alendronate, Fosamax
Prevention of corticosteroid induced osteoporosis in inpatients recently discharged from a tertiary teaching hospital.

Smith MD, Cheah SP, Taylor K, Ahern MJ.

Rheumatology Unit, Repatriation General Hospital, Daw Park, Australia.

OBJECTIVE: To determine the medical conditions for which oral corticosteroids are prescribed and to determine the frequency and type of osteoporosis prophylaxis offered to these patients. METHODS: Medical records of all inpatients for the period March to October 1999 who were documented in pharmacy records as either having received continuous oral steroids for at least 3 months or who had at least 4 courses of oral steroids per year were examined for the following data: age, sex, medical condition for which steroids were required, dose and duration of steroid therapy, whether they were offered bone mineral density (BMD) scans, and whether they were offered drug prophylaxis for steroid induced osteoporosis and the type of drug prophylaxis offered. Followup telephone calls were made to verify patients' use of prophylactic treatment and to validate the chronic use of oral corticosteroids. Use of BMD testing was also validated by comparing the list of patients in this study with the records of bone densitometer units in the area. RESULTS: A total of 189 medical records were examined: 38% were women (n = 72) and 62% were men (n = 117), with an age range of 19-91 years; 73% were taking continuous steroid therapy, the remaining 27% had multiple courses of prednisolone through the year. Steroids were prescribed for respiratory (n = 82, 43%), rheumatological (n = 74, 39%), hematological (n = 16, 8%), dermatological (n = 8, 4%), and gastrointestinal conditions (n = 7, 4%). Chronic obstructive airway disease was the most common respiratory condition for which steroids were prescribed (77, 94%), and polymyalgia rheumatica (36%) and inflammatory arthritis (41%) were the most common rheumatological conditions for which steroids were prescribed. In total, 47% (n = 89) were offered BMD scans while 53% (n = 100) were not. Of the 100 patients not offered BMD scans, 21 (21%) were receiving some form of drug prophylaxis, while 79% of patients were not taking any form of drug prophylaxis. Prophylaxis consisted of calcitriol (64%), alendronate (11%), calcitriol and calcium (7%), calcium alone (7%), alendronate and calcium (3%), etidronate and calcium (2%), alendronate, calcitriol and calcium (1%), alendronate and calcitriol (1%), and hormone replacement therapy (4%). Rheumatologists utilized both BMD testing and prophylactic treatment twice as often in patients taking chronic oral corticosteroid treatment than other specialty physicians. CONCLUSION: Compared to literature reports, the use of prophylaxis for corticosteroid induced osteoporosis was relatively high at this teaching hospital, with a surprisingly large number of patients receiving this treatment with no monitoring by BMD measurements.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11296960&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Apoptosis of osteoclast-like cells induced by alendronate is related to Fas gene expression.

Wang XM, Yu SF, Yang ZP.

Department of Oral Pathology, School of Stomatology, BMU, 38 Bai Shi Qiao Road, Haidian District, Beijing 100081, P. R. China.

OBJECTIVE: To detect the mechanism of alendronate during inhibition of bone resorption by inducing apoptosis of osteoclasts and its relationship with the Fas gene. METHODS: The osteoclast-like cells (OCLs) from a giant cell tumor in vitro were used. After treatment with alendronate for 48 hours, the OCLs were identified by fluorescence microscope, transmission electron microscope, in situ end labeling (TUNEL), HE staining, in situ hybridization with Dig-Fas Probe, and immunohistochemistry with anti-Fas antibodies. RESULTS: The detachment rate of OCLs was 76% after exposure to alendronate, while the control cell detachment rate was only 3%. The nonadherent OCLs showed the features of cell contraction, pyknosis, chromatin condensation connecting with nuclear membrane to form circle or crescent bodies, and occasional nuclear fragmentation. The detached OCLs were positive by in situ end labeling, and the control group was negative. Nonadherent OCLs were ultrastructurally consistent with apoptosis (shrunken cells with pyknotic nuclei, chromatin condensation connecting with nuclear membrane, mitochondria recruitment with intact structure, and loosening of endoplasmic reticulum). The results by in situ hybridization and immunohistochemistry indicated that the Fas gene expression of nonadherent OCLs were positive, but the controls were negative. CONCLUSION: Alendronate promotes apoptosis of the OCLs and it is related with the expression of the Fas gene.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11314515&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Bisphosphonates alendronate and ibandronate inhibit artery calcification at doses comparable to those that inhibit bone resorption.

Price PA, Faus SA, Williamson MK.

Department of Biology, University of California, San Diego, La Jolla 92093-0368, USA. pprice ucsd.edu

The present experiments were carried out to test the hypothesis that artery calcification is linked to bone resorption by determining whether the selective inhibition of bone resorption with the bisphosphonates alendronate and ibandronate will inhibit artery calcification. Artery calcification was first induced by treatment of 42-day-old male rats with warfarin, a procedure that inhibits the gamma-carboxylation of matrix Gla protein and has been shown to cause extensive calcification of the artery media within 2 weeks. These experiments revealed that ibandronate (0.05 mg. kg(-1). d(-1)) and alendronate (0.1 mg x kg(-1) x d(-1)) completely inhibited calcification of all arteries and heart valves examined after 2 and 4 weeks of warfarin treatment. A 10-fold lower dose of alendronate reduced artery calcification by 50% (P<0.005). These bisphosphonate doses are comparable to those that inhibit bone resorption in rats of this age. More rapid artery calcification was induced by treatment with warfarin together with high doses of vitamin D, a procedure that causes extensive artery calcification by 84 hours. Alendronate and ibandronate again completely inhibited calcification of all arteries and heart valves examined. The subcutaneous doses of alendronate and ibandronate necessary to inhibit artery calcification are comparable to the daily subcutaneous doses of these drugs that have previously been shown to inhibit bone resorption in rats of the same age, with 50% inhibition of artery calcification at 20 microg alendronate x kg(-1) x d(-1) and at 1 microg ibandronate x kg(-1) x d(-1) x Bisphosphonate treatment did not affect serum calcium and phosphate, and so the inhibition of artery calcification cannot be due to a simple lowering of the serum calcium phosphate ion product. We conclude that bisphosphonates inhibit the calcification of arteries and heart valves at doses comparable to the doses that inhibit bone resorption. These results support the hypothesis that artery calcification is linked to bone resorption. The mechanism of this linkage remains to be established, however, and an alternative explanation for the present results is also considered.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11348880&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Inhibition of leukotriene function can modulate particulate-induced changes in bone cell differentiation and activity.

Anderson GI, MacQuarrie R, Osinga C, Chen YF, Langman M, Gilbert R.

Dept. of Surgery, Faculties of Dentistry & Medicine, Dalhousie University, Halifax, Nova Scotia B3H 3J5, Canada. gianders is.dal.ca

Aseptic loosening remains the major problem facing arthroplasty longevity with particulates from component materials touted as the cause of periprosthetic osteolysis. Proposed mechanisms in aseptic bone loss include: increased resorption, increased differentiation of osteoclasts (and/or macrophages locally), and decreased osteoblastic bone formation. Leukotrienes participate in osteoclastic bone resorption. We investigated inhibiting leukotrienes synthesis, using ICI 230487, to ameliorate the effects of particulates on osteoclast pit formation and also assessed the effects of alendronate, a bisphosphonate, on pit formation. Three particulates were used: ultra high molecular weight polyethylene (UHMWPE), polymethylmethacrylate (PMMA) and hydroxyapatite (HA). Osteoclast resorption was increased with UHMWPE, PMMA, and HA particles. Interventions with alendronate and ICI 230487 reduced particulate-induced osteoclast resorption. Both ICI 230487 and alendronate reduced osteoclast numbers at higher doses. To assess the effect of particulates on osteoclast and macrophage differentiation, mouse bone marrow was cultured and stained for tartrate resistant acid phosphatase colonies (TRAP+, osteoclasts) and nonspecific esterase positive colonies (NSE+, macrophage precursors). Particulates increased both TRAP+ and NSE+ colony formation. These increases were inhibited by ICI 230487. Particulates also inhibited osteoblast function assessed by the development of mineralized nodules and alkaline phosphatase positive (AP+) colony area. ICI 230487 partly protected osteoblast function from this particulate effect. Blockade of leukotriene production may prove a useful therapeutic intervention for particulate-induced aseptic loosening by inhibiting resorptive activity, reducing the pro-inflammatory cell populations induced and recruited by these particulates, as well as ameliorating the negative effects of inflammatory mediators on osteoblast function.Copyright 2001 John Wiley & Sons, Inc.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11410899&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Alendronate influences bending force of femoral diaphysis after orchidectomy in rats.

Huuskonen J, Arnala I, Olkkonen H, Alhava E.

Department of Surgery, University of Kuopio, Finland. johuusko hytti.uku.fi

BACKGROUND AND AIMS: We examined the effect of alendronate on bone following orchidectomy-induced osteoporosis. MATERIAL AND METHODS: Eighty male rats were used. Group I (C) served as the untreated control. In group II (ALN), alendronate was administered subcutaneously (18 microg/kg). In group III (ORC), rats were castrated only. In group IV (ORC+ALN), administration of alendronate (18 microg/kg) was started immediately after castration, and in group V (ORC + ALN-21) medication was started 21 days after castration. Alendronate was given twice a week for eight weeks in the treatment groups. Bone mineral density (BMD) of the proximal femur, ultimate bending forces of femoral diaphyses, ash weights of femurs (AWcc) and the calcium content (Ca) of femoral ash were determined. Histomorphometric analysis was performed on trabecular bone of proximal tibiae. RESULTS: BMD of the proximal femur was significantly decreased by orchidectomy compared with C and ALN. However, no statistical difference was observed between alendronate-treated groups (ORC + ALN and ORC + ALN-21) and the ORC group. Histologically, alendronate reduced the trabecular bone turnover. Ultimate bending force increased significantly in the ORC+ALN-21 group compared with group C, and had a good correlation with the cortical width of tibia (r = 0.53, p < 0.001). Ash weight per bone volume (AWcc) was lowest in the ORC group, whilst alendronate maintained AWcc after orchidectomy. CONCLUSION: Alendronate increased the ultimate bending force of the femoral diaphysis after orchidectomy. On the other hand, ALN treatment was not able to maintain the BMD of the proximal femur at the pre-orchidectomy level. Our results suggest that the remodelling and modelling of bone may influence the response to ALN treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11459259&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Effect of 17beta-estradiol or alendronate on the bone densitometry, bone histomorphometry and bone metabolism of ovariectomized rats.

da Paz LH, de Falco V, Teng NC, dos Reis LM, Pereira RM, Jorgetti V.

Departamento de Reumatologia, Faculdade de Medicina, Universidade de Sao Paulo, Av. Dr. Arnaldo, 01246-930 Sao Paulo SP, Brazil. vandajor usp.br

The objective of the present study was to evaluate the effect of 17beta-estradiol or alendronate in preventing bone loss in 3-month-old ovariectomized Wistar rats. One group underwent sham ovariectomy (control, N = 10), and the remaining three underwent double ovariectomy. One ovariectomized group did not receive any treatment (OVX, N = 12). A second received subcutaneous 17beta-estradiol at a dose of 30 microg/kg for 6 weeks (OVX-E, N = 11) and a third, subcutaneous alendronate at a dose of 0.1 mg/kg for 6 weeks (OVX-A, N = 8). Histomorphometry, densitometry, osteocalcin and deoxypyridinoline measurements were applied to all groups. After 6 weeks there was a significant decrease in bone mineral density (BMD) at the trabecular site (distal femur) in OVX rats. Both alendronate and 17beta-estradiol increased the BMD of ovariectomized rats, with the BMD of the OVX-A group being higher than that of the OVX-E group. Histomorphometry of the distal femur showed a decrease in trabecular volume in the untreated group (OVX), and an increase in the two treated groups, principally in the alendronate group. In OVX-A there was a greater increase in trabecular number. An increase in trabecular thickness, however, was seen only in the OVX-E group. There was also a decrease in bone turnover in both OVX-E and OVX-A. The osteocalcin and deoxypyridinoline levels were decreased in both treated groups, mainly in OVX-A. Although both drugs were effective in inhibiting bone loss, alendronate proved to be more effective than estradiol at the doses used in increasing bone mass.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11471040&dopt=Abstract alendronate Fosamax