alendronate, Fosamax
Gastroprotective effect of leukotriene receptor blocker montelukast in alendronat-induced lesions of the rat gastric mucosa.

Sener G, Kapucu C, Cetinel S, Cikler E, Ayanoglu-Dulger G.

Department of Pharmacology, School of Pharmacy, Marmara University, Istanbul, Turkey. gokselsener hotmail.com

Alendronate causes serious gastrointestinal adverse effects. We aimed to investigate if montelukast, a leukotriene receptor antagonist, is protective against this damage. Rats were administered 20 mg/kg alendronate by gavage for 4 days, either alone or following treatment with montelukast (10 mg/kg). On the last day, following drug administration, pilor ligation was performed and 2 h later, rats were killed and stomach, liver and kidney tissues were removed. Gastric acidity, gastric tissue ulcer index values and malondialdehyde (MDA); an end product of lipid peroxidation, and glutathione (GSH) levels; a key antioxidant, as well as myeloperoxidase (MPO) activity; an indirect marker of tissue neutrophil infiltration were determined, and the histologic appearance of the stomach, liver and kidney tissues were studied. Chronic oral administration of alendronate induced significant gastric damage, increasing myeloperoxidase activity and lipid peroxidation, while tissue glutathione levels decreased. Similarly, in the alendronate group MDA levels and MPO activities of liver and kidney tissues were increased and GSH levels were decreased. Treatment with montelukast prevented the damage as well as the changes in biochemical parameters in all tissues studied. Findings of the present study suggest that alendronate is a local irritant that causes inflammation through neutrophil infiltration and oxidative damage in tissues, and that montelukast is protective against this damage by its anti-inflammatory effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15589394&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Acetylator phenotyping in patients with malignant lymphomas, using caffeine as the metabolic probe.

Pytlik M, Kaczmarczyk-Sedlak I, Rliwinski L, Janiec W, Rymkiewicz I.

Department of Pharmacology, Silesian Medical University, Jagiellonska 4, PL 41-200 Sosnowiec, Poland.

Retinol is a commonly used vitamin, especially by elderly people. Alendronate sodium, an aminobisphosphonate, is a potent antiresorptive drug used in the treatment of osteoporosis in postmenopausal women. Frequently, alendronate sodium and retinol are used concurrently. There are no reports on the interaction between alendronate sodium and retinol. The aim of the present study was to investigate the effect of concurrent administration of alendronate sodium and retinol on bone remodeling in ovariectomized rats. The histomorphometric parameters of long bones were studied. The experiments were carried out on 3-month-old Wistar rats, divided into 7 groups: I (C) - sham operated control rats, II (OVX) - ovariectomized control rats, III (OVX + ALN) - ovariectomized rats + alendronate sodium (3 mg/kg po), IV (OVX + R-1) - ovariectomized rats + retinol (700 IU/kg po), V (OVX + R-2) - ovariectomized rats + retinol (3500 IU/kg po), VI (OVX + ALN + R-1) - ovariectomized rats + alendronate sodium (3 mg/kg po) + retinol (700 IU/kg po), VII (OVX + ALN + R-2) - ovariectomized rats + alendronate sodium (3 mg/kg po) + retinol (3500 IU/kg po). The drugs were administered to the rats daily by oral gavage (alendronate sodium in the morning, retinol in the afternoon) for 28 days. Body mass gain, bone mass, mineral content in the tibia, femur and L-4 vertebra, histomorphometric parameters of the right tibia (width of osteoid, periosteal and endosteal transverse growth, area of the transverse cross section of the bone marrow cavity and the cortical bone) and the right femur (width of epiphyseal and metaphyseal trabeculae, width of epiphyseal cartilage) were studied. Bilateral ovariectomy induced osteopenic skeletal changes in mature female rats. Alendronate sodium administered at a dose of 3 mg/kg po daily inhibited the development of changes induced by ovariectomy in the skeletal system of rats. Retinol, especially administered at the dose of 3500 IU/kg daily, intensified the changes in the osseous system caused by estrogen deficiency in rats. Retinol administered concurrently with alendronate sodium attenuated the antiresorptive effect of alendronate sodium on the skeletal system in ovariectomized rats.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15591645&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
SEVERELY SUPPRESSED BONE TURNOVER: A POTENTIAL COMPLICATION OF ALENDRONATE THERAPY.

Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY.

Clarita V. Odvina Center for Mineral Metabolism and Clinical Research and Division of Orthopedic Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8885; and Division of Bone and Mineral Metabolism, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202.

Alendronate, an inhibitor of bone resorption, is widely used in osteoporosis treatment. However, concerns have been raised about potential oversuppression of bone turnover during long-term use. We report on 9 patients who sustained spontaneous non-spinal fractures while on alendronate therapy, six of whom displayed either delayed or absent fracture healing for 3 months-2 yr during therapy. Histomorphometric analysis of the cancellous bone showed markedly suppressed bone formation, with reduced or absent osteoblastic surface in most patients. Osteoclastic surface was low or low normal in 8 patients and eroded surface was decreased in 4. Matrix synthesis was markedly diminished with absence of double-tetracycline label and absent or reduced single-tetracycline label in all patients. The same trend was seen in the intracortical and endocortical surfaces. Our findings raise the possibility that severe suppression of bone turnover may develop during long-term alendronate therapy, resulting in increased susceptibility to, and delayed healing of non-spinal fractures. Although co-adminstration of estrogen or glucocorticoids appears to be predisposing factors, this apparent complication can also occur with monotherapy. Our observations emphasize the need for increased awareness and monitoring for the potential development of excessive suppression of bone turnover during long-term alendronate therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15598694&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Comparison of zinc excretion and biochemical markers of bone remodelling in the assessment of the effects of alendronate and calcitonin on bone in postmenopausal osteoporosis.

Gur A, Colpan L, Cevik R, Nas K, Jale Sarac A.

Department of Physical Medicine and Rehabilitation, Medical Faculty of Dicle University, Diyarbakir, Turkey. alig dicle.edu.tr

OBJECTIVES: The aim of this study was to determinate the clinical usefulness of urinary bone resorption markers, urinary zinc excretion, and other biochemical markers in postmenopausal women with osteoporosis. We also evaluated the effects of alendronate and calcitonin therapies on biochemical markers of bone remodeling and urinary zinc excretion over a 6-month period. SUBJECTS AND METHODS: The study design was a randomized placebo controlled study. The patients were randomly assigned to receive alendronate (10 mg/day; 45 patients) or calcitonin (200 IU/day; 45 patients) or placebo (45 patients) for 6 months. All patients received supplemental calcium (1000 mg/day). To assess bone resorption, we measured excretion of cross-linked N-telopeptides of Type I collagen (uNTx); urinary zinc concentrations and standard chemistry determinations were also measured; and osteocalcin (sOC) was measured as a marker of bone formation. All parameters were measured before therapy and again after 1, 3, and 6 months in all groups. RESULTS: A statistically significant decrease occurred in the levels of sOC, uZn, and uNTx after 3 and 6 months in patients receiving calcitonin therapy (P < 0.05). sOC, uZn, and uNTx levels in the calcitonin group were significantly lower after three and 6 months from both placebo and baseline values of calcitonin group. In the alendronate group, a statistically significant decrease was observed in the levels of uNTx and uZn after 1 month and in the sOC, uZn, and uNTx after 3 and 6 months from both placebo and baseline values of alendronate group (P < 0.05). uNTx, sOC, and uZn decreased about 44%, 36%, and 33%, respectively, in the calcitonin group and about 53%, 51%, and 38%, respectively, in the alendronate group below baseline values 6 months after initiating treatment. In the placebo group, there was no significant decrease in sOC, uZn, and uNTx during the course of the study. CONCLUSION: Our study suggests that in postmenopausal women with osteoporosis, both alendronate and calcitonin reduce the concentrations of uNTx, uZn, and sOC, the effect of the alendronate dose administered being significantly earlier and more pronounced. Measurement of uNTx, uZn, and sOC might be a useful biochemical method of observing the positive clinical effect following alendronate or calcitonin therapy in postmenopausal women.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15607319&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Treatment with once-weekly alendronate 70 mg compared with once-weekly risedronate 35 mg in women with postmenopausal osteoporosis: a randomized double-blind study.

Rosen CJ, Hochberg MC, Bonnick SL, McClung M, Miller P, Broy S, Kagan R, Chen E, Petruschke RA, Thompson DE, de Papp AE; Fosamax Actonel Comparison Trial Investigators.

Maine Center of Osteoporosis Research and Education and St Joseph Hospital, Bangor, Maine 04401, USA.

Once-weekly alendronate 70 mg and once-weekly risedronate 35 mg are indicated for the treatment of postmenopausal osteoporosis. These two agents were compared in a 12-month head-to-head trial. Greater gains in BMD and greater reductions in markers of bone turnover were seen with alendronate compared with risedronate with similar tolerability. INTRODUCTION: The nitrogen-containing bisphosphonates, alendronate and risedronate, are available in once-weekly (OW) formulations for the treatment of postmenopausal osteoporosis. A 12-month, head-to-head study was performed to compare these agents in the treatment of postmenopausal women with low BMD. MATERIALS AND METHODS: A total of 1053 patients from 78 U.S. sites were randomized to OW alendronate 70 mg (N = 520) or risedronate 35 mg (N = 533), taken in the morning after fasting. Endpoints included BMD changes over 6 and 12 months at the hip trochanter, total hip, femoral neck, and lumbar spine (LS); percent of patients with predefined levels of change in trochanter and LS BMD at 12 months; and change in biochemical markers of bone turnover at 3, 6, and 12 months. Tolerability was evaluated by adverse experience (AE) reporting. RESULTS: Significantly greater increases in hip trochanter BMD were seen with alendronate (3.4%) than risedronate (2.1%) at 12 months (treatment difference, 1.4%; p < 0.001) as well as 6 months (treatment difference, 1.3%; p < 0.001). Significantly greater gains in BMD were seen with alendronate at all BMD sites measured (12-month difference: total hip, 1.0%; femoral neck, 0.7%; LS, 1.2%). Significant differences were seen as early as 6 months at all sites. A greater percentage of patients had > or =0% (p < 0.001) and > or =3% (p < 0.01) gain in trochanter and spine BMD at 12 months with alendronate than risedronate. Significantly greater (p < 0.001) reductions in all biochemical markers of bone turnover occurred with alendronate compared with risedronate by 3 months. No significant differences were seen between treatment groups in the incidence of upper gastrointestinal AEs or AEs causing discontinuation. CONCLUSIONS: In this 12-month, head-to-head trial of alendronate and risedronate, given in accordance with the approved OW regimens for treatment of osteoporosis in postmenopausal women, alendronate produced greater gains in BMD and greater reductions in markers of bone turnover than risedronate. The greater antiresorptive effect of alendronate was seen as early as 3 months, and the tolerability profiles were similar.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15619680&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Effects of combined systemic administration of low-dose doxycycline and alendronate on endotoxin-induced periodontitis in rats.

Buduneli E, Vardar S, Buduneli N, Berdeli AH, Turkoglu O, Baskesen A, Atilla G.

Ege University, School of Dentistry, Department of Periodontology, Izmir, Turkey. eralp bornova.ege.edu.tr

BACKGROUND: Doxycycline has been widely used in periodontal treatment for its antimicrobial and anti-enzymatic effects. Recently, bisphosphonates have been shown to inhibit alveolar bone resorption. The aim of the present study was to evaluate the effects of doxycycline and the bisphosphonate alendronate on the gingival tissue levels of prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), leukotriene B4 (LTB4), and platelet-activating factor (PAF) in endotoxin-induced periodontal breakdown in rats. METHODS: Experimental periodontitis was induced by repeated injection of Escherichia coli endotoxin (LPS) and 44 adult male Sprague-Dawley rats were divided into five study groups as follows: LPS, doxycycline + LPS, alendronate + LPS, doxycycline + alendronate + LPS, and saline control. Doxycycline and alendronate were given either as a single agent or as a combination therapy during the 7-day study period. At the end of the 1-week protocol, the rats were sacrificed, the gingival tissues were dissected and extracted, and the extracts were analyzed for PGE2, PGF2alpha, LTB4, and PAF levels. The defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by using parametric tests. RESULTS: Alveolar bone loss measurements revealed significantly higher values in LPS, doxycycline + LPS, alendronate + LPS, and doxycycline + alendronate + LPS groups in comparison to the saline control group (P <0.05). Combined administration of doxycycline and alendronate exhibited the most prominent inhibition on gingival tissue levels of PGE2 and PGF2alpha (P<0.05). Doxycycline + alendronate + LPS group also significantly reduced LTB4 and PAF levels, although doxycycline provided the most reduction in the levels of these mediators (P <0.05). CONCLUSIONS: Alendronate and/or doxycycline may provide significant inhibition of the major inflammatory mediators of periodontal tissue destruction, and combined administration of these agents may provide beneficial effects in periodontal treatment. However, this hypothesis must be further verified by clinical human trials before introducing its use in dental practice.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15633329&dopt=Abstract alendronate Fosamax