Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new actonel research articles will be listed here shortly after becoming available to us.
Medical research on actonel
Response to Oral Bisphosphonates in Subgroups of Younger and Older Postmenopausal Women.
J Womens Health (Larchmt). 2010 Feb 8;
Stovall DW, Beard MK, Barbier S, Chen E, Rosenberg E, de Papp AE
Abstract Background: Although the effects of bisphosphonates in bone are known for postmenopausal women, it is not known if younger postmenopausal women have a similar response. Furthermore, it is not known if the effects of alendronate and risedronate differ in postmenopausal women in regard to age, specifically in women at or younger than the mean age of natural menopause. Our aim was to examine the effects of two oral bisphosphonates in postmenopausal women by age. Methods: This was a post-hoc analysis of postmenopausal women /=55 years old with low bone mineral density (BMD), randomized to once weekly alendronate 70 mg or risedronate 35 mg for 1 year with 1-year extensions in U.S. and International Fosamax Actonel Comparison Trials. Results: In both age subgroups of postmenopausal women, alendronate produced significantly greater mean BMD increases from baseline than risedronate at hip trochanter, lumbar spine, total hip, and femoral neck. Changes in BMD were not significantly different between younger and older alendronate-treated women, although treatment differences favoring alendronate were numerically greater for younger than older postmenopausal women at all sites. Significantly greater reductions in bone turnover markers also occurred with alendronate vs. risedronate in both subgroups. Tolerability was similar between treatments. Conclusions: In this post-hoc subgroup analysis of older and younger postmenopausal women receiving alendronate or risedronate, larger treatment differences in BMD gain in younger compared with older women suggest that patient age may affect the relative efficacy of these antiresorptive drugs.
Tunis Med. 2009 Jun; 87(6): 380-1
Bahlous A, Bouzid K, Sahli H, Sallami S, Abdelmoula J
AIM: Bisphosphonates are powerful agents able to prevent bone loss. The objective of the study was to evaluate the efficacy and tolerability of risedronate once a week (35 mg) compared with risedronate 5 mg once daily in women with osteoporosis. METHODS: A randomized, double-blind, active-controlled study enrolled 102 postmenopausal women aged 66.5 + 7.5 years with osteoporotic fractures. All women received risedronate during 6 months. Group 1 (G1, n=51) received risedronate 5 mg once daily and group 2 (G2, n=51) received 35 mg once a week. Serum alkaline phosphatase (ALP), bone alkaline phosphatase (bone ALP), serum C-terminal telopeptide of type I collagen (CTX) were measured at baseline, 3 months and 6 months after treatment in the two groups. RESULTS: We noted no significant difference in markers between women of the 2 groups. After 3 months, bone ALP and CTX decreased (respectively -22.1% and -47.6%) in the 2 groups with no significant difference between them. After 6 months study, bone ALP and CTX decreased respectively by -46.5% and -62.9% with no statistically significant difference between study groups for bone markers. CONCLUSION: Our study found that treatment with once weekly risedronate 35 mg is able to decrease CTX and bone ALP compared with risedronate 5 mg once daily, in postmenopausal women with osteoporotic fractures. We didn't find adverse events with the 35 mg once-a-week dose group compared to the once-daily dose group. Based on these results, the effects of risedronate 35 mg once a week are similar in efficacy to daily dosing and may lead less adverse events than once-a-month dose. This therapeutic protocol may provide an alternative for patients who prefer once-a-week oral dosing.
J Oral Maxillofac Surg. 2009 Dec; 67(12): 2644-8
Kwon YD, Kim DY, Ohe JY, Yoo JY, Walter C
PURPOSE: The aim of the present study was to correlate the staging of bisphosphonate-related osteonecrosis of the jaws (BRONJ) with serum C-terminal cross-linking telopeptide of type I collagen (CTX), which is under debate as an index of risk prediction. Stage I BRONJ was defined as asymptomatic osteonecrotic bone. Stage II BRONJ includes infection, and stage III includes additional complications such as fracture or extraoral fistulas. PATIENTS AND METHODS: The serum CTX values of 18 patients (mean age 74 years) who were diagnosed with osteonecrosis of the jaws caused by oral bisphosphonate were investigated. RESULTS: The serum CTX values ranged from 10 to 262 pg/mL (mean 112 +/- 76.1). The mean duration of bisphosphonate therapy was 3.9 years, and 17 of the 18 patients had received once weekly 70 mg aldendronate and 1 patient once weekly 35 mg risedronate. The risk assessment was rated according to the CTX values of the individual patient (minimal risk, more than 150 pg/mL; moderate, 100 to 150 pg/mL; and high, less than 100 pg/mL). Next, the BRONJ scores were calculated according to the number of the BRONJ lesions and their stage. The risk assessment and BRONJ scores were correlated. The result was statistically significant (P = .019). CONCLUSIONS: BRONJ is relatively rare but has been increasingly recognized in our clinic. The usefulness of the serum CTX value as an index of risk prediction continues to be debated. Considering the staging of lesions and the number of lesions, we found a significant correlation between the disease severity and the risk assessment using serum CTX.
J Endod. 2009 Nov; 35(11): 1525-8
Hsiao A, Glickman G, He J
INTRODUCTION: Bisphosphonates have been related to impaired bone remodeling. The impact of oral bisphosphonates on periradicular healing has not been studied. The purpose of this study was to evaluate the healing of periradicular lesions in patients taking oral bisphosphonates after root canal therapy. METHODS: Thirty-four teeth with preoperative periradicular radiolucencies were identified in patients undergoing oral bisphosphonate therapy. These cases were examined clinically and radiographically to determine treatment outcome. Thirty-eight control teeth were selected from a pool of patients not taking bisphosphonates. Nonsurgical root canal treatment and retreatment was performed by endodontic residents and undergraduate dental students at Baylor College of Dentistry using nonstandardized protocols. RESULTS: In the bisphosphonate group, 73.5% of the lesions healed, whereas the control cases had a healing rate of 81.6%. There was no statistically significant difference between the groups (p > 0.05). CONCLUSION: The results of this preliminary short-term study suggest that patients taking long-term oral bisphosphonates can expect a satisfactory outcome with evidence of periradicular healing after conventional root canal treatment. Thus, root canal treatment may be considered a safe and realistic alternative to extraction in patients on bisphosphonate therapy.
Curr Med Res Opin. 2009 Dec; 25(12): 2951-60
Epstein S, Jeglitsch M, McCloskey E
BACKGROUND: Patient adherence to daily and weekly bisphosphonate treatments is poor and adversely affects their clinical outcome. To increase compliance, bisphosphonate therapies with longer dose-free intervals, such as oral once monthly, were developed. METHODS: The aim of this review is to provide a summary of the efficacy and safety of the two once-monthly oral bisphosphonates, ibandronate 150 mg and risedronate 150 mg. Fracture trials were initially performed with daily formulations, then bridging trials, in which the efficacy of intermittent dosing was assessed versus daily using validated surrogate endpoints for fracture. Two literature searches were carried out using the MEDLINE and BIOSIS online scientific citation database of published, peer-reviewed manuscripts up to and including December 2008. FINDINGS: The relative risk reduction (RRR) of new vertebral fractures with risedronate 5 mg daily was 41% (p = 0.003), and 49% (p < 0.001) versus placebo after 3 years in two Phase III studies. In patients at risk of incident fracture, the relative risk of non-vertebral fractures was significantly reduced by 39% (p = 0.02) with 5 mg risedronate versus placebo. In a post-hoc pooled analysis of 2.5 mg and 5 mg risedronate doses, also in patients at high risk of fracture, the relative risks of non-vertebral and hip fractures were significantly reduced by 20% (p = 0.03) and 30% (p = 0.02), respectively. In a Phase III study, the RRR of new vertebral fractures with 2.5 mg daily ibandronate was 62% (p = 0.0001) versus placebo after 3 years. Two pooled analyses of data from key randomised, double-blind, controlled trials with ibandronate dose levels consistent with 150 mg once-monthly reported significant RRRs in non-vertebral fractures of 38% (p = 0.038) and 30% (p = 0.041). In a bridging study, 150 mg once-monthly risedronate was non-inferior to 5 mg daily treatment for improvements in bone mineral density (BMD), but was significantly inferior for reductions in bone turnover markers (BTMs) (p < 0.05). Ibandronate 150 mg once monthly was superior to daily at 2 years in both surrogate marker measures, with significantly superior BMD gains reported at all sites (p < 0.05). In an extension of the bridging study, lumbar spine BMD progressively improved and previously reported femoral neck BMD gains were maintained with monthly ibandronate. Serum sCTX remained reduced within the premenopausal range. CONCLUSIONS: Risedronate 150 mg once monthly has demonstrated less reduction of BTM and non-inferior BMD gains versus daily, whereas 150 mg once monthly ibandronate has demonstrated BTM suppression within the premenopausal range and BMD gains superior to the daily regimen. Furthermore, ibandronate has demonstrated antifracture efficacy with intermittent dosing in two pooled analyses. Risedronate has yet to demonstrate anti-fracture efficacy with an extended (intermittent) dosing regimen.
Profound muscle weakness and pain after one dose of actonel.
Case Report Med. 2009; 2009: 693014
Badayan I, Cudkowicz ME
The World Health Organization (WHO) defines osteopenia as a bone density between 1 and 2.5 standard deviation (SD) below the bone density of a normal young adult Iqbal 2000. Osteoporosis is defined as 2.5 SD or more below that reference point Iqbal 2000. Bisphosphonates are a group of medications used to treat osteoporosis, Padget's disease of bone, and osteopenia. We report a woman who developed profound muscle weakness and pain after one dose of Risedronate (Actonel).
Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure.
J Oral Maxillofac Surg. 2010 Feb; 68(2): 243-53
Lo JC, O'Ryan FS, Gordon NP, Yang J, Hui RL, Martin D, Hutchinson M, Lathon PV, Sanchez G, Silver P, Chandra M, McCloskey CA, Staffa JA, Willy M, Selby JV, Go AS,
PURPOSE: Osteonecrosis of the jaw (ONJ) is a serious complication associated with bisphosphonate therapy, but its epidemiology in the setting of oral bisphosphonate therapy is poorly understood. The present study examined the prevalence of ONJ in patients receiving chronic oral bisphosphonate therapy. MATERIALS AND METHODS: We mailed a survey to 13,946 members who had received chronic oral bisphosphonate therapy as of 2006 within a large integrated health care delivery system in Northern California. Respondents who reported ONJ, exposed bone or gingival sores, moderate periodontal disease, persistent symptoms, or complications after dental procedures were invited for examination or to have their dental records reviewed. ONJ was defined as exposed bone (of >8 weeks' duration) in the maxillofacial region in the absence of previous radiotherapy. RESULTS: Of the 8,572 survey respondents (71 +/- 9 years, 93% women), 2,159 (25%) reported pertinent dental symptoms. Of these 2,159 patients, 1,005 were examined and an additional 536 provided dental records. Nine ONJ cases were identified, representing a prevalence of 0.10% (95% confidence interval 0.05% to 0.20%) among the survey respondents. Of the 9 cases, 5 had occurred spontaneously (3 in palatal tori) and 4 occurred in previous extraction sites. An additional 3 patients had mandibular osteomyelitis (2 after extraction and 1 with implant failure) but without exposed bone. Finally, 7 other patients had bone exposure that did not fulfill the criteria for ONJ. CONCLUSIONS: ONJ occurred in 1 of 952 survey respondents with oral bisphosphonate exposure (minimum prevalence of 1 in 1,537 of the entire mailed cohort). A similar number had select features concerning for ONJ that did not meet the criteria. The results of the present study provide important data on the spectrum of jaw complications among patients with oral bisphosphonate exposure.
Corticosteroids: no drug prevention of fractures needed.
Prescrire Int. 2009 Aug; 18(102): 175
Long-term corticosteroid therapy increases the risk of fractures, which depends on the dose and duration of treatment. No drugs have been demonstrated to reduce the incidence of symptomatic fractures in this setting. It is better to keep the dose and duration of steroid therapy to the effective minimum, and to choose non-drug preventive measures.
Genome Biol. 2009; 10(9): R93
Bivi N, Romanello M, Harrison R, Clarke I, Hoyle DC, Moro L, Ortolani F, Bonetti A, Quadrifoglio F, Tell G, Delneri D
BACKGROUND : Nitrogen-containing bisphosphonates are the elected drugs for the treatment of diseases in which excessive bone resorption occurs, for example, osteoporosis and cancer-induced bone diseases. The only known target of nitrogen-containing bisphosphonates is farnesyl pyrophosphate synthase, which ensures prenylation of prosurvival proteins, such as Ras. However, it is likely that the action of nitrogen-containing bisphosphonates involves additional unknown mechanisms. To identify novel targets of nitrogen-containing bisphosphonates, we used a genome-wide high-throughput screening in which 5,936 Saccharomyces cerevisiae heterozygote barcoded mutants were grown competitively in the presence of sub-lethal doses of three nitrogen-containing bisphosphonates (risedronate, alendronate and ibandronate). Strains carrying deletions in genes encoding potential drug targets show a variation of the intensity of their corresponding barcodes on the hybridization array over the time. RESULTS : With this approach, we identified novel targets of nitrogen-containing bisphosphonates, such as tubulin cofactor B and ASK/DBF4 (Activator of S-phase kinase). The up-regulation of tubulin cofactor B may explain some previously unknown effects of nitrogen-containing bisphosphonates on microtubule dynamics and organization. As nitrogen-containing bisphosphonates induce extensive DNA damage, we also document the role of DBF4 as a key player in nitrogen-containing bisphosphonate-induced cytotoxicity, thus explaining the effects on the cell-cycle. CONCLUSIONS : The dataset obtained from the yeast screen was validated in a mammalian system, allowing the discovery of new biological processes involved in the cellular response to nitrogen-containing bisphosphonates and opening up opportunities for development of new anticancer drugs.
Nanostructured polyelectrolyte multilayer drug delivery systems for bone metastasis prevention.
Biomaterials. 2009 Oct; 30(31): 6367-73
Daubiné F, Cortial D, Ladam G, Atmani H, Haïkel Y, Voegel JC, Clézardin P, Benkirane-Jessel N
Polyelectrolyte multilayers (PEM) are well established nanoarchitectures with numerous potential applications, in particular as biomaterial coatings. They may exhibit specific biological properties in terms of controlled cell activation or local drug delivery. Here, in a new approach for bone metastasis prevention, we employed poly-l-lysine covalently grafted with beta-cyclodextrin as a polycationic vector (PLL-CD) for the antitumor bisphosphonate drug risedronate (RIS). Molar ratio for maximum loading of the PLL-CD vector with RIS was determined by Raman microspectroscopy. The efficacy of RIS at inhibiting cancer cell invasion in vitro was strongly enhanced upon complexation, whatever PLL-CD:RIS complexes were in solution or embedded into PEM nanoarchitectures. Complexes in solution also clearly prevented cancer-induced bone metastasis in animals. Incorporation of the complexes into PEM nanoarchitectures covering bone implants appears of interest for in situ prevention of bone metastasis after ablation.