alendronate, Fosamax
The influence of alendronate on bone formation after autogenous free bone grafting in rats.

Altundal H, Gursoy B.

Objective This study was undertaken to investigate the influence of alendronate on bone formation after autogenous free bone grafting in rats. Study design Fifty-six male Wistar-Albino rats were divided into 3 groups: baseline, saline-treated, and alendronate-treated groups, and followed up at 2, 4, and 12 weeks. In the femur of the rats, autogenous free bone grafts 3 mm in diameter and 2 mm in length were harvested with a standard trephine bur. The bone defects 3 mm in diameter and 2 mm in length were created 5 mm from the donor sites. Each graft was placed in the bone defect and stabilized by perifemoral wiring. The alendronate-treated rats were administered 0.25 mg/kg alendronate subcutaneously daily. The saline-treated rats were given daily saline solution. Serum calcium, phosphate, parathyroid hormone, 1,25-dihydroxyvitamin D, bone alkaline phosphatase (BAP), osteocalcin, and urine calcium were measured. The changes in the number of osteoblasts bordering active bone formation surface and osteoid and lamellar bone formation were evaluated to measure anabolic bone activity. Results Alendronate caused significant increase in serum osteocalcin and BAP levels biochemically and the number of osteoblasts histopathologically. Conclusion Alendronate may be considered among therapeutic options to improve bone formation process in different bone remodeling cases. Further detailed studies should be focused on dosage- and time-dependent effects of alendronate on bone formation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15716833&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Reversal of HIV-1-associated osteoporosis with once-weekly alendronate.

Negredo E, Martinez-Lopez E, Paredes R, Rosales J, Perez-Alvarez N, Holgado S, Gel S, Rio LD, Tena X, Rey-Joly C, Clotet B.

aLluita contra la SIDA Foundation bClinical Nutrition Unit cRheumatology dInternal Medicine, Germans Trias i Pujol University Hospital, Badalona, Barcelona, Spain eCETIR Centre Medic, Barcelona, Spain.

HIV-1-infected patients with osteoporosis were randomly assigned to alendronate 70 mg once-weekly plus dietary counselling (n = 11) or diet counselling alone (n = 14). At week 96, 27% of patients on alendronate versus 96% of controls presented with osteoporosis. Spine bone mineral density (BMD) increases were detected at week 48, and progressed thereafter. Improvements in trochanter BMD were obtained after 2 years. Once-weekly oral alendronate may be an effective and safe treatment for HIV-1-associated osteoporosis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15718847&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
A systematic review of the effect of alendronate on bone mineral density in men.

Sawka AM, Thabane L, Papaioannou A, Gafni A, Hanley DA, Adachi JD.

McMaster University, Hamilton, Ontario, Canada L8N 1Y2; and St. Joseph's Healthcare, Hamilton, Ontario, Canada L8N1Y2.

Alendronate is known to increase bone mineral density (BMD) at the lumbar spine and hip in women, but less information is available in men. We conducted a systematic review of randomized controlled trials to determine whether oral alendronate improves BMD at the lumbar spine and hip in men with low bone mass or prevalent fractures, compared with men treated with placebo, calcium, or vitamin D. In three trials in men, BMD (measured by dual-energy X-ray absorptiometry) increased at 2-3 yr (compared to baseline) at the lumbar spine and femoral neck in alendronate-treated patients compared to controls. The pooled estimates of changes in BMD with 10 mg of alendronate daily compared to controls were as follows: 7.8% over 2-3 yr (95% confidence interval [CI] = 4.8- 10.8) at the lumbar spine and 3.8% (95% CI = 2.3-5.3) at the femoral neck (p < 0.001 for treatment effect in each analysis). Statistically significant heterogeneity of treatment effect was noted between trials. We conclude that 10 mg of oral daily alendronate is significantly associated with increase in BMD at the lumbar spine and hip in men over 2-3 yr and that these changes are similar to those previously observed in postmenopausal women.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15722581&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Upper gastrointestinal tolerability of once weekly alendronate 70 mg with concomitant non-steroidal anti-inflammatory drug use.

Cryer B, Miller P, Petruschke RA, Chen E, Geba GP, Papp AE.

Department of Medicine, University of Texas Southwestern Medical School, Dallas, TX, USA.

Summary Background : Both oral bisphosphonates and non-steroidal anti-inflammatory drugs have the potential to irritate the upper gastrointestinal mucosa, and are frequently used by the same patient population. Aim : To determine the rate of upper gastrointestinal adverse events with once weekly alendronate 70 mg and concomitant non-steroidal anti-inflammatory drug use. Methods : A post hoc analysis was performed on 222 patients who received both medications concomitantly during a 3-month placebo-controlled study. A total of 450 (224 alendronate; 226 placebo) postmenopausal women and men with osteoporosis were randomized. Concomitant non-steroidal anti-inflammatory drug users were defined as patients who received >/=7 continuous days of any dose of a dual cyclo-oxygenase-1 and cyclo-oxygenase-2 inhibiting non-steroidal anti-inflammatory drug, a selective cyclo-oxygenase-2 inhibitor, or aspirin. A survival analysis was performed, and significance assessed. Logistic regression was used to assess consistency of treatment effect on rate of upper gastrointestinal adverse events across non-steroidal anti-inflammatory drug subgroups. Results : Similar percentages of alendronate (52.7%) and placebo (46.0%) patients used non-steroidal anti-inflammatory drugs regularly. Among concomitant non-steroidal anti-inflammatory drug users, 11 alendronate and 11 placebo patients experienced upper gastrointestinal adverse events (9.3% and 10.8%, respectively, P = 0.744). Logistic regression revealed no significant interaction (P = 0.722) between alendronate and concomitant non-steroidal anti-inflammatory drug use. Conclusion : Based on this subgroup analysis, once weekly alendronate 70 mg used concomitantly with non-steroidal anti-inflammatory drugs, did not increase upper gastrointestinal adverse events relative to placebo over 3-months.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15740544&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Reversibility of alendronate-induced contraction in human osteoclast-like cells formed from bone marrow cells in culture.

Koshihara Y, Kodama S, Ishibashi H, Azuma Y, Ohta T, Karube S.

Department of Nutrition, Tokyo Metropolitan Institute of Gerontology, Japan.

Alendronate is a powerful therapeutic agent for the treatment of hypercalcemia in malignancy and osteoporosis and has recently been developed as a treatment for hypercalcemia of malignancy. In this study, time-lapse cinemicrography was used to investigate the effects of this agent on the morphology and the motility of human osteoclast-like multinucleated cells (MNCs) from human bone marrow. Alendronate at 10(-5)M induced contraction of the cells starting 7.5 h after its addition. Contraction was markedly induced immediately after alendronate removal. However, contraction almost disappeared 18h after removal, and osteoclast-like MNCs recovered their original sizes and shape. There was only partial recovery from contraction after alendronate treatment at 10(-4)M. In contrast, untreated control cells did not change their morphology after washing with culture medium. Motility analysis showed that osteoclast-like MNCs treated with 10(-5)M alendronate moved actively after washing, but at 10(-4)M the motility locus was very narrow. At 10(-4)M, the actin ring in the cells began to break down, beginning 6h after addition. The effects of alendronate on human osteoclast-like MNCs morphology and motility were reversible at 10(-5)M, suggesting that alendronate dose not cause any cellular damages in human osteoclasts up to 10(-5)M, which is an effective dose for bone resorption.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10340636&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Alendronate induces antinociception in mice, not related with its effects in bone.

Goicoechea C, Porras E, Alfaro MJ, Martin MI.

Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense de Madrid, Spain.

The antinociceptive effect of alendronate was studied. The bisphosphonate was i.p. administered and two tests were carried out: acetic acid in mice and formalin test in rats. In the acetic acid test, alendronate induced a dose-dependent antinociceptive effect that was statistically significant for the doses of 10, 20 and 40 mg/kg, and could be detected 48 hr after its administration. In the formalin test, however, alendronate, at the doses of 10 and 20 mg/kg, did not modify the pain score nor the number of flinches, when it was administered either 30 or 60 min before the test. However it must be noted that doses inducing analgesic effect are close to those inducing toxicity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10361882&dopt=Abstract alendronate Fosamax