alendronate, Fosamax
[Esophagitis associated with use of alendronate in 5 postmenopausic patients]

[Article in Spanish]

Luciani J, Pigatto V, Naves A, Fay M, Silvestre Begnis M, Piola JC, Prada DB, Pedrana R.

Servicio de Toxicologia del Sanatorio de Ninos, Alvear 845, Rosario, Argentina.

The bisphosphonate, alendronate sodium (e.g. Fosamax) is a bone resorption inhibitor used to treat postmenopausal osteoporotic women and osseous Paget's disease. Esophagitis is one of the adverse effects (AE) associated to its use. Five (5) patients with alendronate-associated esophagitis assisted in the Gastroenterologic Center, Rosario, Argentina, between October 1996 and December 1999 are described. The aim is to correlate the clinical, endoscopic and histopathological findings in 5 women (ages 57-71) complaining for upper digestive symptoms (dysphagia, epigastralgia, retrosternal pain.). All had osteoporosis treated with alendronate 10 mg/day and received detailed instructions about how to take the medication. The time from the beginning of alendronate intake and the appearance of the symptoms was elapsed 30, 35, 67, 85 and 90 days. The esophagitis was graded according to the Savary-Miller Classification. The videoscopy disclosed esophagitis of III and IV grades. Three patients had also antral and antroduodenal lesions, one of them associated to Helicobacter Pylori. Anatomopathologic findings confirm esophagitis and esophagic ulceration. Some authors claim that bisphosphonates as a new class of gastrotoxic drugs with AE similar to aspirin. Even when it is administrated according to the instructions of the manufacturers it should be used with caution. Our contribution emphasize the importance of this AE and suggest measures to diminish or suppress them, and take into consideration those patients who are taking aspirin. With alendronate, as well as with other potentially corrosive agents, is very important to take in mind the measures to prevent AE.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11471319&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Effect of alendronate on bone mineral density in male idiopathic osteoporosis.

Weber TJ, Drezner MK.

Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.

Idiopathic osteoporosis in men is an increasingly recognized disorder accounting for up to 200,000 hip fractures worldwide each year. Although there is no widely accepted or proven efficacious treatment for men with idiopathic osteoporosis, we attempted to examine the effectiveness of alendronate in this disorder. We retrospectively compared the clinical records of male patients with osteopenia (hip or spine T scores less than -1.0, with or without low-trauma fractures) treated either with alendronate 10 mg orally/day and calcium and vitamin D replacement versus conservative treatment with calcium and vitamin D alone. Review included analysis of laboratory studies and bone turnover markers in a subset of patients. We documented bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) and repeated BMD after an average follow-up of 1.9 and 2.7 years in the alendronate-treated and conservative treatment groups, respectively. At baseline, conservatively-treated and alendronate-treated patients had similar BMD at the lumbar spine and hip. Over the period of observation, the conservatively-treated patients exhibited insignificant changes in BMD at all measured sites. In contrast, alendronate treatment resulted in a significant increase in BMD of the spine (+4.6%, P =.002), trochanter (+6.4%, P =.002), and total hip (+4.7%, P =.002). Indeed, compared with conservative treatment, alendronate-treated patients sustained a significant annualized percent increment of the BMD in the spine (2.7 +/- 0.6 v 1.1 +/- 0.3, P =.025), trochanter (4.7 +/- 1.7 v 0.7 +/- 0.6, P =.025), and total hip BMD (3.3 +/- 0.9 v 0.1 +/- 0.4, P =.0009). These data are among the first that illustrate the potential efficacy of alendronate in the management of idiopathic osteoporosis in men. Copyright 2001 by W.B. Saunders Company

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11474478&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Effect of topical alendronate on root resorption of dried replanted dog teeth.

Levin L, Bryson EC, Caplan D, Trope M.

Department of Endodontics, School of Dentistry, University of North Carolina at Chapel Hill, 27599-7450, USA. llevin dentistry.unc.edu

Alendronate (ALN) is a third generation bisphosphonate with demonstrated osteoclast inhibitory activity that may slow down the resorptive process after severe traumatic injuries. Eighty-two premolar roots of five mongrel dogs were endodontically treated and restored, extracted and treated as follows: 70 roots were bench dried for either 40 or 60 min. Thirty-eight of these roots were then soaked for 5 min in a 1 mM solution of ALN in Hanks' Balanced Salt Solution (HBSS) and replanted. Thirty-two roots were soaked for 5 min in HBSS and replanted. In the remaining 12 roots which were not exposed to the bench drying procedure, a 0.5 mM deep lingual mid-root cemental defect was made. Six of these roots were soaked in a 1 mM solution of ALN in HBSS for 5 min and replanted. The other six roots were soaked for 5 min in HBSS and replanted. Historical negative and positive controls were used from similarly treated teeth in our previous studies. After 4 months the dogs were killed and the roots prepared for histological evaluation. Five-microm-thick cross-sections of the root and surrounding tissue taken every 70 microm were evaluated for healing according to the criteria of Andreasen. In the 12 roots with cemental defects, healing with cementum of the damaged root surface was evaluated. In addition, residual root mass was also measured to determine the extent of root structure loss for each soaking method. Cemental healing took place in all 12 artificially damaged roots, indicating that these soaking media did not inhibit cementogenesis. The alendronate-soaked roots had statistically significantly more healing than the roots soaked in HBSS without alendronate. This improvement in healing was seen in all dogs except one and in all teeth except the first premolar. Soaking in alendronate also resulted in significantly less loss in root mass due to resorption compared to those teeth soaked in HBSS without alendronate.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11499761&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Alendronate does not interfere with 99mTc-methylene diphosphonate bone scanning.

Carrasquillo JA, Whatley M, Dyer V, Figg WD, Dahut W.

Nuclear Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892-1180, USA.

Several studies have found that administration of etidronate results in competitive interference with 99mTc-labeled bone scanning reagents. In contrast, in other studies this problem was not encountered with other bisphosphonates. METHODS: We prospectively studied 9 patients with hormone-refractory prostate cancer. 99mTc-methylene diphosphonate (MDP) bone scanning was performed before they received alendronate, and scanning was repeated a mean of 16.6 d afterward, when the patients had been receiving 40 mg alendronate daily for a mean of 6 d. In addition, 7 patients who underwent delayed scanning when they had been receiving alendronate for a mean of 111 d were also restudied. Quantitative whole-body bone scanning was performed, and radioactivity deposited in the bone metastasis was determined using region-of-interest analysis. RESULTS: A <6% increase in whole-body retention of 99mTc-MDP was seen on the initial postalendronate scan compared with the baseline scan. No significant differences in activity were seen in the bone lesion evaluated on the baseline and initial postalendronate studies. The delayed postalendronate scan generally showed similar or higher tracer accumulation compared with the baseline scan. CONCLUSION: Alendronate did not competitively inhibit uptake of 99mTc-MDP in the skeleton or tumor metastasis. Use of alendronate before bone scanning is unlikely to result in decreased detection of lesions or falsely decreased 99mTc-MDP activity at metastatic bone tumor sites.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11535725&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
The influence of alendronate on bone formation and resorption in a rat ectopic bone development model.

Yaffe A, Kollerman R, Bahar H, Binderman I.

Department of Prosthodontics, Hebrew University Hadassah School of Dental Medicine, Jerusalem, Israel. yaffeavi netvision.net.il

BACKGROUND: Most bone grafting techniques that include bone marrow, alloplastic materials, and extracellular bone matrix produce new bone mass, filling bone defects unpredictably. In most cases, the new bone undergoes resorption due to low local strains, resulting in significant bone loss. Recently, it was shown that alendronate and other bisphosphonates reduce bone loss when administered systemically or locally. The aim of this study was to investigate whether alendronate is effective on bone formation or bone resorption. METHODS: A total of 64 rats were divided into 2 main groups. In all the rats, fresh bone marrow removed from DA young rats was placed into demineralized rat femur cylinders (DBMC) and implanted into subcutaneous sites of host DA rats, to form new bone. Group A served as an alendronate treatment group, and group B served as a non-treated control. Group A received 100 microl of 1.5 mg/ml alendronate solution at 1, 2, and 3 weeks (group A1) and at 3, 4, and 5 weeks (group A2). At designated times, the rats were sacrificed, and the implanted DBMC was dissected out of the thorax and processed for histological and microradiography image analysis. RESULTS: Alendronate given at 1, 2, and 3 weeks (during the bone formation phase) did not increase the amount of bone or the visual bone density in comparison to the time-matched control, after 4 and 8 weeks. When alendronate was injected at 3, 4, and 5 weeks, the bone mass increased by 70% and by 166% after 6 and 10 weeks, respectively, in comparison to the untreated control. The visual bone density in group A2 was maintained at the level of 140 +/- 15 at 6 weeks and 152 +/- 15 at 10 weeks. The matched, non-treated control group B2 was significantly lower, 106 +/- 20 and 108 +/- 15, respectively. The histological sections showed that alendronate treatment at 3, 4, and 5 weeks maintained the normal appearance of the ossicle at 6 and 10 weeks in comparison to the osteopenic bone appearance in the matched controls. CONCLUSIONS: This study suggests that alendronate is effective in inhibiting bone loss, but ineffective during the bone formation phase. We suggest, therefore, that alendronate should be administered in procedures where bone resorption is expected.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12593595&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Comparison of calcitonin, alendronate and fluorophosphate effects on ovariectomized rat bone.

Giavaresi G, Fini M, Gnudi S, Aldini NN, Rocca M, Carpi A, Giardino R.

Experimental Surgery Department, Istituto di Ricerca Codivilla-Putti IOR, Bologna, Italy. gianluca.giavaresi ior.it

The effects of calcitonin, alendronate and fluorophosphate preventive treatment on ovariectomized rat femur were studied by comparing densitometric, mechanical, mineralogical and histomorphometric data. Sixty retired breeder female Sprague-Dawley rats, aged 10 months, were randomly divided into six groups. A group (baseline) was euthanized at the beginning of the study as a baseline group; four groups were ovariectomized and one was sham-operated (sham) and considered as a sham-aged group. A group of ovariectomized rats was used as a sham-therapy control (OVX) and received only deionized drinking water, while the other three received: a) salmon calcitonin (SCN) at a dose of 2 IU/kg/d s.c. (OVX + SCN); b) alendronate sodium salt (ALN) at a dose of 6 microg/kg/d administered by gavage (OVX + ALN); and c) L-glutamine monofluorophosphate (G-MFP) and calcium at a rate of 1:30 F/Ca at a dose of 0.21 mg F/6.30 mg Ca per kg/d by gavage (OVX + MFP). Significant increases (P < 0.05) of about 15 and 27% in femoral proximal epiphysis bone mineral density (BMD) of the OVX + ALN group were observed versus healthy groups and the OVX group, respectively. The OVX + ALN group also showed significant increases in femoral mid-diaphysis BMD when compared to OVX (18%, P < 0.001), OVX + SCN (14%, P < 0.05) and OVX + MFP (18%, P < 0.001) groups. In the OVX + MFP group, the three-point bending test demonstrated significant increases (P < 0.05) in maximal load of 21 and 22% when compared to the OVX and OVX + SCN groups, respectively. Also, stiffness data showed significant increases of the OVX + MFP (17%) and sham (14%) groups in comparison with the OVX group. A decrease in Mg (42%, P < 0.05), and increases in Ca (15%, P < 0.0001) and PO4 (8%, P < 0.005) content were found by comparing OVX + MFP and OVX groups. Trabecular bone volume results showed significant increases by comparing OVX + ALN and OVX groups (12.20%, P < 0.0005), as well as control groups. Tested agents were able to reduce the bone loss due to estrogen deficiency, but this did not always produce an increase in strength of the treated bone. Alendronate treatment prevented a decrease in bone mineral density and maintained bone mechanical properties after ovariectomy without impairment of bone mineralization in aged rats.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11669503&dopt=Abstract alendronate Fosamax