alendronate, Fosamax
[Weekly and daily intake of alendronate: comparison of tolerance in osteoporosis treatment]

[Article in Croatian]

Sakic D, Badovinac O, Delija A, Sakic VA.

Odjel za fizikalnu medicinu i rehabilitaciju, Klinicka bolnica Dubrava, Avenija G. Suska 6, 10000 Zagreb.

In this study we analyzed, considering complains of patients, tolerance of taking alendronate 70 mg once a week in comparison with daily intake of alendronate 10 mg. Subjects were patients that were treated for osteoporosis at Department for physical medicine and rehabilitation in Clinical hospital Dubrava. The diagnosis of osteoporosis was established by DXA densitometry. Pains in oesophagus were the main reason for ceasing of use of alondronate. According to our research patients tolerate taking alendronate 70 weekly 4,22 times better than alendronate 10 daily.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15554368&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Characterization of tumor reactivity of human V gamma 9V delta 2 gamma delta T cells in vitro and in SCID mice in vivo.

Kabelitz D, Wesch D, Pitters E, Zoller M.

Institute of Immunology, Universitatsklinikum Schleswig-Holstein Campus Kiel, Germany. kabelitz immunologie.uni-kiel.de

Human Vgamma9Vdelta2 gammadelta T cells are selectively activated by bacterial phosphoantigens and aminobisphosphonates and exert potent cytotoxicity toward various tumor cells. In this study we have characterized the cytotoxic reactivity of gammadelta T cell lines established from healthy donors by stimulation with aminobisphosphonate alendronate toward melanoma MeWo and pancreatic adenocarcinomas Colo357 and PancTu1 lines in vitro and in vivo upon adoptive transfer into SCID mice. Lysis of all tumor cells was enhanced when gammadelta effector cells were preactivated with phosphoantigens. Recognition of MeWo was TCR dependent, as shown by anti-TCR Ab blockade, whereas only the phosphoantigen-mediated increased, but not the basal, lysis of Colo357 and PancTu1 was inhibited by anti-TCR Ab. Furthermore, lysis of Colo357, but not that of MeWo or PancTu1, was completely inhibited by the pan-caspase inhibitor zVAD, indicating different recognition and effector mechanisms involved in the gammadelta T cell/tumor cell interactions. Upon transfer into SCID mice, alendronate-activated gammadelta T cells given together with IL-2 and alendronate significantly prolonged the survival of SCID mice inoculated with human tumor cells. The best results were thus obtained when gammadelta T cells were repetitively given five times over a period of 30 days. With this protocol, human gammadelta T cells prolonged the mean survival of mice inoculated with MeWo melanoma from 28.5 to 87.3 days (p < 0.0001) and in the case of PancTu1 adenocarcinoma from 23.0 to 48.4 days (p < 0.0001). We conclude that an effective gammadelta T cell-based immunotherapy might require activation of endogenous gammadelta T cells with aminobisphosphonate (or phosphoantigen) and IL-2, followed by adoptive transfer of in vitro expanded gammadelta T cells.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15557170&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Efficacy of alendronate, a bisphosphonate, in the treatment of AVN of the hip. A prospective open-label study.

Agarwala S, Jain D, Joshi VR, Sule A.

P. D. Hinduja Hospital, Mahim, Mumbai 400 016, India. dr_vjoshi hindujahospital.com.

OBJECTIVE: To study the efficacy of alendronate, in the treatment of avascular necrosis (AVN) of the hip. METHODS: Sixty patients with AVN of the hip (100 hips with AVN) were studied. The follow-up period ranged from 3 months to 5 yr. The most common cause of AVN was steroids. Parameters studied were walking time, standing time, pain and disability on a visual analogue scale (VAS), range of motion of the hip, X-ray and MRI of the hip. All patients were treated with alendronate 10 mg/day (or 70 mg/week) along with 500-1000 mg of daily calcium and vitamin D supplements, and were advised to avoid weight-bearing. NSAIDs and analgesics were permitted as needed and were recorded. RESULTS: Forty-one patients (71 AVN hips) with AVN have been followed up for a minimum of 1 yr, 24 patients (42 AVN hips) for 2 yr and 21 patients (37 AVN hips) for more than 2 yr (average 37 month). Fourteen patients have been followed up for less than 1 yr (3-9 months). Significant reduction in pain and disability scores (P<0.001) and significant increase in standing and walking time (P<0.001) were observed. All hip movements improved at 1 yr (P value 0.000-0.009) with an insignificant decline after that (P>0.001). Radiologically, the hips either stabilized in the same grade or progressed by one grade. MRI showed a decrease in marrow oedema in most cases at the 1-yr follow-up. Six patients (10 hips) required surgery and there were two (three hips) dropouts. The drug was well tolerated and there was a reduction in NSAID requirement. CONCLUSION: Alendronate reduces pain, improves function and retards AVN progression. Early surgical intervention can be avoided in most patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15572396&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Health-economic comparison of three recommended drugs for the treatment of osteoporosis.

Brecht JG, Kruse HP, Mohrke W, Oestreich A, Huppertz E.

InForMed - Outcomes Research and Health Economics, Ingolstadt, Germany. jg.brecht informed.de

Osteoporosis is a large and growing disease with significant health consequences. Based on an evaluation of clinical evidence, the German osteology umbrella organization DVO (Dachverband Osteologie deutschsprachiger wissenschaftlicher Fachgesellschaften) published guidelines in March 2003 for the diagnosis and treatment of osteoporosis. For prevention of fractures in women with postmenopausal and senile osteoporosis, these guidelines recommend three treatment options as first-line therapy: risedronate, alendronate and raloxifene. No evidence is currently available for the reduction of hip fractures by raloxifene. Only risedronate and alendronate, therefore, are recommended for prevention of hip fractures. Information on the cost-effectiveness of preventing and treating osteoporosis may support decision makers in more efficient allocation of resources. Accordingly, the objective of this study is the comparative assessment of the cost-effectiveness of risedronate, alendronate and raloxifene for patient populations in Germany at high risk of osteoporotic fracture due to low bone mineral density (BMD) (i.e., T-score < -2.5) and resulting from a history of at least one previous vertebral fracture, as compared to osteoporotic patients with no treatment. Target variables for the economic comparison are costs per hip fracture avoided and costs per quality-adjusted life year (QALY) gained. Hip fractures are the most costly and best-documented complication of osteoporosis. A cost-effectiveness analysis was therefore conducted, using as criteria for evaluating intervention the incremental cost per hip fracture avoided and the cost per QALY gained. We used a fracture-incidence-based Markov model of osteoporosis, with analysis of patients' transition across outcome states over time (e.g., fracture, healthy, dead). Base-case analysis was conducted on a cohort of 1,000 women aged 70 with low spine BMD and prevalent vertebral fracture, over 3 years of treatment with risedronate, alendronate or raloxifene, and with application of a 10-year analytic time horizon. Model inputs included hip and vertebral fracture incidence rates; relative risk of fracture given low BMD and prevalent vertebral fracture, fracture cost, treatment prices/day (risedronate: 35 mg, 1.76 euro; alendronate: 70 mg, 1.82 euro; raloxifene: 60 mg, 1.82 euro); health utility; and efficacy in terms of relative-risk reduction of fracture of the hip (60% risedronate; 51% alendronate; not significant raloxifene) and vertebrae (49% risedronate; 47% alendronate; 30% raloxifene). A 5% discount rate was applied to cost and outcomes. In the base case, treatment with risedronate reduces costs from the social insurance perspective with respect to both endpoints: i.e., costs per averted hip fracture and QALY. Over the 3-year treatment period and 10-year observation, furthermore, risedronate proved superior to alendronate and raloxifene (i.e., risedronate was less expensive and more effective). From the perspective of statutory health insurance, the cost per averted hip fracture is 37,348 euro for risedronate and 48,349 euro for alendronate (costs for raloxifene were not calculated due to a nonsignificant effect on prevention of hip fractures); and cost per QALY gained is 32,092 euro for risedronate, in comparison to patients in Germany with no therapy (alendronate 41,302 euro; raloxifene 1,247,119 euro). This cost-effectiveness analysis gives evidence that bisphosphonates are cost effective. Under consideration of current prices and the published clinical evidence, risedronate dominates the comparison of DVO-recommended drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15575171&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Comparison of the effects of alendronate and risedronate on bone mineral density and bone turnover markers in postmenopausal osteoporosis.

Sarioglu M, Tuzun C, Unlu Z, Tikiz C, Taneli F, Uyanik BS.

Department of Physical Medicine and Rehabilitation, Faculty of Medicine, University of Celal Bayar, 1748 sokak No. 26 Daire 4, 35530, Karsiyaka, Izmir, Manisa, Turkey, canan.tikiz bayar.edu.tr.

The aim of the study was to compare the effects of once-weekly alendronate sodium and daily risedronate sodium treatment on bone mineral density (BMD) and bone turnover markers in postmenopausal osteoporotic subjects. For this purpose, 50 patients were included in this study and randomly classified into two groups. Group I (n=25) received risedronate (5 mg/day) and group II (n=25) received alendronate Na (70 mg/week). The study duration was limited to 12 months. The efficacy of the treatment was evaluated by BMD measurements at spine and hip at 6th and 12th months of the treatment, as well as by the measurement of bone turnover markers such as serum osteocalcin (OC), bone-specific alkaline phosphatase (BASP), urine deoxypyridinoline (DPD) and calcium/creatine ratio in 24-h urine at 1st, 3rd, 6th and 12th months. The evaluation of the changes in BMD in all regions revealed a significant increase in BMD in both groups compared to baseline values except for spine (L2-L4) in alendronate group at 6th and 12th month and femoral neck in risedronate group at 6th month. However, the difference in percentage increase in BMD measurements was not statistically significant between the two groups at 6th and 12th months. In both groups, serum OC, BSAP and urine DPD were found to be significantly attenuated at 1st month of the treatment period, and continued to be lowered throughout the 3rd, 6th and 12th months (P<0.05). However, there was no statistically-significant difference between both groups of patients (P>0.05). In conclusion, our results suggest that both treatment protocols provide treatment options of similar efficiencyfor postmenopausal osteoporosis, and have almost-similar effects in enhancing the BMD and in slowing the bone turnover. Risedronate seems to havea more potent effect in the spinal region than that of alendronate, although this potency was not statistically significant.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15580349&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Risk of fracture among women who lose bone density during treatment with alendronate. The Fracture Intervention Trial.

Chapurlat RD, Palermo L, Ramsay P, Cummings SR.

Department of Rheumatology and Bone Diseases and INSERM U403, E. Herriot Hospital, 69437, Lyon, France.

It is commonly believed that the response to treatment in patients on alendronate is proportional to the increase in bone mineral density (BMD), and that those who lose BMD during treatment might not respond to treatment. In the Fracture Intervention Trial 6,459 women were randomly assigned to treatment with alendronate or placebo; BMD was measured annually, and new spine fractures were assessed by lateral spine films, taken at baseline and end of follow-up. Among subjects who took at least 70% of the study drug (5,220 women), we compared reductions in risk of spine fractures at end of follow-up (3 or 4 years) within various levels of change in total hip and spine BMD after 1 and 2 years of treatment, after adjustment for differences in characteristics between the treatment and control groups. Women "losing" BMD at the lumbar spine (0% to 4%) while on alendronate had a reduction of 60% in vertebral fracture risk [OR=0.40 (0.16, 0.99)] compared to their counterparts in the placebo group. The few women that lost more than 4% did not have a significant benefit [OR=0.15 (0.02, 1.29)]. Those who "gained" BMD (0% to 4%) during treatment had a reduction in risk of 51% [OR=0.49 (0.30, 0.78)]. Similarly, women who "lost" total hip BMD (0% to 4%) during the first year on alendronate had a 53% decreased risk of vertebral fracture compared to their controls taking placebo [OR=0.47 (0.27, 0.81)], whereas those "gaining" BMD (0% to 4%) had a comparable risk reduction [OR=0.49 (0.34, 0.71)]. This was not observed for the few women who lost more than 4% [OR=0.61 (0.11, 3.45)]. Patients who lost BMD at both the hip and spine were not protected by alendronate. Among patients who adhere to treatment with alendronate, even those who lose BMD benefit from a substantial reduction in risk of vertebral fracture. So, the reduction in bone turnover induced by alendronate might be more important than BMD changes. The few women who lose the most BMD (more than 4% per year) might not benefit from the treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15580479&dopt=Abstract alendronate Fosamax