the recombinant-DNA technique. It shows remarkable trophic and anabolic actions on the bones, and proved to be very useful for treating the osteoporosis in general. This study describes our experience in using teriparatide for the treatment of SO in a sample of 141 elderly women of mean age 73.4+/-5.8 years, with a mean number of fractures of 3.0+/-0.85, with a spine deformity index (SDI) of 5.92+/-1.27 and a mean vertebral T-Score (L1-L4) of -3.15+/-0.39, and a mean femoral T-Score of -2.50+/-0.28. All these patients had been treated with antiresorptive drugs for at least 1 year: specifically 70 of them with Alendronate, 42 of them with Risedronate and 29 of them with Raloxifene. For 18 months, all these patients were injected subcutaneously with 20mug of teriparatide, with the daily addition of 1g of calcium and 880IU of vitamin D. The study was continued for 24 months, at the end of which the patients continued to take only calcium and vitamin D. The patients underwent a CBM-DEXA control of vertebral column and femur every 6 months, and they were also administered a Quality-of-Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO). The QUALEFFO (41 items) questionnaire to evaluate the changes in the quality-of-life (QoL) and the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) was also recorded. The results showed that teriparatide protected 96.5% against new fractures (only five new fractures occurred), bone mineral density (BMD) increased approximately by 12% in the vertebral column and by 11% in the femur, consumption of NSAIDs was reduced at the early stage approximately 80%, the QoL improved considerably and remained so during the 18 months of teriparatide treatment, with only a slight decrease during the 6 subsequent months.
Vitamin D status and response to treatment in post-menopausal osteoporosis.
Osteoporos Int. 2008 Jun 13;
Adami S, Giannini S, Bianchi G, Sinigaglia L, Di Munno O, Fiore CE, Minisola S, Rossini M
Treatment with anti-resorptive agents over 13 months was associated with for three to fivefold lower bone mineral density changes and 1.5-fold increased risk of incidence fracture in vitamin D insufficient as compared to vitamin D repleted postmenopausal osteoporotic women. INTRODUCTION: Several drugs were registered for the treatment of osteoporosis on the basis of clinical trials in which vitamin D repletion was a pre-requisite inclusion criteria and vitamin D supplements were used as adjunctive therapy. However, in routine clinical practice these supplements are not consistently recommended. METHODS: We studied 1515 women with postmenopausal osteoporosis under treatment with anti-resorbing agents (alendronate, risedronate, raloxifene) for 13.1 months with an adherence > 75%. The patients were classified as vitamin D deficient (N = 514) or vitamin D repleted (N = 1001) according to risk factors (N = 1062) or the level of 25(OH) vitamin D [25(OH)D] above or below 50 nmol/l (N = 453). RESULTS: Vitamin D deficient and vitamin D repleted subjects differed significantly for annualized spine and hip bone mineral density (BMD) changes adjusted for all available confounding factors (type of treatment, age, global calcium intake, baseline BMD values). One hundred fifty one patients suffered from a new incident clinical fracture. The adjusted odds ratio for incident fractures in vitamin D deficient as compared to vitamin D repleted women was 1.77 (1.20 - 2.59, 95% CI; p = 0.004). CONCLUSIONS: Optimal vitamin D repletion seems to be necessary to maximize the response to anti-resorbers in terms of both BMD changes and anti-fracture efficacy.
Effect of Risedronate on Bone Mass, Remodelling and Biomechanical Strength in Orchidectomized Rats.
Horm Res. 2008 Jun 12; 70(2): 93-99
Díaz-Curiel M, de la Piedra C, Romero FI, Montero M, Gómez S, Lefort M, Carrascal MT, Phipps RJ
Background: The ability of risedronate to prevent and/or treat orchidectomy-induced osteoporosis in male rats was studied. Methods: Ninety-five 10-week-old male Wistar rats were sham-operated or orchidectomized. Prevention study: Sham: sham-operated rats; ORX: orchidectomized rats; ORX + RSD: orchidectomized rats, treated for 6 weeks with risedronate. Animals were sacrificed 6 weeks after surgery. Treatment study: Sham(1) and ORX(1): sham and orchidectomized rats sacrificed 3 months after orchidectomy; Sham(2), ORX(2) and ORX(2) + RSD: sham-operated, and orchidectomized rats treated with placebo or risedronate for 6 weeks starting 3 months after orchidectomy, and then sacrificed. Risedronate (0.5 mg/kg/day) and placebo (saline) were administered via oral gavage. After sacrifice, bone mineral density by DEXA, bone volume (BV/TV), osteocalcin (BGP), and serum carboxyterminal telopeptide of collagen type I (CTX) were measured. Femur low-rate torsion testing was performed. Results:Orchidectomy produced an increase in bone remodelling with loss of BV/TV, without effects on torsional strength. Risedronate treatment partially prevented these effects. In the treatment study, risedronate reduced bone remodelling and restored BV/TV to levels higher than those of the sham group, improving biomechanical parameters. Conclusions: These results suggest that risedronate could be used as a prevention or treatment of male osteoporosis due to hypogonadism.
Calcif Tissue Int. 2008 Jun 10;
Iwamoto J, Matsumoto H, Takeda T, Sato Y, Liu X, Yeh JK
The purpose of the present study was to examine the effects of vitamin K(2) and risedronate on bone formation and resorption, the osteocyte lacunar system, and porosity in the cortical bone of glucocorticoid (GC)-treated rats. Forty-nine female Sprague-Dawley rats, 3 months of age, were randomized into five groups according to the following treatment schedule: age-matched control, GC administration, and GC administration with concomitant administration of vitamin K(2), risedronate, or vitamin K(2) + risedronate. At the end of the 8-week experiment, classical bone histomorphometric analysis was performed, and the osteocyte lacunar system and porosity were evaluated on the cortical bone of the tibial diaphysis. GC administration decreased percent cortical bone area and increased percent marrow area as a result of decreased periosteal bone formation, and increased endocortical bone erosion, and increased cortical porosity. Vitamin K(2) prevented a reduction in periosteal bone formation but did not affect percent cortical bone and marrow areas. Risedronate prevented a reduction in periosteal bone formation and an increase in endocortical bone erosion, resulting in prevention of alterations in percent cortical bone and marrow areas. Both vitamin K(2) and risedronate increased osteocyte density and lacunar occupancy and prevented a GC-induced increase in cortical porosity. Vitamin K(2) and risedronate had additive effects on osteocyte density and lacunar occupancy and a synergistic effect on cortical porosity. The present study showed the efficacy of vitamin K(2) and risedronate for bone formation and resorption, the osteocyte lacunar system, and porosity in the cortical bone of GC-treated rats.
Secondary osteoporosis in long-term bedridden patients with cerebral palsy.
Pediatr Int. 2008 Jun; 50(3): 269-75
Iwasaki T, Takei K, Nakamura S, Hosoda N, Yokota Y, Ishii M
BACKGROUND: The aim of the present paper was to investigate 20 pediatric patients with cerebral palsy and secondary osteoporosis and consider the efficacy, influence and index of treatment. METHODS: A total of 10 boys and 10 girls, age 1-16 years (mean 7.6 years) with secondary osteoporosis and cerebral palsy treated for 6 months, were studied. Bone mineral density (BMD) was measured. The bone turnover markers were measured just before and 4 months after treatment or at the time of early discontinuation of treatment. The treatment was classified into two groups: vitamin D (alfacarcidol) only; and with bisphosphonate (risedronate). RESULTS: Monotherapy with alfacarcidol was effective for secondary osteoporosis in children, but when used in combination with risedronate it was even more effective in improving BMD. In the two groups, bone-specific alkaline phosphate (BAP) decreased from pretreatment to post-treatment assessment in all but one case, but there was no significant correlation in the difference in DeltaBAP with DeltaBMD. DeltaBAP assumed changes in BAP in treatment either before or after, and DeltaBMD also assumed changes in BMD. N-telopeptides of type I collagen (NTX)/Cr decreased in all cases. The correlation of DeltaNTX/Cr with DeltaBMD was not significant. The therapy and its efficacy did not correlate to the patients' age, sex, medicine regimen or enteral nutrition. CONCLUSIONS: Risedronate therapy is effective for patients presenting with secondary osteoporosis with cerebral palsy. Moreover, it is desirable to treat patients more aggressively from the early stage because risedronate is not affected by the patients' other factors.
Bone. 2008 Apr 15;
van Londen GJ, Perera S, Vujevich KT, Sereika SM, Bhattacharya R, Greenspan SL
INTRODUCTION: Chemotherapy-induced menopause is associated with bone loss. The effect on structural geometry is unknown. Our objective was to determine if oral bisphosphonate therapy could maintain or improve femoral geometry in breast cancer patients with chemotherapy-induced menopause. METHODS: This preplanned 1 year interim, secondary analysis of the Risedronate's Effect on Bone loss in Breast CAncer Study (REBBeCA Study) examined hip structure analysis (HSA), i.e. changes in the bone cross-sectional area (bone CSA), section modulus (SM: measure of bending strength), cortical thickness (CT) and buckling ratio (BR: index of cortical bone stability), in a double-blind trial of 87 newly postmenopausal, nonmetastatic breast cancer patients, randomized to risedronate, 35 mg once weekly (RIS) versus placebo (PBO). RESULTS: After 12 months, intertrochanteric parameters demonstrated percentage improvement (RIS vs. PBO) from baseline in bone CSA (mean+/-SD: 4.25+/-6.29 vs. 0.60+/-5.99%), SM (3.97+/-6.40 vs. 0.80+/-7.08%), and CT [5.20+/-6.98 vs. 1.13+/-6.87% (all p-values
Bone. 2008 Apr 22;
Luckish A, Cernes R, Boaz M, Gavish D, Matas Z, Fux A, Shargorodsky M
Accumulating evidence suggests that osteoporosis and coronary artery disease have epidemiologic similarities. Moreover, the anti-atherogenic effects of bisphosphonates have been observed in vitro and in animal models. The present study investigated the effect of risedronate on indices of arterial compliance, serum osteoprotegerin (OPG) level, inflammatory and metabolic parameters in osteoporotic women with cardiovascular risk factors. In an open label, prospective study 68 postmenopausal osteoporotic women were evaluated for the study. Patients received risedronate orally in a dose of 35 mg per week, daily supplements of calcium and cholecalciferol during 6month treatment period. Patients were evaluated for lipid profile, HbA1C, insulin, C-peptide, fibrinogen, hs-CRP and plasma osreoprotegerin. Arterial elasticity was evaluated using pulse wave contour analysis (HDI CR 2000, Eagan, Minnesota). Large artery elasticity index (LAEI) increased from 9.86+/-3.66 to 11.54+/-">+/-3.16 ml/mm HgX10 (p
Fracture Outcomes Related to Persistence and Compliance with Oral Bisphosphonates.
J Bone Miner Res. 2008 May 27;
Gallagher A, Rietbrock S, Olson M, van Staa T
Abstract The effects of low persistence on fracture risk have not been fully addressed. The objectives of this study were to describe the persistence and compliance with bisphosphonates and to evaluate the association with fracture risk. The General Practice Research database was used to identify patients aged 18+ years prescribed alendronate or risedronate. The follow-up was divided into periods of current and past use. Time-dependent Cox regression was used. The study population included 44,531 patients. 58.3% of the patients continued bisphosphonate treatment for more than 1 year and 23.6% for more than 5 years. The risk of hip/femur fracture (adjusted relative rate [RR] 0.78, 95% confidence interval [CI] 0.64-0.94) and osteoporotic fracture (RR 0.85, CI 0.76-0.94), were lower with current compared to past bisphosphonate use. The largest reduction in hip/femur and osteoporotic fracture risk was observed in patients treated for at least 6 months, and no reduction in those treated for less than 6 months. The risks of hip/femur and osteoporotic fractures followed the pattern of non-osteoporotic fractures in the first 6 months but then started to reduce after 6 to 12 months of treatment. Increased risks of osteoporotic and hip/femur fractures were found in patients with low compliance. Use of bisphosphonates was associated with fracture risk reductions after 6-12 months of treatment but only 58% of the patients were treated for at least 1 year. Improvement in long-term persistence to bisphosphonate treatment may be important in order to reduce the impact of osteoporosis-related fractures .
Clin Ther. 2008 Apr; 30(4): 605-21
Lewiecki EM, Babbitt AM, Piziak VK, Ozturk ZE, Bone HG
Background: Gastrointestinal (GI) symptoms and high dosing frequency have been cited as reasons for inadequate adherence to daily or weekly oral bisphosphonate therapy. Inadequate adherence may lead to poor therapeutic outcomes. Objective: The PRIOR study evaluated adherence to and GI tolerability of monthly therapy with oral and quarterly intravenous ibandronate in postmenopausal women with osteoporosis or osteopenia. Methods: This 12-month, multicenter, prospective, nonrandomized, open-label, noninferiority study included postmenopausal women with osteoporosis or osteopenia who had discontinued previous daily or weekly oral bisphosphonate therapy because of GI intolerance. Participants chose to receive either monthly oral ibandronate 150 mg or quarterly intravenous ibandronate 3 mg and were permitted to switch formulations once during the study. For oral treatment, adherence was assessed based on doses taken, as recorded on the case-report form; for intravenous treatment, adherence was assessed based on doses administered, as recorded by study site personnel. Participants who took >/=75% of protocol-specified doses were considered adherent. The rate of adherence to oral ibandronate was protocol defined as noninferior to that of intravenous ibandronate if the upper limit of the 2-sided 90% CI for the adjusted difference in adherence rates was >20%. At screening, participants assessed the tolerability of their previous bisphosphonate therapy using the GI Experience Survey; using the same instrument, they assessed the tolerability of ibandronate 1 month from baseline and at months 4, 7, and 10. Results: Of 543 participants in the intent-to-treat population, 147 (27.1%) chose to receive oral treatment and 396 (72.9%) chose to receive intravenous treatment. The mean age of participants was 90% of participants were white. A significantly greater proportion of participants who selected intravenous versus oral treatment had a primary diagnosis of osteoporosis (72.2% vs 57.1%, respectively; P < 0.001) and a history of fracture as an adult (35.6% vs 22.4%; P >/= 0.004); significantly fewer recipients of intravenous versus oral ibandronate were currently working (29.0% vs 39.5%; P >/= 0.021). Overall, 82.9% of participants had previously received alendronate and 44.9% had previously received risedronate. Eleven participants switched from oral to intravenous therapy and 16 switched from intravenous to oral therapy during the study. In the perprotocol population, 69.7% of participants in the oral group (101/145) and 82.9% of participants in the intravenous group (325/392) were adherent to their originally selected therapy. Adherence to oral therapy fell within the prespecified boundary for noninferiority to intravenous therapy (adjusted difference: 12.4%; 90% CI, 5.1-19.7). Mean GI tolerance scores were significantly improved from screening at all subsequent assessment times in both treatment groups (P < 0.001); >75% of participants had a >/=10% increase in GI tolerability scores from screening. Both dosing regimens were generally well tolerated. Conclusion: Self-selected monthly oral or quarterly intravenous ibandronate therapy was associated with high adherence rates among these postmenopausal women with osteoporosis or osteopenia who had previously discontinued oral bisphosphonate treatment because of GI intolerance.