Potential Alendronate Sodium drug carrier by preparation and characterization of sodium alginate cross-linked Montmorillonite

Abstract In drug therapy, it is important to provide therapeutic levels of drug to the site of action and maintain them during the treatment. This work describes the in vitro release of alendronate from sodium alginate cross-linked Montmorillonite (MMT) composite beads. Effect of crosslinking cation, concentration of montmorillonite and media on encapsulation efficiencies, and release profiles of alendronate were studied. Beads were characterized using equilibrium swelling ability study, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Energy-dispersive x-ray spectroscopy (EDX) and scanning electron microscopy (SEM). Results indicate that addition of montmorillonite increases the encapsulation efficiencies and slows down the release rates significantly.

Effect of ProRoot MTA® and Biodentine® on osteoclastic differentiation and activity of mouse bone marrow macrophages

Abstract Objectives This investigation aimed to assess the differentiation inhibitory effects of ProRoot MTA® (PMTA) and Biodentine® (BIOD) on osteoclasts originated from murine bone marrow macrophages (BMMs) and compare these effects with those of alendronate (ALD). Materials and Methods Mouse BMMs were cultured to differentiate into osteoclasts with macrophage colony-stimulating factor and receptor activator of NF-κB (RANKL), treated with lipopolysaccharide. After application with PMTA, BIOD, or ALD, cell toxicities were examined using WST-1 assay kit, and RANKL-induced osteoclast differentiation and activities were determined by resorption pit formation assay and tartrate-resistant acid phosphate (TRAP) staining. The mRNA levels of osteoclast activity-related genes were detected with quantitative real time polymerase chain reaction. Expressions of molecular signaling pathways were assessed by western blot. All data were statistically analyzed with one-way ANOVA and Tukey's post-hoc test (p<0.05). Results Mouse BMMs applied with PMTA, BIOD, or ALD showed highly reduced levels of TRAP-positive osteoclasts. The BIOD treated specimens suppressed mRNA expressions of cathepsin K, TRAP, and c-Fos. Nonetheless, it showed a lower effect than PMTA or ALD applications. Compared with ALD, PMTA and BIOD decreased RANKL-mediated phosphorylation of ERK1/2 and IκBα. Conclusions PMTA and BIOD showed the inhibitory effect on osteoclast differentiation and activities similar to that of ALD through IκB phosphorylation and suppression of ERK signaling pathways.

Effect of local application of alendronate and parathyroid hormone on craniofacial bone repair - a preliminary study

Abstract This study aimed to evaluate the effect of two methods of local application of alendronate and parathyroid hormone (PTH) on bone repair and the systemic implications. A critically sized defect (5 mm) was created in the cranial region of twenty-five male Wistar rats, and the bone removed was particulated, and grafted back to the defect with different treatments. The animals were randomly divided into five groups: A1- bone graft immersion in alendronate solution (3 mg/kg) for 5 minutes; P1- bone graft immersion in PTH solution (20 µg); A2- weekly local applications of alendronate 1 mg/kg; P2- weekly local applications of PTH (20 µg); C- no drugs were used. The animals were euthanized 60 days after surgery. Cranial bone blocks were removed for histological, histomorphometric, and immunohistochemical analyses. MMP-2 and MMP-9 were used for immunolabeling. The kidneys, liver, and brain were also removed from all the rats for histological analysis. The data were submitted for statistical analysis with a level of significance of 0.05 (One-way ANOVA). The group C and group P2 presented a higher quantity of viable bone particles than the remaining groups. Groups A1, A2, and P1 presented with fewer viable bone particles than the control group, with a predominance of non-mineralized connective tissue. The histomorphometric analysis revealed no differences in relative bone area or MMP-2 or MMP-9 immunolabeling between the groups (p>0.05). Group A2 showed presence of fat in the liver consistent with hepatic steatosis. Changes in brain tissue were observed in groups A1 and P1.

Resumo Este estudo visou avaliar o efeito de dois métodos de aplicação local de alendronato e de paratormônio (PTH) no reparo ósseo e avaliar as implicações sistêmicas. Um defeito de tamanho crítico (5 mm) foi criado na calota craniana de vinte e cinco ratos Wistar machos, e o osso removido foi particulado e enxertado de volta no defeito com diferentes tratamentos. Os animais foram divididos aleatoriamente em cinco grupos: A1: imersão do enxerto ósseo em solução de alendronato (3 mg/kg) durante 5 min; P1- imersão do osso em solução de PTH (20 μg); A2- aplicações locais semanais de alendronato 1 mg/kg; P2- aplicações locais semanais de PTH 20 μg; C: não foram utilizados medicamentos. Os animais foram eutanasiados 60 dias após a cirurgia. Foram removidos os blocos ósseos envolvendo a região do defeito para realização das análises histológica, histomorfométrica e imuno-histoquímica. MMP2 e MMP9 foram as imunomarcações utilizadas. Os rins, fígado e cérebro também foram removidos de todos os ratos para análise histológica. Os dados foram submetidos à análise estatística com um nível de significância de 0,05 (One-way ANOVA). A análise histológica revelou que o grupo C e o grupo P2 apresentaram maior quantidade de partículas ósseas viáveis do que as apresentadas pelos demais grupos. Os grupos A1, A2 e P1 apresentaram menos partículas ósseas viáveis em comparação com o grupo controle com predominância de tecido conjuntivo não mineralizado. A análise histomorfométrica não revelou diferenças entres os grupos na área óssea relativa ou em MMP2 e MMP9 (p>0,05). O grupo A2 mostrou presença de gordura no fígado consistente com esteatose hepática. Alterações no tecido cerebral foram observadas nos grupos A1 e P1.

Combination therapy of curcumin and alendronate modulates bone turnover markers and enhances bone mineral density in postmenopausal women with osteoporosis

ABSTRACT Objective: This study evaluated the effects of combination therapy of curcumin and alendronate on BMD and bone turnover markers in postmenopausal women with osteoporosis. Subjects and methods: In a randomized, double-blind trial study, 60 postmenopausal women were divided into three groups: control, alendronate, and alendronate + curcumin. Each group included 20 patients. Total body, total hip, lumbar spine and femoral neck BMDs were measured by dual-energy X-ray absorptiometry (DXA) at baseline and after 12 months of therapy. Bone turnover markers such as bone-specific alkaline phosphatase (BALP), osteocalcin and C-terminal cross-linking telopeptide of type I collagen (CTx) were measured at the outset and 6 months later. Results: Patients in the control group suffered a significant decrease in BMD and increased bone turnover markers at the end of study. The group treated with only alendronate showed significantly decreased levels of BALP and CTx and increased levels of osteocalcin compared to the control group. The alendronate group also showed significant increases in the total body, total hip, lumbar spine and femoral neck BMDs at the end of study compared to the control group. In the curcumin + alendronate group, BALP and CTx levels decreased and osteocalcin levels increased significantly at the end of study compared to the control and alendronate groups. BMD indexes also increased in four areas significantly at the end of study compared to the control and alendronate groups. Conclusion: The combination of curcumin and alendronate has beneficial effects on BMD and bone turnover markers among postmenopausal women with osteoporosis. Arch Endocrinol Metab. 2018;62(4):438-45

Avaliação dos níveis séricos de glicose e insulina no uso de alendronato de sódio e atorvastatina cálcica na osteoporose induzida com dexametasona / Evaluation of serum levels of glucose and insulin in the use of sodium alendronate and atorvastatin calcium in dexamethasone-induced osteoporosis

Introdução: Além da indução da osteoporose, os glicocorticoides ocasionam aumento da resistência à insulina e gliconeogênese hepática, tendo como consequência a hiperglicemia. Objetivo: Avaliar comparativamente os efeitos do alendronato de sódio e da atorvastatina cálcica nos níveis séricos de glicose e insulina na osteoporose induzida com dexametasona. Métodos: A indução da osteoporose consistiu na administração de dexametasona na dose de 7,5 mg/kg de peso corporal, uma vez por semana durante 4 semanas, à exceção dos animais do grupo controle (G1). Os animais foram distribuídos nos seguintes grupos: G1 (grupo controle sem osteoporose), G2 (controle com osteoporose sem tratamento), G3 (com osteoporose tratado com alendronato de sódio 0,2 mg/kg) e G4 (com osteoporose tratado com atorvastatina cálcica 1,2 mg/kg). No período de 30 e 60 após o início do tratamento, foram coletadas amostras de sangue para as dosagens dos níveis séricos de glicose e insulina. Resultados: Os grupos G2 e G3, quando comparados com o grupo normal G1, apresentaram aumento da glicemia e insulinemia durante todo o período experimental. O grupo G4 apresentou, com 30 dias, aumento da glicemia e insulinemia e, com 60 dias, aumento da glicemia e queda da insulinemia. Conclusão: Os resultados demonstraram o quadro de hiperglicemia consequente do aumento da resistência à insulina, presentes na indução da osteoporose pela dexametasona. O alendronato de sódio não ocasionou nenhuma melhora da glicemia e insulinemia. A atorvastatina cálcica ocasionou agravamento da hiperglicemia e hiperinsulinemia, potencializando o quadro de resistência à insulina e levando a uma insuficiência relativa de insulina característica do diabetes mellitus tipo 2.

Introduction: In addition to the induction of osteoporosis, glucocorticoids cause increased insulin resistance and hepatic gluconeogenesis resulting in hyperglycemia. Objective: Evaluate the effects of sodium alendronate and atorvastatin calcium on serum glucose and insulin levels in osteoporosis induced by dexamethasone. Methods: The induction of osteoporosis consisted of the administration of dexamethasone at a dose of 7.5 mg / kg body weight, once a week for 4 weeks, except for the control animals (G1). The animals were divided into the following groups: G1 (control group without osteoporosis), G2 (control with untreated osteoporosis), G3 (with osteoporosis treated with sodium alendronate 0.2 mg / kg) and G4 (with osteoporosis treated with atorvastatin calcium 1,2 mg / kg). In the 30 and 60 period after the start of the treatment blood samples were collected for dosages of serum glucose and insulin levels. Results: The G2 and G3 groups, when compared with the normal group G1, presented increased glycemia and insulinemia throughout the experimental period. The G4 group presented a 30-day increase in glycemia and insulinemia and at 60 days increased glycemia and decreased insulinemia. Conclusion: The results demonstrated the hyperglycaemia associated with the increase in insulin resistance present in the induction of osteoporosis by dexamethasone. Sodium alendronate did not cause any improvement in glycemia and insulinemia. Atorvastatin calcium caused worsening of hyperglycemia and hyperinsulinemia enhancing insulin resistance, leading to a relative insufficiency of insulin characteristic of type 2 diabetes mellitus.

Short term sodium alendronate administration improves the peri-implant bone quality in osteoporotic animals

Abstract Sodium alendronate is a bisphosphonate drug that exerts antiresorptive action and is used to treat osteoporosis. Objective The aim of this study was to evaluate the bone repair process at the bone/implant interface of osteoporotic rats treated with sodium alendronate through the analysis of microtomography, real time polymerase chain reactions and immunohistochemistry (RUNX2 protein, bone sialoprotein (BSP), alkaline phosphatase, osteopontin and osteocalcin). Material and Methods A total of 42 rats were used and divided in to the following experimental groups: CTL: control group (rats submitted to fictitious surgery and fed with a balanced diet), OST: osteoporosis group (rats submitted to a bilateral ovariectomy and fed with a low calcium diet) and ALE: alendronate group (rats submitted to a bilateral ovariectomy, fed with a low calcium diet and treated with sodium alendronate). A surface treated implant was installed in both tibial metaphyses of each rat. Euthanasia of the animals was conducted at 14 (immunhostochemistry) and 42 days (immunohistochemistry, micro CT and PCR). Data were subjected to statistical analysis with a 5% significance level. Results Bone volume (BV) and total pore volume were higher for ALE group (P<0.05). Molecular data for RUNX2 and BSP proteins were significantly expressed in the ALE group (P<0.05), in comparison with the other groups. ALP expression was higher in the CTL group (P<0.05). The immunostaining for RUNX2 and osteopontin was positive in the osteoblastic lineage cells of neoformed bone for the CTL and ALE groups in both periods (14 and 42 days). Alkaline phosphatase presented a lower staining area in the OST group compared to the CTL in both periods and the ALE at 42 days. Conclusion There was a decrease of osteocalcin precipitation at 42 days for the ALE and OST groups. Therefore, treatment with short-term sodium alendronate improved bone repair around the implants installed in the tibia of osteoporotic rats.

Estudio radiográfico de la asociación de antioxidantes y bifosfonatos en remodelación ósea peri-Implantaria / Radiographic antioxidants association and biphosphonates study in bone remodeling peri-implant

Estudios previos han demostrado que los bisfosfonatos son potentes inhibidores de la resorción ósea. El aceite de oliva (O) es rico en ácidos grasos monoinsaturados con potentes propiedades anti-oxidantes. El objetivo de este estudio fue estudiar el efecto del tratamiento de alendronato (AL) y pamidronato (PA) y de O sobre la regeneración tisular. Las fórmulas se dosificaron 0,5 mg/kg de peso para AL, y de 0,6 mg/kg de peso para PA. El O se administró en la dieta, 50 g/ Kg. Cincuenta y cuatro ratas macho de la línea Wistar se dividieron en 6 grupos. El grupo control (C), recibió semanalmente 0,3 ml/100g de peso corporal de solución salina vía subcutánea. El grupo (AL) recibió semanalmente por vía subcutánea en el miembro posterior izquierdo. El grupo (PA) se colocó igual que el grupo anterior. El grupo (O) fue tratado en la alimentación y en las áreas de la cirugía recibieron inyección subcutánea con solución fisiológica. El grupo (ALO) recibió tratamiento combinado con AL y O. El grupo (PAO) se trató igual al anterior. La cirugía consistió en una incisión longitudinal en las tibias realizando un defecto circular en la parte plana de cada tibia hasta llegar al hueso medular. Se tomaron radiografías a los 0, 7, 15, 30, 60 y 90 días y fueron analizadas con el Software Image Pro Plus. Los estudios estadísticos se realizaron a través del análisis de la variancia a dos y tres criterios de clasificación. Se evidencio un incremento en la densidad mineral ósea promedio (DMO) conforme avanza el tiempo en todos los grupos, siendo evidentes con PA a los 60 días. El tratamiento O mostró eficacia en la remodelación ósea, observándose un pico a los 60 días. Esto sugiere que O representa una opción terapéutica para el tratamiento de las patologías óseas.

Previous studies have shown that bisphosphonates are potent inhibitors of bone resorption. Olive oil (O) is rich in monounsaturated fatty acids with potent anti-oxidant properties. The objective of this work was to study the effect of alendronate treatment (AL) and pamidronate (PA) and O on tissue regeneration. Formulas 0.5 mg / kg for AL dosed, and 0.6 mg / kg for PA. O was administered in the diet, 50 g / kg. Fifty-four male rats Wistar were divided into 6 groups. The control group (C) received weekly 0.3 ml / 100g body weight of saline subcutaneously. The group (AL) received a weekly dose subcutaneously in the left posterior limb. The group (PA) was placed as the previous group. The group (O) was treated in food and in the areas of surgery received subcutaneousinjection with saline. The group (ALO) received combined treatment with Al and O. The group (PAO) was treated the same as before. Surgery consisted of a longitudinal incision in the warm using a circular on the flat side of each tibia until the medullary bone defect. X-rays at 0, 7, 15, 30, 60 and 90 days were taken and analyzed with Image Pro Plus Software. Statistical studies were conducted through analysis of variance to two and three classification criteria. Results: an increase in the average bone mineral density (BMD) was evident as time progresses in all groups, with PA still evident at 60 days. Or treatment showed efficacy in bone remodeling observed a peak at 60 days. Conclusions: This suggests that O represents a therapeutic option for the treatment of bone disease.

New methodology for evaluating osteoclastic activity induced by orthodontic load

Orthodontic tooth movement (OTM) is a dynamic process of bone modeling involving osteoclast-driven resorption on the compression side. Consequently, to estimate the influence of various situations on tooth movement, experimental studies need to analyze this cell. Objectives The aim of this study was to test and validate a new method for evaluating osteoclastic activity stimulated by mechanical loading based on the fractal analysis of the periodontal ligament (PDL)-bone interface. Material and Methods The mandibular right first molars of 14 rabbits were tipped mesially by a coil spring exerting a constant force of 85 cN. To evaluate the actual influence of osteoclasts on fractal dimension of bone surface, alendronate (3 mg/Kg) was injected weekly in seven of those rabbits. After 21 days, the animals were killed and their jaws were processed for histological evaluation. Osteoclast counts and fractal analysis (by the box counting method) of the PDL-bone interface were performed in histological sections of the right and left sides of the mandible. Results An increase in the number of osteoclasts and in fractal dimension after OTM only happened when alendronate was not administered. Strong correlation was found between the number of osteoclasts and fractal dimension. Conclusions Our results suggest that osteoclastic activity leads to an increase in bone surface irregularity, which can be quantified by its fractal dimension. This makes fractal analysis by the box counting method a potential tool for the assessment of osteoclastic activity on bone surfaces in microscopic examination. .

Alendronate a promising/ multi aspect drug in the management of ostoeoporosis

Recently, osteoporosis is regarded as a major health concern due to increase in its incidence, associated morbidities and mortalities. Among antiresorptives, alendronate which is a bisphosphonate is FDA [Food and Drug Administration] approved drug of choice for postmenopausal and glucorticoid induced osteoporosis. It has been also recommended for the prevention of bone loss in perimenopausal women. Currently, it has been also viewed as a treatment option in osteoporotic males. Several clinical trials have highlighted the significant role of alendronate in the management of osteoporosis. Although it was proved to be a safe drug for long time periods but very recently some studies have reported the risk of low energy subtrochanteric and diaphyseal femoral shaft fractures in the chronic users of alendronate. The current review is undertaken to elaborate the different aspects related to this drug in the scenario of osteoporosis management

Análise histomorfométrica do reparo ósseo em tíbias de ratos castrados submetidos ao efeito do alendronato sódico / Histomorphometric analysis of bone repair in tibias of castrated rats submitted to the effects of sodium alendronate

OBJETIVO: Avaliar por meio da análise histomoerfométrica o efeito do alendronato sódico, utilizado para tratamento da osteoporose, na reparação óssea em defeitos previamente confeccionados em tíbias direitas de ratos submetidos à castração. MÉTODOS: Os ratos tratados receberam, uma vez por semana, injeção subcutânea de alendronato sódico diluído em solução salina na dose de 0,7mg/kg e os controles, a mesma dose de salina. Aos 16, 30 e 44 dias após a aplicação da primeira dose do alendronato sódico, os animais foram sacrificados, as tíbias direitas removidas e processadas para análise histomorfométrica. A densidade volumétrica foi estimada por um método de contagem diferencial de pontos, em imagens histológicas analisadas ao microscópio munido de uma ocular (10X) contendo um retículo com 25 pontos equidistantes totalizando 100 pontos para cada animal analisado. RESULTADOS: A análise demonstrou que a administração do alendronato sódico, em ratos castrados, estimulou a formação de tecido ósseo, em todos os períodos observados, sendo mais significante, nos períodos de 16 e 30 dias. CONCLUSÃO: O alendronato sódico interferiu na homeostasia mineral, favorecendo o reparo ósseo.

OBJECTIVE: This study used histomorphometric analysis to investigate the effect of sodium alendronate, used for the treatment of osteoporosis, on the repair of surgically-induced bone defects in the tibia of castrated rats. METHODS: The castrated animals were given subcutaneous injections of sodium alendronate (0.7mg/Kg) diluted in saline once a week; the control animals were given the same dose of saline. At 16, 30 and 44 days after the first injection of sodium alendronate, the animals were sacrificed and the right tibias were removed and processed for histomorphometric analysis. The volumetric bone mineral density was estimated by a reticular grid (25 points) attached to a light microscope. The number of points on the bone tissue was counted in the histological sections, totaling 100 points/animal. RESULTS: The results revealed that sodium alendronate stimulated bone formation in castrated rats in all occasions, mainly at 16 and 30 days. CONCLUSION: Sodium alendronate affects mineral homeostasis, promoting bone repair.

Influence of bisphosphonates on alveolar bone density: a histomorphometric analysis

This study is a histomorphometrical analysis of the influence of the bisphosphonate alendronate on alveolar bone density. Eighteen male Wistar rats were randomly assigned to a control group (n = 9) that received no medication and an experimental group (n = 9) that received oral alendronate (1 mg/kg) from birth until euthanization at 3 months of age. Semi-serial 4-µm-thick transverse sections were obtained from the region between the roots of the left maxillary first molar, stained with hematoxylin and eosin, and examined with a Zeiss Axioskop II optical microscope for histomorphometric analysis. The images were captured with a digital camera coupled with the microscope and connected to a computer, and were analyzed using Image J 1.34s image-analysis software. A 1,200-point grid was positioned onto each digitized image. The number of intersection points of grid lines in the bone tissue was counted. The ratio between the number of points in the bone tissue and the total number of points of the grid (1,200) was used to determine the bone density of the analyzed tissue. Data from the control and experimental groups were compared and analyzed statistically by the Student's t-test (p = 0.05). There was no statistically significant difference (p = 0.3754) in the alveolar bone density between the control and alendronate-treated animals. It may be concluded that the bisphosphonate alendronate did not alter the morphology of the alveolar bone, maintaining its structural tissue characteristics in healthy animals.

Acute Effects of Intravenous Administration of Pamidronate in Patients with Osteoporosis

We investigated acute effects of intermittent large dose bisphophonate therapy in osteoporotic patients. Peripheral blood mononuclear cells were incubated with alendronate (100 micrometer) for 18 hr, in vitro and cytokine expressions were measured by real-time RT-PCR. Pamidronate 30 mg was administered on 26 osteoporotic patients; and acute phase reactants, inflammatory cytokines and bone biomarkers were measured. The in vitro study showed significant increase in mRNA expression of IL-6, TNF-alpha and IFN-gamma. A notable rise in serum C-reactive protein (CRP) was observed over 3 days after pamidronate infusion (P=0.026). Serum levels of TNF-alpha, IL-6 and IFN-gamma were also significantly increased (P=0.009, 0.014, 0.035, respectively) and the increase in IL-6 levels were strongly correlated with CRP levels (P=0.04). Serum calcium and c-telopeptide levels rapidly decreased after the treatment (P=0.02, <0.001, respectively). This study showed that mRNA expression of inflammatory cytokines at peripheral blood mononuclear cells (PBMC) level were observed within 18 hr and marked elevation of inflammatory cytokines and acute phase reactants were demonstrated after pamidronate infusion at the dose for osteoporosis. Our studies confirmed that intermittent large dose aminobisphosphonate causes acute inflammation.

Comparison of the Effects of Alendronate and Alfacalcidol on Hip Bone Mineral Density and Bone Turnover in Japanese Men Having Osteoporosis or Osteopenia with Clinical Risk Factors for Fractures

PURPOSE: The comparative effects of alendronate and alfacalcidol on bone mineral density (BMD) and bone turnover have already been established in postmenopausal women with osteoporosis. An open-labeled prospective study was conducted to compare the treatment effects of alendronate and alfacalcidol on hip BMD and bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures. MATERIALS AND METHODS: One hundred twelve men with osteoporosis or osteopenia with clinical risk factors for fractures (mean age: 71.4 years) were randomly divided into two groups of 56 patients each: the alendronate (5 mg daily) and alfacalcidol (1 microgram daily) groups. The BMD of the total hip, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of bone-specific alkaline phosphatase (BSAP) were measured during the 12-month-treatment period. RESULTS: Forty-five patients in the alendronate group and 42 patients in the alfacalcidol group completed the trial. Alendronate increased BMD (+2.3% at 12 months) following reductions in the urinary level of NTX (-46.4% at 3 months) and serum level of BSAP (-34.1% at 12 months), while alfacalcidol sustained BMD (-1.9% at 12 months) as well as the urinary level of NTX (+13.2% at 3 months) and serum level of BSAP (+1.8% at 12 months). CONCLUSION: The present study confirmed that alendronate has better efficacy than alfacalcidol (active control) in increasing hip BMD and reducing bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures.

Comparison of the Effects of Alendronate and Alfacalcidol on Hip Bone Mineral Density and Bone Turnover in Japanese Men Having Osteoporosis or Osteopenia with Clinical Risk Factors for Fractures

PURPOSE: The comparative effects of alendronate and alfacalcidol on bone mineral density (BMD) and bone turnover have already been established in postmenopausal women with osteoporosis. An open-labeled prospective study was conducted to compare the treatment effects of alendronate and alfacalcidol on hip BMD and bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures. MATERIALS AND METHODS: One hundred twelve men with osteoporosis or osteopenia with clinical risk factors for fractures (mean age: 71.4 years) were randomly divided into two groups of 56 patients each: the alendronate (5 mg daily) and alfacalcidol (1 microgram daily) groups. The BMD of the total hip, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of bone-specific alkaline phosphatase (BSAP) were measured during the 12-month-treatment period. RESULTS: Forty-five patients in the alendronate group and 42 patients in the alfacalcidol group completed the trial. Alendronate increased BMD (+2.3% at 12 months) following reductions in the urinary level of NTX (-46.4% at 3 months) and serum level of BSAP (-34.1% at 12 months), while alfacalcidol sustained BMD (-1.9% at 12 months) as well as the urinary level of NTX (+13.2% at 3 months) and serum level of BSAP (+1.8% at 12 months). CONCLUSION: The present study confirmed that alendronate has better efficacy than alfacalcidol (active control) in increasing hip BMD and reducing bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures.

Ação local do alendronato sódico na reparação óssea de ratos espontaneamente hipertensos (SHR) / Local action of sodium alendronate in bone repair of spontaneously hypertensive rat (SHR)

FUNDAMENTO: A hipertensão arterial é uma desordem caracterizada por alterações relevantes no tecido ósseo. O alendronato sódico tem indicação no tratamento de doenças ósseas, por causa de sua afinidade pela hidroxiapatita, inibindo as reabsorções ósseas. OBJETIVO: Analisar a ação local do alendronato sódico na reparação óssea de ratos espontaneamente hipertensos (SHR). MÉTODOS: Um defeito ósseo foi criado no fêmur esquerdo de 80 ratos. De acordo com o material utilizado no local, criaram-se quatro grupos: controle (C), amido (Am), alendronato 1 mol (A1) e alendronato 2 mol (A2). Após 7 e 21 dias, os animais foram sacrificados. Foram realizadas análises histológicas e histomorfométricas e os dados foram submetidos a análise de variância (ANOVA) e teste de Tukey (5 por cento). RESULTADOS: Aos 7 dias, observou-se, na área do defeito, tecido conjuntivo com hemorragia e inflamação em todos os grupos. Alguns apresentavam matriz osteóide. Os grupos A1 e A2 apresentaram, ainda, uma rede de fibrina. Aos 21 dias, as trabéculas ósseas fechavam praticamente a extensão do defeito nos grupos C e Am. No grupo A1 de animais machos, observaram-se trabéculas que se irradiavam do canal medular até a área do defeito. Nos grupos A1 e A2, constatou-se apenas a presença de tecido conjuntivo com mínima deposição de osteóide. Um achado histológico marcante foi a formação de tecido ósseo extracortical subperiosteal nos animais dos grupos A1 e A2. CONCLUSÃO: Concluiu-se que a administração do alendronato sódico não contribuiu para o reparo ósseo nos ratos SHR, mas possivelmente tenha sido responsável pelas formações ósseas extracorticais observadas.

BACKGROUND: The arterial hypertension is a disorder characterized by relevant alterations in the bone tissue. The sodium alendronate is indicated in the treatment of bone diseases, because of its affinity with the hydroxyapatite, inhibiting the bone reabsorptions. OBJECTIVE: To analyze local action of the sodium alendronate in the bone repair of spontaneously hypertensive rat (SHR). METHODS: A bone defect was created in the left femur of 80 rat. In agreement with the material used at the place, four groups were created: control (C), starch (St), alendronate 1 mol (A1) and alendronate 2 mol (A2). After 7 and 21 days, the animals were sacrificed. Histomorfometrical and histological analyses were accomplished and the data were submitted the variance analysis (ANOVA) and test of Tukey (5 percent). RESULTS: At 7 days, in the area of the defect, conjunctive tissue with hemorrhage and inflammation in all of the groups was observed. Some presented osteoid matrix. The groups A1 and A2 presented, further, a fibrin net. At 21 days, the bone trabeculae practically closed the extension of the defect in the groups C and St. In the group A1 of male animals, trabeculae were observed that irradiated from the medullary canal to the area of the defect. In the groups A1 and A2, only presence of conjunctive fabric with low osteoid deposit was observed. An outstanding histological discovery was the formation of extracortical subperiosteal bone tissue in animals of the groups A1 and A2. CONCLUSION: The administration of sodium alendronate did not contribute to bone repair in SHR rat, but possibly has been responsible for the extracortical bone formation observed.

effect of bisphosphonate on prevention of glucocorticoid-induced osteoporosis

Glucocorticoid therapy can induce osteoporosis. Bone mineral density [BMD] measurement has been used to assess the risk of fracture in these patients. The most important mechanism is diminished bone formation mainly at the sites with trabecular bone. The objective of this study is to evaluate the effect of alendronate on prevention of glucocorticoid-induced osteoporosis. During 18 months, in a prospective clinical trial, 72 patients with autoimmune disease were randomly divided into 2 equal groups. Group 1 [n=36] was treated with oral vitamin-D, 50000 IU twice weekly and calcium, 500 mg twice daily. Group 2 [n=36] was treated with oral vitamin-D, 50000 IU twice weekly, calcium, 500 mg twice daily, and alendronate, 10 mg per day. The patients were followed clinically, undergoing densitometry and X-ray of the spine and hip area for 18 months. Change of BMD in the lumbar spine after 18 months of therapy was -1/67% and +2.4% in groups 1 and 2, respectively. Change in femoral neck BMD was -2.1% in group 1 and +1.8% in group 2. The administration of alendronate plus vitamin D and calcium was more effective in preventing bone loss due to glucocorticoid-induced osteoporosis than vitamin-D and calcium alone

Caracterização do uso de alendronato de sódio no tratamento de osteoporose por clínicos da rede privada de duas cidades do interior de São Paulo / Survey of the use of sodium alendronate in osteoporosis treatment by physicians in the private health system in two towns in São Paulo

O estudo mostrou como os clínicos da rede privada de Amparo e Pedreira, no interior do estado de São Paulo, utilizam o alendronato de sódio como recurso terapêutico na osteoporose. Esta enfermidade é de alta prevalência na população idosa, sendo tratada por médicos de diferentes especialidades. Este estudo, do tipo observacional, transversal e descritivo, foi realizado pormeio de entrevistas com 32 médicos para obtenção de dados sobre indicação, forma de utilização, seguimento de tratamento, medidas não farmacológicas e referencial teórico utilizado pelos entrevistados. Os resultadosmostraram que há concordância com o preconizado em consensos e guias terapêuticos em relação à indicação,doses recomendadas e medidas não farmacológicas, porém, foram verificadas falhas no seguimento dotratamento e na orientação dada ao paciente para a administração correta do medicamento, além de descrição imprecisa de fontes de informação. Concluiu-se que a atualização científica em fontes referenciais (ensaios randomizados controlados, metanálises) é indispensável para ajudar os clínicos na promoção do uso racional do alendronato de sódio no tratamento de osteoporose.

This is a study of how physicians working in the private health system in the towns of Amparo and Pedreira (upstate São Paulo, 75 miles away from the State capital) use sodium alendronate in the treatment of osteoporosis. This disease is highly prevalent in the elderly population and is treated by consultant clinicians/various specialities. The paper describes an observational, cross-sectional study that was carried out by interviewing 32 clinicians to evaluate: indication, usage, follow-up and evaluation of treatment, non pharmacological measures and source of information used by interviewees. The results show that clinical practice is in conformity with what is recommended in clinical guidelines and the general consensus, concerning indication, doses, and nonpharmacological measures. However, some faults were found in the course of treatment and in the advice given to the patients on how to take the drug, as well as imprecise descriptions of the sources of information by the doctors interviewed. It is concluded that constant scientific updating based on sources of reference (Randomized Controlled Trial, Meta- Analysis) is an indispensable aid to these clinicians in promoting the rational use of sodium alendronate inthe treatment of osteoporosis.

Efeitos de alendronato de sódio, atorvastatina cálcica e ipriflavona sobre a osteoporose induzida com dexametasona em ratas / Effects of alendronate, atorvastatin and ipriflavone on dexamethasone-induced osteoporosis

O crescente aumento da prevalência da osteoporose tem sido considerado um grave problema de saúde pública no mundo. A osteoporose é uma doença caracterizada por diminuição da massa óssea, com conseqüente aumento do risco de fraturas, necessitando, portanto, de métodos preventivos e de tratamentos eficazes. O presente trabalho teve como objetivo verificar, comparativamente, os efeitos do bifosfonato alendronato de sódio, da estatina atorvastatina cálcica e do flavonóide ipriflavona sobre a osteoporose induzida pelo glicocorticóide dexametasona em ratas. Os efeitos desses fármacos foram avaliados pelos marcadores bioquímicos cálcio e fósforo sérico, fosfatase alcalina óssea e exame histomorfométrico. Os resultados obtidos a partir da análise dos marcadores bioquímicos não foram significativos, não fornecendo subsídios para o diagnóstico e acompanhamento do tratamento da osteoporose. No entanto, a avaliação histomorfométrica permitiu a análise estática e dinâmica, bem como detecção de alterações teciduais na unidade metabólica óssea, particularmente, no osso trabecular. Verificou-se que os tratamentos testados determinaram resultados significativos no aumento da densidade trabecular óssea, destacando-se o bifosfonato que apresentou o melhor resultado, alcançando níveis de densidade trabecular óssea semelhantes aos dos animais intactos. Além disso, a histomorfometria se mostrou válida na detecção da osteoporose, podendo servir de modelo para o estudo de drogas sobre este distúrbio ósteo-metabólico

Oral bisphosphonates in polyostotic fibrous dysplasia.

The bisphosphonates inhibit osteoclastic bone resorption and have been used as an intravenous infusion in fibrous dysplasia of the bone. Oral bisphosphonates are cheaper and also easy to administer. We report a case of polyostotic fibrous dysplasia in a three-year-old child who showed significant improvement in bone mineral density after treatment with oral alendronate.

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

The objective of the present study was to evaluate the effect of 17á-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 17á-estradiol at a dose of 30 æg/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 17á-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