alendronate, Fosamax
Alendronate inhibits intraperitoneal dissemination in in vivo ovarian cancer model.

Hashimoto K, Morishige K, Sawada K, Tahara M, Kawagishi R, Ikebuchi Y, Sakata M, Tasaka K, Murata Y.

Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan.

Ovarian cancer is characterized by diffuse peritoneal carcinomatosis and often by large volumes of ascites. We previously reported that alendronate, a nitrogen-containing bisphosphonate, inhibited ovarian cancer cell migration by attenuating the activation of Rho through inhibiting the mevalonate pathway. However, questions remain about the ability of alendronate to inhibit the invasiveness of cancer cells to the adherent tissues and the growth of disseminated ovarian cancer in vivo. We established an in vivo ovarian cancer model with i.p. carcinomatosis in athymic immunodeficient mice. In the prevention model, in which alendronate administration started from the day after tumor inoculation, alendronate prevented the stromal invasion, reduced the tumor burden, and inhibited ascites accumulation. Histologic observation revealed that alendronate treatment decreased the stromal invasion of the i.p. tumor while inhibiting the metalloproteinase-2 activity in ascites. This antitumor effect might result from the inhibition of cancer cell migration and proteolytic activity. In the treatment model, in which alendronate was given from 10 days after tumor inoculation when macroscopic tumors are already implanted in the peritoneum, the antitumor effect was weaker but still significant. Furthermore, alendronate administration decreased the serum CA-125 levels of mice bearing disseminated ovarian cancer compared with those of nontreated mice. The potent effects of alendronate in reducing stromal invasion, tumor burden, and ascites suggest that it will be of value in regimens for treatment of women with ovarian cancer.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15695397&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Effect of alendronate on bone mineral density in spinal cord injury patients: a pilot study.

Moran de Brito CM, Battistella LR, Saito ET, Sakamoto H.

1Department of Rehabilitation Medicine of the University of Sao Paulo Hospital das Clinicas, Sao Paulo, Brazil.

STUDY DESIGN:: Prospective, randomised controlled trial. OBJECTIVE:: To evaluate the effect of alendronate on bone mineral density in chronic spinal cord injury (SCI) patients. SETTING:: University-based rehabilitation centre in Sao Paulo, Brazil. METHODS:: A total of 19 chronic SCI patients were evaluated, divided into a control group and an experimental group. Control group patients received 1000 mg of calcium daily, and experimental group patients received 1000 mg of calcium plus 10 mg of alendronate daily. The study duration was 6 months. In all, 12 densitometric parameters were analysed using whole-body dual-energy X-ray absorptiometry at baseline and after 6 months. RESULTS:: The experimental group presented increases in nine densitometric parameters, although statistical significance was attained in only two of those parameters. In the control group, an increase was observed in only one parameter, whereas the remaining 11 presented either no alteration or a decrease. CONCLUSION:: The use of alendronate had a positive effect on bone mineral density in SCI patients and therefore represents a potential tool for prevention and treatment of osteoporosis in this population.Spinal Cord advance online publication, 8 February 2005; doi:10.1038/sj.sc.3101725.

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alendronate, Fosamax
Alendronate in the treatment of low bone mass in steroid-treated boys with Duchennes muscular dystrophy.

Hawker GA, Ridout R, Harris VA, Chase CC, Fielding LJ, Biggar WD.

Abstract Hawker GA, Ridout R, Harris VA, Chase CC, Fielding LJ, Biggar WD. Alendronate in the treatment of low bone mass in steroid-treated boys with Duchennes muscular dystrophy. Objective To examine alendronates side-effect profile and effect on bone mineral density (BMD) in deflazacort-treated boys with Duchennes muscular dystrophy (DMD) and low BMD. Design Before-after trial. Setting Neuromuscular clinic at a childrens hospital in Canada between 1999 and 2000. Participants All consenting boys with DMD who had z scores less than -1.00 (spine and/or total body) and in whom BMD testing was feasible. Intervention Boys received .08mg.kg -1 .d -1 of alendronate orally, with 750mg of daily calcium and 1000IU of vitamin D. BMD, height, weight, physical activity, Tanner stage, and adverse effects were followed for 2 years. Main outcome measures BMD z scores at the lumbar spine (L1-4) and total body. Results Of the 42 eligible boys assessed, 23 had low BMD; for 16 of the 23, future BMD testing was feasible. Mean age was 10.8 years (range, 6.9-15.6y). Mean baseline z scores at the total body and spine were -0.80 and -1.94, respectively. At 2 years, mean z scores were unchanged. Furthermore, alendronate response varied by baseline age. In multivariable analysis, improvement in total body and spine z scores was associated with younger age at baseline ( P =.01 for both). Conclusions In deflazacort-treated boys, alendronate had a positive effect on BMD z scores; the effect was greatest when given early in the course of disease.

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alendronate, Fosamax
Response to therapy with once-weekly alendronate 70 mg compared to once-weekly risedronate 35 mg in the treatment of postmenopausal osteoporosis.

Sebba AI, Bonnick SL, Kagan R, Thompson DE, Skalky CS, Chen E, de Papp AE; Fosamax Actonel Comparison Trial investigators.

Arthritis Associates, Palm Harbor, FL 34684, USA. asebba tampabay.rr.com

OBJECTIVE: The FACT study (Fosamax Actonel Comparison Trial) was a 1-year-head-to-head trial comparing the efficacy and tolerability of once weekly (DW) alendronate 70 mg and OW risedronate 35 mg for the treatment of postmenopausal osteoporosis. The present analysis was performed to determine the percentage of patients who had changes during the study in BMD and biochemical markers (BCMs) of bone turnover above or below specific cut-off points. A subgroup analysis of upper gastrointestinal (UGI) tolerability was also performed. RESEARCH DESIGN AND METHODS: 1053 postmenopausal women with low BMD were randomized to alendronate 70 mg OW (N = 520) or risedronate 35 mg OW (N = 533). The percentage of patients who had measured BMD gains > or = 3%, and > or = 5% after 12 months at the hip trochanter, total hip, femoral neck, and lumbar spine (LS) was analyzed. The percentage of patients who experienced any bone loss, and those with measured losses of 3% or more at these sites after 12 months, was determined. The percentage of patients achieving reductions in urinary N-telopeptide of type 1 human collagen (NTX) > or = 40%, and serum C-telopeptide of type 1 collagen (CTx) > or = 60%, bone-specific phosphatase (BSAP) > or = 30%, and N terminal propeptide of type 1 procollagen (P1NP) > or = 50% at 3 months and 12 months was also determined. Tolerability, based on adverse experience reporting, was evaluated in a subgroup of patients with history of UGI disorders at baseline. RESULTS: A greater percentage of alendronate- than risedronate-treated patients had measured BMD gains (> or = 0%) (p < 0.05) at all sites at 12 months. Significantly more (p < 0.01) alendronate- than risedronate-treated patients had measured gains in BMD > or = 3% and > or = 5% at the hip trochanter, total hip, and LS spine. Significantly more (p < 0.05) risedronate- than alendronate-treated patients had an apparent loss of BMD (> 0% and > or = 3% loss) at the same sites. After 3 months, significantly (p < 0.001) more alendronate- than risedronate- treated patients achieved predefined reductions in all BCMs. Similar tolerability was demonstrated in both treatment groups, regardless of whether or not patients had a history of UGI disorders at baseline. CONCLUSIONS: Significantly more alendronate- than risedronate-treated patients achieved predefined increases in BMD at 12 months and reductions in BCMs at 3 months. Significantly more risedronate- than alendronate-treated patients were classified as apparent 'non-responders' (i.e. experienced any bone loss) after 12 months of therapy. The tolerability profiles of the two medications were similar.

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alendronate, Fosamax
Suppression of viability and acetyl-LDL metabolism in RAW 264 macrophage-like and smooth muscle cells by bisphosphonates in vitro.

Tuominen OM, Hollmen M, Jaakkola O, Monkkonen J, Ylitalo R.

Department of Pharmacological Sciences, University of Tampere, Tampere, Finland.

Etidronate and clodronate are bisphosphonates that inhibit the development of experimental atherosclerosis. Etidronate decreases the intimamedia thickness of carotid artery even in man. Liposome-encapsulated bisphosphonates inhibit the cellular metabolism of atherogenic, modified low-density lipoprotein (acetyl-LDL) by cultured macrophages. In the present study, the effects of new bisphosphonate tiludronate and nitrogen-containing bisphosphonate alendronate on cell viability and cellular uptake and degradation of acetyl-LDL were investigated in vitro with macrophages and arterial smooth muscle cells, which have a significant role in atherogenesis. Tiludronate and alendronate decreased the viability of RAW 264 macrophages at high concentration (1,000 microM; p < 0.05), while liposome-encapsulated drugs suppressed the viability at concentrations of 30-300 microM. At concentrations greater than or equal to 10 microM, tiludronate and alendronate inhibited the uptake and degradation of acetyl-LDL by RAW 264 cells in a concentration-dependent manner (p < 0.001). None of the bisphosphonates affected the viability of smooth muscle cells, and none but alendronate at a high concentration (1,000 microM) inhibited the uptake and degradation of acetyl-LDL by smooth muscle cells. The results show that tiludronate and alendronate inhibit the atherogenic activity of macrophages in vitro, as shown previously with etidronate and clodronate, providing further evidence for the antiatherogenic effects of bisphosphonates.

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alendronate, Fosamax
Early Changes in Biochemical Markers of Bone Turnover are Associated with Long-term Changes in Bone Mineral Density in Elderly Women on Alendronate, Hormone Replacement Therapy, or Combination Therapy: A 3-Year, Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

Greenspan SL, Resnick NM, Parker RA.

Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh; Division of Geriatric Medicine, Department of Medicine, University of Pittsburgh; Center for Biostatistics in AIDS Research, Harvard School of Public Health.

Elderly women on combination therapy with alendronate and hormone replacement for osteoporosis have greater gains in bone mass than those on monotherapy. It is not known if early changes in markers can predict the long-term changes in bone density with therapy. We assessed bone density and biochemical markers of bone turnover (urine N-telopeptide crosslinked collagen type 1 [NTx], serum bone-specific alkaline phosphatase [BSAP], and osteocalcin) every 6 months for 3 yr in a double-blind, placebo-controlled, randomized clinical trial. Following a 3-month run-in phase, 373 community-dwelling, elderly women were randomized to 1) alendronate, 2) hormone replacement therapy, 3) combination therapy with alendronate and hormone replacement therapy, or 4) placebo. Women on active treatment with the greatest decrease in markers of bone turnover at 6 months had the greatest increases in spine and hip bone density at 3 yr. The response to alendronate was generally associated with greater reductions in markers than the response to hormone replacement, and was associated with greater increases in bone density at the spine and hip. Those in the tertile with the greatest decrease in urinary NTx had a 10.1% increase in spine bone density and a 6.1% increase in hip bone density compared with those in the lowest tertile, who had a 5.9% increase in spine bone density and a 2.1% increase in hip bone density. In women on active treatment, the area under the receiver operator curve for a 6-month change in markers to predict a response in BMD at 3 yr was highest for urine NTx (range 75-78%) and lowest for osteocalcin (range 60-66%). We conclude that short-term changes in biochemical markers of bone turnover at 6 months predict bone density changes at the spine and hip at 3 yr in elderly women on alendronate, hormone replacement therapy, or combination therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15713726&dopt=Abstract alendronate Fosamax