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.

Fracturas atípicas de fémur asociadas al uso de bifosfonatos / Bisphosphonate associated atypical femur fractures

Resumen Los bifosfonatos son medicamentos ampliamente conocidos por su efecto antagonista de la resorción ósea y la consecuente reducción del riesgo de fracturas en los pacientes con osteoporosis. La literatura actual provee evidencia en términos de datos clínicos y experimentales que asocian el uso prolongado de estos medicamentos con un aumento en el riesgo de fracturas atípicas de fémur. Para establecer si esta asociación es clínicamente relevante, se requiere realizar estudios posteriores que incluyan la relación entre otros factores que podrían influir en la aparición de este tipo de fracturas como lo es la propia enfermedad osteoporótica, el tipo de bifosfonato utilizado, el mecanismo lesional que originó la fractura, medicamentos concomitantes y patologías asociadas.

Abstract Bisphosphonates are medications that are widely known for their antagonizing effect on bone resorption and their consequent reduction in the risk of fractures in patients with osteoporosis. Current literature provides evidence in terms of experimental and clinical data associating prolonged use of these drugs with an increase in the risk of atypical femur fractures. To establish if this association is clinically relevant, there lies a need for further studies that take into account other factors that might influence the occurrence of these type of fractures, like the osteoporotic disease itself, age, intake of other drugs and associated systemic illnesses.

Efectividad del alendronato más calcio y vitamina D, comparado con calcio y vitamina D para la prevención de la fractura de cadera / Hip fractures prevention: Effectiveness with alendronate plus calcium+vitamin D compared with calcium +vitamin (control group

Resumen:Objetivo:establecer la efectividad del alendronato, comparado con un grupo control, para prevenir la fractura de cadera y perfilar la mortalidad a corto plazo.Métodos:estudio observacional, analítico, con todos los pacientes atendidos en la Seguridad Social con tratamiento con alendronato, calcio y vitamina D (grupo A), o con calcio y vitamina D (grupo control, C), que recibieron tratamiento continuo por 1 año como mínimo, y lo mantuvieron durante el periodo de observación y seguimiento, 3 años o hasta que ocurrió el evento de fractura, según el registro institucional por diagnóstico y la condición de egreso (vivo o fallecido).Resultados:en total se incluyó una muestra de 10395 pacientes que cumplieron con el tratamiento continuo previo y durante el seguimiento a 3 años; n= 5 570 (53,58%) expuestos al alendronato 70 mg semanal junto con calcio y vitamina D y como control, n= 4 825 (46,42%) que recibieron calcio y vitamina D. Durante el seguimiento a 3 años de ambos grupos, se registró un total de 108 fracturas de cadera; el evento ocurrió en el 1,08% de los pacientes que recibieron alendronato y en el 0,99% del control. La efectividad del tratamiento con alendronato (junto con calcio y vitamina D) para prevenir la fractura de cadera, se estableció en el 98,92%, similar a lo registrado para el grupo control (99,01%). La mortalidad aguda por fractura de cadera registrada en un tiempo máximo de 35 días de hospitalización (Cuadro 2), en el grupo alendronato alcanzó el 11,66% y todas eran mujeres. En el grupo control, la mortalidad aguda llegó al 22,91% y un 72,72% eran mujeres.Conclusiones:no hubo diferencias significativas en los grupos evaluados en número de fracturas ni mortalidad. Los adultos mayores resultaron más vulnerables para sufrir este evento y para un desenlace fatal a corto plazo.

Abstract:Objective:To establish the effectiveness of alendronate, compared to a control group, in preventing hip fracture and outline the short-term mortality.Methods:Observational, analytical study, with all patients treated at the Social Security, for at least 1 continuous year, with alendronate, calcium and vitamin D (group A) and control group (C) with calcium and vitamin D, follow up by three years or until the event occurred (hip fracture) according to the institutional record for diagnosis and discharge status (alive or deceased). Subgroup analyzes> 65 years.Results:The total sample included 10395 patients that followed the pretreatment and the 3-year follow up. Group A n = 5.570 (53.58%) exposed to weekly 70mg alendronate with calcium and vitamin D, 95% female, mean age 69 years, median treatment period before event 749 days. Control group C n = 4.825, that received calcium and vitamin D, 89% female, 66 years old and 775 days of treatment, respectively. During the studied period (three years) 108 fractures were registered, 60 in group A (1.08%) and 48 in group C (0.99%). The effectiveness of the treatment with alendronate (with calcium and vitamin D) to prevent hip fracture was established in the 98.92%, similar to that registered for the control group (99.01). The acute mortality for hip fracture, registered in a maximum time of 35 days of hospitalization (table 2), in the alendronate group reached the 11.66% and were all women. In the control group acute mortality reached 22.91% and 72.72% were women.Conclusions:Alendronate showed similar effectiveness to control to prevent hip fractures. Older adults were more vulnerable to suffer this event and a short-term fatal outcome.

Considerações sobre a determinação quantitativa de alendronato de sódio: titulometria x cromatografia / Observations on the quantitative determination of alendronate sodium: titrimetry vs. chromatography

O alendronato de sódio é um composto aminodifosfonado capaz de se fixar à matriz óssea e inibir a reabsorção mediada por osteoclastos. A escassez de metodologias oficiais para a determinação quantitativa deste fármaco levou ao desenvolvimento de diversos métodos, os quais empregam, em sua maioria, a cromatografia líquida de alta eficiência (CLAE), com a derivatização do fármaco para poder empregar detectores de ultravioleta. Também há relatos sobre metodologias mais simples para a análise do alendronato, utilizando titulometria ou análise espectrofotométrica. Neste trabalho foi avaliado o emprego da titulometria de neutralização na determinação quantitativa do alendronato de sódio em três lotes de matéria-prima, utilizando NaOH 0,1 M como titulante. Os resultados obtidos na titulometria foram comparados aos encontrados em método cromatográfico de referência (CLAE com derivatização por 9-fluorenilmetilcloroformato ou FMOC), descrito na Farmacopéia Americana (United States Pharmacopeia), os quais apresentaram valores estatisticamente diferentes. Ensaios para a caracterização das amostras também foram realizados e foi observado comportamento distinto das 3 matérias-primas em relação à substância de referência (padrão secundário). O método titulométrico apresentou adequada precisão, mas não mostrou especificidade para a determinação das matérias-primas, embora possa ser validado para determinação do fármaco em produto acabado.

Alendronate sodium is an aminobisphosphonate compound that can bind to the bone matrix and inhibit its osteoclast-mediated resorption. The lack of official monographs on the quantitative analysis of this drug has led to the proposal of a number of different methods for its determination, most of which employ high performance liquid chromatography (HPLC), performed after derivatization of the drug to enable ultraviolet detection. Simpler methodologies based on titrimetry and spectrophotometry have also been described. In this paper, the results obtained by acid-base titration of three batches of bulk alendronate, with 0.1 M sodium hydroxide as titrant, were compared with those achieved by a chromatographic reference method (HPLC of an FMOC derivative of the drug) published in the United States Pharmacopeia. The two methods gave statistically different results for the analysis of the three samples. Also, physical and chemical characterization of these samples showed differences between them and the reference substance (brand-name drug). The acid-base titrimetry was precise but not specific for determination of the bulk drug. However, it may be employed in the quality control of alendronate sodium dosage forms, since the excipients do not interfere with the analysis.

Implante de biomateriais e a consolidação óssea em cadelas submetidas à ovariossalpingo-histerectomia / Influence of biomaterials on the bony consolidation in spayed female dogs

Avaliou-se a hidroxiapatita com alandronato e hidroxiapatita com colágeno na aceleração da consolidação óssea do rádio de cadelas adultas submetidas à ovariossalpingo-histerectomia (OSH). Utilizaram-se 14 cadelas adultas, distribuídas aleatoriamente em dois grupos: grupo-controle e grupo OSH (submetidas à OSH). Quatro meses após a OSH, as cadelas dos dois grupos foram submetidas à cirurgia para produção de uma falha óssea de 4mm de diâmetro nos terços distal e proximal do rádio. No terço distal do membro direito, foi utilizada a hidroxiapatita com alandronato e, no membro esquerdo, a hidroxiapatita com colágeno; no terço proximal, não se utilizou nenhum biomaterial. Houve retardo na consolidação das falhas ósseas nas cadelas submetidas à OSH comparadas com as não submetidas. A hidroxiapatita com alandronato acelerou o processo de reparação e, em todos os animais dos dois grupos, a densidade óssea foi significativamente maior no terço distal onde foi implantada. Os dois biomateriais apresentaram biocompatibilidade, constatada pela ausência de reação inflamatória ou outra reação indesejável.

The hydroxyapatite with alendronate and hydroxyapatite with collagen were evaluated in the acceleration of the bony consolidation of adult spayed bitch radius. For that, 14 adult bitches were distributed in two groups (control and spayed). Four months after ovariohysterectomy, the groups were submitted to the surgery for production of a 4mm diameter bony flaw in the distal and proximal third regions of the radius. In the distal region of the right thoracic limb, hydroxyapatite with alendronate was used. In the distal region of the left thoracic limb, hydroxyapatite with collagen was used. Any biomaterial was used in proximal part of the limb. There was a retard in bony flaws consolidation in the spayed bitches. Hydroxyapatite with alendronate showed better result, since the place it was implanted considerably increased the bony formation. Both biomaterials presented biocompatibility, verified by the absence of inflammatory reaction or other undesirable reaction.