Oral alendronate induces progressive increases in bone mass of the spine, hip, and total body over 3 years in postmenopausal women with osteoporosis

Devogelaer, JP; Bröll, H; Correa-Rotter, R; Cumming, David C.; Deuxchaisnes, C Nagant de; Geusens, Piet; Hosking, D. J.; Jaeger, P; Kaufman, Jean; Leite, Marco; Leon, J. Perez; Liberman, Uri; Menkès, Charles-Joël; Meunier, Pierre J.; Reid, I.R.; Rodriguez, Jose A.; Romanowicz, A.; Seeman, Ego; Vermeulen, A.; Hirsch, Laurence; Lombardi, Antonio; Plezia, K.; Santora, Arthur C.; Yates, A.J.P.; Yuan, Weiying

doi:10.1016/8756-3282(95)00436-x

Cited by 166 publications

(47 citation statements)

References 29 publications

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“…These two doses were also determined to span the boundary dose to show a significant ameliorative effect on OVXinduced bone loss based on our previous study (11). All analyses in this study revealed the dose-dependent anabolic effects of the single treatment of alendronate; however, they were much weaker than those reported in previous clinical studies (53,54) and only the high dose of alendronate showed significant stimulation of bone strength. Since the gastrointestinal absorption of bisphosphonates is very poor, especially in the presence of calcium, this relatively weak effect may be due to the paucity of alendronate absorption in rats that cannot be treated in a fasting condition like humans.…”

Section: Discussioncontrasting

confidence: 51%

Curative Effect of Combined Treatment With Alendronate and 1 α-Hydroxyvitamin D3 on Bone Loss by Ovariectomy in Aged Rats

Ito

Azuma

Takagi

et al. 2002

Japanese Journal of Pharmacology

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ABSTRACT-We investigated the combined effects of alendronate and 1a-hydroxyvitamin D3 (1a(OH)D3) on the bone mass and strength in aged ovariectomized rats and compared them with those of single treatments. Forty-week-old female rats underwent ovariectomy or sham operation, and after 15 weeks, ovariectomized rats were daily administered vehicle alone, alendronate (0.2 or 1.0 mg /kg, p.o.), 1a(OH)D 3 (0.02 mg/kg, p.o.), or the combinations of 0.2 or 1.0 mg /kg of alendronate and 1a(OH)D 3 . After 12 weeks, the groups receiving combined treatments had significantly increased bone density and mechanical strength of the 4th lumbar vertebral body and the midfemur compared to the vehicle-treated group, and the effects were almost equal to or slightly less than the addition of those of the respective single treatments. The increase in mechanical strength was proportional to that in bone mineral density, suggesting that the stimulatory effects of these treatments on bone strength are ascribable primarily to those on bone mass. Analyses of histology, computed tomography, and biochemical markers confirmed the strong effect of the combined treatment on trabecular bone in particular, which was associated with increased trabecular number and decreased bone turnover. We propose that the combination of daily alendronate and 1a (OH)D 3 is clinically promising as a curative treatment of established postmenopausal osteoporosis.Keywords: Combined treatment, Alendronate, 1a -Hydroxyvitamin D3, Ovariectomy, Osteoporosis Estrogen deficiency after menopause is associated with bone loss leading to fractures that constitute a serious health problem in many countries (1). Many bone-sparing drugs have successively been developed for the treatment of postmenopausal osteoporosis (2). However, the effects of the combined treatments of these drugs have not been well investigated despite the fact that postmenopausal osteoporosis is frequently treated with combination therapy.Bisphosphonates, potent anti-resorptive agents, are known to be one of the most reliable and prevalent drugs in osteoporosis treatment. Alendronate (sodium 4-amino-1-hydroxybutilidene-1,1-bisphosphonate trihydrate), an aminobisphosphonate, is well known as a potent inhibitor of osteoclastic bone resorption (3 -5). The efficacy of bisphosphonates has been demonstrated in osteoporosis (6 -8) as well as in various other metabolic bone disorders such as Paget's disease (9) and hypercalcemia of malignancy (10). Alendronate has also been reported to increase the bone mass and strength in ovariectomized (OVX) rats (11 -13). The modes of action of alendronate include suppression of the differentiation of osteoclast precursors (14 -16) and the activation of mature osteoclast function (17), resulting in the decrease in bone turnover. Recent studies on its molecular mechanism show that aminobisphosphonates such as alendronate can inhibit enzymes of the mevalonate pathway (18).Vitamin D and vitamin D derivatives may also have a role in osteoporosis (19), and the activated form of vitam...

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Section: Discussioncontrasting

confidence: 51%

Curative Effect of Combined Treatment With Alendronate and 1 α-Hydroxyvitamin D3 on Bone Loss by Ovariectomy in Aged Rats

Ito

Azuma

Takagi

et al. 2002

Japanese Journal of Pharmacology

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“…Data indicate that alendronate is one of the most potent bisphosphonates in inhibiting bone resorption both in vitro and in vivo (9,11,29). Besides its systemic effects, alendronate has also been shown to reduce tooth resorption, graft resorption and alveolar bone loss in the dental fields (5,10,24).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Effects of Local Application of Hydroxyapatite Graft Soaked with Alendronate Solution and Pure Hydroxyapatite Graft in the Mandible of Ovariectomized Rats

Arslan

Altundal

Çevik

et al. 2011

Biotechnology & Biotechnological Equipment

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“…В наиболее ранних крупных исследованиях с однотип-ным дизайном [27,77], включавших в себя соответс-твенно 516 и 478 пациенток, показано достоверное по сравнению с группой плацебо повышение МПКТ на фоне 3 лет лечения 10 мг АЛ L 1 -L 4 , ШБ, большом вертеле, во всем теле на 9,6%, 4,7%, 7,4% и 1,6% соот-ветственно [77] и на 7,4%, 5,5%, 7,2% соответственно в исследовании Devogelaer JP и соавт. [27]. В этих работах не было выявлено достоверного повыше-ния МПКТ только в лучевой кости.…”

Section: постменопаузальный опunclassified

“…За основу были взяты два 3-летних исследования с одинаковым дизайном, в которые было включено 994 женщины [27,57,77], в них было убедительно по-казано повышение МПКТ во всех измеряемых точках (данные по этим работам см. выше).…”

Section: постменопаузальный опunclassified

“…В большинстве исследований эффективности АЛ при ОП авторы изучали его влияние на показатели как костеобразования, так и резорбции, которые снижа-лись в процессе лечения [11,17,27,77].…”

Section: влияние ал на биохимические маркеры кост-ного обмена и парамunclassified

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ROL' I MESTO BISFOSFONATOV V PROFILAKTIKE I LEChENII OSTEOPOROZA. 10-LETNIY OPYT PRIMENENIYa ALENDRONATA (FOSAMAKSA)Obzor literatury

Дедов¹,

ROZhINSKAYa²,

Belaya³

2005

Osteopor Bone Dis

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Oral alendronate induces progressive increases in bone mass of the spine, hip, and total body over 3 years in postmenopausal women with osteoporosis

Cited by 166 publications

References 29 publications

Curative Effect of Combined Treatment With Alendronate and 1 α-Hydroxyvitamin D3 on Bone Loss by Ovariectomy in Aged Rats

Curative Effect of Combined Treatment With Alendronate and 1 α-Hydroxyvitamin D3 on Bone Loss by Ovariectomy in Aged Rats

Comparison of the Effects of Local Application of Hydroxyapatite Graft Soaked with Alendronate Solution and Pure Hydroxyapatite Graft in the Mandible of Ovariectomized Rats

ROL' I MESTO BISFOSFONATOV V PROFILAKTIKE I LEChENII OSTEOPOROZA. 10-LETNIY OPYT PRIMENENIYa ALENDRONATA (FOSAMAKSA)Obzor literatury

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