alendronate, Fosamax
[Quality of life of patients suffering from osteoporosis treated with alendronate and salmon calcitonin]

[Article in Polish]

Sapula RA, Ostrowski T, Bojar I.

Zakladu Zarzadzania i Ekonomiki Ochrony Zdrowia Akademii Medycznej w Lublinie.

Osteoporosis is a disease of skeletal system characterized by low bone mass, disturbed bone tissue microarchitecture which lead to high risk fractures. Pharmacological treatment of patients suffering from osteoporosis is long-term. Anti reabsorption drugs as alendronate and nasal salmon calcitonin have antifracture effect confirmed in accordance with Evidence Based Medicine but they differ in administration, tolerance, side effects which result in patients' quality of life. The study comparing influence of treatment on quality of life was carried out on the group of 78 women who were patients of Medical Rehabilitation Ward and outpatient clinic of John Paul II Hospital in Zamosc. All patients underwent densitometry (DEXA) which confirmed osteoporosis (BMD: T-score < -2.5 SD). Patients' age ranged from 52 to 73. 46 women were treated with nasal calcitonin and 32 with alendronate. The observation lasted 6 months. Questionnaire was used in the study. Comfort and quality of life were evaluated in the study (comfort of administration, painkilling effect, necessity of additional painkillers and drug tolerance. We also studied which of the drugs better improved patients' life activity. Apart from pharmacotherapy patients were also treated with kinesitherapy, physical activity and with 1000 mg Calcium and 400 u. Vit. D. We used test chi 2 in the study. We stated (p < 0.001) better quality of life in those patients who used nasal salmon calcitonin. It is very important when we take into consideration that patients suffering from osteoporosis should be treated till the end of life. Osteoporosis treatment should be joint therapy including prevention, rehabilitation and pharmacology.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15002282&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Octreotide ameliorates alendronate-induced gastric injury.

Sener G, Paskaloglu K, Kapucu C, Cetinel S, Contuk G, Ayanoglu-Dulger G.

Department of Pharmacology, School of Pharmacy, Marmara University, Haydarpasa, 34668 Istanbul, Turkey. gokselsener hotmail.com

Alendronate causes serious gastrointestinal adverse effects. The aim of this study was to investigate whether octreotide, a synthetic somatostatin analogue, improves the alendronate-induced gastric injury. Rats were administered 20mg/kg alendronate by gavage for 4 days, either alone or following treatment with octreotide (0.1 ng/kg, i.p.). On the last day, following drug administration, pilor ligation was performed and 2h later, rats were killed and stomachs were removed. Gastric acidity and tissue ulcer index values, lipid peroxidation (as assessed by malondialdehyde, MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity as well as the histologic appearance of the stomach tissues were determined. Chronic oral administration of alendronate induced significant gastric damage, increasing lipid peroxidation (37.1+/-3.2 nmol/g) and myeloperoxidase activity (57.6+/-3.7 U/g), while tissue glutathione levels (09.+/-0.1 micromol/g) decreased. Treatment with octreotide prevented this damage as well as the changes in biochemical parameters (MDA: 23.4+/-1.3 nmol/g; MPO: 31.68 U/g; GSH: 15.+/-0.1 micromol/g). Findings of the present study suggest that alendronate induces oxidative gastric damage by a local irritant effect, and that octreotide ameliorates this damage by inhibiting neutrophil infiltration and reducing lipid peroxidation. Therefore, its therapeutic role as a "ulcer healing" agent must be further elucidated in alendronate-induced gastric mucosal injury.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15003363&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Effects of bisphosphonates on joint damage and bone loss in rat adjuvant-induced arthritis.

Harada H, Nakayama T, Nanaka T, Katsumata T.

Research Division, Sumitomo Pharmaceuticals Co. Ltd., 1-98 Kasugade-naka 3-chome, Osaka, 554-0022, Japan. hharada sumitomopharm.co.jp

OBJECTIVE AND DESIGN: Examination of the effects of bisphosphonates on joint damage and generalized bone loss. MATERIALS: Adjuvant-arthritis was induced by injection of Mycobacterium butyricum into the footpad of the right hind paw of Lewis rats (8 animals/group) on day 0. TREATMENT: Arthritic rats were treated with the vehicle (saline), etidronate or alendronate (subcutaneously, daily 5 times a week for 3 weeks from day 1 to day 21). Experiment-1: Etidronate (0.1, 0.5, 2.5, 12.5 mg/kg) or alendronate (0.02, 0.1, 0.5, 2.5 mg/kg), Experiment-2: Etidronate (2.5, 5, 10mg/ kg) or alendronate (0.001, 0.01, 0.1 mg/kg). METHODS: In the adjuvant-injected side of the hind limbs, paw swelling was evaluated at 1-week intervals, and bone mineral density (BMD) in the proximal tibia, histopathology and radiographical findings in the tibio-tarsal region were evaluated at the time of sacrifice (on day 21). RESULTS: In all treatment schedules, both bisphosphonates significantly prevented paw swelling and bone loss. Alendronate reduced paw swelling at higher doses (over 0.1 mg/ kg) compared with its effect on BMD decrease (over 0.001 mg/kg). In contrast, etidronate reduced paw swelling and joint damage at doses similar to those (over 2.5 mg/kg) prevented BMD decrease. CONCLUSIONS: Both etidronate and alendronate are effective in reducing arthritic damage, but their effective dose ranges for inflammatory responses and BMD decrease clearly differ; i.e., the etidronate dose ranges for anti-inflammatory and anti-resorptive effects are similar, whereas the dose range for anti-inflammatory effects of alendronate is 100-fold higher than that for its anti-resorptive effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15021968&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Comparison of risedronate to alendronate and calcitonin for early reduction of nonvertebral fracture risk: results from a managed care administrative claims database.

Watts NB, Worley K, Solis A, Doyle J, Sheer R.

University of Cincinnati Bone Health and Osteoporosis Center, 222 Piedmont Ave., Suite 4300, Cincinnati, OH, 45219, USA. nelson.watts uc.edu

OBJECTIVE: Recent randomized clinical trials have shown that risedronate reduces the risk of nonvertebral fractures and clinical vertebral fractures within 6 months of initiating treatment. The objective of the current study was to determine whether this early antifracture effect could be demonstrated in nonvertebral fractures for risedronate and other osteoporosis therapies in an observational administrative claims database. METHODS: A proprietary administrative claims database was used to identify managed care members who received a new prescription for risedronate, alendronate, or nasal calcitonin from July 1, 2000, to December 31, 2001. Patient records were analyzed for the incidence of nonvertebral fractures (clavicle, humerus, wrist, pelvis, hip, and leg) in the first 6 and 12 months following initiation of treatment. A Cox proportional hazards regression model was used to estimate relative risk (RR) of fracture at 6 and 12 months. RESULTS: In the 6-month analysis, 774 patients (11%) received calcitonin, 5,307 (75%) received alendronate, and 1,000 (14%) received risedronate. Twelve-month data were available for a subset (71%) of patients (656 calcitonin [13%], 3,716 alendronate [74%], and 652 risedronate [13%]). Most were women (93%); mean age was similar for alendronate and risedronate, and nasal calcitonin patients were about 3 years older, on average. Risedronate and alendronate patients were more likely to have used estrogen, while nasal calcitonin patients were more likely to have been hospitalized and had higher use of concomitant medications and more physician visits. Relative risks were adjusted for these differences. Risedronate and alendronate patients were similar with respect to these indicators of general health status. In the 6-month analysis, nonvertebral fractures were observed in 2.2% of patients receiving nasal calcitonin, 1.4% of patients receiving alendronate, and 0.6% of patients receiving risedronate. The adjusted RR reduction was 69% for risedronate versus calcitonin (RR = 0.31; 95% CI, 0.12 to 0.81; P = 0.02), 54% for risedronate versus alendronate (RR = 0.46; 95% CI, 0.20 to 1.06; P = 0.07), and 26% for alendronate versus calcitonin (RR = 0.74; 95% CI, 0.43 to 1.27; P = 0.28). In the 12-month analysis, nonvertebral fracture rates were 2.9% for nasal calcitonin, 2.4% for alendronate, and 0.9% for risedronate patients. The adjusted RR reduction was 75% for risedronate versus calcitonin (RR = 0.25; 95% CI, 0.10 to 0.64; P<0.01), 59% for risedronate versus alendronate (RR = 0.41; 95% CI, 0.18 to 0.94; P = 0.04), and 25% for alendronate versus calcitonin (RR = 0.75; 95% CI, 0.45 to 1.25; P = 0.27). CONCLUSIONS: This analysis of medical and pharmacy claims contained in an administrative database confirms the early fracture reduction with risedronate that was shown in randomized clinical trials. Risedronate was more effective than calcitonin in reducing the risk of nonvertebral fractures within the first 6 months of treatment. Risedronate was more effective than either calcitonin or alendronate in reducing the risk of nonvertebral fractures within 12 months of treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15032563&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Effects of risedronate, alendronate, and etidronate on the viability and activity of rat bone marrow stromal cells in vitro.

Still K, Phipps RJ, Scutt A.

Child Health, University of Sheffield Medical School, Western Bank, Sheffield S10 2TH, UK.

The effects of risedronate, alendronate, and etidronate were assessed in calcifying fibroblastic colony-forming unit (CFU-f) cultures of rat bone marrow cells in vitro. Biphasic effects on the formation of bone-like colonies were observed. Treatment with high concentrations (10(-5)-10(-4)M) of alendronate and risedronate caused a total inhibition of colony formation whereas etidronate had relatively little effect. It was also found that intermediate concentrations (10(-6)M) of alendronate and risedronate decreased the formation of colonies displaying osteoblastic characteristics such as alkaline phosphatase expression, collagen accumulation, and calcification. At lower concentrations (10(-9)-10(-7)M), risedronate and alendronate increased the formation of fibroblastic colonies, suggesting a mild anabolic effect, however, the formation of colonies with osteoblastic properties was not affected. Treating the cells with a combination of bisphosphonate and 1 mM geranylgeraniol could to some extent abrogate the cytotoxic effects of alendronate or risedronate, suggesting the involvement of the mevalonate pathway. The colony-stimulating activity of these bisphosphonates was, however, unaffected.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12457261&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Alendronate regulates cell invasion and MMP-2 secretion in human osteosarcoma cell lines.

Cheng YY, Huang L, Lee KM, Li K, Kumta SM.

Department of Orthopaedics and Traumatology, Chinese University of Hong Kong, Hong Kong.

BACKGROUND: Osteosarcoma is the most common malignant bone tumor of childhood. Significant proportions of these patients eventually develop pulmonary metastases and succumb to their disease even after conventional multi-agent chemotherapy and surgical excision. Matrix metalloproteinase (MMP)-2 induced degradation of blood vessel basement membranes is an important pre-requisite for tumor invasion and metastasis. Bisphosphonates (BPs) have been known to inhibit tumor growth and metastasis in some tumors such as breast cancer, renal cell carcinoma, and prostate cancer, and may do so through inhibition of MMP secretion. We, therefore, tested the effect of BPs on tumor cell invasion, MMP-2 secretion, and apoptosis of osteosarcoma cell lines. PROCEDURE: Two osteosarcoma cell lines (SaOS-2, U(2)OS) were treated with alendronate (50, 100, and 150 microM) for 24 and 48 hr. Matrigel invasion assay was used to investigate the invasive potential of osteosarcoma cell lines before and after alendronate treatment. Real-time quantitative RT-PCR was used to determine the mRNA level of MMP-2 with and without alendronate treatment. Enzyme-linked immunosorbent assay (ELISA) was used to quantify the cytokine level of MMP-2 secreted in the condition medium. BP-induced cell apoptosis was evaluated by fluorescent flow cytometric analysis. RESULTS AND CONCLUSIONS: The results showed that alendronate inhibited cell invasion of both osteosarcoma cell lines in a dose-dependent manner. Alendronate reduced the mRNA level and cellular level of MMP-2 in both cell lines in a time and dose-dependent manner. Alendronate also induced significant apoptosis in both cell lines. Our finding suggests that alendronate downregulates MMP-2 secretion and induces apoptosis in osteosarcoma cells, which may both contribute to the reduction of invasive potential of the tumor cells. Copyright 2004 Wiley-Liss, Inc.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15049011&dopt=Abstract alendronate Fosamax