Análisis costo-efectividad de alternativas de tratamiento para osteoporosis en mujeres postmenopáusicas en México / Cost-effectiveness analysis of treatment alternatives for osteoporosis in postmenopausal women in Mexico

Resumen Objetivo: Identificar el tratamiento de osteoporosis más costo- efectivo en la prevención de fracturas de cadera en mujeres mexicanas postmenopáusicas sin seguridad social en el primer nivel de atención. Material y Métodos: Se realizó un análisis de costo-efectividad para tres esquemas de tratamiento de osteoporosis seleccionados por sus diferentes vías de aplicación y dosificación. Los tratamientos se estimaron para el periodo de un año. Los costos de cada intervención se estimaron desde la perspectiva del proveedor y se tomaron los precios del mercado mexicano disponibles en julio de 2021. La efectividad se determinó a partir de estudios previos sobre el efecto de los medicamentos sobre la fractura de cadera. Se determinó el coeficiente costo-efectividad de cada tratamiento. Resultados: La intervención con mayor costo-efectividad fue el tratamiento con alendronato de 10 mg, medicamento de administración diaria por vía oral, para el cual se obtuvo un costo de $188,482.40 USD, una tasa de efectividad de 55% y un coeficiente de efectividad de 0.0343. El tratamiento con denosumab fue el más costoso ($725,625.05 USD) y el menos costo- efectivo (Coeficiente C-E 0.1814), mientras que el ácido zoledrónico tuvo un costo de $377,291.92 USD y un coeficiente C-E de 0.0920. Conclusiones: El alendronato es el tratamiento de la osteoporosis más costo-efectivo para la prevención de fracturas de cadera en mujeres postmenopáusicas, por lo cual debería recomendarse como primera opción en estas pacientes.

Abstract Objective: To identify the most cost-effective treatment for osteoporosis in the prevention of hip fractures in postmenopausal Mexican women without social security in the first level of care. Material and Methods: A cost-effectiveness analysis was performed for three osteoporosis treatment schemes selected for their different administration routes and dosage. The treatments were estimated for a one-year period. The costs of each intervention were estimated from the provider's perspective and the prices from the Mexican market available for July 2021 were considered. Treatment effectiveness was determined from previous studies on the effect of each treatment on the prevention of hip fractures. The cost-effectiveness coefficient was calculated for each treatment. Results: The most cost-effective treatment was 10 mg alendronate, a daily oral treatment, with a $188,548.61 USD cost, a 55% effectiveness and a 0.0377 cost-effectiveness coefficient. Treatment with denosumab was the most expensive ($725,625.05 USD) and the least effective (C-E coefficient 0.1814), zoledronic acid had a $377,291.92 USD cost and a 0.0920 C-E coefficient. Conclusions: Alendronate is the most cost-effective treatment of osteoporosis for the prevention of hip fractures in postmenopausal women and should be recommended as the first-line treatment in these patients.

An inconvenient status in anti-osteoporotic treatment process: corticosteroid use

SUMMARY OBJECTIVE: There are limited studies investigating the comparison of the efficacy of anti-osteoporotic drugs in different conditions resulting in osteoporosis in older adults. This study aimed to compare the effectiveness of anti-osteoporotic agents in older adults with or without glucocorticoid-induced osteoporosis. METHODS: This retrospective study included 364 patients with osteoporosis, aged 65 years and older. Bone mineral density measurement was performed, and the percent change from baseline was calculated at month 24. RESULTS: Of the 364 patients, 80 were glucocorticoid users. Similar changes in the bone mineral density of the lumbar spine and femoral neck and fracture risk were found in patients with or without glucocorticoid-induced osteoporosis. There was no significant difference in bone mineral density changes between the groups in terms of anti-osteoporotic agents used. CONCLUSIONS: This study demonstrated that the response to anti-osteoporotic agents was similar in older adults with glucocorticoid-induced osteoporosis and those without glucocorticoid-induced osteoporosis. The results of our study may guide osteoporosis treatment in older individuals with glucocorticoid-induced osteoporosis.

Histomorphometry of Bone Microarchitecture in Rats Treated with Vitamin D and Bisphosphonate in the Management of Osteoporosis / Histomorfometria da microarquitetura óssea em ratas tratadas com vitamina D e bisfosfonato no manejo da osteoporose

Abstract Objective To verify how the combined administration of alendronate (ALN) and vitamin D3 (VD) acts on the bone microarchitecture in rats with glucocorticoid-induced osteoporosis. Methods The experiment used 32 90-day-old female Wistar rats weighing between 300 and 400g. The induction of osteoporosis consisted of intramuscular administration of dexamethasone at a dose of 7.5 mg/kg of body weight once a week for 5 weeks, except for the animals in the control group. The animals were separated into the following groups: G1 (control group without osteoporosis), G2 (control group with osteoporosis without treatment), G3 (group with osteoporosis treated with ALN 0.2 mg/kg), G4 (group with osteoporosis treated with VD 10,000UI/500μL), and G5 (group with osteoporosis treated with ALN þ VD). The right femurs of the rats were fixed in 10% buffered formaldehyde, decalcified, and processed for inclusion in paraffin. Histological sections were stained with hematoxylin-eosin for histomorphometric analysis. Cortical thickness and medullary cavity were measured in cross-sections. Results There was a statistical difference (p< 0.05) between groups G3 and G5 compared with the positive control group (G2), both related to the measurement of cortical thickness and to the total diameter of the bone. In the evaluation of the spinal area, only the G3 group has shown to be statistically different from the G2 group. Conclusion Concomitant treatment with daily ALN and weekly VD is effective in preventing glucocorticoid-induced bone loss. However, there was no difference between the therapy tested and treatment with ALN alone.

Resumo Objetivo Verificar como a administração conjunta de alendronato de sódio (ALN) e vitamina D3 (VD) atua na microarquitetura óssea em ratas com osteoporose induzida por glicocorticoide. Métodos O experimento utilizou 32 ratas da linhagem Wistar, com peso médio de 300 a 400g, com 90 dias de vida. A indução da osteoporose consistiu na administração de dexametasona na dose de 7,5 mg/kg de peso corporal, por via intramuscular, 1 vez por semana durante 5 semanas, à exceção dos animais do grupo controle. Os animais foram distribuídos nos seguintes grupos: G1 (grupo controle sem osteoporose), G2 (grupo controle com osteoporose sem tratamento), G3 (grupo com osteoporose tratado com ALN 0,2 mg/kg), G4 (grupo com osteoporose tratado com VD 10.000UI/500μL) e G5 (grupo com osteoporose tratado com ALN þ VD). Os fêmures direitos das ratas foram fixados em formol a 10% tamponado, descalcificados e processados para inclusão em parafina. Os cortes histológicos foram corados com hematoxilina-eosina para análise histomorfométrica. A espessura cortical e a cavidade medular foram medidas em cortes transversais. Resultados Houve diferença estatística (p< 0,05) entre os grupos G3 e G5 em relação ao grupo controle positivo (G2), tanto em relação à medida da espessura cortical quanto em relação ao diâmetro total do osso. Na avaliação da área medular, apenas o grupo G3 se mostrou estatisticamente diferente do grupo G2. Conclusão O tratamento concomitante com ALN diário e VD semanal é eficaz para prevenir a perda óssea induzida por glicocorticoide. No entanto, não houve diferença entre esta terapia testada e o tratamento apenas com o ALN.

Experimental study of alendronate sodium in the treatment of denervated skeletal muscle atrophy / 中华骨科杂志

Objective:To observe the effects of alendronate (ALN) on the expression of autophagy signaling pathway related proteins LC3, Beclin-1 and P62 in the muscle tissue of mice with denervated skeletal muscle atrophy, and to explore the potential molecular biological mechanism of ALN in the treatment of skeletal muscle atrophy.Methods:Thirty males C57BL/6 mice were divided into three groups with 10 mices in each group by random number method, including blank control group: sciatic nerve exposed without resection, model group: sciatic nerve exposed and resection, ALN group: sciatic nerve resection +ALN intervention. At the intervention stage, mices were given 1 mg/kg ALN by intragastric administration. The weight of gastrocnemius muscle was weighed by wet weight method. Atpase staining was used to distinguish muscle fiber types. HE staining was used to observe the arrangement and cross-sectional area of gastrocnemius muscle fibers in each group, and further quantitative analysis was performed by Image J 1.48 software. Western blotting and immunohistochemical staining were performed to detect the expressions of MHC and MuRF1 as well as LC3, Beclin-1 and P62 in gastrocnemius tissues of each group.Results:The weight of gastrocnemius muscle in the model group 137±7.80 mg was significantly lower than that in the blank control group 203±10.34 mg, which proved that the denervation muscle atrophy mouse model was successfully established. After intervention, the gastrocnemius muscle weight of ALN group 177±11.65 mg was significantly higher than that of model group, and the muscle mass was significantly improved. HE staining showed that muscle fibers in the model group were loosely arranged and the cross-sectional area was significantly smaller than that in the blank control group, and there were more blue stains among muscle fibers. Atpase staining showed that the distribution of type II muscle fibers in the model group was increased compared with that in the blank control group, and the distribution of type II muscle fibers in the ALN group was decreased compared with that in the model group, but higher than that in the blank control group. The results showed that the most widely distributed muscle fiber cross-sectional area was 600-800μm 2 in the blank control group, 200-400 μm 2 in the model group, and 400-600 μm 2 in the ALN group. The results of quantitative calculation of muscle fiber cross-sectional area by Image J 1.48 showed that the mean value of muscle fiber cross-sectional area in the model group was (352±18) μm 2, which was significantly reduced compared with the blank control group 794±20 μm 2. After ALN treatment, muscle fiber cross-sectional area recovered somewhat. The mean muscle fiber cross-sectional area of ALN group was 578±23 μm 2, which increased muscle fiber cross-sectional area by 29%. Western blotting results showed that the expressions of MHC, LC3 and Beclin-1 in model group were significantly lower than those in blank control group ( P<0.05), while MuRF1 and P62 proteins were significantly higher than those in blank control group ( P<0.05). The MHC, LC3 and Beclin-1 proteins in ALN group were significantly higher than those in model group (0.12±0.01 vs. 0.10±0.003, 0.15±0.02 vs. 0.10±0.02, 0.13±0.03 vs. 0.09±0.04). MuRF1 and P62 proteins in ALN group were significantly lower than those in model group (0.10±0.004 vs. 0.15±0.01, 0.16±0.03 vs. 0.20±0.03). MHC immunohistochemical staining showed that the expression of MHC in gastrocnemius of mice in model group was significantly lower than that in blank control group, and the expression of MHC in gastrocnemius of mice in ALN group was higher than that in model group ( P<0.05). Conclusion:ALN has a therapeutic effect on skeletal muscle atrophy, and its mechanism may be realized by moderately activating the LC3/Beclin-1 autophagy signaling pathway.

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.

Alendronato de sódio e vitamina D na osteoporose pós-menopausa: revisão sistemática / Alendronate sodium and vitamin D in postmenopausal osteoporosis: a systematic review

Objetivo: avaliar a eficácia da utilização da terapia combinada de alendronato de sódio e vitamina D no metabolismo ósseo de mulheres em tratamento de osteoporose pós-menopausa. Métodos: trata-se de uma revisão sistemática, a qual foram pesquisados ensaios clínicos randomizados (ECR) indexados nas bases de dados BVS, ISI Web of Science, PubMed, SciELO, ScienceDirect e Scopus que comparavam a associação de alendronato sódico e vitamina D com a monoterapia de alendronato de sódio. Resultados: um total de seis ECR contemplou os critérios para serem inclusos nesse estudo, compreendendo um total de 4164 participantes e seus respectivos dados. Os estudos avaliaram diferentes domínios do metabolismo ósseo, como níveis séricos de vitamina D, paratormônio, densidade mineral óssea e marcadores de turnover ósseo. A terapia combinada produziu melhora significativa nos marcadores metabólicos ósseos. Conclusão: a terapia combinada de alendronato de sódio com vitamina D promove melhora no metabolismo ósseo de mulheres com osteoporose pós-menopausa.

Aim: to evaluate the effectiveness of using the combined therapy of sodium alendronate and vitamin D on bone metabolism in women undergoing postmenopausal osteoporosis. Methods: this is a systematic review. The studies included were Randomized Controlled Trials (RCT) indexed in the BVS, ISI Web of Science, PubMed, SciELO, ScienceDirect and Scopus Databases which compared the association of sodium alendronate and vitamin D to monotherapy of sodium alendronate. Results: a total of six RCT met the criteria to be included in this study, comprising a total of 4164 participants and their respective data. The studies evaluated different domains of bone metabolism, such as serum levels of vitamin D, parathyroid hormone, bone mineral density and bone turnover markers. Combination therapy produced significant improvement in bone metabolic markers. Conclusion: combined therapy of sodium alendronate with vitamin D promotes improved bone metabolism in women with postmenopausal osteoporosis.

Sodium alendronate: proposal and reliability of indicators

Abstract The present study proposes and evaluates the test-retest reliability of indicators of the correct use of sodium alendronate in elderly patients. This is a test-retest reliability study for use of sodium alendronate. Six questions to evaluate the correct use of this medicine were elaborated after analysis of information in the literature. Data collection was performed through questionnaires in face-to-face in-home interviews by previously trained interviewers. The participants were initially interviewed (test) when they agreed to participate in the study, and secondly (retest), after a period of 7 to 14 days from the first interview. The reliability of the questions was evaluated by means of the agreement percentage and the Kappa coefficient. Fifty-seven pairs (test-retest) were obtained. The mean age was 69.3 (SD = 6.9) years, the majority (92.5%) completed elementary education, and declared themselves white (50.9%). All the questions presented high concordance ranging from 79.0% to 98.3%. The Kappa values ranged from 0.1 (low) to 0.83 (very good). The agreement percentage and the Kappa values suggest adequate reliability of the proposed questions. We suggest that they can be used as a simple and quick way to evaluate the quality of sodium alendronate use among the elderly.

Alendronato de sódio tópico associado ao osso bovino liofilizado no reparo ósseo / Topical alendronate associated with lyophilized bovine bone in bone repair

Introdução: O osso bovino inorgânico é o enxerto mais utilizado na Odontologia, tendo como desvantagem longo tempo de integração ao leito receptor. Os bifosfonatos têm sido utilizados para modular a quantidade e a qualidade do osso regenerado e diminuir o tempo de integração do enxerto. Objetivo: Avaliar o efeito do bifosfonato alendronato de sódio (ALN) 0,5%, associado ou não ao osso bovino inorgânico, na reparação de defeitos ósseos. Material e método: Dois defeitos ósseos foram confeccionados na calvária de 12 coelhos, sendo a cavidade esquerda/experimental preenchida com: GI = osso bovino inorgânico (Bio-Oss®); GII = Bio-Oss® + ALN 0,5%; GIII = ALN 0,5%; e a cavidade direita por coágulo sanguíneo (controle). Os animais foram mortos aos 60 dias pós-operatórios. Por meio de análise histomorfométrica calculou-se o percentual de osso neoformado e remanescente do biomaterial em relação à área total do defeito. Resultado: Osso neoformado: GI = 38,16 ± 15,44%; GII = 55,77 ± 16,75%; GII I = 60,28 ± 11,45%. Controle = 45,11 ± 11,09%. Remanescente do enxerto: GI = 7,02 ± 5,36% e GII = 16,59 ± 9,56%. Não houve diferença quanto ao percentual de osso neoformado entre os grupos (ANOVA p = 0,15512; teste de Tukey F = 2,089). O percentual de remanescente do enxerto também foi estatisticamente semelhante entre os grupos GI e GII (teste de Tukey F = 5,019). Conclusão: O uso tópico da solução de ALN 0,5% isoladamente ou associado ao osso bovino liofilizado não alterou o percentual de neoformação óssea nem a degradação dos grânulos do enxerto.

Introduction: Inorganic bovine bone is the most used graft in dentistry, with the disadvantage of long integration time into the receptor bed. Bisphosphonates have been used to modulate the quantity and quality of regenerated bone and decrease graft integration time. Objective: To evaluate the effect of alendronate sodium bisphosphonate (ALN) 0.5%, associated or not with Inorganic bovine bone, in the repair of bone defects. Material and method Two bone defects were made in the calvaria of 12 rabbits, and the left/experimental cavity was filled with: GI = Inorganic bovine bone (Bio-Oss®); GII = Bio-Oss® + 0.5% ALN; GIII = 0.5% ALN; and the right cavity/blood clot control. The animals were killed at 60 days after surgery. Through histomorphometric analysis, the percentage of newly formed bone and remnant biomaterial relative to the total area of the defect was calculated. Result: Neoformed bone: GI = 38.16 ± 15.44%, GII = 55.77 ± 16.75%; GIII= 60.28 ± 11.45%; Control=45,11 ± 11,09%. Graft remnant: GI = 7.02 ± 5.36% and GII = 16.59 ± 9.56%. There was no difference in the percentage of newly formed bone between the groups (ANOVA p = 0.15512; Tukey's test F = 2.089). The percentage of graft remnant was also statistically similar between groups GI and GII (Tukey's test F = 5019). Conclusion: Topical use of 0.5% ALN solution alone or associated with lyophilized bovine bone did not change the percentage of bone neoformation, nor the degradation of graft granules.

Alendronate combined with Lactobacillus rhamnosus to combat bone loss in ovariectomized mice / 中华创伤骨科杂志

Objective:To study the protective effect of alendronate combined with Lactobacillus rhamnosus on bone loss in ovariectomized mice.Methods:Fifty female C57BL/6 mice were divided into 5 equal groups ( n=10). Ovariotomy was performed in groups A, B, C and D while a sham operation was performed in group E. Group A was subjected to combined administration of alendronate and Lactobacillus rhamnosus, group B to administration of alendronate, group C to administration of Lactobacillus rhamnosus, and groups D and E to administration of physiological saline only. At 3 months after operation, all the mice were sacrificed to harvest their femurs. Micro CT scanning was performed to detect the bone mineral density (BMD), trabecular relative volume, bone surface area/bone volume, and trabecular thickness and number of trabecular bone. Three-point bending test was used to detect the maximum load, stiffness, ultimate load, Young＇s modulus, and fracture energy. Osteocalcin and alkaline phosphatase levels were measured using blood samples from the mice eyeballs. The 2 groups were compared in terms of all the above indexes. Results:The BMD [(669.87±67.87) mg/cm 3], maximum load [(14.35±0.75) N] and fracture energy [(1,497.43±38.29) J/m 2] in group A were significantly higher than those in group B [(520.07±9.01) mg/cm 3, (11.94±0.82) N and(1,277.61±35.12) J/m 2] and group C [(388.15±25.61) mg/cm 3, (11.10±0.93) N and (1,115.27±63.24) J/m 2] (all P<0.05). The osteocalcin level in group A [(22.25±1.78) ng/mL] was significantly higher than that in group B [(19.08±1.45) ng/mL] and group D [(19.33±1.66) ng/mL] (both P<0.05). The alkaline phosphatase level in group A [(83.21±9.69) ng/mL] was significantly lower than that in group C [(113.16±14.44) ng/mL] and group D [(137.96±14.01) g/mL] (both P<0.05). Conclusion:Alendronate combined with Lactobacillus rhamnosus may play a synergistic role in prevention of bone loss in ovariectomized mice, because combined administration of the two is more effective than administration of either of the two.

Effect of atorvastatin combined with alendronate in the treatment of T2DM with osteoporosis on bone metabolism, TNF-α, IL-6, and 25- (OH) D levels / 中华内分泌外科杂志

Objective:To investigate the effects of atorvastatin combined with alendronate in the treatment of type 2 diabetes mellitus (T2DM) with osteoporosis (OP) on bone metabolism, tumor necrosis factor alpha (TNF-α) , interleukin 6 (IL-6) , and 25-hydroxyvitamin D[25- (OH) D] level.Methods:A total of 152 patients with T2DM and OP who were diagnosed and treated in our hospital from Jul. 2017 to Jul. 2020 were selected. According to the different treatment methods, they were divided into control group (73 cases with alendronate treatment) and study group (79 cases receiving atova Statins combined with alendronate sodium treatment) . The two groups were compared in terms of bone metabolism indexes, bone mineral density, changes in serum TNF-α, IL-6, 25- (OH) D levels, and adverse reactions before and after treatment.Results:After treatment, osteocalcin (BGP) , bone-specific alkaline phosphatase (BAP) , lumbar spine L1-4 bone mineral density, femoral neck bone mineral density, and 25- (OH) D of the two groups increased ( P< 0.001) , and the study group was significantly higher than the control group (BGP: 7.68±0.89 vs 6.88±0.93; BAP: 18.62±3.97 vs 16.82±3.24; lumbar spine L1-4: 0.95±0.08 vs 0.92±0.05; femoral neck: 0.79±0.07 vs 0.75±0.06; 25- (OH) D: 31.35±10.1 vs 26.54±7.14; all P<0.05) . After treatment, the serum type I collagen C-terminal peptide (s-CTX) , human tartrate acid phosphatase (TRAP-5b) , TNF-α, IL-6 were decreased for both groups ( P<0.001) , and they were significantly lower in the study group than those in the control group (s-CTX:0.37±0.12 vs 0.55±0.12; TRAP-5b: 2.43±0.66 vs 2.99±0.75; TNF-α: 9.93±1.91 vs 11.77±2.69; IL-6: 10.65±1.26 vs 12.91±1.21; all P<0.001) . The incidence of adverse reactions in the study group was significantly lower than that in the control group (16.46% vs 39.73%, P=0.001) . Conclusion:Atorvastatin combined with alendronate in the treatment of T2DM patients with OP can effectively increase 25- (OH) D levels, reduce inflammation, and promote bone metabolism and bone density.

Early predictive value of bone turnover markers for the changes of bone mineral densities in postmenopausal patients with osteoporosis treated with alendronate / 中华内分泌代谢杂志

Objective:To investigate the effect of alendronate treatment and assess the value of bone turnover markers (BTMs) in predicting the changes of bone mineral densities (BMDs) in postmenopausal women with osteoporosis.Methods:In this retrospective study, 409 postmenopausal women with osteoporosis aged (64.86±7.21) years in the Department of Osteoporosis and Bone Disease, Shanghai Sixth People′s Hospital were enrolled from 2012 to 2020. BMDs at lumbar spine 1-4, femoral neck, and total hip, serum β cross-linked C-telopeptide of type 1 collagen (β-CTX), and osteocalcin (OC) were measured before and after treatment.Results:After alendronate treatment for 1 year, BMDs at lumbar spine 1-4, femoral neck and total hip increased 4.84%, 2.13%, and 2.89%, respectively ( P<0.05). At 6 months and 1 year on treatment, β-CTX and OC levels decreased by 77.7%, 42.3% and 78.2%, 49.5%, respectively ( P<0.05). Linear regression analysis showed that for every 10% decrease in the change of β-CTX at 6 months after alendronate treatment, the rate changes in BMDs at the lumbar spine 1-4, femoral neck, and total hip decreased by 0.417%, 0.127%, and 0.213% at 1 year after alendronate treatment; for every 10% decrease in OC, the change rates in BMDs at the lumbar spine 1-4, femoral neck, and total hip decreased by 0.582%, 0.258%, and 0.375%. Conclusions:Alendronate significantly increases BMDs and decreases BTMs levels in elderly women with osteoporosis. BTMs have a predictive value for the changes of BMDs, allowing early monitoring for the effect of alendronate treatment.

Efecto sinérgico de un bifosfonato con vitamina D / Synergic effect of a biphosphonate with vitamin D

Introducción: Los bifosfonatos son considerados como un grupo de fármacos de gran utilidad en el tratamiento de enfermedades del tejido óseo ya que promueven su resorción. Han sido la primera línea para el tratamiento de la osteoporosis, enfermedad de Paget, mieloma múltiple e hipercalcemia maligna. Por su parte, la vitamina D es un nutriente esencial cuya función principal es la homeostasis de calcio (Ca+2) y fosfato (P4 3-). Objetivo: Describir los aspectos moleculares y farmacológicos de la acción de un bifosfonato (alendronato sódico) y la vitamina D, por los cuales potencian mutuamente sus efectos en enfermedades óseas. Métodos: Fueron seleccionadas las referencias más actualizadas que abordaran aspectos relevantes acerca del alendronato y la vitamina D. Se consultaron las bases de datos de PubMed, Uniprot y Protein Databank. Conclusiones: El sinergismo entre alendronarto y vitamina D generan efectos benéficos en el tejido óseo. Sin embargo, existen efectos colaterales que pueden afectar a otros tejidos, por lo que su uso debe ser controlado(AU)

Introduction: Biphosphonates are considered to be a group of very useful drugs used to treat osseous tissue conditions, since they foster resorption. They are first line in the treatment of osteoporosis, Paget's disease, multiple myeloma and malignant hypercalcemia. Vitamin D, on the other hand, is an essential nutrient whose main function is calcium (Ca+2) and phosphate (P4 3-) homeostasis. Objective: Describe the molecular and pharmacological aspects of the action of a biphosphonate (alendronate sodium) and vitamin D on osseous diseases. Methods: A selection was made of the most updated references about relevant aspects of alendronate and vitamin D. The databases consulted were Pubmed, Uniprot and Protein Databank. Conclusions: The synergy between alendronate and vitamin D generates beneficial effects on osseous tissue. However, their use should be controlled, since side-effects may affect other tissues(AU)

Alendronato de sódio, levotiroxina e inibidores da bomba de prótons: há interação entre eles? / Sodium alendronate, levothyroxine and proton pump inhibitors: is there an interaction between them? / Alendronato de sodio, levotiroxina e inhibidores de la bomba de protones: ¿hay alguna interacción entre ellos?

Introdução: As interações medicamentosas podem alterar a segurança e/ou efetividade no tratamento das doenças. Alguns medicamentos precisam ser utilizados em jejum e a literatura apresenta informações divergentes sobre o real impacto clínico do uso destes no mesmo horário. Objetivos: Analisar as evidências sobre a relevância clínica de potenciais interações entre inibidores da bomba de prótons (IBPs), levotiroxina e alendronato de sódio. Métodos: Realizou-se uma revisão narrativa de artigos disponíveis na base de dados PubMed, além de consulta de potenciais interações medicamentosas em fontes de informações sobre medicamentos disponíveis na World Wide Web. Resultados: Em apenas três das 17 fontes de informações consultadas foi relatado uma possível redução dos níveis plasmáticos e/ou da efetividade da levotiroxina, quando administrada de forma concomitante com omeprazol ou outro da classe. Somente uma fonte relata leve redução dos níveis plasmáticos de alendronato de sódio por interação com a levotiroxina, e apenas duas fontes evidenciam possível redução do efeito terapêutico do alendronato de sódio por interação com IBPs. Apenas dois estudos relatam resultados significativos relacionados à existência de interação entre levotiroxina ou alendronato no uso concomitante de IBPs. Em todas as fontes consultadas, as interações são descritas como menores, leves, moderadas ou de significado desconhecido. Todas as fontes de informações sugerem a continuidade da terapia para manejo da interação. Conclusão: Até o momento não há evidências robustas que demonstrem impedimento de uso de inibidores da bomba de prótons, levotiroxina e alendronato de sódio no mesmo horário, sendo essencial o acompanhamento dos parâmetros clínicos e laboratoriais.

Introduction: Drug interactions can alter safety and/or effectiveness in the treatment of diseases. Some medications need to be used on an empty stomach and the literature presents divergent information about the real clinical impact of using them at the same time. Objectives: To analyze the evidence on the clinical relevance of potential interactions between proton pump inhibitors, levothyroxine and sodium alendronate. Methods: A narrative review of articles available in the PubMed database was carried out, in addition to consulting potential drug interactions in sources of information on drugs available on the World Wide Web. Results: In only three of the 17 information sources consulted, a report was reported possible reduction in plasma levels and the effectiveness of levothyroxine, when administered concomitantly with omeprazole or another in the class. Only one source reports a slight reduction in plasma sodium alendronate levels due to interaction with levothyroxine, and only two sources show a possible reduction in the therapeutic effect of sodium alendronate through interaction with PPIs. Only two studies report significant results related to the existence of an interaction between levothyroxine or alendronate in concomitant use of PPIs. In all sources consulted, interactions are described as minor, mild, moderate or of unknown significance. All sources of information suggest the continuity of therapy to manage the interaction. Conclusion: To date, there is no robust evidence demonstrating that it is impossible to use proton pump inhibitors, levothyroxine and sodium alendronate at the same time, and it is essential to monitor clinical and laboratory parameters.

Introducción: Las interacciones farmacológicas pueden alterar la seguridad y / o efectividad en el tratamiento de enfermedades. Algunos medicamentos deben usarse con el estómago vacío y la literatura presenta información divergente sobre el impacto clínico real de usarlos al mismo tiempo. Objetivo: Analizar la evidencia sobre la relevancia clínica de las posibles interacciones entre los inhibidores de la bomba de protones, la levotiroxina y el alendronato de sodio. Métodos: Se realizó una revisión narrativa de los artículos disponibles en la base de datos Pubmed, además de la consulta de posibles interacciones farmacológicas en las fuentes de información sobre medicamentos disponibles en la World Wide Web. Resultados: En solo tres de las 17 fuentes de información consultadas, se informó posible reducción en los niveles plasmáticos y la efectividad de la levotiroxina, cuando se administra concomitantemente con omeprazol u otro en la clase. Solo una fuente informa una ligera reducción en los niveles plasmáticos de alendronato de sodio debido a la interacción con levotiroxina, y solo dos fuentes muestran una posible reducción en el efecto terapéutico del alendronato de sodio a través de la interacción con los IBP. Solo dos estudios informan resultados significativos relacionados con la existencia de una interacción entre levotiroxina o alendronato en el uso concomitante de IBP. En todas las fuentes consultadas, las interacciones se describen como leves, moderadas o de significancia desconocida. Todas las fuentes de información sugieren la continuidad de la terapia para gestionar la interacción. Conclusión: Hasta la fecha, no existe evidencia sólida que demuestre que es imposible usar inhibidores de la bomba de protones, levotiroxina y alendronato de sodio al mismo tiempo, y es esencial monitorear los parámetros clínicos y de laboratorio.

Microemulsion assisted transdermal delivery of a hydrophilic anti-osteoporotic drug: Formulation, in vivo pharmacokinetic studies, in vitro cell osteogenic activity

Gastrointestinal adverse effects such as esophageal irritation and ulcers are the major disadvantages of the oraladministration of alendronate (ALD) and nitrogen-containing bisphosphonate. We hypothesized that the transdermaldelivery of ALD via water in oil (w/o) microemulsion might help to prevent the aforementioned side effects withoutcompromising the efficacy. The pseudo-ternary phase diagrams were constructed with varying ratios of surfactantmixture and oil to recognize the concentration range of excipients required to form a monophasic microemulsion.Globule size, morphology transmission electron microscopy, and thermal behavior differential scanning colorimetryof drug-loaded microemulsion were investigated. The in vitro permeation studies revealed significantly enhancedpermeation of ALD through microemulsion than pure solution across the rat skin (p < 0.01). In an in vivopharmacokinetic study in Wistar rats, microemulsion achieved around two folds higher bioavailability than pure drugsolution (p < 0.05) when given in equal doses (30 mg/kg). Cell viability assay with human osteoblastic osteosarcoma(MG-63) cells exhibited the positive effects of ALD microemulsion on cell growth. Moreover, alkaline phosphataseand mineralization studies proved that microemulsion as a carrier retains distinct osteogenic properties of ALD.Overall, these outcomes demonstrated that the w/o microemulsion as a transdermal carrier is a promising approach forthe effective delivery of ALD, bypassing the adverse effects associated with oral administration

Irrational use of alendronate sodium by the elderly / Uso irracional de alendronato de sódio por idosos / Uso irracional de alendronato de sodio en los ancianos

Introduction: The effectiveness and safety of alendronate sodium are dependent on patient adherence to very specific guidelines regarding use. This study aims to estimate the rational use of alendronate sodium in the elderly. Methods: This is a cross-sectional study carried out with a structured questionnaire containing form of use and occurrence of adverse events related to alendronate sodium. The patients were recruited in their own homes. Rational use was considered as being the participants who: a) took the tablet in the morning; b) were fasting; c) waited at least 30 minutes before eating; d) ingested with a full glass of water; e) ingested the whole tablet; f) and remained in the orthostatic position for at least 30 minutes after use. Additionally, the odds ratio (OR) was used to analyze the association between the irrational use of alendronate sodium and the independent variables. Results and Discussion: Of the 248 participants in the study, most of the participants administered the medication in the morning (95.2%), with fasting (89.1%), waited at least 30 minutes to eat the first meal of the day (87.9%), and were in the orthostatic position until the time of the first meal (78.6%), but less than half ingested the tablet with a full glass of water (43.6%). Rational use of the medication was observed in only 30.7% of the participants. Regarding possible adverse events, 13.3% of the participants reported some event. Among the most prevalent were dry cough (6.5%), stomach pain (5.2%) and some throat discomfort (4.8%). The irrational use of this medication is associated with age and education level. Conclusion: The prevalence of irrational use of alendronate sodium in the elderly is high, and this use is associated with patients' sociodemographic factors.

Introdução: A efetividade e segurança do alendronato de sódio são dependentes da adesão dos pacientes em relação às orientações específicas sobre o uso. Assim, este trabalho, tem como objetivo estimar a racionalidade de uso do alendronato de sódio em idosos. Metodologia: Trata-se de um estudo transversal realizado através de um questionário estruturado contendo a forma de utilização e a ocorrência de eventos adversos relacionados ao uso do medicamento. Os pacientes foram recrutados em suas próprias casas. Considerou-se uso racional os participantes que: a) tomaram o comprimido pela manhã; b) em jejum; c) esperaram pelo menos 30 minutos para se alimentar; d) ingeriu com um copo cheio de água; e) ingeriu o comprimido inteiro; f) e permaneceu na posição ortostática por pelo menos 30 minutos após o uso. Adicionalmente, o odds ratio (OR) foi utilizado para analisar associação entre o uso irracional do alendronato de sódio e as variáveis independentes. Resultados e Discussão: Dos 248 participantes do estudo a maioria administravam o medicamento pela manhã (95,2%), em jejum (89,1%), aguardavam pelo menos 30 minutos para realizar a primeira refeição do dia (87,9%), ficavam em posição ortostática até o horário da primeira refeição (78,6%), porém menos da metade ingeria o comprimido com um copo cheio de água (43,6%). O uso racional do medicamento foi observado em apenas 30,7% dos participantes. Em relação aos possíveis eventos adversos, 13,3% dos participantes relataram algum evento. Dentre os mais prevalentes, destacaram-se a tosse seca (6,5%), dor de estômago (5,2%) e algum desconforto na garganta (4,8%). O uso irracional deste medicamento está associado à idade e ao nível de escolaridade. Conclusão: É elevada a prevalência de uso irracional do alendronato de sódio em idosos e este uso está associado a fatores sociodemográficos dos pacientes.

Introducción: La eficacia y seguridad del alendronato sódico dependen de la adherencia de los pacientes en relación con directrices específicas sobre el uso. Por lo tanto, este trabajo tiene como objetivo estimar la racionalidad del uso del alendronato sódico en los ancianos. Metodos: Este es un estudio transversal realizado a través de un cuestionario estructurado que contiene la forma de uso y la ocurrencia de eventos adversos relacionados con el uso de la droga. Los pacientes fueron reclutados en sus propios habitación. Se consideró el uso racional como los participantes que: a) tomaron la tableta por la mañana, b) en ayuno, c) esperaron al menos 30 minutos antes de comer; d) Ingerido con un vaso lleno de agua; e) ingirió toda la tableta, f) y permaneció en la posición ortostática durante al menos 30 minutos después de su uso. Además, el odds ratio (OR) se utilizó para analizar la asociación entre el uso irracional de alendronato de sodio y las variables independientes. Resultados y Discusión: De los 248 participantes en el estudio, la mayoría administró el medicamento por la mañana (95,2%), em ayuno (89,1%), esperó al menos 30 minutos para realizar la primera comida del día (87,9%), estaban en posición ortostática hasta el momento de La primera comida (78,6%), pero menos de la mitad ingeriría el comprimido con un vaso lleno de agua (43,6%). El uso racional de la droga se observó en sólo 30.7% de los participantes. En cuanto a los posibles acontecimientos adversos, el 13,3% de los participantes informaron de algún evento. Entre los más frecuentes, tos seca (6,5%), dolor de estómago (5,2%) Y algunas molestias en la garganta (4,8%). El uso irracional del medicamento está asociado a la ida y al nivel de escolaridad. Conclusión: La prevalencia del uso irracional del alendronato de sodio en los ancianos es alta, y este uso está asociado a factores sociodemográficos de los pacientes.

Research progress in effect of alendronate on healing of osteoporotic fracture / 中华创伤杂志

Fracture healing is a complex physiological process involving osteoblasts,osteoclasts and other cells and molecules.Typical fracture healing can be divided into four stages:inflammatory response,soft callus formation,hard callus formation,and bone remodeling.Osteoclasts play a leading role in hard callus formation and bone remodeling.Alendronate can inhibit osteoclast activity and bone loss in patients with osteoporosis,but it may also inhibit fracture healing.Therefore,whether alendronate can be used after osteoporotic fracture is controversial.In recent years,it has been found that alendronate can not affect the fracture healing,but also reduce the risk of secondary fracture and improve the prognosis of patients.In this article,the mechanism of alendronate and its effect on osteoporotic fracture healing by systemic and local use are reviewed,which can provide a reference for clinical selection of therapeutic drugs.

Effects of Alendronate Sodium on the Postoperative Indexes in the Osteoporosis Patients with Thoracolumbar Fracture / 中国药房

OBJECTIVE：To investigate the effects of alendronate sodium on postoperative indexes in the osteoporosis patients with thoracolumbar fracture. METHODS ：Totally 170 patients with osteoporotic thoracolumbar fracture admitted in 416 Hospital of Nuclear Industry during Jan.-Dec. 2018 were divided into control group （85 cases）and observation group （85 cases）according to random number table . All patients underwent percutaneous vertebroplasty or percutaneous kyphoplasty. After operation ，control group received symptomatic and supportive treatment. Observation group was additionally given Alendronate sodium tablets 70 mg orally，once a week ，on the basis of control group. Treatment course of 2 groups lasted for one year. VAS score ，bone metabolism indexes [serum phosphorus （P）， calcium （Ca）， osteocalcin （OST）， bone alkaline phosphatase （BAP）]， contents of osteoprotegerin（OPG）and nuclear factor-κB receptor activator ligand（RANKL），cytokines（TNF-α，IFN-γ，IL-10）levels were observed in 2 groups before and after 1，3，6，12 months of treatment，and ADR were recorded . RESULTS ：Before treatment ， there was no significant difference in VAS score ，bone metabolism indexes ，contents of OPG and RANKL and cytokines levels between 2 groups （P＞0.05）. After treatment ，VAS scores of 2 groups were significantly lower than before treatment ，the observation group was significantly lower than the control group after 1，3，6 months of treatment （P＜0.05）. OST and BAP contents of observation group after 3，6，12 months treatment as well as OPG and RANKL contents ，TNF-α and IFN-γ levels after 1，3，6，12 months of treatment were significantly lower than before treatment and control group at the same period ；IL-10 level was significantly was higher than before treatment and control group at the same period （P＜0.05）. There was no statistical significance in P or Ca of 2 groups before and after treatment ，OST，BAP，OPG，RANKL contents and cytokines levels of control group before and after treatment （P＞0.05）. There was no statistical significance in total incidence of ADR between 2 group（P＞ 0.05）. CONCLUSIONS ：Alendronate sodium can significantly relieve the pain and improve cytokines ，bone metabolism indexes ， and inhibit expression of releated pathways in osteoporosis patients with thoracolumbar fracture ，with good safety.

Research progress in effect of alendronate on healing of osteoporotic fracture / 中华创伤杂志

Fracture healing is a complex physiological process involving osteoblasts, osteoclasts and other cells and molecules. Typical fracture healing can be divided into four stages: inflammatory response, soft callus formation, hard callus formation, and bone remodeling. Osteoclasts play a leading role in hard callus formation and bone remodeling. Alendronate can inhibit osteoclast activity and bone loss in patients with osteoporosis, but it may also inhibit fracture healing. Therefore, whether alendronate can be used after osteoporotic fracture is controversial. In recent years, it has been found that alendronate can not affect the fracture healing, but also reduce the risk of secondary fracture and improve the prognosis of patients. In this article, the mechanism of alendronate and its effect on osteoporotic fracture healing by systemic and local use are reviewed, which can provide a reference for clinical selection of therapeutic drugs.

Evaluación de la Administración Infiltrativa de vitamina E y alendronato en la Reparación de Alvéolos Post Exodoncia de Ratas / Evaluation of the Infiltrative Administration of Vitamin E and Alendronate in the Repair of Alveoli Post-Extraction in Rats

RESUMEN: Los bisfosfonatos (BP) disminuyen la resorción ósea al frenar la actividad de los osteoclastos. La vitamina E es antioxidante y su efecto positivo en el hueso sería mediante la prevención del estrés oxidativo. Se estudió la administración infiltrativa de Alendronato y Vitamina E para determinar si favorecían la formación de hueso en la reparación ósea del alvéolo postexodoncia. Se utilizaron ratas machos Wistar (n=96), de 90 ± 15 g, se les realizó la exodoncia de los primeros molares inferiores. Fueron dividos en 4 grupos: Un grupo control (C) recibió solución salina. El grupo AL 0,5 mg/ Kg; grupo E recibió 20 mg/kg; y grupo con tratamiento combinado AL y E. Los animales se sacrificaron a los 0, 7, 15 y 30 días postextracción. Se realizó la resección de las mandíbulas; las muestras fueron descalcificadas con EDTA y luego se incluyeron en parafina. Se realizaron cortes histológicos y se colorearon con Hematoxilina/Eosina. Se realizó análisis histológico e histomorfométrico. Se utilizó análisis de Varianza (ANOVA). En el análisis histológico, a los 7 y 15 días el grupo E presentó mayor neoformación de tejido óseo que los otros grupos. A los 30 días se observó hueso maduro con presencia de osteonas en el grupo E. En el estudio histomorfométrico a los 15 y 30 días se evidencian diferencias significativas en el número de osteoblastos por mm lineal, entre el grupo AL + E y C (p<0,01) y a los 30 días se encontró diferencia entre el grupo E y C (p<0,01). Al medir espesor trabecular se observó a los 30 días diferencias significativas entre el grupo AL+E y C (p<0,01) y entre el grupo C y E (p<0,01). La Vitamina E demostró que administrada por vía infiltrativa favorece la remodelación ósea en los alvéolos post exodoncia.

ABSTRACT: Bisphosphonates (BP) decrease bone resorption to curb the activity of the osteoclasts. Vitamin E is an antioxidant and its positive effect on the bone would be by preventing oxidative stress. Infiltrative Alendronate and vitamin E administration wasstudied to determine if they favored the formation of bone in bone repair of the postextraction alveolus. Male Wistar rats were used (n = 96), 90 ± 15 g, underwent extraction of the lower first molars. They were divided into 4 groups: A control group (C) received saline. The Group at the 0.5 mg/Kg; Group E received 20 mg/kg; and combined treatment group to AL and E. The animals were sacrificed at days 0, 7, 15 and 30 post extraction. With the resection of the jaws; samples were decalcified with EDTA and then included in paraffin. Histological cuts were made and colored with Hematoxylin/ eosin. Histomorphometric and histological analysis was performed. We used analysis of variance (ANOVA). In the histological analysis, 7 to 15 days the Group E presented greater neoformation of bone tissue than other groups. At 30 days mature bone was observed, with presence of osteons in the Group E. Study shows significant differences in the number of osteoblast histomorphometric function to 15 to 30 days by linear mm, among the group to the + E and C (p < 0.01) and 30-day difference was found among the Group E and C (p < 0.01). When measuring thick trabecular, significant differences were observed at 30 days between the AL+E and C Group (p < 0.01) and between C and E (p < 0.01). Vitamin E showed that administered infiltrative favors the bone remodeling in post extraction sockets.

Gastric toxicity of Alendronate and Methotrexate in Walker 256 carcinosarcoma jaw model / Toxicidade gástrica de Alendronato e Metotrexato em modelo de carcinossarcoma de Walker 256 em mandíbula

Introduction: Experimental animal models represent a key tool used to elucidate the mechanisms of action and toxicity of anticancer drugs. Objective: The purpose was to establish a correlation of neoplastic growth with the combinatorial therapeutic application of sodium alendronate (ALD) and methotrexate (MTX), and to evaluate the gastrointestinal toxicity of these drugs, in the rat Walker 256 carcinosarcoma inoculation model. Methods: Female rats were selected and randomly distributed into 5 groups (n=10): negative control (NC), positive control (PC), MTX-treated group, ALD-treated group, and MTX-ALD-treated group (MTX/ALD). Tumor cells were inoculated as a suspension of 1x106cells/mL into the alveolar cavities produced by exodontia procedures. The following parameters were evaluated: body weight, tumor volume and percentage of tumor inhibition, and gastrointestinal toxicity. Results: The body weight variation was statistically significant between NC animals and PC animals, and between NC animals and ALD-treated group (p<0.01). Tumor volume variation was statistically significant between PC animals, MTX-treated group and MTX/ALD-co-treated group (p<0.05). Analysis of gastric toxicity of MTX-treated group reveled slight reduction of chief (Ch) and parietal (Pr) cellular populations; ALD-treated group exhibited gastric mucosa without histological alterations of Ch cells but intense reduction of Pr cellular population; and MTX/ALD-co-treated group presented reduction of Ch and Pr cellular populations. Conclusions: ALD does not elicit significant antitumor effects on Walker 256 carcinosarcoma cells and decreases antitumor effects of MTX due to toxicity on the gastric epithelium, which is intensified with MTX association.

Introdução: Modelos experimentais em animais representam um instrumento fundamental para elucidar os mecanismos de ação e toxicidade de drogas anticâncer. Objetivo: estabelecer uma correlação do crescimento neoplásico com a aplicação terapêutica combinatória de alendronato de sódio (ALD) e metotrexato (MTX), e avaliar a toxicidade gastrointestinal dessas drogas, no modelo de inoculação de carcinossarcoma de Walker 256 em ratos. Métodos: Ratas fêmeas foram selecionadas e distribuídas aleatoriamente em 5 grupos (n = 10): controle negativo (NC), controle positivo (PC), grupo tratado com MTX, grupo tratado com ALD e grupo tratado com MTX-ALD (MTX/ALD). As células tumorais foram inoculadas como uma suspensão de 1x106 células/mL nas cavidades alveolares produzidas por procedimentos de exodontia. Os seguintes parâmetros foram avaliados: peso corporal, volume tumoral e porcentagem de inibição tumoral e toxicidade gastrointestinal. Resultados: A variação do peso corporal foi estatisticamente significante entre animais NC e animais PC, e entre animais NC e grupo tratado com ALD (p <0,01). A variação do volume tumoral foi estatisticamente significativa entre animais PC, grupo tratado com MTX e grupo tratado com MTX / ALD (p <0,05). A análise da toxicidade gástrica do grupo tratado com MTX revelou uma ligeira redução das populações celulares principais (Ch) e parietais (Pr); o grupo tratado com ALD exibiu mucosa gástrica sem alterações histológicas de células Ch mas intensa redução da população celular Pr; e o grupo tratado com MTX / ALD apresentou redução das populações celulares Ch e Pr. Conclusões: O ALD não provoca efeitos antitumorais significativos nas células do carcinossarcoma Walker 256 e diminui os efeitos antitumorais do MTX devido à toxicidade no epitélio gástrico, que é intensificada com a associação MTX.