alendronate, Fosamax
The effect of alendronate in the treatment of postmenopausal osteoporosis.

Rozkydal Z, Janicek P.

Ist Orthopaedic Department, St. Anna's Hospital, Masarykiensis University, Brno, Czech Republic. zrozkyd med.muni.cz

OBJECTIVES: The aim of the study was the evaluation of the effect of alendronate in the treatment of postmenopausal osteoporosis on subjective criteria and on bone mineral density after two years. MATERIAL AND METHODS: The authors collected data from 44 women by questionaire and analysed the data from DEXA examination. The patients were given Fosamax 10 mg and calcium 500 mg per day in the years 2001-2002. RESULTS: The compliance of alendronate was good in 42 women (95.5%). 15 patients were very satisfied with the treatment, 22 were satisfied and 5 patients claimed no improvement at the end of the study. A positive effect of the treatment was seen in 37 patients (88.1%). 21 patients claimed to have no pain and 15 patients suffered mild intermitent pain at the end of the study. 24 patients used no analgetics and 9 patients used them irregularly. 11 patients claimed to have normal activity and 22 patients had mildly diminished activity in daily life. The authors encountered no symptomatic vertebral or nonvertebral fracture during the study. The mean BMD in the lumbar spine improved in T score by 0.38 SD after one year and 0.35 SD after the second year. The mean BMD has improved in the neck region in T score by 0.21 SD after the first year and 0.21 SD after the second year. The mean BMD in lumbar spine has improved in Z score by 0.31 SD after one year and 0.02 SD after the second year. The mean BMD in the neck region has improved in Z score by 0.31 SD after the first year and 0.16 SD after the second year. The mean change of bone mineral density in lumbar spine was +4.17% after the first years and +4.19% after the second year. The mean change of BMD in the femoral neck region was +4.46% after the first years and + 3.71% after the second year. According to student t-test all the data of increased BMD were statisticaly significant at the 5% level of the significance (p < 0.05). CONCLUSION: Alendronate therapy significantly reduced the pain and the need for analgesics. It improved the daily activity and mobility of the spine in the patients with postmenopausal osteoporosis. It resulted in a positive change of BMD in vertebral region of +8.36% and +8.17% in the femoral neck region after two years. The fracture risk in vertebral region was diminished by 31% and in the femoral neck region by 38% at the end of the study. (Tab. 11, Ref. 14.).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15055730&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Alendronate inhibits urinary calcium microlith formation in a three-dimensional culture model.

Senzaki H, Yasui T, Okada A, Ito Y, Tozawa K, Kohri K.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.

Osteoporosis is associated with the pathogenesis of urinary stone formation. Urinary stones are similar to bone diseases such as osteoporosis and bone metabolism in terms of pathogenesis. Bisphosphonates are potent inhibitors of bone resorption, and are used in the management of bone disease. Furthermore, bisphosphonates have a strong affinity for calcium, and a reported inhibitory effect on calcium oxalate crystallization in vitro. Thus, bisphosphonates might also inhibit urinary stone formation. Madin-Darby canine kidney (MDCK) cells form calcium phosphate microliths at the basolateral side in vitro. We investigated the inhibitory effects of new generation bisphosphonates (alendronate and incadronate) on calcium phosphate microlith formation and on the expression of osteopontin, which is an important urinary stone matrix. MDCK cells formed two types of colonies in three-dimensional soft agar culture; dark colonies containing calcium phosphate microliths and clear colonies free from microliths. We applied purified alendronate and incadronate at concentrations of 10(-11), 10(-9), 10(-7) and 10(-5) M to MDCK cells cultured in three-dimensional soft agar and investigated the efficiency of colony formation and the dark colony ratio (number of dark colonies relative to the total number of colonies). The administration of 10(-9) and 10(-7) M alendronate decreased the dark colony ratio compared with controls, whereas incadronate did not significantly alter this colony ratio compared with controls. The expression of osteopontin in cultured cells was inhibited by the 10(-7) M alendronate administration. The present findings show that alendronate inhibits calcium stone formation, suggesting that it is effective in the prevention of urolithiasis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15064876&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Effects of clodronate and alendronate on local and systemic changes in bone metabolism in rats with adjuvant arthritis.

Itoh F, Aoyagi S, Kusama H, Kojima M, Kogo H.

Department of Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan. fumiaki_ito pharm.kissei.co.jp

We compared the effects of nonaminobisphosphonate (nonamino-BP; clodronate) and amino-BP (alendronate) on the changes in local and systemic bone metabolism associated with chronic inflammation in adjuvant-arthritis rats. A given rat received one of the BPs orally each day for 28 days from the day of adjuvant inoculation. Hindpaw swelling was observed from day 10 after adjuvant inoculation up to day 28 (peak, day 21). Clodronate slightly decreased the hindpaw swelling at doses of 12.5 and 25 mg/kg, p.o./day; however, alendronate (0.125-0.5 mg/kg) did not. Radiological examination of the distal limb joints revealed that only clodronate decreased bone deformation. Urinary deoxypyridinoline increased as arthritis developed, and it was decreased by clodronate. On day 29, pQCT analysis of the 5th lumbar vertebra revealed trabecular bone loss and cortical bone thinning in the arthritis control group, leading to compressive strength being reduced. Both BPs prevented this bone loss and strength reduction. These data suggest that only clodronate decreases inflammation and local bone deformation, while both BPs inhibit the arthritis-related decreases in systemic bone mass and bone strength. Clodronate would be useful in the treatment of inflammation-induced bone deformation and osteopenia.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15072226&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Mucosal irritative and healing impairment action of risedronate in rat stomachs: comparison with alendronate.

Kanatsu K, Aihara E, Okayama M, Kato S, Takeuchi K.

Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607, Japan.

BACKGROUND AND AIM: We used alendronate and risedronate as bisphosphonates and examined whether or not these agents have a mucosal irritative action in the stomach and impair the healing of pre-existing gastric ulcers in rats. METHODS: Male Sprague Dawley (SD) rats were used in the following two studies: (i) the effects of risedronate and alendronate on gastric potential difference (PD), gastric mucosal blood flow (GMBF) and acid back-diffusion in the stomach mounted on ex vivo chamber under urethane anesthesia and; (ii) the influence of daily treatment with these drugs on the healing of acetic acid-induced gastric ulcers was examined. RESULTS: Mucosal application of risedronate produced PD reduction in the saline-perfused stomachs in a dose-dependent manner. Alendronate also produced a marked PD reduction, the effect being more potent than that of risedronate. In the stomach exposed to acid (100 mM HCl), both drugs produced a marked reduction in PD, followed by acid back-diffusion and a small increase in GMBF, resulting in hemorrhagic lesions, and the effects again were more pronounced with alendronate. These irritative effects were dependent on the pH of drug solution and the action was more potent at pH 7 than pH 4. Conversely, the healing of acetic acid-induced gastric ulcers was significantly delayed by daily administration of these drugs, yet this effect was less pronounced in the case of risedronate. The healing impairing effect of these bisphosphonates was potentiated by coadministration of indomethacin. CONCLUSION: Both alendronate and risedronate have mucosal irritative and healing impairing effects in the stomach, yet the effect of risedronate was much less pronounced compared to alendronate. It is assumed that risedronate is safer than alendronate as the antiresorptive agent in patients with diseases related to bone remodeling.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15086594&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
[Comparison of early bone histomorphometric effects of parathormone and alendronate in osteoporotic women]

[Article in French]

Arlot M, Roux JP, Portero N, Boivin G, Meunier PJ.

INSERM U 403, Laboratoire d'histodynamique Faculte Laennec Rue Paradin F-69008 Lyon. arlot laennec.univ-lyon1.fr

Alendronate and teparatide, recombinant human PTH (1-34) are available treatment for osteoporosis in postmenopausal women. They act through opposite mechanisms of action. Alendronate reduces the remodeling of bone and thus increases secondary mineralization without any change in the amount of bone. Teriparatide, 20 micrograms/day, a bone forming agent would increase the amount of bone through two mechanisms, modeling--formation without resorption, and remodeling--resorption then formation with formation higher than resorption. Theses effects are present at the sixth month.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15095621&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Efficacy of intermittent low dose alendronate in Thai postmenopausal osteoporosis.

Chailurkit LO, Aunphongpuwanart S, Ongphiphadhanakul B, Jongjaroenprasert W, Sae-tung S, Rajatanavin R.

Division of Endocrinology and Metabolism, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. ralcl mahidol.ac.th

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.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15098917&dopt=Abstract alendronate Fosamax