alendronate, Fosamax
In vitro toxicity of bisphosphonates on human neuroblastoma cell lines.

Vorotnjak M, Boos J, Lanvers-Kaminsky C.

University Children's Hospital, Department of Pediatric Hematology and Oncology, Munster, Germany.

Neuroblastoma is the commonest extracranial solid tumor of childhood and frequently metastasizes to the bone. Bisphosphonates are standard treatment of osteolytic lesions by bone metastasis. Since recent studies suggested direct antitumor effects of bisphosphonates, we screened the toxicity of different bisphosphonates on neuroblastoma cell lines. The nitrogen-containing bisphosphonate pamidronate was significantly more toxic on a panel of eight neuroblastoma cell lines than the non-nitrogen-containing bisphosphonates, clodronate and tiludronate. After 72 h, GI50 concentrations (inhibiting cell growth by 50% compared to untreated controls) for pamidronate ranged from 12.8 to >500 microM. CHLA-90 and SH-SY5Y were the most sensitive cell lines. In CHLA-90, zoledronate was the most cytotoxic bisphosphonate, followed by alendronate, pamidronate and ibandronate. In SH-SY5Y, alendronate was the most cytotoxic bisphosphonate, followed by ibandronate, pamidronate and zoledronate. The GI50 values after 72 h were 34.1 (SH-SY5Y) and 3.97 microM (CHLA-90) for zoledronate, and 22.4 (SH-SY5Y) and 9.55 microM (CHLA-90) for alendronate. Neuroblastoma cells treated with bisphosphonates showed signs of differentiation and finally underwent apoptosis. The observed GI50 concentrations suggest that local nitrogen-containing bisphosphonate concentrations at the bone interface can directly target neuroblastoma cell penetration into the bone matrix. In summary, these observations warrant the investigation of adjuvant bisphosphonate treatment in controlled clinical trials.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15494642&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Intravenous pamidronate compared with oral alendronate for the treatment of postmenopausal osteoporosis.

Heijckmann AC, Juttmann JR, Wolffenbuttel BH.

Department of Internal Medicine, Hospital Bernhoven Veghel/OssHoh, Burg. De Kuyperlaan 7, 5461 AA Veghel, The Netherlands. c.heijckmann bernhoven.nl

There are several options for the treatment of osteoporosis in postmenopausal women. One of the options is treatment with bisphosphonates, which are very potent inhibitors of osteoclast-mediated bone resorption in vitro and in vivo. The most potent bisphosphonates have a nitrogen side chain and can be given orally or intravenously (i.v.). In the present study we evaluated retrospectively the effect of intravenously administered pamidronate (60 mg monthly) in comparison with oral alendronate with regard to bone mineral density (BMD) and vertebral fractures. A total of 117 consecutive women aged 46 to 78 years were seen in the outpatient clinic because of postmenopausal osteoporosis. Three-year follow-up data were available for a total of 45 patients treated with pamidronate i.v. and 40 patients on alendronate for at least three years. In the pamidronate group mean T score of lumbar spine BMD increased from -3.49 +/- 0.72 to -2.81 +/- 0.74 SDs after three years of treatment (p < 0.001). In the 40 patients treated with alendronate we observed an increase in the T score from -2.95 +/- 0.67 to -2.33 +/- 0.74 SDs (p < 0.001) during the same observation period. X-rays of the lumbar and thoracic spine were analysed from 25 patients in each group who had been treated for at least three years. At baseline nine patients (36%) in the pamidronate group had one or more vertebral fractures compared with seven patients (28%) in the alendronate group. After three years of treatment no new fractures were observed, while only three women in the pamidronate group and two in the alendronate group showed a deterioration of one or more pre-existing vertebral fractures (p = ns between groups). This retrospective analysis demonstrates that monthly intravenous administration of pamidronate is at least as good as alendronate taken orally in the treatment of women with postmenopausal osteoporosis, with regard to improvement of bone mineral density of the lumbar spine. We conclude that it is a good alternative for the more widely used oral bisphosphonates as it is effective, well-tolerated and easy to administer.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12481878&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Alendronate may protect against increased periodontitis-related bone loss in estrogen-deficient rats.

Duarte PM, de Assis DR, Casati MZ, Sallum AW, Sallum EA, Nociti FH Jr.

Department of Prosthodontics and Periodontics, Division of Periodontics, School of Dentistry at Piracicaba, University of Campinas, Piracicaba, Sao Paulo, Brazil.

BACKGROUND: The aim of this study was to evaluate the impact of alendronate (ALD) and estrogen (EST) therapies and their withdrawal on bone loss in experimental periodontitis in ovariectomized rats. METHODS: Eighty-seven Wistar rats were divided into six groups: group 1 (N = 15): sham surgery; group 2 (N = 15): ovariectomy (OVX); group 3 (N = 15): OVX plus alendronate administration for 80 days (AT); group 4 (N = 14): OVX plus alendronate administration for 40 days (AW); group 5 (N = 14): OVX plus 17beta estradiol administration for 80 days (ET); and group 6 (N = 14): OVX plus 17beta estradiol administration for 40 days (EW). Twenty-one days after ovariectomy or sham surgery, one mandibular molar was randomly assigned to receive a ligature, while the contralateral tooth was left unligated. Sixty days later, the animals were sacrificed and the specimens processed. RESULTS: OVX presented a direct impact on alveolar bone, regardless of plaque accumulation and significantly increased bone loss resulting from periodontitis (P < 0.05). The effect of OVX on unligated sites was significantly reduced by AT, AW, and ET (P < 0.05), but not by EW (P > 0.05). In addition, alendronate administration (AT/AW) significantly reduced the impact of OVX on periodontitis-related bone loss (P < 0.05), while estradiol did not (P > 0.05). CONCLUSION: Within the limits of this study, alendronate administration, but not estrogen replacement, may protect against the impact of estrogen deficiency on alveolar bone presenting a significant residual effect after its withdrawal.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15515333&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Alendronate and risedronate for the treatment of postmenopausal osteoporosis: clinical profiles of the once-weekly and once-daily dosing formulations.

Emkey R.

Emkey Arthritis & Osteoporosis, Wyomissing, Pennsylvania, USA.

OBJECTIVE: The objective of this review is to present the clinical profiles of the once-weekly and once-daily dosing formulations of alendronate and risedronate, the 2 bisphosphonates currently available in the United States for the prevention and treatment of postmenopausal osteoporosis. DATA SOURCE/STUDY SELECTION: Data were obtained from a MEDLINE literature search of all English language articles published between January 1996 and April 2004 using generic names of the bisphosphonates alendronate and risedronate. Results were refined by incorporating terms such as "osteoporosis," "bone mineral density," "fracture risk," and "adverse events." Randomized, controlled trials of once-daily and once-weekly bisphosphonate therapies were selected. Also selected for review were post hoc analyses and extension studies of the original controlled trials, including more recent data from published abstracts from scientific meetings. DATA EXTRACTION: Relevant portions of articles obtained from the literature search were used to summarize the efficacy and tolerability of the 2 therapies. CONCLUSIONS: In prospective trials, both bisphosphonates were effective in reducing vertebral and hip fractures in women with postmenopausal osteoporosis. In the only prospective trial evaluating hip fracture risk reduction as the primary end point, risedronate was effective at reducing hip fracture vs placebo. Both alendronate and risedronate are available in once-weekly formulations that have efficacy and tolerability profiles similar to the once-daily doses. Clinicians should review all available data for both agents as well as the medical history of the patient to make the most appropriate treatment choice.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15520628&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
The relationship of antiresorptive drug use to structural findings and symptoms of knee osteoarthritis.

Carbone LD, Nevitt MC, Wildy K, Barrow KD, Harris F, Felson D, Peterfy C, Visser M, Harris TB, Wang BW, Kritchevsky SB; Health, Aging and Body Composition Study.

University of Tennessee Health Sciences Center, 956 Court Avenue, Rm. E336 Coleman Building, Memphis, TN 38163, USA. lcarbone utmem.edu

OBJECTIVE: To examine the cross-sectional association between use of medications that have a bone antiresorptive effect (estrogen, raloxifene, and alendronate) and both the structural features of knee osteoarthritis (OA), assessed by magnetic resonance imaging (MRI) and radiography, and the symptoms of knee OA in elderly women. METHODS: Women in the Health, Aging and Body Composition Study underwent MRI and radiography of the knee if they reported symptoms of knee OA, and women without significant knee symptoms were selected as controls. MR images of the knee were assessed for multiple features of OA using the Whole-Organ MRI scoring method, and radiographs were read for Kellgren and Lawrence grade and individual features of OA. Concurrent medication use and knee symptoms were assessed by interview, and knee pain severity was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: There were 818 postmenopausal women from whom we obtained MR images of the knee and data on medication use. Among these women, 214 (26.2%) were receiving antiresorptive drugs. We found no significant association between overall use of antiresorptive drugs and the presence of knee pain and radiographic changes of OA of the knee. Use of alendronate, but not estrogen, was associated with less severity of knee pain as assessed by WOMAC scores. Both alendronate use and estrogen use were associated with significantly less subchondral bone attrition and bone marrow edema-like abnormalities in the knee as assessed by MRI, as compared with women who had not received these medications. CONCLUSION: Elderly women being treated with alendronate and estrogen had a significantly decreased prevalence of knee OA-related subchondral bone lesions compared with those reporting no use of these medications. Alendronate use was also associated with a reduction in knee pain according to the WOMAC scores.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15529367&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Changes in bone density and turnover after alendronate or estrogen withdrawal.

Wasnich RD, Bagger YZ, Hosking DJ, McClung MR, Wu M, Mantz AM, Yates JJ, Ross PD, Alexandersen P, Ravn P, Christiansen C, Santora AC 2nd; Early Postmenopausal Intervention Cohort Study Group.

Radiant Research-Honolulu, Honolulu, HI 96814, USA. richardwasnich radiantresearch.com

OBJECTIVE: To compare bone mineral density (BMD) and bone turnover changes after therapy withdrawal in postmenopausal women treated with alendronate or estrogen-progestin. DESIGN: In this randomized, blinded, multinational, placebo-controlled trial, 1,609 healthy postmenopausal women ages 45 to 59 years were assigned to receive alendronate, placebo, or open-label estrogen-progestin (conjugated equine estrogens plus medroxyprogesterone acetate or a cyclic regimen of 17 beta-estradiol, norethisterone acetate and estradiol). Of the original women, one third after year 2 and one third after year 4 were switched from alendronate to placebo, while remaining blinded to treatment assignment. The women taking estrogen-progestin in years 1 to 4 were followed off therapy in years 5 and 6. BMD at the lumbar spine and hip and biochemical markers of bone turnover were measured. RESULTS: The treatment groups described in the current report represent 860 women at baseline; 481 women entered year 5, and 430 completed 6 years. BMD steadily decreased in the placebo group during all 6 years. In contrast, spine and hip BMD increased during the first 4 years in the groups receiving daily continuous alendronate 5 mg and estrogen-progestin. During years 5 and 6, BMD decreased at the lumbar spine -2.42% (95% CI = -4.10, -0.74) and total hip -1.09% (-2.60, 0.41) in the group previously treated with alendronate 5 mg for 4 years. In comparison, large BMD decreases were observed at the spine [-7.69% (-8.96, -6.41)] and total hip [-5.16% (-6.30, -4.01)] among women who had received estrogen-progestin for 4 years. CONCLUSION: Alendronate produces greater residual skeletal effects than estrogen-progestin after therapy discontinuation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15545790&dopt=Abstract alendronate Fosamax