alendronate, Fosamax
EFFECT OF ALENDRONATE TREATMENT ON BONE MINERAL DENSITY IN MALE PATIENTS WITH OSTEOPOROSIS.

Drake III MD AJ, Brietzke MD FACE SA, Aprill MD BS, Shakir MD FACE KM.

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Naval Medical Center, Bethesda, Maryland.

Objective: To assess the efficacy of alendronate therapy on bone mineral density (BMD) at the lumbar spine and hip in men with osteoporosis. Methods: Medical records of male patients with osteoporosis, who had undergone follow-up in the Endocrinology Clinic at the National Naval Medical Center, were reviewed, and nine patients treated with alendronate for at least 1 year were identified. Patients were excluded from analysis if they had evidence of osteomalacia or if baseline and follow-up BMD results on the same dual-energy x-ray absorptiometry (DEXA) densitometer, at least 10 months apart, were not available. DEXA BMD results at the lumbar spine and hip, before and after at least 10 months of alendronate treatment, were analyzed for significant differences. Patients were also receiving calcium supplementation (1,000 to 1,500 mg/day), and all but one patient received vitamin D (400 to 800 U/day). Results: Lumbar spine BMD increased by 6.4 +/- 1.8% per year with alendronate treatment (P = 0.008). A mean absolute gain of 0.052 +/- 0.010 g/cm 2 (P = 0.005) in lumbar spine BMD was noted for the entire study group (N = 9), after a mean duration of treatment of 14 +/- 1 months. The mean lumbar spine BMD Z score improved by 0.40 +/- 0.09 (P = 0.002) with alendronate therapy. The femoral neck BMD also increased by 4.5 +/- 1.4% per year with alendronate treatment (P = 0.013). The mean absolute gain in femoral neck BMD was 0.028 +/- 0.009 g/cm 2 (P = 0.013) for the study group (N = 9) after 14 +/- 1 months of therapy. The mean femoral neck BMD Z score improved 0.30 +/- 0.08 (P = 0.005) with treatment. BMD gains at the greater trochanter of 3.2 +/- 1.5% per year (P = 0.067) and at Ward's triangle of 9.1 +/- 4.2% per year (P = 0.061) were not statistically significant. Two patients discontinued alendronate treatment after 1 year because of epigastric or retrosternal pain. Conclusion: Oral alendronate treatment, given in combination with calcium supplementation and physiologic doses of vitamin D, resulted in significant improvements in lumbar spine and femoral neck BMD after a 14-month period in this small group of men with osteoporosis. Although controlled, prospective trials involving larger numbers of male patients with fracture incidence data are needed before definitive conclusions can be made, alendronate treatment seems to be effective in improving BMD in men with osteoporosis, similar to its efficacy in women.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15251673&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
The effect of alendronate on resorption of the alveolar bone following tooth extraction.

Altundal H, Guvener O.

Department of Oral Surgery, Faculty of Dentistry, Yeditepe University, Istanbul, Turkey. haticealtundal yahoo.com

Maintenance of alveolar bone width and height following tooth loss is essential with regard to the restoration of missing teeth with endosseous dental implants or prosthodontics approaches. A various amount of alveolar ridge resorption is likely to occur after tooth extraction at the buccal and lingual alveolar bone plates. Bisphosphonates, alendronate, is well known for its potent inhibition of osteoclast-mediated bone resorption. The objective of this study was to examine the inhibitory effect of alendronate on alveolar bone resorption following tooth extraction in rats. Male Wistar Albino rats were divided into three groups: baseline group, saline-treated group and alendronate-treated group. The saline-treated group was administered with daily saline solution for 2 and 4 weeks respectively while the alendronate-treated group was given a daily amount of 0.25 mg/kg alendronate subcutaneously for the same periods. The level of urinary calcium, creatinine, and serum calcium, alkaline phosphatase and phosphate were measured. Serum alkaline phosphatase level was measured as a marker of osteoblastic activity. Histopathological sections of 4 microm thickness were obtained from the right first mandibular molar region in a bucco-lingual direction. The number of osteoclasts, osteoblasts, and haversian canals, the number and size of resorptive lacunae, and osteoid formation were evaluated histopathologically. The mean thickness of buccal and lingual alveolar bone was measured. In the alendronate-treated group, both buccal and lingual alveolar bone volume reduction was significantly less than the saline treated group. Significant reduction in serum and urinary calcium levels and the number of osteoclasts revealed the pronounced suppression of bone resorption in the alendronate-treated group.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15287313&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
High-dose alendronate uncouples osteoclast and osteoblast function: a study in a rat spine pseudarthrosis model.

Sama AA, Khan SN, Myers ER, Huang RC, Cammisa FP Jr, Sandhu HS, Lane JM.

Facility for Comparative Research, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA. samaa hss.edu

The effect of alendronate on osteoclast and osteoblast function was studied in a novel spine pseudarthrosis model in rats. Sixty-three Sprague-Dawley rats were divided into three groups: control group (saline), therapeutic dose group (1 microg/kg/week), and one-log overdose group (10 microg/kg/week). Animals had L4-L5 posterior intertransverse process fusion with limited bone graft and were sacrificed at 2, 4, and 6 weeks. Manual palpation showed no notable differences among groups. Treatment group radiographic scores were equal to or better than control group scores and were higher than the overdose group at 2 and 6 weeks. Qualitatively, limited histologic remodeling and poor osteoclastic and osteoblastic function were noted in the alendronate treated groups. Quantitative histologic analysis showed fewer osteoclasts in the therapeutic and high-dose groups (p < 0.001). The percent osteoblasts per bone surface area was lower in the high-dose group (p < 0.05). The results suggest that the effect of alendronate was dose dependent and animal model dependent and that supranormal doses of alendronate had a deleterious effect on osteoclastic and osteoblastic function in this model.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15292798&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Gynecologists' trends and attitudes toward prescribing hormone replacement therapy during menopause.

Kaplan B, Aschkenazi-Steinberg S, Yogev Y, Nahum R, Sulkes J, Phisher M.

Department of Obstetrics and Gynecology, Rabin Medical Center, Petah Tikva, Israel. bkaplan obgyn.net.depressivedepressive

OBJECTIVE: To examine the attitudes and prescription practices of gynecologists in the United States and Israel with regard to hormone replacement therapy (HRT) for postmenopausal women. The current recommendations for the use of HRT for menopausal symptoms were reviewed. DESIGN: An eight-item questionnaire was sent by electronic mail or posted to randomly selected members of The North American Menopause Society ( = 250) and the Israeli Menopausal Society ( = 250), all of whom were physician gynecologists. RESULTS: Eighty-seven percent of the questionnaires ( = 435) were completed and were eligible for analysis. Results showed that 400 physicians (92%) routinely offered HRT to their menopausal patients. For women with an intact uterus, 72.5% preferred to use a continuous estrogen-progesterone regimen, and 27.5% preferred to use a sequential combined regimen. The treatment was prescribed for 10 years or more by 86.4% of the American gynecologists, compared with only 66.3% of the Israeli gynecologists ( = 0.001). Overall, the majority of physicians recommended alendronate for recalcitrant osteoporosis and dietary supplements for all women. However, significant differences were found between the American and Israeli groups: 71% of the Americans versus 55.6% of the Israelis prescribed alendronate ( = 0.02); 97.8% versus 71.33% recommended calcium and vitamin D; and 51.6% versus 38.8% recommended multivitamins ( = 0.001 for both groups). Phytoestrogens, alone or in combination with HRT, were recommended by 57.5% ( = NS between groups), and antidepressive drugs were prescribed by only 11% (15.1% of the Americans and 6.3% of the Israelis; = 0.001). CONCLUSION: Most gynecologists recommend HRT during menopause. For women with an intact uterus, the preferred regimen was continuous-combined HRT with estrogen and progesterone. The treatment duration is subject to wide variations, from no time limit to discontinuation after 5 to 10 years. Dietary supplements as well as alendronate, alone or in combination with HRT, are popular for severe osteoporosis. We suggest that, until definitive guidelines become available, an individualized approach should be applied, with careful consideration of both the benefits and risks of treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12218724&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
The effect of the bisphosphonate alendronate on viability of canine osteosarcoma cells in vitro.

Farese JP, Ashton J, Milner R, Ambrose LL, Van Gilder J.

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA. faresej mail.vetmed.ufl.edu

The objective of this study was to determine the effect of alendronate on the viability of canine osteosarcoma cells and nonneoplastic canine cells. The sample population was composed of canine osteosarcoma tumor cells. Osteosarcoma cells and canine fibroblasts were maintained in culture under standard conditions. The MTT assay for cell viability was performed after 24, 48, and 72 h of incubation with alendronate (0.001 to 1000 microM) or no drug (control). Plates were set up so that each concentration and the control had a sample number of 8. The optical density (OD) of each well was measured at 540 nm using an enzyme-linked immunosorbent assay microplate reader. The percent viability was determined for each concentration and for each incubation time. After 24 h of incubation of POS (parent osteosarcoma) and HMPOS cells with alendronate, there was no significant difference in mean OD at any drug concentration when compared with control samples. A significant concentration- and time-dependent reduction in mean OD of osteosarcoma cells was observed after 48 and 72 h of incubation, with alendronate concentrations ranging from 10 to 1000 microM. The lowest percent cell viability observed in treated cells was 35%. Conversely, alendronate did not significantly affect mean OD in fibroblasts, and the lowest percent cell viability observed was 76%. Our data indicate that alendronate may have the potential to inhibit canine osteosarcoma tumor growth. It will be important to determine the clinical relevance of these in vitro findings. If similar findings are observed in vivo, use of alendronate may also be indicated as an adjuvant to existing chemotherapeutic protocols.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15311969&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Bone cancer pain: the effects of the bisphosphonate alendronate on pain, skeletal remodeling, tumor growth and tumor necrosis.

Sevcik MA, Luger NM, Mach DB, Sabino MA, Peters CM, Ghilardi JR, Schwei MJ, Rohrich H, De Felipe C, Kuskowski MA, Mantyh PW.

Department of Preventive Sciences, University of Minnesota, 515 Delaware Street, Minneapolis, MN 55455, USA.

Patients with metastatic breast, lung or prostate cancer frequently have significant bone cancer pain. In the present report we address, in a single in vivo mouse model, the effects the bisphosphonate alendronate has on bone cancer pain, bone remodeling and tumor growth and necrosis. Following injection and confinement of green fluorescent protein-transfected murine osteolytic tumor cells into the marrow space of the femur of male C3H/HeJ mice, alendronate was administered chronically from the time the tumor was established until the bone cancer pain became severe. Alendronate therapy reduced ongoing and movement-evoked bone cancer pain, bone destruction and the destruction of sensory nerve fibers that innervate the bone. Whereas, alendronate treatment did not change viable tumor burden, both tumor growth and tumor necrosis increased. These data emphasize that it is essential to utilize a model where pain, skeletal remodeling and tumor growth can be simultaneously assessed, as each of these can significantly impact patient quality of life and survival.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15327821&dopt=Abstract alendronate Fosamax