Review of the safety and efficacy of risedronate for the treatment of male osteoporosis

Osteoporosis in men is an increasingly recognized problem with associated fracture morbidity and mortality. Treatment is limited, with the bisphosphonates being the mainstay of therapy. Risedronate has demonstrated fracture efficacy in women and efficacy has been recently been investigated in men. In men, risedronate either maintains or increases bone mineral density. In placebo controlled trials it has been shown to be safe and effective in preventing fractures.     

Optimizing dosing frequencies for bisphosphonates in the management of postmenopausal osteoporosis: patient considerations

Postmenopausal osteoporosis is common and underrecognized among elderly women. Osteoporotic fractures cause disability and disfigurement and threaten patients’ mobility, independence, and survival. Care for incident fractures in this age group must go beyond orthopedic repair, to assessment and treatment of the underlying bone fragility. Fracture risk can be reduced by vitamin D and calcium supplementation along with antiresorptive drug treatment. First-line osteoporosis pharmacotherapy employs nitrogen-containing bisphosphonates. The inconvenience of daily oral treatment has motivated development of weekly, monthly, and intermittent oral regimens, as well as quarterly and yearly intravenous (iv) regimens. Ibandronate is the first bisphosphonate to have shown direct anti-fracture efficacy with a non-daily regimen; it was approved for once-monthly oral dosing in 2005 and for quarterly iv dosing in 2006. Intermittent oral risedronate and yearly iv zoledronic acid were approved in 2007. Newly available regimens with extended dosing intervals reduce the inconvenience of bisphosphonate therapy and provide patients with a range of options from which to select a maximally sustainable course of treatment. This review discusses the development, efficacy, safety, and tolerability of extended-interval bisphosphonate regimens and examines their potential to improve patient acceptance and long-term success of osteoporosis treatment.     

Prevalence of Periapical Lesions in Patients with Osteoporosis

IntroductionOsteoporosis is a major systemic disease that can significantly deteriorate the quality of life of the affected individuals. It is more common in women, particularly after menopause. Osteoporosis may be associated with alterations in oral health. Treatment of osteoporotic patients mainly involves the administration of bisphosphonates (BPs). Nitrogen-containing BPs are more potent therapeutically and more commonly used. The purpose of this study was to assess the prevalence of periapical lesions in patients with osteoporosis and to evaluate the difference in the prevalence of periapical lesions in patients treated with alendronate and risedronate, 2 nitrogen-containing types of BPs.MethodsIntegrated data of hospital patients were used. Data from the corresponding diagnosis codes for osteoporosis and periapical periodontitis were retrieved by searching the appropriate query in the database. The odds ratio (OR) of periapical lesions, its association with osteoporosis, and the use of 2 BP medications were calculated and analyzed statistically.ResultsOf 1,644,953 hospital patients, 8715 presented with periapical lesions. A total of 42,292 patients were diagnosed with osteoporosis. A total of 754 patients diagnosed with osteoporosis presented with periapical lesions. The prevalence of periapical lesions in patients with osteoporosis was 1.78% compared with 0.52% in the general patient population of the hospital. The OR for the prevalence of periapical lesions in patients with osteoporosis was 3.36 and was statistically significant (P < .0001). Patients with osteoporosis treated with any type of BPs showed a prevalence of periapical lesions in 1.25% of cases compared with 0.52% in the general patient population of the hospital. The difference in the OR was statistically significant (P < .0001). The OR for the presence of periapical lesions in the osteoporosis group treated with BPs was 2.35 compared with 3.52 in the osteoporosis group not treated with BP. The difference in the OR was statistically significant (P < .0001). Patients treated with alendronate showed an OR of 1.6 for the prevalence of periapical lesions, and the difference in the OR was statistically significant (P < .0001). Patients treated with risedronate showed an OR of 1.34 for the prevalence of periapical lesions, and the difference in the OR was not statistically significant (P = .3502).ConclusionsUnder the conditions of this study, it appears that the prevalence of periapical lesions is significantly higher in osteoporotic patients. Osteoporotic patients treated with BPs showed a marked reduction in the prevalence of periapical lesions, especially when risedronate was used.     

Risedronate reduces intracortical porosity in women with osteoporosis

Nonvertebral fractures account for 80% of all fractures and their accompanying morbidity and mortality. Despite this, the effect of drug therapy on cortical morphology has received limited attention, partly because cortical bone is believed to remodel less and decrease less with age than trabecular bone. However, the haversian canals traversing the cortex provide a surface for remodeling that produces bone loss, porosity, and cortical fragility. We developed a new method of 3D micro‐computed tomography (µCT) to quantify intracortical porosity and the effects of treatment. Women with osteoporosis randomized to risedronate (5 mg/day, n = 28) or placebo (n = 21) had paired transiliac biopsies at baseline and 5 years imaged using 3D µCT. Pores determined from 8 to 12 slices were stratified by their minor axis length into those 25 to 100 µm (closing cone of haversian canals), 100 to 300 µm (cutting cone of haversian canals), and >300 µm (coalescent cavities). Porosity was analyzed as pore area (percent bone area) and pore density (pore number/mm²). Medians are reported. Risedronate reduced pore area in the 25 to 100, 100 to 300, and 300 to 500 µm ranges over 5 years (p = .0008, .04, NS, respectively) corresponding to an 18% to 25% reduction. In the placebo group, pore area was unchanged. At 5 years, pore area and pore number/mm² in the 25 to 100 µm range were each 17% lower in the risedronate group than in the placebo group (p = .02 and .04, respectively). Risedronate is likely to maintain bone strength and reduce nonvertebral fracture risk in part by reducing remodeling and therefore the number and size of intracortical cavities. © 2010 American Society for Bone and Mineral Research     

3-吡啶乙酸盐酸盐的合成

以烟酸乙酯为原料，经还原、氯代、氰化、水解等反应合成了骨吸收抑制剂利塞膦酸钠中间体3－吡啶乙酸盐酸盐。原料易得，反应条件温和，操作方便，总收率28．4％。     

Efficacy and Safety of Risedronate Sodium in Treatment of Postmenopausal Osteoporosis

With the aging of the population,the inci-dence of pri mary osteoporosis is getting higher andhigher,among which post menopausal osteoporosis(PMOP)is the most commontype.As an effectivemedicine to inhibit bone absorption,bisphospho-nates has become the main medicationtotreat oste-oporosis.In this clinical trial,we investigated theefficacy of residronate sodium,the third-generationbisphosphonates made in China,in the treat mentof PMOP by exploring its effect on bone mineraldensity(BMD)and b…     

Risedronate Gastrointestinal Absorption Is Independent of Site and Rate of Administration

Purpose. Two studies were conducted to compare the absorption of risedronate administered as a solution to three different gastrointestinal sites (study A) and to determine the extent of absorption of risedronate solution administered by rapid and slow infusion to the second part of the duodenum (study B). Methods. Each study was designed as a single-dose, crossover (three periods, study A; two periods, study B) trial in healthy male subjects, with a 14-day washout period between dosing. Subjects fasted overnight before drug administration and for 4 hours after drug administration. In study A, a risedronate solution of 40 mg in 30 mL of water was administered directly into the stomach, the second part of the duodenum, or the terminal ileum over 1 minute via a nasoenteral tube in a three-period crossover design. In study B, a risedronate solution of 40 mg in 30 mL of water was administered directly into the second part of the duodenum over 1 minute and over 1 hour in a randomized, two-period crossover design. Serum and urine samples were obtained for 48 hours after dosing for risedronate analysis. Results. Eight subjects completed each study. No statistically significant site-specific differences in any pharmacokinetic parameter were observed (study A). Based on the area under the serum concentration-time profile and the amount of drug excreted in the urine unchanged, the extent of risedronate absorption did not differ significantly following a rapid or a slow infusion (study B). Only minor symptomatic complaints were reported by subjects, such as headaches and body aches. Conclusions. These studies indicate that the rate and extent of risedronate absorption are independent of the site of administration along the gastrointestinal tract, and that the extent of absorption is not affected by the rate of administration.     

Additive effects of glucosamine or risedronate for the treatment of osteoarthritis of the knee combined with home exercise: a prospective randomized 18-month trial

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.     

In vitro disintegration studies of weekly generic and branded risedronate sodium formulations available in Canada

Abstract

Objective:

The aim of this study was to evaluate the in vitro disintegration of the five newly available Canadian generic risedronate 35?mg tablets compared to the innovator (branded) product, ACTONEL (risedronate sodium) 35?mg.     

高效液相色谱法测定利塞膦酸钠的含量

目的建立测定利塞膦酸钠含量的高效液相色谱法。方法色谱柱为汉邦C18柱（250mm×4．6mm,5um）,流动相为缓冲液（含5mmol／L磷酸二氢铵、2mmol／L四丁基溴化铵、1．5mmol／L乙二胺四乙酸二钠,用氢氧化钠调节pH至7．2）-甲醇（75：25,v／v）,流速为1mL／min,检测波长262nm。结果辅料及中间体对样品测定不产生干扰,利塞膦酸钠质量浓度在4．2～37．8ug／mL范围内与峰面积有良好的线性关系,平均回收率为100．5％,RSD为1．1％（n=9）。结论该法可以用于利塞膦酸钠的含量测定。