alendronate, Fosamax
Monitoring response to osteoporosis therapy with alendronate by a multisite ultrasound device: a prospective study.

Weiss M, Koren-Michowitz M, Segal E, Ish-Shalom S.

Endocrine Institute, Assaf Harofeh Medical Center, Zerifin, Israel.

BACKGROUND: Osteoporotic fractures are a major health problem among postmenopausal women. A significant proportion of subjects with low bone density are currently undiagnosed. Peripheral devices can be used for osteoporosis diagnosis, but their role in long-term monitoring of skeletal changes is unclear. The current study evaluated the ability of quantitative ultrasound (QUS) measurements to follow osteoporotic subjects treated with alendronate. METHODS: QUS measurements were done with Sunlight Omnisense (Omnisense, Sunlight Medical Ltd., Tel Aviv, Israel), which determines the bone speed of sound (SOS) in several skeletal sites. Postmenopausal women with T-scores of -2 or less at one site were recruited and treated with alendronate for at least 1 yr. Follow-up was done with QUS and dual-energy X-ray absorptiometry (DXA) (Lunar DPX scanner, Madison, WI, USA) measurements. RESULTS: After 12 mo, bone mineral density (BMD) increased significantly at the lumbar spine (LS) (0.34 +/- 0.08 T-score, p = 0.0001 with 95% CI [0.19, 0.49]) and QUS at the tibia (TIB) (0.21 +/- 0.09 T-score, p = 0.02 with 95% CI [0.03, 0.39]). After 12 mo, a significant increase in mean T-scores was demonstrated in all sites assessed according to baseline T-score of -2 or less. CONCLUSIONS: Peripheral QUS measurement may be considered for follow-up on skeletal changes in response to alendronate treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14514990&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
[Simulation through the method of finite element of alendronate in a model of bone remodeling based on damage mechanics]

[Article in Spanish]

Zeman ME, Garcia JM, Doblare M.

Centro de Bioingenieria, Instituto de Materiales y Modelos Estructurales, Facultad de Ingenieria, Universidad Central de Venezuela, Caracas-Venezuela. avizem cantv.net

Mechanical loads are one of the main factors that affect bone remodelling process. This phenomenon is widely applied to the study of prosthetic replacement, for example hip prosthesis. Elderly people are the most common patient to receive a hip replacement surgery. Alendronate is a drug that is being used to increase bone mineral content in patients with poor bone quality. This work uses a mechanical model based on damage mechanics, which considers bone's porosity as the damage variable, a mechanical stimulus associated thermodynamically to this variable, a damage criterion and an evolution damage law. Our approach simulates the degree of mineralization changes as well as the decrease of BMU activation frequency due to Alendronate doses. The biological changes generated by the drug directly affect the damage's evolution law. As a first approach the two biological parameters to be modeled are the surface of remodelling as well as the degree of mineralization (ash fraction) of the bone. Results show a good correlation with experimental data from alendronate's treatments for short term simulations (1-2 years).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14515765&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Adherence to bisphosphonates and hormone replacement therapy in a tertiary care setting of patients in the CANDOO database.

Papaioannou A, Ioannidis G, Adachi JD, Sebaldt RJ, Ferko N, Puglia M, Brown J, Tenenhouse A, Olszynski WP, Boulos P, Hanley DA, Josse R, Murray TM, Petrie A, Goldsmith CH.

Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Therapies for osteoporosis must be taken for at least 1 year to be effective. The purpose of this study was to determine the difference in adherence to etidronate, alendronate and hormone replacement therapy in a group of patients seen at our tertiary care centres. The Canadian Database of Osteoporosis and Osteopenia (CANDOO), a prospective observational database designed to capture clinical data, was searched for patients who started therapy following entry into CANDOO. There were 1196 initiating etidronate, 477 alendronate and 294 hormone replacement therapy women and men aged (mean, SD) 65.8 (8.7) years in the study. A Cox proportional hazards regression model was used to assess differences between treatment groups in the time to discontinuation of therapy. Several potential covariates such as anthropometry, medications, illnesses, fractures and lifestyle factors were entered into the model. A forward selection technique was used to generate the final model. Hazard ratios and 95% confidence intervals (CI) were calculated. Adjusted results indicated that alendronate-treated patients were more likely to discontinue therapy as compared with etidronate-treated patients (1.404; 95% CI: 1.150, 1.714). After 1 year, 90.3% of patients were still taking etidronate compared with 77.6% for alendronate. No statistically significant differences were found between hormone replacement therapy and etidronate users (0.971; 95% CI: 0.862, 1.093) and hormone replacement therapy and alendronate users (0.824; 95% CI: 0.624, 1.088) after controlling for potential covariates. After 1 year, 80.1% of patients were still taking hormone replacement therapy, which decreased to 44.5% after 6 years. Increasing age and presence of incident non-vertebral fractures were found to be independent predictors of adherence. In conclusion, alendronate users were more likely to discontinue therapy than etidronate users over the follow-up period. Potential barriers to long-term patient adherence to osteoporosis therapies need to be evaluated.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14523610&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
A histopathological investigation on the effect of systemic administration of the bisphosphonate alendronate on resorptive phase following mucoperiosteal flap surgery in the rat mandible.

Kaynak D, Meffert R, Bostanci H, Gunhan O, Ozkaya OG.

Ankara University, Faculty of Dentistry, Department of Periodontology, Ankara, Turkey. denizkaynak06530 yahoo.com

BACKGROUND: The present study was designed to assess histopathologically whether the systemic administration of aminobisphosphonate (alendronate), 0.5 mg/kg body weight, is effective in preventing alveolar bone resorption following mucoperiosteal flap surgery, and whether alendronate modulates tissue factors. METHODS: The effect of alendronate on bone resorption was evaluated in mucoperiosteal flaps used as a resorptive model. The animals were given subcutaneous injections of either saline (control group) or 0.5 mg/kg of alendronate (experimental group). The alendronate or saline was administered subcutaneously 1 week prior to surgery, immediately prior to surgery, and 1 week after surgery. The parameters determined with a semiquantitative subjective method for histopathological evaluation were as follows: inflammatory cell infiltration (ICI) of adjacent periodontal tissue, degree of fibrosis and collagen bundle formation, number and morphology of osteoclasts of the alveolar bone and interdental septum, resorption lacunae (osteoclast surfaces), and osteoblastic activity (forming surfaces). RESULTS: There were no statistically significant differences between the saline and alendronate groups with regard to inflammatory cell infiltration, number of osteoclasts, and osteoblastic activity. Fibrosis and collagen bundle formation, osteoclast morphologies, and resorption lacunae formation were significantly different between the two groups, in favor of the alendronate group. CONCLUSIONS: The systemic administration of 0.5 mg/kg alendronate was effective in preventing alveolar bone loss and in modulating tissue factors. These findings indicate that alendronate would be a valuable addition to the therapeutic armamentarium available for the treatment of periodontal diseases, either alone or in combination with regenerative components such as anti-inflammatory drugs, bone graft materials, and guided tissue regeneration techniques, and even with dental implants.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14584869&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Liposomal alendronate inhibits systemic innate immunity and reduces in-stent neointimal hyperplasia in rabbits.

Danenberg HD, Golomb G, Groothuis A, Gao J, Epstein H, Swaminathan RV, Seifert P, Edelman ER.

Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Mass 02139, USA. danen mit.edu

BACKGROUND: Innate immunity is of major importance in vascular repair. The present study evaluated whether systemic and transient depletion of monocytes and macrophages with liposome-encapsulated bisphosphonates inhibits experimental in-stent neointimal formation. METHODS AND RESULTS: Rabbits fed on a hypercholesterolemic diet underwent bilateral iliac artery balloon denudation and stent deployment. Liposomal alendronate (3 or 6 mg/kg) was given concurrently with stenting. Monocyte counts were reduced by >90% 24 to 48 hours after a single injection of liposomal alendronate, returning to basal levels at 6 days. This treatment significantly reduced intimal area at 28 days, from 3.88+/-0.93 to 2.08+/-0.58 and 2.16+/-0.62 mm2. Lumen area was increased from 2.87+/-0.44 to 3.57+/-0.65 and 3.45+/-0.58 mm2, and arterial stenosis was reduced from 58+/-11% to 37+/-8% and 38+/-7% in controls, rabbits treated with 3 mg/kg, and rabbits treated with 6 mg/kg, respectively (mean+/-SD, n=8 rabbits/group, P<0.01 for all 3 parameters). No drug-related adverse effects were observed. Reduction in neointimal formation was associated with reduced arterial macrophage infiltration and proliferation at 6 days and with an equal reduction in intimal macrophage and smooth muscle cell content at 28 days after injury. Conversely, drug regimens ineffective in reducing monocyte levels did not inhibit neointimal formation. CONCLUSIONS: Systemic transient depletion of monocytes and macrophages, by a single liposomal bisphosphonates injection concurrent with injury, reduces in-stent neointimal formation and arterial stenosis in hypercholesterolemic rabbits.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14610008&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Modeling the annual costs of postmenopausal prevention therapy: raloxifene, alendronate, or estrogen-progestin therapy.

Mullins CD, Ohsfeldt RL.

University of Maryland School of Pharmacy, 515 W. Lombard St., Room 262, Baltimore, MD 21201-1563, USA. dmullins rx.umaryland.edu

OBJECTIVE: To estimate the annual cost and outcome impacts attributable to raloxifene, alendronate, and estrogen-progestin therapy as prevention therapies among postmenopausal women over the first 7 years of hormone replacement therapy (HRT). METHODS: A budget-impact model was devised to compare the costs, benefits, and costs per event avoided for various postmenopausal therapies (raloxifene, alendronate, or estrogen-progestin combination therapy), compared to no intervention, taking into account the persistency rates. Net costs are direct medical costs attributable to treatments relative to no intervention. Net benefits are defined as the number of events avoided as a result of therapy. The main outcome measures are annual total net costs, net benefits, and costs per event avoided compared to no intervention among postmenopausal white women with intact uteri and normal baseline risks for osteoporotic hip or vertebral fractures, fatal or nonfatal myocardial infarction, and breast cancer. Data and model assumptions are based on clinical trial data and published retrospective studies. RESULTS: The average annual net cost of therapy declines after the first year of therapy for all interventions, primarily due to discontinuation, and continues to decline over time due to savings in medical costs for events avoided. Net events avoided are greater for raloxifene than alendronate, but HRT use results in net harm. The cost per event avoided is lower for raloxifene than alendronate. Improved persistence improves the cost-effectiveness for both interventions. Sensitivity analyses indicate the model results are most sensitive to the assumed impact of raloxifene on coronary heart disease and breast cancer risk. Alendronate as a prevention intervention is dominated by raloxifene under almost all model scenarios. CONCLUSION: The annual cost of long-term postmenopausal prevention therapy is highest during the first few years of therapy. Long-term prevention does not provide a return on investment in fewer than 3 years, but savings in medical costs partially offset intervention costs after 2 years. For postmenopausal women, pharmacologic interventions with multiple prevention benefits tend to be more cost effective than interventions with a single source of health benefit.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14613344&dopt=Abstract alendronate Fosamax