Alendronate and risedronate for the treatment of postmenopausal osteoporosis: clinical profiles of the once-weekly and once-daily dosing formulations.
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OBJECTIVE: The objective of this review is to present the clinical profiles of the once-weekly and once-daily dosing formulations of alendronate and risedronate, the 2 bisphosphonates currently available in the United States for the prevention and treatment of postmenopausal osteoporosis. DATA SOURCE/STUDY SELECTION: Data were obtained from a MEDLINE literature search of all English language articles published between January 1996 and April 2004 using generic names of the bisphosphonates alendronate and risedronate. Results were refined by incorporating terms such as "osteoporosis," "bone mineral density," "fracture risk," and "adverse events." Randomized, controlled trials of once-daily and once-weekly bisphosphonate therapies were selected. Also selected for review were post hoc analyses and extension studies of the original controlled trials, including more recent data from published abstracts from scientific meetings. DATA EXTRACTION: Relevant portions of articles obtained from the literature search were used to summarize the efficacy and tolerability of the 2 therapies. CONCLUSIONS: In prospective trials, both bisphosphonates were effective in reducing vertebral and hip fractures in women with postmenopausal osteoporosis. In the only prospective trial evaluating hip fracture risk reduction as the primary end point, risedronate was effective at reducing hip fracture vs placebo. Both alendronate and risedronate are available in once-weekly formulations that have efficacy and tolerability profiles similar to the once-daily doses. Clinicians should review all available data for both agents as well as the medical history of the patient to make the most appropriate treatment choice. (+info)
The effect of intravenous zoledronic acid on glucocorticoid-induced multiple vertebral fractures in juvenile systemic lupus erythematosus.
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Glucocorticoids are widely used in the treatment of lupus patients, and adverse effects, which include osteoporosis and associated fractures, are frequent. Treatment of osteoporosis of young patients should be effective and not harmful to bone growth and remodeling. Bisphosphonates are drugs that decrease the incidence of bone fractures, but their use in juvenile patients is still controversial because of their possible side effects on the growing skeleton. However, recently published studies showed that linear growth continued normally after treatment with these drugs, and there was no excessive suppression of bone remodeling or mineralization defects. Zoledronic acid is a new intravenous bisphosphonate that has been approved by the US FDA for use with hypercalcemia of malignancies and might be an effective treatment for postmenopausal osteoporosis. The authors report a case of a young girl with systemic lupus who developed multiple vertebral collapses due to glucocorticoid therapy, and zoledronic acid was used producing significant clinical and densitometric improvement. (+info)
Management of androgen-independent prostate cancer.
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BACKGROUND: Although androgen withdrawal can control prostate cancer for long periods in many patients, controversy exists regarding management when the tumor becomes androgen independent. Several options are now available. METHODS: A review of the pertinent literature of the last 20 years was conducted to provide guidance in defining and managing hormone-refractory prostate cancer. RESULTS: Stage D prostate cancer can be subclassified to correlate tumor biology with disease stage. Secondary hormone manipulations may induce responses in patients after failure of initial androgen suppression, and chemotherapy with docetaxel has prolonged survival in patients with androgen-independent prostate cancer (AIPC). The weight of evidence supports the maintenance of castrate levels of testosterone in metastatic AIPC. Bisphosphonates decrease skeletal complications. CONCLUSIONS: Secondary hormone therapy, chemotherapy, and bisphosphonate therapy may provide benefits for selected patients. Correlation of disease stage with biologic characteristics of the tumor and host facilitates proper choices of interventions. Docetaxel-based chemotherapy regimens should be considered for first-line treatment of patients with progressive metastatic AIPC. (+info)
Effect of administration of alendronate sodium and retinol on the mechanical properties of the femur in ovariectomized rats.
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Alendronate sodium, an aminobisphosphonate with potent antiresorptive activity, is used in the treatment of postmenopausal osteoporosis. Retinol, as a component of multivitamin preparations, is frequently used especially by elderly people. There are no reports on the interaction of alendronate sodium and retinol. The aim of the present study was to investigate the effect of administration of alendronate sodium and retinol on mechanical properties of the femoral bone in bilaterally ovariectomized rats. The experiments were carried out on 3-month-old Wistar rats, divided into 7 groups: I - sham-operated control rats, II - ovariectomized control rats, III - ovariectomy + alendronate sodium 3 mg/kg po, IV - ovariectomy + retinol 700 IU/kg po, V - ovariectomy + retinol 3500 IU/kg po, VI - ovariectomy + alendronate sodium 3 mg/kg po + retinol 700 IU/kg po, VII - ovariectomy + alendronate sodium 3 mg/kg po + retinol 3500 IU/kg po. The drugs were administered to the rats daily by oral gavage for 28 days. Body mass gain, bone mass, bone mineral content and calcium content in the femur and L-4 vertebra and mechanical properties of the whole femur (extrinsic stiffness, ultimate load, breaking load, deformation caused by the ultimate load) and the neck of the femur (load at fracture), were examined. Bilateral ovariectomy induced osteopenic changes in the rat skeletal system. Alendronate sodium (3 mg/kg po) counteracted the development of osteopenia induced by ovariectomy. Retinol at both used doses unfavorably affected the examined bone parameters of ovariectomized rats. Retinol administered with alendronate sodium lessened the preventive action of alendronate on the development of osteopenic changes in the skeletal system of ovariectomized rats. (+info)
Osteonecrosis of the maxilla in a patient with a history of bisphosphonate therapy.
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Bisphosphonates, which inhibit osteoclasts, alleviate many of the devastating consequences of metastatic bone disease. However, bisphosphonates may play a role in the development of osteonecrosis of the jaws. We report our experience in the management of a patient with a history of bisphosphonate therapy who presented with osteonecrosis of the jaws following dental extraction to make others, particularly the broader dental community, aware of this potential complication. We also review the pharmacologic properties of bisphosphonates and their possible role in the pathophysiology of osteonecrosis. Until more is known about the role of bisphosphonates in the development of osteonecrosis of the jaws, we recommend that measures be taken to prevent osteonecrosis in those at risk, including, when feasible, a dental consultation before initiating bisphosphonate therapy. (+info)
Effect of adminitration of etidronate and retinol on bone mechanical properties in ovariectomized rats.
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The experiments were carried out on rats, divided into 7 groups: I-sham-operated control rats, II-ovariectomized (OVX) control rats, II- OVX+etidronate (10 mg/kg po), IV-OVX+retinol (700 IU/kg po), V-OVX+retinol (3,500 IU/kg po), VI-OVX+etidronate (10 mg/kg po)+retinol (700 IU/kg po), VII-OVX+etidronate (10 mg/kg po)+retinol (3 500 IU/kg po). The drugs were administered once a day for 4 weeks. Bone mass, content of mineral substances and calcium were examined in the femur, tibia and L-4 vertebra. In the femur, mechanical properties of the whole bone supported on its epiphyses (the ultimate load, the breaking load and the deformation caused by the applied load) and of the femoral neck (the load causing the fracture) were studied. Bilateral ovariectomy induced unfavorable changes in mechanical properties of rat bones, which were partially prevented by administration of etidronate. Retinol at 3,500 IU/kg po caused intensification of the osteoporotic changes, especially it worsened the mechanical properties of bones. The results of the present study do not indicate the existence of any interaction between retinol and etidronate concerning mechanical properties of bones in OVX rats. (+info)
A systematic review and economic evaluation of alendronate, etidronate, risedronate, raloxifene and teriparatide for the prevention and treatment of postmenopausal osteoporosis.
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OBJECTIVES: To establish the clinical effectiveness and cost-effectiveness of selective oestrogen receptor modulators, bisphosphonates and parathyroid hormone (subject to licensing) for the prevention and treatment of osteoporosis and the prevention of osteoporotic fractures in postmenopausal women. DATA SOURCES: Electronic databases. REVIEW METHODS: Studies that met the review's entry criteria were eligible for inclusion in the meta-analyses provided that they reported fracture incidence in terms of the number of patients suffering fractures. Meta-analysis was carried out using the random-effects model. A model was constructed to estimate the cost-effectiveness of osteoporosis interventions. The model calculated the number of fractures that occurred and provided the costs associated with osteoporotic fractures, and the quality-adjusted life-years (QALYs). In addition, the conditions of breast cancer and coronary heart disease (CHD) were modelled, as some interventions have been shown to affect the risk of these conditions. RESULTS: Ninety randomised controlled trials (RCTs) met the inclusion criteria. They related to the five interventions (alendronate, etidronate, risedronate, raloxifene and teriparatide) and to five comparators (calcium, calcium plus vitamin D, calcitriol, hormone replacement therapy and exercise), as well as placebo or no treatment. All five interventions have been shown to reduce the risk of vertebral fracture in women with severe osteoporosis with adequate calcium intakes. However, none of these drugs has been demonstrated, by direct comparison, to be significantly more effective than either each other or the other active interventions reviewed in this report. The intervention costs of treating all osteoporotic women, for a period of 5 years, were in the region of pound 900-1500 million for alendronate, etidronate, risedronate and raloxifene. The cost per QALY ratios fell dramatically with age. Assuming the risks of a woman with severe osteoporosis at the threshold of osteoporosis, no treatment had a cost per QALY below pound 35,000 at 50 years of age. At 60 years of age, the cost per QALY of raloxifene was pound 26,000 assuming no impact on hip fractures, and pound 31,000 assuming an adverse effect. However, these results are driven by the effect on breast cancer and the assumptions made regarding this disease state. No other intervention had a cost per QALY below pound 35,000. When analyses were conducted assuming that the fracture risk is doubled at each site, alendronate and risedronate had cost per QALY ratios below pound 30,000 at all ages. For women at the threshold of osteoporosis, without a prior fracture and aged 70 years, the cost per QALY of the three bisphosphonates ranged from pound 34,000 to pound 41,000. Raloxifene had a cost per QALY of pound 23,000, assuming no effect on hip fracture, given assumptions regarding breast cancer. At 80 years of age, the cost per QALY of alendronate and risedronate was below pound 20,000. This was true for etidronate when incorporating observational data, but the value rose to pound 69,000 when only RCT data were used. No other intervention had a cost per QALY below pound 35,000. It was assumed that doubling the risk of fracture for women without a prior fracture would give results similar to patients at the threshold of osteoporosis with a prior fracture. CONCLUSIONS: Of the five interventions, only raloxifene appeared to reduce the risk of vertebral fracture in postmenopausal women unselected for low bone mineral density (BMD). However, as the full data have not been made public, there is some uncertainty regarding this result. None of the five interventions has been shown to reduce the risk of non-vertebral fracture in women unselected for low BMD. All of the proposed interventions provided gains in QALYs compared with no treatment in women with sufficient calcium and vitamin D intakes. The size of the QALY gain for each intervention was strongly related to the age of the patient. The estimated costs varied widely for the interventions. These net costs were markedly different by age, with some interventions becoming cost-saving at higher age ranges in patients with a prior fracture. Areas for future research include: the evidence base for the efficacy of fracture prevention in the very elderly, reanalysis of raloxifene using a dedicated breast cancer and CHD model, and more trials considering the cost-effectiveness of teriparatide. (+info)
Does alendronate reduce the risk of fracture in men? A meta-analysis incorporating prior knowledge of anti-fracture efficacy in women.
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BACKGROUND: Alendronate has been found to reduce the risk of fractures in postmenopausal women as demonstrated in multiple randomized controlled trials enrolling thousands of women. Yet there is a paucity of such randomized controlled trials in osteoporotic men. Our objective was to systematically review the anti-fracture efficacy of alendronate in men with low bone mass or with a history of prevalent fracture(s) and incorporate prior knowledge of alendronate efficacy in women in the analysis. METHODS: We examined randomized controlled trials in men comparing the anti-fracture efficacy of alendronate to placebo or calcium or vitamin D, or any combination of these. Studies of men with secondary causes of osteoporosis other than hypogonadism were excluded. We searched the following electronic databases (without language restrictions) for potentially relevant citations: Medline, Medline in Process (1966-May 24/2004), and Embase (1996-2004). We also contacted the manufacturer of the drug in search of other relevant trials. Two reviewers independently identified two trials (including 375 men), which met all inclusion criteria. Data were abstracted by one reviewer and checked by another. Results of the male trials were pooled using Bayesian random effects models, incorporating prior information of anti-fracture efficacy from meta-analyses of women. RESULTS: The odds ratios of incident fractures in men (with 95% credibility intervals) with alendronate (10 mg daily) were: vertebral fractures, 0.44 (0.23, 0.83) and non-vertebral fractures, 0.60 (0.29, 1.44). CONCLUSION: In conclusion, alendronate decreases the risk of vertebral fractures in men at risk. There is currently insufficient evidence of a statistically significant reduction of non-vertebral fractures, but the paucity of trials in men limit the statistical power to detect such an effect. (+info)