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.
Related Sponsors
Medical research on actonel
J Bone Miner Metab. 2008; 26(3): 279-87
Kawasaki T, Kurosawa H, Ikeda H, Kim SG, Osawa A, Takazawa Y, Kubota M, Ishijima M
We have previously demonstrated the efficacy of therapeutic exercise for osteoarthritis (OA) of the knee. This study was performed to examine the additive effects of glucosamine or risedronate on the exercise therapy. In this study, 142 female patients with moderate OA of the knee, who had been recommended to undergo home exercise at the first visit to the hospital, were randomly given glucosamine hydrochloride, risedronate, or no additive. Although improvement after 18 months was observed in all groups using individual scales for evaluation of pain and function of the knee, no significant differences were observed between the groups regarding any of the scales, indicating no significant additive effect of glucosamine or risedronate. One reason for the lack of effect of glucosamine or risedronate on OA of the knee may be that the effect of these agents was occluded by the effect of therapeutic exercise to improve pain and function of the knee. This finding means that even if glucosamine and risedronate were to have an effect on OA of the knee, the effect would not be greater than the effect of knee exercise to improve the symptoms.
Relative effectiveness of osteoporosis drugs for preventing nonvertebral fracture.
Ann Intern Med. 2008 May 6; 148(9): 637-46
Cadarette SM, Katz JN, Brookhart MA, Stürmer T, Stedman MR, Solomon DH
BACKGROUND: Little information is available on the comparative effectiveness of osteoporosis pharmacotherapies. OBJECTIVE: To compare the relative effectiveness of osteoporosis treatments to reduce nonvertebral fracture risk among older adults. DESIGN: Cohort study. SETTING: Enrollees in 2 statewide pharmaceutical benefit programs for persons age 65 years or older. PATIENTS: 43,135 new recipients of oral bisphosphonates, nasal calcitonin, and raloxifene who began treatment from 2000 to 2005. The mean age was 79 years (SD, 6.9), and 96% were women. MEASUREMENTS: The primary outcome was nonvertebral fracture (hip, humerus, or radius or ulna) within 12 months of treatment initiation. Cox proportional hazard models stratified by state and adjusted for risk factors for fracture were used to compare fracture rates. Alendronate was the reference category in all analyses. RESULTS: A total of 1051 nonvertebral fractures were observed within 12 months (2.62 fractures per 100 person-years). No large differences in fracture risk were found between risedronate (hazard ratio [HR], 1.01 [95% CI, 0.85 to 1.21]) or raloxifene (HR, 1.18 [CI, 0.96 to 1.46]) and alendronate. However, among those with a fracture history, raloxifene recipients experienced more nonvertebral fractures within 12 months (HR, 1.78 [CI, 1.20 to 2.63]) compared with alendronate recipients. Patients who received calcitonin experienced more nonvertebral fractures than those who received alendronate (HR, 1.40, [CI, 1.20 to 1.63]). Results were similar in sensitivity analyses that examined different lengths of follow-up (6 months and 24 months), were restricted to hip fracture as the outcome, and were completed in various subgroups. LIMITATION: Confounder adjustment was limited to health care utilization data, and the confidence bounds of some comparisons were too wide to rule out potential clinically important differences between agents. CONCLUSION: Differences in fracture risk between risedronate or raloxifene and alendronate were small. Nasal calcitonin recipients may have a higher risk for nonvertebral fractures compared with alendronate recipients. Future studies that can better adjust for possible confounding may further clarify these relationships.
Summaries for patients. Drug therapy for osteoporosis.
Ann Intern Med. 2008 May 6; 148(9): I28
The utilisation and expenditure of medicines for the prophylaxis and treatment of osteoporosis.
Ir Med J. 2008 Feb; 101(2): 38-41
McGowan B, Bennett K, Barry M, Canny M
The elderly population represent the fastest growing age-group and the incidence of osteoporotic related fractures is likely to increase with continued ageing of the population. This study determined the prescribing patterns on the Health Services Executive's (HSE) Primary Care Reimbursement Services Scheme (HSE-PCRS) of medicines dispensed for the prophylaxis and treatment of osteoporosis in Ireland. The HSE - PCRS prescription databases were analysed for the years 2004/2005. Approximately 65% of patients (total 60,000) were dispensed either Alendronate (Fosamax once weekly) or Risedronate (Actonel once weekly). The majority of the patients (69.3%) were over 70 years. The study identified that the longer a patient was prescribed prednisolone the greater the likelihood of subsequently being prescribed a bisphosphonate. Approximately 50% of patients on long-term steroids did not receive prophylaxis for osteoporosis. There were low levels of co-prescribing (2.5%) with potentially interacting drugs. Levels of co-prescribing with proton pump inhibitors was 22%.
[Osteoporosis in the elderly--diagnosis and treatment]
MMW Fortschr Med. 2005 Feb 17; 147(7): 33, 35-6
Gärtner R
In contrast to postmenopausal osteoporosis, the overriding objective in senior citizens older than 75 years is to avoid fractures of the hip, which are associated with a high mortality rate. Bone density measurement obtained at the neck of the femur using DXA provides reliable data on the risk of an individual patient of sustaining a fracture close to the hip joint. A physical examination can help to assess the patient's risk of falling, while diagnostic laboratory studies can help to exclude secondary osteoporosis. As a preventive measure, physical activity can increase bone density also in old age. Calcium and vitamin D improve muscular strength and coordination, and thus also may be helpful in preventing falls. In manifest osteoporosis, risedronate and alendronate reduce the risk of fractures close to the hip and of vertebrae by 50%. In addition, raloxifene can be employed to prevent vertebral fractures.
J Clin Oncol. 2008 Jun 1; 26(16): 2644-52
Greenspan SL, Brufsky A, Lembersky BC, Bhattacharya R, Vujevich KT, Perera S, Sereika SM, Vogel VG
PURPOSE: Limited data are available on the efficacy of oral bisphosphonate therapy in breast cancer survivors. Our goal was to examine prevention of breast cancer-related bone loss in this cohort. PATIENTS AND METHODS: Eighty-seven postmenopausal women after chemotherapy for breast cancer were randomly assigned to once-weekly risedronate 35 mg or placebo for 24 months. Outcomes included bone mineral density (BMD) and turnover markers. RESULTS: At study initiation, 13% of patients were on an aromatase inhibitor (AI). After 24 months, there were differences of 1.6 to 2.5% (P < .05) at the spine and hip BMD between the placebo and risedronate groups. At study completion, 44% were on an AI. Adjusting for an AI, women on placebo plus AI had a decrease in BMD of (mean +/- SE) 4.8% +/- 0.8% at the spine and 2.8% +/- 0.5% at the total hip (both P < .001). In women on risedronate + AI, the spine decreased by 2.4% +/- 1.1% (P < .05) and was stable at the hip. Women in the placebo group not on an AI, maintained BMD at the spine, and had a 1.2% +/- 0.5% loss at the total hip (P < .05). Women who received risedronate but no AI had the greatest improvement in BMD of 2.2% +/- 0.9% (P < .05) at the total hip. Bone turnover was reduced with risedronate. There were no differences in adverse events between the groups. CONCLUSION: We conclude that in postmenopausal women with breast cancer with or without AI therapy, once-weekly oral risedronate was beneficial for spine and hip BMD, reduced bone turnover, and was well tolerated.
Efficacy of risedronate in Japanese male patients with primary osteoporosis.
Intern Med. 2008; 47(8): 717-23
Majima T, Shimatsu A, Komatsu Y, Satoh N, Fukao A, Ninomiya K, Matsumura T, Nakao K
OBJECTIVE: Although osteoporosis in men previously was relatively neglected, bisphosphonates have been strongly suggested as potent therapeutic agents. However, there are few studies on the effects of risedronate in male osteoporosis, especially in Japanese with primary osteoporosis. The aim of our study was to prospectively evaluate the effects of risedronate on bone mineral density (BMD) and bone turnover in Japanese male patients. METHODS: According to the therapeutic regimen, the subjects were divided into two groups (group A, 22 with risedronate; group B, 10 without risedronate). During a one-year study duration, we measured bone-specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I collagen (NTx) every 3 months, and BMD at 7 sites by dual-energy X-ray absorptiometry every 6 months. PATIENTS: The subjects were 32 Japanese male patients with untreated primary osteoporosis. RESULTS: In group A, but not in group B, BMD was significantly increased at the lumbar spine both at 6 months and 12 months, and at the femoral neck at 12 months, compared with baseline. Likewise, in group A, but not in group B, both BAP and NTx were significantly decreased at all time points measured (3 months, 6 months, and 12 months), compared with baseline. CONCLUSION: These results confirmed the beneficial effects of risedronate upon increasing BMD and reducing bone turnover markers in Japanese male patients with primary osteoporosis, comparable to those previously reported in postmenopausal patients with osteoporosis.
[Risedronate (Actonel)--from randomized clinical trials to real life]
Reumatizam. 2007; 54(2): 85-6
Anić B
Curr Med Res Opin. 2008 Apr; 24(4): 1137-45
Dansereau RJ, Crail DJ, Perkins AC
OBJECTIVE: The aim of this study was to evaluate the in vitro disintegration and dissolution of 26 alendronic acid tablets (70 mg) on the market in Canada, Germany, the Netherlands, and the United Kingdom compared to the branded product (Fosamax). RESEARCH DESIGN AND METHODS: The disintegration and dissolution times were determined using the methods described in the United States Pharmacopeia 30 (USP 30). The disintegration of four orally disintegrating tablets (non-bisphosphonates) and branded film-coated risedronate sodium tablets were included for comparison. RESULTS: The mean disintegration times of the alendronic acid tablets ranged from 14 s for Pharmachemie (Netherlands) to 342 s (5.7 min) for Betapharm (Germany). The mean disintegration time of the branded product tablets ranged from 43 to 78 s. Six of the 26 companies market alendronic acid tablets with very rapid disintegration times which are similar to those of orally disintegrating tablets (non-bisphosphonates). The alendronic acid tablets with very rapid mean disintegration times are as follows: Pharmachemie (Netherlands), 14 s; Novopharm (Canada), 13-24 s; GRY-Pharma (Germany), 21 s; Juta Pharma (Germany), 30 s; APS/Teva (United Kingdom), 26 and 37 s; and Teva (UK), 14-29 s. Since there is no established disintegration time for alendronic acid tablets there can be no assurance that the copy tablets are equivalent to the branded product in terms of esophageal drug exposure. However, the in vitro disintegration times have not been correlated with in vivo disintegration and performance. The dissolution of all the bisphosphonate tablets was rapid with greater than 80% dissolved in 15 min and all products conformed to the USP 30 specification. CONCLUSIONS: The dissolution of all alendronic acid tablets was rapid and complete and conformed to the established USP 30 specifications which should ensure adequate drug absorption from the copy products. However, copies of alendronic acid tablets are approved based on the results of single-dose bioavailability studies in healthy subjects and this is not adequate to establish similar disintegration characteristics.
Visualizing mineral binding and uptake of bisphosphonate by osteoclasts and non-resorbing cells.
Bone. 2008 May; 42(5): 848-60
Coxon FP, Thompson K, Roelofs AJ, Ebetino FH, Rogers MJ
Bisphosphonates (BPs) target bone due to their high affinity for calcium ions. During osteoclastic resorption, these drugs are released from the acidified bone surface and taken up by osteoclasts, where they act by inhibiting the prenylation of small GTPases essential for osteoclast function. However, it remains unclear exactly how osteoclasts internalise BPs from bone and whether other cells in the bone microenvironment can also take up BPs from the bone surface. We have investigated this using a novel fluorescently-labelled alendronate analogue (FL-ALN), and by examining changes in protein prenylation following treatment of cells with risedronate (RIS). Confocal microscopic analysis showed that FL-ALN was efficiently internalised from solution or from the surface of dentine by resorbing osteoclasts into intracellular vesicles. Accordingly, unprenylated Rap1A accumulated to the same extent whether osteoclasts were cultured on RIS-coated dentine or with RIS in solution. By contrast, J774 macrophages internalised FL-ALN and RIS from solution, but took up comparatively little from dentine, due to their inability to resorb the mineral. Calvarial osteoblasts and MCF-7 tumour cells internalised even less FL-ALN and RIS, both from solution and from the surface of dentine. Accordingly, the viability of J774 and MCF-7 cells was drastically reduced when cultured with RIS in solution, but not when cultured on dentine pre-coated with RIS. However, when J774 macrophages were co-cultured with rabbit osteoclasts, J774 cells that were adjacent to resorbing osteoclasts frequently internalised more FL-ALN than J774 cells more distant from osteoclasts. This was possibly a result of increased availability of BP to these J774 cells due to transcytosis through osteoclasts, since FL-ALN partially co-localised with trancytosed, resorbed matrix protein within osteoclasts. In addition, J774 cells occupying resorption pits internalised more FL-ALN than those on unresorbed surfaces. These data demonstrate that osteoclasts are able to take up large amounts of BP, due to their ability to release the BP from the dentine surface during resorption. By contrast, non-resorbing cells take up only small amounts of BP that becomes available due to natural desorption from the dentine surface. However, BP uptake by non-resorbing cells can be increased when cultured in the presence of resorbing osteoclasts.