Intravenous pamidronate in the treatment and prevention of osteoporosis

Abstract Background : Potent oral bisphosphonates are the mainstay of therapy for osteoporosis. However, there are patients who cannot have oral bisphosphonates (e.g. because of gastrointestinal side‐effects). Therefore, we wanted to examine the effects of intermittent i.v. pamidronate (APD) on bone mineral density (BMD) in patients who needed bisphosphonate therapy but could not have oral bisphosphonates. Aim : To assess BMD before and after intermittent i.v. APD in patients requiring a bisphosphonate either for the prevention of osteoporosis on concurrent steroid therapy or for the treatment of osteoporosis. Methods: This was a retrospective audit of 84 consecutive patients at risk of fractures commencing APD between October 1997 and May 2000. Patients were treated with intermittent i.v. APD. BMD as measured by dual‐energy X‐ray absorptiometry before and after APD was the main outcome. Results: The mean length of treatment and mean total APD dose were 16.8 ± 7.0 months and 186.1 ± 79.5 mg respectively. The reasons for using APD were failure to qualify for oral bisphosphonates on the pharmaceutical benefits scheme due to lack of documented minimal trauma fractures (58%), symptomatic gastro‐­oesophageal disease (20%), intolerance of oral bisphosphonates (18%) and lack of efficacy of calcitriol (4%). Mean baseline T‐score at lumbar (L) 2?4 spine and femoral neck were ?1.54 ± 1.22 and ? 2.87 ± 1.19, respectively. From baseline to after APD treatment, there was a significant increase in L2?4 BMD (0.883 ± 0.175 vs 0.912 ± 0.176 g/cm², P < 0.001, mean increase +3.5%), in femoral neck BMD (0.667 ± 0.137 vs 0.680 ± 0.134 g/cm², P= 0.001, mean increase +2.1%) and in trochanteric BMD (0.549 ± 0.129 vs 0.566 ± 0.132 g/cm², P < 0.001, mean increase +3.1%). One‐third of the patients were on oral glucocorticoids at the time of the present study and they had a similar increase in BMD compared to patients not on gluco­corticoids. Mild side‐effects occurred in seven patients, none of whom discontinued treatment. Conclusion : Intermittent APD increases BMD and may be a suitable alternative for patients who cannot have oral bisphosphonates. (Intern Med J 2004; 34: 162?166)     

口服国产阿伦膦酸钠治疗绝经后骨质疏松症的疗效评价

目的为评价国产阿伦膦酸钠（ＡＬＮ）治疗绝经后骨质疏松症（ＰＭＯ）的有效性和安全性。方法将确诊的１８９例ＰＭＯ患者的前１２０例随机地分为试验组与对照组，其余６９例作为开放组。试验组与开放组口服ＡＬＮ１０ｍｇ／日，对照组服安慰剂。三组均日服等量的磷酸氢钙（含元素钙５１０ｍｇ），疗程为１年。结果试验组与开放组腰椎骨密度分别增加了６．３％及６．０％，明显高于对照组１．７％，且两组椎体无新发压缩性骨折发生，而对照组新发６例。骨痛缓解率也明显高于对照组。骨吸收与骨形成指标（尿Ｈｙｐ／Ｃｒ、ＡＬＰ、骨特异性ＡＬＰ、骨钙素），于治疗第３、６及１２月下降幅度亦明显大于对照组（Ｐ＜０．０５～０．００１）。部分病例有轻度、一过性胃肠道反应，但不影响治疗。三组血、尿常规及肝、肾功能未见异常改变。结论国产ＡＬＮ１０ｍｇ／日治疗ＰＭＯ有效、安全。     

Meta-analyses of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women

OBJECTIVE: To review the effect of alendronate on bone density and fractures in postmenopausal women. DATA SOURCE: We searched MEDLINE, EMBASE, Current Contents, and the Cochrane Controlled trials registry from 1980 to 1999, and we examined citations of relevant articles and proceedings of international meetings. STUDY SELECTION: We included 11 trials that randomized women to alendronate or placebo and measured bone density for at least 1 yr. DATA EXTRACTION: For each trial, three independent reviewers assessed the methodological quality and abstracted data. DATA SYNTHESIS: The pooled relative risk (RR) for vertebral fractures in patients given 5 mg or more of alendronate was 0.52 [95% confidence interval (CI), 0.43-0.65]. The RR of nonvertebral fractures in patients given 10 mg or more of alendronate was 0.51 (95% CI 0.38-0.69), an appreciably greater effect than for the 5 mg dose. We found a similar reduction in RR across nonvertebral fracture types; in particular, RR reductions for fractures traditionally thought to be "osteoporotic," such as hip and forearm, were very similar to RR reductions for "nonosteoporotic" fractures. Individual studies showed similar results, reflected in the P values of the test of heterogeneity (P = 0.99 for vertebral and 0.88 for nonvertebral fractures). Alendronate produced positive effects on the percentage change in bone density, which increased with both dose and time. After 3 yr of treatment with 10 mg of alendronate or more, the pooled estimate of the difference in percentage change between alendronate and placebo was 7.48% (95% CI 6.12-8.85) for the lumbar spine (2-3 yr), 5.60% (95% CI 4.80-6.39) for the hip (3-4 yr), 2.08% (95% CI 1.53-2.63) for the forearm (2-4 yr), and 2.73% (95% CI 2.27-3.20) for the total body (3 yr). Heterogeneity of the treatment effect of alendronate was not consistently explained by any of our a priori hypotheses; in particular, the effect was very similar in prevention and treatment studies. The pooled RR for discontinuing medication due to adverse effects for 5 mg or greater of alendronate was 1.15 (95% CI 0.93-1.42). The pooled RR for discontinuing medication due to gastro-intestinal (GI) side effects for 5 mg or greater was 1.03 (0.81-1.30, P = 0.83), and the pooled RR for GI adverse effects with continuation of medication was 1.03 (0.98 to 1.07) P = 0.23. CONCLUSIONS: Alendronate increases bone density in both early postmenopausal women and those with established osteoporosis while reducing the rate of vertebral fracture over 2-3 yr of treatment. Reductions in nonvertebral fractures are evident among postmenopausal women without prevalent fractures and have bone mineral density (BMD) levels below the World Health Organization threshold for osteoporosis. The impact on fractures appears consistent across all fracture types, casting doubt on traditional distinctions between osteoporotic and nonosteoporotic fractures.     

阿仑膦酸钠对绝经后骨质疏松症患者生活质量的影响

目的评价不同剂量阿仑膦酸钠对绝经后骨质疏松或骨量减少女性患者短期生活质量的影响。方法 100例平均年龄(65.06±6.86)岁的绝经后骨量减少或骨质疏松女性纳入本研究,随机分为阿仑膦酸钠标准剂量(70 mg/周)组或低剂量(70 mg/2周)组,均治疗1年。治疗前后采用SF-36量表进行生活质量测评,包括生理功能(PF)、生理职能(RP)、身体疼痛(BP)、总体健康(GH)、活力(VT)、社会功能(SF)、情感职能(RE)、精神健康(MH)8个维度及1项健康变化(HT)指标。用双能X线骨吸收仪测量腰椎和股骨近端骨密度(BMD)。分别用自动分析仪和化学发光法测量骨转换生化指标碱性磷酸酶(ALP)及Ⅰ型胶原羧基端肽交联(β-CTX)水平。用化学发光法测量治疗前25羟维生素D(25OHD)水平。结果共92例患者完成随访。治疗1年时,2组患者血清ALP、β-CTX水平均较治疗前显著降低(P0.05),各部位BMD显著升高(P0.05);标准剂量组血清β-CTX水平降低程度较低剂量组更为明显(P0.05),2组间其他指标治疗前后差异无统计学意义。标准剂量组PF(P=0.006)、RP(P=0.002)、BP(P=0.049)、VT(P=0.006)、RE(P=0.012)5个维度评分显著高于治疗前;低剂量组PF(P=0.015)、GH(P=0.000)、SF(P=0.041)3个维度评分较治疗前明显提高。结论采用阿仑膦酸钠70 mg/周或70 mg/2周治疗不仅能显著降低绝经后骨质疏松或骨量减少女性患者血清骨吸收指标水平、增加腰椎和股骨近端骨密度,而且能明显改善生活质量。     

Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women

This study compared the effects of oral alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. Women at least 5 yr postmenopause (n = 299) were randomized to either 10 mg alendronate, matching alendronate placebo, or open-label intranasal calcitonin 200 IU daily for 12 months. Hip and spine bone mineral density (BMD) and markers of bone turnover were measured, and safety and tolerability were assessed. Alendronate produced greater increases in BMD than calcitonin at 12 months at the lumbar spine (5.16% vs. 1.18%; P < 0.001), trochanter (4.73% vs. 0.47%; P < 0.001), and femoral neck (2.78% vs. 0.58%; P < 0.001). Changes in BMD with calcitonin were greater than with placebo at the femoral neck, but were not different from placebo at either the trochanter or lumbar spine. Greater decreases in bone turnover were seen with alendronate than with calcitonin (serum bone-specific alkaline phosphatase, 43% vs. 9%, P < 0.001; urinary N-telopeptide, 62% vs. 11%, P < 0.001). Similar percentages of patients in each group reported an adverse experience during the study. We conclude that, in postmenopausal women with osteoporosis, 12 months of therapy with alendronate produced significantly greater increases in BMD of the hip and spine and greater decreases in bone turnover than intranasal calcitonin.     

Intravenous ceftriaxone compared with oral doxycycline for the treatment of Lyme neuroborreliosis

This prospective, open-label, non-randomized trial at the University Departments of Infectious Diseases in Ljubljana, Slovenia, and G?teborg, Sweden, was conducted to compare the kinetics of the cerebrospinal fluid (CSF) mononuclear cell count after 10-14 d of ceftriaxone or doxycycline for treatment of Lyme neuroborreliosis. 29 patients were treated with intravenous ceftriaxone 2 g daily in Ljubljana and 36 patients with oral doxycycline 400 mg daily in G?teborg. The study protocol included lumbar puncture before and 6-8 weeks after treatment initiation. There was a marked decrease (1.2 log10 x 10(6)/l) of the median CSF mononuclear cell count following treatment. With the assumption of a linear regression of the logarithmic mononuclear cell counts between the 2 lumbar punctures, no significant difference between the 2 antibiotic treatments could be found. All patients were clinically much improved after treatment. At 6 months follow-up 23 (79%) of the ceftriaxone- and 26 (72%) of the doxycycline-treated patients were completely recovered. Intravenous ceftriaxone or oral doxycycline was found to be effective, safe, and convenient for treatment of Lyme neuroborreliosis.     

Comparison of weekly treatment of postmenopausal osteoporosis with alendronate versus risedronate over two years

OBJECTIVE: A 1-yr extension of the Fosamax Actonel Comparison Trial was completed to compare changes in bone mineral density (BMD), bone turnover, and upper gastrointestinal tolerability over 2 yr of treatment. DESIGN: This was a randomized, double-blind extension conducted at 72 U.S. sites. PATIENTS AND METHODS: Of the 1053 women who completed yr 1, 833 postmenopausal women with low BMD entered the extension, continuing their same treatment allocation [once-weekly (OW) alendronate 70 mg or OW risedronate 35 mg]. Changes in BMD at the hip trochanter, total hip, femoral neck, and lumbar spine and in markers of bone turnover were compared at 24 months. Tolerability was assessed by adverse experience reporting. RESULTS: Alendronate produced greater increases from baseline in BMD at 24 months than did risedronate at the trochanter (alendronate, 4.6%; risedronate, 2.5%, P < 0.001) as well as at all other BMD sites. Significantly more alendronate than risedronate patients had measured BMD increases of 0% or more and 3% or more at all BMD sites (P < 0.001), and fewer alendronate patients had measured decreases of 3% or more at all BMD sites. Significantly greater reductions in all biochemical markers of bone turnover occurred with alendronate, compared with risedronate. No differences were seen in occurrence or discontinuations due to upper gastrointestinal adverse experiences. CONCLUSIONS: Patients receiving 70 mg OW alendronate had greater gains in BMD, were more likely to maintain or gain BMD, and had greater reductions in bone turnover markers than patients receiving 35 mg OW risedronate after 24 months, with no differences in upper gastrointestinal tolerability.     

The effect of raloxifene after discontinuation of long-term alendronate treatment of postmenopausal osteoporosis

OBJECTIVE: The aim of this study was to compare bone mineral density (BMD) and biochemical markers of bone turnover in patients receiving long-term alendronate therapy who continued alendronate, were switched to raloxifene, or discontinued antiresorptive therapy. DESIGN, PATIENTS, AND INTERVENTIONS: Ninety-nine ambulatory women who were diagnosed with postmenopausal osteoporosis and treated with alendronate (10 mg/d) for a mean period of 43 months were randomized to double-blind raloxifene (60 mg/d; n = 33), placebo (n = 33), or continuation of open-label alendronate (n = 33) for 12 months. Patients continued their assigned treatment in a subsequent 12-month, open-label extension phase. All patients received supplemental calcium (500 mg/d) and vitamin D (800 IU/d). MAIN OUTCOME MEASURES: BMD (lumbar spine, total femur, femoral neck, distal forearm, and total body) and biochemical markers (serum intact amino-terminal propeptide of type I procollagen, type 1 collagen cross-linked C-telopeptide, and osteocalcin) were measured at baseline and follow-up visits. RESULTS: Discontinuation of alendronate therapy resulted in a decrease in lumbar spine BMD at 12 months (-2.66%; P < 0.05), but did not change total femur BMD (+0.35%; nonsignificant). Raloxifene and alendronate, compared with discontinuation, prevented lumbar spine BMD loss (-0.75% and -0.54% at 12 months, respectively; P < 0.05). Raloxifene and alendronate caused a similar increase in total femur BMD at 12 months (1.45% and 1.56%; both P < 0.05 vs. baseline; nonsignificant vs. discontinuation). Patients, who discontinued alendronate therapy experienced an increase in bone turnover. Bone turnover increases were less pronounced in patients taking raloxifene and were absent in those who continued alendronate. Of the three groups, mean bone turnover in raloxifene patients was the closest to premenopausal mean values. CONCLUSIONS: BMD preservation and increase were most pronounced in patients continuing alendronate. Raloxifene treatment, compared with placebo, demonstrated beneficial effects on BMD and bone turnover after discontinuation of long-term alendronate therapy.     

Hip fracture protection by alendronate treatment in postmenopausal women with osteoporosis: a review of the literature

Osteoporosis most commonly affects postmenopausal women, placing them at a significant risk of fractures. In particular, hip fractures are an important cause of mortality and morbidity among postmenopausal women. Anti-resorptive therapies that produce greater decreases in bone turnover markers together with greater increases in bone mineral density (BMD) are associated with greater reductions in fracture risk, especially at sites primarily composed of cortical bone such as the hip. Thus, treatment with potent anti-resorptive drugs like alendronate is a strategy for preventing hip fractures in postmenopausal women with osteoporosis. The purpose of this paper is to discuss the efficacy of alendronate against hip fractures and the mechanism for this anti-fracture efficacy in postmenopausal women with osteoporosis. A meta-analysis of randomized controlled trials has shown that alendronate reduces the risk of hip fractures by 55% in postmenopausal women with osteoporosis. According to the analyses of the Fracture Intervention Trial, each 1 standard deviation reduction in a 1-year change in bone-specific alkaline phosphatase (BSAP) is associated with 39% fewer hip fractures in alendronate-treated postmenopausal women, and those with at least 30% reduction in BSAP have a 74% lower risk of hip fractures relative to those with less than 30%. Alendronate is effective in reducing the risk of hip fractures across a spectrum of ages. The mechanism for this anti-fracture efficacy has been clarified; alendronate strongly suppresses bone turnover and subsequently increases hip BMD, decreases cortical porosity, improves parameters of hip structure geometry (cortical thickness, cross-sectional area, section modulus, and buckling ratio), and produces more uniform mineralization (increases the mean degree of mineralization of bone) in cortical bone. A once-weekly regimen of alendronate administration provides better patient compliance and persistence with the treatment than the once-daily dosing regimen, leading to greater efficacy against hip fractures. Thus, the efficacy of alendronate against hip fractures has been confirmed in postmenopausal women with osteoporosis, especially with a once-weekly dosing regimen.     

Effectiveness of alendronate treatment in postmenopausal women with osteoporosis: relationship with BsmI vitamin D receptor genotypes

OBJECTIVE: To assess whether there is a relationship between the effectiveness of alendronate treatment in postmenopausal women with osteoporosis and BsmI vitamin D receptor (VDR) genotypes. DESIGN: Prospective baseline-controlled clinical trial. PATIENTS: Sixty-eight Italian osteoporotic women were enrolled and treated with alendronate at a dose of 10 mg/day for 12 months. MEASUREMENTS: At entry and after treatment, lumbar bone mineral density (BMD) and serum osteocalcin (OC) and urinary deoxypyridinoline/creatinine ratio (DPD-Cr) levels were evaluated. DNA was extracted from blood and analysed for the BsmI polymorphism of the VDR gene. RESULTS: The mean percentage (% +/- SD) change from baseline in lumbar BMD was significantly higher (P < 0.01) in bb than in BB BsmI VDR genotypes (7.92 +/- 4.31 vs. 3.40 +/- 1.81). No significant difference in lumbar BMD was observed in Bb VDR patients (6.01 +/- 3.89) in comparison with other groups. The mean percentage of change in serum OC and urinary DPD-Cr levels was significantly (P < 0.01) lower in individuals with bb than in those with BB BsmI VDR genotypes (-14.34 +/- 2.87 vs.-10.39 +/- 1.43 and -9.61 +/- 5.56 vs.-4.61 +/- 2.31). No significant difference in serum OC and urinary DPD-Cr levels was observed in Bb VDR patients (-12.31 +/- 2.11 and -6.52 +/- 2.65) in comparison with other groups. CONCLUSION: The different BsmI vitamin D receptor genotypes modify the pharmacological response to alendronate treatment in postmenopausal women with osteoporosis.     

Intravenous pamidronate in the treatment of sternoclavicular hyperostosis

The SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) is a rare clinical entity in which osteosclerosis and osteolysis are consistent radiological findings. We present a patient with SAPHO syndrome manifesting as painful sternoclavicular hyperostosis treated successfully with pamidronate. For the first time, a reduction in isotope bone scan activity was documented in parallel to a favourable clinical response. Bisphosphonates have potent antiosteoclastic and anti-inflammatory effects. By virtue of their dual effects on bone remodelling and inflammation, they seem an appropriate therapy in the management of SAPHO syndrome. This case demonstrates the efficacy of pamidronate, both clinically and radiologically, as first line therapy for patients with isolated hyperostosis.     

绝经后骨质疏松的治疗探讨

对经X线骨密度仪检测L2～4的骨密度（BMD）诊断为绝经后骨质疏松（PMO）的86例妇女的血清雌二醇（E2）含量进行RIA测定．其E2含量均值为61．38pmol／L。对本组86例PMO妇女给予小剂量利维爱为主的联合用药治疗6个月．对照观察用药前后BMD、血清钙（Ca）、磷（P）、碱性磷酸酶（ALP）的变化。结果显示．用药后BMD均有不同程度的提高．以绝经时间≤10年者尤为明显（P＜0.01）；绝经时间＞10年者虽有提高．但差异不显著（P＞0.05）。治疗前血清Ca增高30例．占34.88％；P降低29例．占33.72％；ALP增高51例．占59．3％。治疗后均恢复正常。提示联合用药可减少利维爱的用量，是PMO较为理想的治疗方案。绝经后任何时期用药都可防止骨的继续丢失，早期治疗效果更好。     

Site-dependent bone mineral density response to oral pamidronate and calcium in postmenopausal osteoporosis: A preliminary report

Summary Radiologically diagnosed postmenopausal osteoporotic patients with at least one nontraumatic vertebral flattening were treated for one year with either oral pamidronate (APD), 300 mg/day plus calcium 1 g/day (n=39) or with calcium alone (n=21). Bone mineral density (BMD) was assessed in lumbar spine, femoral neck, trochanter and Ward's triangle by dual X-ray absorptiometry in order to determine the number of responders at each site. As no densitometric inclusion criteria were stipulated, wide inter- and intra-individual variations in both regional basal BMD and response to therapy were found. However, the APD-treated group showed significant mean BMD increases in spine (+3.1%; p<0.001) and femoral neck (+3.2%; p<0.002) versus basal level, whereas the calcium only group failed to exhibit significant differences. The entire 60-strong population was then split into two groups, according to whether individual BMD content was greater or less than the mean basal value for each skeletal site evaluated. For either treatment, subpopulations with lower basal BMD tended to achieve greater bone gain, though statistically significant differences were only disclosed at trochanter (p<0.004) with APD and at femoral neck (p<0.002) in the calcium only group. Globally speaking, increases in BMD were observed in 60–80% of patients receiving either treatment — who were thus defined as responders — at each particular skeletal area assessed. However, when only skeletal areas with low basal BMD were considered, the number of responders reached 60–100%. Responsive sites varied among patients: out of 56 cases, 9 (24%) on APD and 6 (32%) on calcium alone responded in all 4 areas evaluated, while a single case on the latter treatment failed to show BMD response at any site. Overall, the mean number of responsive sites was 2.7. Odds ratios were calculated considering treatment modality and high or low basal BMD as parameters, but no significant differences were found in the number of responders. It may be concluded that APD induces moderate lumbar and femoral neck bone mass gain in severe postmenopausal osteoporosis, whereas calcium alone leads to non significant variations, both findings being in agreement with reported data. Therefore, evaluated APD doses enhance mineralization in responsive sites alone, but fail to increase the total number of responders. Interestingly, responsive sites seem to be those realitively spared by the course of the disease.This paper was partially presented at the 15th Annual Meeting of the American Society for Bone and Mineral Research, Tampa (FL) USA, September 9–14, 1993.     

Efficacy of intermittent low dose alendronate in Thai postmenopausal osteoporosis

Alendronate has been proven to be effective in the prevention and treatment of postmenopausal osteoporosis with the recommended daily dose of 10 mg. However, a constraining requirement for dosing limited its general acceptance in treatment. Since alendronate is potent and has a long half-life, weekly administration of alendronate in lower total doses might be safer and more convenient. The purpose of this study was to determine the efficacy of low dose once-weekly 20 mg alendronate in Thai postmenopausal women with osteoporosis. Thirty-nine postmenopausal women with osteoporosis received alendronate 20 mg once a week plus 750 mg elemental calcium daily. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) at baseline and 6 and 12 months after treatment. Serum C-terminal telopeptide of type I collagen (CTx-I) was measured by electrochemiluminescence immunoassay at baseline and 3 months after treatment. By the end of 1 year, once weekly 20 mg alendronate significantly increased vertebral BMD (+6.2%, p < 0.001 vs baseline) from baseline whereas there was a reduction of 60.7% in serum CTx-I at 3 months. However, the BMD at femur did not increase significantly (+0.64%). Conclusion. Low-dose intermittent once-weekly 20 mg alendronate was effective, cost saving and had a good safety profile in increasing vertebral BMD and stabilizing BMD at the femoral neck in postmenopausal osteoporosis.     

老年男性骨质疏松症患者口服阿仑膦酸钠的依从性分析

  目的 调查老年男性骨质疏松症患者口服阿仑膦酸钠的依从性,探讨影响服药依从性的相关因素。方法 入选2011年1—6月在解放军总医院门诊确诊骨质疏松症并开始口服阿仑膦酸钠治疗的老年男性患者145例,调查其服该药1年的依从性,根据药物占有率（MPR）分为依从性好组（MPR≥80%）和差组（MPR<80%）,比较两组差异,分析影响依从性的因素。结果 随访到139例患者,其中依从性好者32例（23.02％),依从性差者107例（76.98％);对筛选出的影响服药依从性的因素进行logistic回归分析,结果显示,骨痛(OR值0.69,P=0.043)、无人提醒用药（OR值1.37,P=0.025）、担心药物副作用(OR值1.49,P=0.018)、服药种类＞7种(OR值1.30,P=0.036)、不清楚远期疗效(OR值1.39,P=0.021)为影响服药依从性的因素。结论 老年男性骨质疏松症患者口服阿仑膦酸钠治疗的依从性差;降低服药依从性的因素有：无人提醒服药、担心药物副作用、服药种类＞7种和不清楚远期疗效;骨痛可提高患者服药依从性。     

Effect of estrogen replacement plus low-dose alendronate treatment on bone density in surgically postmenopausal women with osteoporosis

This prospective randomized, double-blind, placebo-controlled, clinical trial was performed to evaluate the effectiveness of estrogens plus low-dose alendronate on bone metabolism. A total of 150 surgically postmenopausal women with osteoporosis were randomized in three groups: group A, micronized E2 (2 mg/d) plus standard-dose alendronate (10 mg/d); group B, micronized E2 plus low-dose alendronate (5 mg/d); and group C, micronized E2 plus placebo (one tablet per day). In all women, bone mineral density (BMD) and serum bone metabolism markers were assessed at admission and every 6 months for 2 yr. After 2 yr, BMD significantly increased compared with baseline in all groups. The percentage BMD change was significantly higher in groups A and B than in group C. The differences in BMD detected between groups A and B were not statistically significant. Since the 6-month follow-up and throughout the study, serum osteocalcin and bone alkaline phosphatase levels and urinary deoxypyridinoline and pyrilinks-D excretion were significantly reduced in all groups. Serum bone alkaline phosphatase levels significantly decreased in groups A and B, without difference between them, in comparison with group C. In conclusion, in surgically postmenopausal osteoporotic women treated with estrogen replacement, the addition of alendronate at a low dose of 5 mg daily induces a gain of bone mass not significantly different in comparison with that obtained using a standard dose of 10 mg daily.     

Intramuscular clodronate in nonresponders to oral alendronate therapy for osteoporosis

OBJECTIVE: Oral alendronate is effective in increasing bone mineral density (BMD) and in reducing fracture incidence. However, a large proportion of patients under treatment do not show significant changes in BMD, or even bone loss. Incorrect administration, low intestinal absorption, and poor compliance are among factors that may account for this effect. In this subgroup of patients we evaluated whether intramuscular (im) clodronate increased the number of responders. METHODS: Using an open case-control design we studied 60 postmenopausal osteoporotic women (mean age 58.9 years +/- 4.8 SD) after one year of therapy with oral alendronate who had an increase in BMD that was lower than the in vivo densitometry measurement error (2%). Subjects were divided into 2 groups: the first continued aledronate treatment (AL group); the second began weekly im injections of clodronate 100 mg (CL group). BMD measurements were performed at the right femoral neck by the same operator, using dual energy x-ray absorptiometry. RESULTS: After 12 months of therapy the prevalence of responders (increase in BMD > 2%) was 40% in the AL group and 66% in the CL group (prevalence rate ratio = 1.65; 95% CI 1.25-2.04). The treatment group was the only variable that showed a significant correlation with being a responder (beta = 1.13; p = 0.03), as analyzed by multiple logistic regression to account for the effect of confounding factors. In the CL group the difference in the mean value of BMD between time T0 and time T+12 was greater than in the AL group, but did not reach statistical significance. The mean percentage variation of BMD was significantly greater in the CL group (+3.21%) compared to the AL group (+0.98%) (p < 0.001, t test) (f value = 8.4; p < 0.01, by multiple linear regression analysis using the same covariates). CONCLUSION: Treatment with weekly intramuscular injection of clodronate in nonresponders to oral alendronate showed a higher number of subjects with a significant increase in BMD, compared to continuation of therapy with alendronate.     

Intravenous zoledronic acid and oral alendronate in patients with a low trauma fracture: experience from an osteoporosis clinic

Background/Aims: Oral bisphosphonates have been shown to be effective in treating osteoporosis. However, there has been a significant problem with compliance. Newer intravenous bisphosphonates are available for osteoporosis management, but have not been compared with oral bisphosphonates in a clinical setting. The aim of this study was to compare the safety and effectiveness of intravenous zoledronic acid (ZOL) and oral alendronate (ALN) in osteoporotic patients following a low trauma fracture. Methods: A non‐randomized, retrospective cohort study was conducted of 169 patients with a low trauma fracture and reduced bone mineral density (BMD). Patients were treated with either an infusion of 4 mg ZOL or ALN 70 mg weekly. The outcomes measured were change in BMD after 12 months of treatment with either bisphosphonate, and new osteoporotic fractures. All adverse events were documented. Results: Lumbar spine BMD (L2–L4) improved 5.6% in the ZOL group (P < 0.001) and 5.5% in the ALN group (P < 0.001). Total hip BMD improved 2% in the ZOL group (P < 0.01) and 2.5% in the ALN group (P < 0.001). There was no significant difference in BMD change between the groups. There were significantly more new fractures (P < 0.001) in the ZOL group (7.2%) than the ALN group (1%). The ZOL group were significantly older (P < 0.01) and had a significantly higher proportion of males (P < 0.05) at baseline. There were no serious adverse reactions in either group. Conclusion: ZOL and ALN both produce a significant increase in BMD and are well tolerated in patients with osteoporotic, low trauma fractures. Yearly ZOL provides a safe, convenient alternative to weekly oral bisphosphonates.