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PURPOSE: Fracture Liaison Services programs reduce mortality and the risk of refracture and increase treatment and adherence rates. Greater coverage is an important priority for the future. The aim was to determine the characteristics of patients over 50 years old who suffered fractures and the effectiveness of a Fracture Liaison Services program in a health care institution in Colombia. METHODS: This was a retrospective follow-up study of a cohort of patients with vertebral and nonvertebral fractures managed in a Fracture Liaison Services program. Sociodemographic, clinical and pharmacological variables were identified. Key performance indicators were used to evaluate the effectiveness of the program. Descriptive and bivariate analysis was performed. RESULTS: A total of 438 patients were analyzed. The average age was 77.5 years, and 78.5% were women. Hip and vertebral fractures were the most common (25.3% and 24.9%, respectively). Vertebral fractures prevailed in men (33.0% vs 22.7%; p = 0.041) and those of the radius/ulna in women (20.3% vs 10.6%; p = 0.031). A total of 29.7% had experienced a previous fracture, and 16.7% had received antiosteoporosis drugs. A total of 63.5% of the cases were managed surgically. At discharge, 58.8% received prescriptions for calcium/vitamin D, and 50.7% with prescriptions of antiosteoporotic therapy, especially teriparatide (21.2%) and denosumab (16.4%), without significant differences by sex. However, in women with hip fractures, anti-osteoporotic management prevailed (83.7% vs 64.0; p = 0.032). The effectiveness of the overall program per year was 74.6%. On follow-up, only 9.1% of patients had experienced a new fall, and of those 3.7% presented a new fracture. A total of 4.3% died during follow-up. CONCLUSIONS: Good adherence to the recommendations of the country's clinical practice guidelines was found, and overall, the effectiveness of the program was very satisfactory, with a low incidence of new fractures during follow-up. Fracture Liaison Services programs reduce mortality and the risk of refracture. A retrospective follow-up study of a cohort of patients with vertebral and nonvertebral fractures managed in a Fracture Liaison Services, showed that the effectiveness was 73.6%. On follow-up, 9.1% of patients had experienced a new fall, and of those 3.7% presented a new fracture.
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Conservadores da Densidade Óssea , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Masculino , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Conservadores da Densidade Óssea/uso terapêutico , Colômbia/epidemiologia , Seguimentos , Estudos Retrospectivos , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/terapiaRESUMO
(1) Background: The objective of this study was to evaluate the morphometry of peri-implant bone tissue in orchiectomized rats, treated with vitamin D isolated or associated with teriparatide. (2) Methods: 24 rats were divided into 4 groups: ORQ-orchiectomy, without drug treatment, ORQ+D-orchiectomy, treated with vitamin D, ORQTERI-orchiectomy, treated with teriparatide and ORQTERI+D-orchiectomy, treated with teriparatide + vitamin D. Each animal received an implant in the tibial metaphysis. Euthanasia occurred 60 days after implant surgery. Computed microtomography (micro-CT) was performed to evaluate the parameters of volume and percentage of bone volume (BV, BV/TV), trabecular thickness (Tb.Th), number and separation of trabeculae (Tb.N, Tb.Sp) and percentage of total porosity (Po-tot). Data were subjected to 1-way ANOVA and Tukey post-test, with a significance level of 5%. (3) Results: For the parameters BV, BV/TV, Tb.Th, the ORQTERI+D group showed the highest values in relation to the other groups and for Po-tot, the lowest values were for ORQTERI+D. For Tb.Sp and Tb.N, there was no statistically significant difference when comparing intragroup results (p > 0.05). (4) Conclusions: It was possible to conclude that treatment with vitamin D associated with teriparatide increases bone volume and improves bone quality.
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With the increase in the population's life expectancy, there has also been an increase in the rate of osteoporosis, which has expanded the search for strategies to regenerate bone tissue. The ultrasonic sonochemical technique was chosen for the functionalization of the 45S5 bioglass. The samples after the sonochemical process were divided into (a) functionalized bioglass (BG) and (b) functionalized bioglass with 10% teriparatide (BGT). Isolated mesenchymal cells (hMSC) from femurs of ovariectomized rats were differentiated into osteoblasts and submitted to in vitro tests. Bilateral ovariectomy (OVX) and sham ovariectomy (Sham) surgeries were performed in fifty-five female Wistar rats. After a period of 60 days, critical bone defects of 5.0 mm were created in the calvaria of these animals. For biomechanical evaluation, critical bone defects of 3.0 mm were performed in the tibias of some of these rats. The groups were divided into the clot (control) group, the BG group, and the BGT group. After the sonochemical process, the samples showed modified chemical topographic and morphological characteristics, indicating that the surface was chemically altered by the functionalization of the particles. The cell environment was conducive to cell adhesion and differentiation, and the BG and BGT groups did not show cytotoxicity. In addition, the experimental groups exhibited characteristics of new bone formation with the presence of bone tissue in both periods, with the BGT group and the OVX group statistically differing from the other groups (p < 0.05) in both periods. Local treatment with the drug teriparatide in ovariectomized animals promoted positive effects on bone tissue, and longitudinal studies should be carried out to provide additional information on the biological performance of the mutual action between the bioglass and the release of the drug teriparatide.
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ABSTRACT: Currently, there are no guidelines for treating osteoporosis in spinal surgery. The rate of complications such as screw loosening, proximal junction kyphosis, cage subsidence, and loss of reduction in fractures is high. Objective: To evaluate the use of teriparatide and denosumab in planning spinal surgery in an osteoporotic patient with degenerative pathology, emphasizing the fusion rate, bone mineral density, and decreased complications. Method: A systematic search was performed in medical reference databases for comparative studies of teriparatide and denosumab in spinal surgery to evaluate fusion, screw loosening, bone mineral density, and decrease in the incidence of vertebral fractures. χ2 was implemented for the statistical analysis, according to PRISMA (2020). Result: Fusion rate with teriparatide was 79.28% in the first six months, 95% CI (OR 2.62) and decreased screw loosening rate 81.9% 95% CI (OR 0.6). Increase in bone mineral density 15.5% OR 1.49 (0.77 - 2.86) and decrease in vertebral fracture rate 85.4% OR 0.5. Conclusions: Teriparatide and denosumab should be considered in perioperative spinal planning due to their effectiveness, synergism, and low adverse effects; to improve bone mineral density and decrease the rate of complications. Clinical, comparative, and statistically significant studies are required to confirm this. Level of Evidence II; Systematic Review and Meta-analysis.
RESUMO: Atualmente não existem diretrizes para o tratamento da osteoporose em cirurgia da coluna vertebral. A taxa de complicações como afrouxamento de parafuso, cifose da junção proximal, subsidência da gaiola e perda de redução nas fraturas é alta. Objetivo: Avaliar o uso de teriparatida e/ou denosumabe no planejamento da cirurgia da coluna vertebral em pacientes osteoporóticos com patologia degenerativa, enfatizando a taxa de fusão, densidade mineral óssea e diminuição de complicações. Método: Foi realizada uma busca sistemática em bases de dados de referência médica para estudos comparativos de teriparatida e denosumabe em cirurgia da coluna vertebral, a fim de avaliar fusão, soltura de parafuso, densidade mineral óssea e diminuição da incidência de fraturas vertebrais. O χ2 foi implementado para a análise estatística, de acordo com PRISMA (2020). Resultado: A taxa de fusão com teriparatida foi de 79,28% nos primeiros 6 meses IC 95% (OR 2,62) e diminuiu a taxa de afrouxamento do parafuso 81,9% IC 95% (OR 0,6). O aumento da densidade mineral óssea foi de 15,5% OR 1,49 (0,77 - 2,86) e a diminuição da taxa de fratura vertebral atingiu 85,4% OR 0,5. Conclusões: A teriparatida e o denosumabe devem ser considerados no planejamento espinhal perioperatório devido à sua efetividade, sinergismo e baixos efeitos adversos, melhorando a densidade mineral óssea e diminuir a taxa de complicações. Estudos clínicos, comparativos e estatisticamente significativos são necessários para confirmar os achados. Nível de Evidência II; Revisão Sistemática e Meta-análise.
RESUMEN: Actualmente no existen pautas para el tratamiento de la osteoporosis en cirugía espinal. La tasa de complicaciones como el aflojamiento de los tornillos, la cifosis de la unión proximal, el hundimiento del aparato Ilizarov y la pérdida de reducción de las fracturas es alta. Objetivo: Evaluar el uso de teriparatida y/o denosumab en la planificación de la cirugía de columna en el paciente osteoporótico con patología degenerativa haciendo hincapié en la tasa de fusión, la densidad mineral ósea y la disminución de las complicaciones. Método: Se realizó una búsqueda sistemática en bases de datos de referencia médica para estudios comparativos de teriparatida y denosumab en cirugía espinal con el fin de evaluar la fusión, el aflojamiento de tornillos, la densidad mineral ósea y la disminución de la incidencia de fracturas vertebrales. χ2 se implementó para el análisis estadístico, según PRISMA (2020). Resultado: La tasa de fusión con teriparatida fue del 79,28% en los primeros 6 meses IC 95% (OR 2,62) y disminuyó la tasa de aflojamiento del tornillo 81,9% IC 95% (OR 0,6). Aumento de la densidad mineral ósea 15,5% O 1,49 (0,77 - 2,86) y disminución de la tasa de fractura vertebral 85,4% O 0,5. Conclusiones: La teriparatida y el denosumab deben ser considerados en la planificación espinal perioperatoria debido a su efectividad, sinergismo y bajos efectos adversos; con el fin de mejorar la densidad mineral ósea y disminuir la tasa de complicaciones. Se requieren estudios clínicos, comparativos y estadísticamente significativos para confirmarlo. Nivel de Evidencia II; Revisión sistemática y metaanálisis.
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Ortopedia , Coluna VertebralRESUMO
Anabolic agents for the treatment of osteoporosis increase bone density, improve bone strength, and reduce fracture risk. They are distinguished from antiresorptive drugs by their property of increasing osteoblastic bone formation. Teriparatide and abaloparatide are parathyroid hormone receptor agonists that increase bone remodeling with bone formation increasing more than bone resorption. Romosozumab is a humanized monoclonal antibody to sclerostin that has a "dual effect" of increasing bone formation while decreasing bone resorption. The bone forming effects of anabolic therapy appear to be self-limited, making it imperative that it be followed by antiresorptive therapy to enhance or consolidate the beneficial effects achieved. Teriparatide, abaloparatide, and romosozumab each have unique pharmacological properties that must be appreciated when using them to treat patients at high risk for fracture. Clinical trials have shown a favorable balance of expected benefits and possible risks. Anabolic therapy is superior to bisphosphonates for high-risk patients, with greater benefit when initial treatment is with an anabolic agent followed by an antiresorptive drug, rather than the reverse sequence of therapy. Recent clinical practice guidelines have included recommendations with examples of patients who are candidates with anabolic therapy.
Assuntos
Conservadores da Densidade Óssea , Reabsorção Óssea , Osteoporose , Humanos , Teriparatida/uso terapêutico , Teriparatida/farmacologia , Osteoporose/tratamento farmacológico , Conservadores da Densidade Óssea/efeitos adversos , Densidade Óssea , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/tratamento farmacológicoRESUMO
Several drugs are available for the treatment of osteoporosis in postmenopausal women. Over the last decades, most patients requiring pharmacological intervention were offered antiresorptive drugs as first-line therapy, while anabolic agents were considered a last resource for those with therapeutic failure. However, recent randomized trials in patients with severe osteoporosis have shown that anabolic agents reduce fractures to a greater extent than antiresorptive medications. Additionally, evidence indicates that increases in bone mineral density (BMD) are maximized when patients are treated with anabolic agents first, followed by antiresorptive therapy. This evidence is key, considering that greater increases in BMD during osteoporosis treatment are associated with a more pronounced reduction in fracture risk. Thus, international guidelines have recently proposed an individualized approach to osteoporosis treatment based on fracture risk stratification, in which the stratification risk has been refined to include a category of patients at very high risk of fracture who should be managed with anabolic agents as first-line therapy. In this document, the Brazilian Society of Endocrinology and Metabolism and the Brazilian Association of Bone Assessment and Metabolism propose the definition of very high risk of osteoporotic fracture in postmenopausal women, for whom anabolic agents should be considered as first-line therapy. This document also reviews the factors associated with increased fracture risk, trials comparing anabolic versus antiresorptive agents, efficacy of anabolic agents in patients who are treatment naïve versus those previously treated with antiresorptive agents, and safety of anabolic agents.
Assuntos
Anabolizantes , Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Osteoporose , Fraturas por Osteoporose , Humanos , Feminino , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Anabolizantes/uso terapêutico , Brasil , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Fraturas por Osteoporose/tratamento farmacológico , Densidade ÓsseaRESUMO
ABSTRACT Anabolic agents for the treatment of osteoporosis increase bone density, improve bone strength, and reduce fracture risk. They are distinguished from antiresorptive drugs by their property of increasing osteoblastic bone formation. Teriparatide and abaloparatide are parathyroid hormone receptor agonists that increase bone remodeling with bone formation increasing more than bone resorption. Romosozumab is a humanized monoclonal antibody to sclerostin that has a "dual effect" of increasing bone formation while decreasing bone resorption. The bone forming effects of anabolic therapy appear to be self-limited, making it imperative that it be followed by antiresorptive therapy to enhance or consolidate the beneficial effects achieved. Teriparatide, abaloparatide, and romosozumab each have unique pharmacological properties that must be appreciated when using them to treat patients at high risk for fracture. Clinical trials have shown a favorable balance of expected benefits and possible risks. Anabolic therapy is superior to bisphosphonates for high-risk patients, with greater benefit when initial treatment is with an anabolic agent followed by an antiresorptive drug, rather than the reverse sequence of therapy. Recent clinical practice guidelines have included recommendations with examples of patients who are candidates with anabolic therapy.
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ABSTRACT Several drugs are available for the treatment of osteoporosis in postmenopausal women. Over the last decades, most patients requiring pharmacological intervention were offered antiresorptive drugs as first-line therapy, while anabolic agents were considered a last resource for those with therapeutic failure. However, recent randomized trials in patients with severe osteoporosis have shown that anabolic agents reduce fractures to a greater extent than antiresorptive medications. Additionally, evidence indicates that increases in bone mineral density (BMD) are maximized when patients are treated with anabolic agents first, followed by antiresorptive therapy. This evidence is key, considering that greater increases in BMD during osteoporosis treatment are associated with a more pronounced reduction in fracture risk. Thus, international guidelines have recently proposed an individualized approach to osteoporosis treatment based on fracture risk stratification, in which the stratification risk has been refined to include a category of patients at very high risk of fracture who should be managed with anabolic agents as first-line therapy. In this document, the Brazilian Society of Endocrinology and Metabolism and the Brazilian Association of Bone Assessment and Metabolism propose the definition of very high risk of osteoporotic fracture in postmenopausal women, for whom anabolic agents should be considered as first-line therapy. This document also reviews the factors associated with increased fracture risk, trials comparing anabolic versus antiresorptive agents, efficacy of anabolic agents in patients who are treatment naïve versus those previously treated with antiresorptive agents, and safety of anabolic agents.
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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.
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The present study aimed to evaluate the effect of parathormone (PTH) administered directly to the implant's surface prior to insertion, using a large translational animal model. Sixty titanium implants were divided into four groups: (i) Collagen, control group, where implants were coated with Type-I Bovine-collagen, and three experimental groups, where implants received varying doses of PTH: (ii) 12.5, (iii) 25, and (iv) 50 µg, prior to placement. Fifteen female sheep (~2 years old, weighing ~65 kg) received four implants in an interpolated fashion in C3, C4 or C5 vertebral bodies. After 3-, 6- and 12-weeks, samples were harvested, histologically processed, qualitatively and quantitatively assessed for bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). BIC yielded lower values at 6-weeks for 50 µg relative to the control group, with no significant differences, when compared to the 12.5- and 25-µg. No significant differences were detected at 6-weeks between collagen, 12.5- and 25-µg groups. At 3- and 12-weeks, no differences were detected for BIC among PTH groups. With respect to BAFO, no significant differences were observed between the control and experimental groups independent of PTH concentration and time in vivo. Qualitative observations at 3-weeks indicated the presence of a more mature bone near the implant's surface with the application of PTH, however, no significant differences in new bone formation or healing patterns were observed at 6- and 12-weeks. Single local application of different concentrations of PTH on titanium implant's surface did not influence the osseointegration at any time-point evaluation in low-density bone.
Assuntos
Implantes Dentários , Osseointegração , Animais , Osso e Ossos , Bovinos , Feminino , Hormônio Paratireóideo/farmacologia , Próteses e Implantes , Ovinos , Propriedades de Superfície , Titânio/farmacologiaRESUMO
ABSTRACT Objective: This study aimed to evaluate the effects of systemic teriparatide on sutural bone formation after premaxillary suture expansion in rats. Material and Methods: Twenty Wistar male rats (8-10 weeks old) were randomly divided into two groups, namely, control (C, n=10) and teriparatide (T, n=10). An expansion force was applied to the maxillary incisors using helical spring for a seven-day expansion period, for both groups. On the eighth day, the rats were kept for a seven-day consolidation period, and then 60 µg/kg teriparatide (once a day) was administered to group T subcutaneously for seven days. Then, all the rats were sacrificed, and histological sections were stained with hemotoxylin-eosin for examination. Anti-osteonectin, anti-osteocalcin, anti-Vascular endothelial growth factor (VEGF) and anti-transforming growth factor beta (TGF-β) were evaluated by immunohistochemical analysis in the midpalatal suture area. Results: Histologically, the newly formed bone tissue was observed to be larger in group T than in group C. The number of immunoreactive osteoblasts for osteonectin, osteocalcin and VEGF antibodies was significantly higher in group T than in group C (p = 0.0001). The TGF-β antibody showed a mild reaction in group T, but did not reach significance in comparison with group C (p ˃ 0.05). Conclusion: Systemic teriparatide application following the premaxillary expansion of the suture area may stimulate bone formation and add to the consolidation of the expansion in rats by regulating osteonectin, osteocalcin and VEGF.
RESUMO Objetivo: O presente estudo teve como objetivo avaliar os efeitos do uso sistêmico da teriparatida na formação óssea sutural após a expansão da pré-maxila em ratos. Material e Métodos: Vinte ratos machos da raça Wistar (com oito a dez semanas de vida) foram divididos aleatoriamente em dois grupos: controle (C, n=10) e teriparatida (T, n=10). Uma força de expansão foi aplicada aos incisivos superiores, usando uma mola helicoidal, por um período de expansão de sete dias em ambos os grupos. No oitavo dia, os ratos iniciaram um período de sete dias de consolidação, nos quais 60 µg/kg de teriparatida foram administrados (uma vez ao dia), por via subcutânea, para o grupo T. Posteriormente, todos os ratos foram sacrificados e cortes histológicos corados com hemotolixina-eosina foram examinados. Por meio de análise imuno-histoquímica da região da sutura palatina mediana, avaliou-se a presença de anti-ostenectina, anti-osteocalcina, anti-fator de crescimento endotelial vascular (VEGF) e anti- fator transformador de crescimento (TGF-β). Resultados: Histologicamente, observou-se que o tecido ósseo recém-formado foi maior no grupo T do que no grupo C. O número de osteoblastos imunorreativos para anticorpos de osteonectina, osteocalcina e VEGF foi significativamente maior no grupo T do que no grupo C (p = 0,0001). O anticorpo TGF-β mostrou uma pequena reação no grupo T; porém, sem diferença significativa para o grupo C (p ˃ 0,05). Conclusão: O uso sistêmico de teriparatida após a expansão da sutura na região da pré-maxila pode estimular a formação óssea e melhorar a consolidação da expansão em ratos, por meio da regulação de osteonectina, osteocalcina e VEGF.
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Anabolic drugs are the treatment of choice for osteoporotic patients with very high risk of fractures. Post anabolic treatment with an antiresorptive drug maintains the bone mineral density (BMD) gained. The recommendations regarding the ideal antiresorptive drug are not precise. The aim of this paper is to compare the usefulness of zoledronate and denosumab in a group of 28 women with very high risk of fractures. All of them completed at least one year of treatment with teripatide and latter 14 received zolendronate and 14 denosumab for another year. We retrospectively review their biochemical and densitometric changes. Both treatment groups experienced a reduction in bone turnover markers of the same magnitude at the end of the second year. In Lumbar Spine BMD increase of 3.96 ± 8.56% Median (Me) 2.54 p = 0.21 in zolendronate group and 3.55 ± 5.36% (Me 5.14) p = 0.07 in denosumab group. Femoral Neck BMD changed -0.09 ± 6.50% (Me 0.29) p = 0.85 in zolendronate group, and - 3.41 ± 5.08% (Me 5.35) p = 0.59 in denosumab group, with no difference between both groups. In Total Hip BMD an increase of 0.55 ± 4.20% (Me 0.43) p = 0.70 in zoledronate group, and 4.53 ± 5.13% (Me 0.64) p = 0.04 with denosumab. We conclude that both antiresortive treatments have a similar effect in biochemical markers after one year of treatment. BMD increase significantly in total hip and changed with a trend toward in lumbar spine with denosumab, but without differences between both groups of treatment.
Los anabólicos son el tratamiento de elección en la osteoporosis con muy alto riesgo de fracturas. Después del tratamiento anabólico un fármaco antirresortivo mantiene la densidad mineral ósea (DMO) ganada. Las recomendaciones sobre el fármaco antirresortivo ideal no son precisas. El objetivo de este trabajo es comparar la utilidad de zoledronato y denosumab en un grupo de 28 mujeres con muy alto riesgo de fracturas. Todas ellas completaron al menos un año de tratamiento con teripatide y luego 14 recibieron zolendronato y 14 denosumab durante un año. Revisamos retrospectivamente sus cambios bioquímicos y densitométricos. Ambos grupos de tratamiento experimentaron una reducción de los marcadores de recambio óseo de la misma magnitud al final del segundo año. En columna lumbar la DMO aumentó 3.96 ± 8.56% Mediana (Me) 2.54, p = 0.21 en el grupo zolendronato y 3.55 ± 5.36% (Me 5.14) p = 0.07 en el grupo denosumab. La DMO del cuello femoral cambió -0.09 ± 6.50% (Me 0.29) p = 0.85 en el grupo zolendronato y - 3.41 ± 5.08% (Me 5.35) p = 0.59 en el grupo de denosumab, sin diferencias entre ambos grupos. En la Cadera Total la DMO aumentó 0.55 ± 4.20% (Me 0.43) p = 0.70 con zoledronato y 4.53 ± 5.13% (Me 0.64) p = 0.04 con denosumab. Concluimos que ambos tratamientos antiresortivos tuvieron un efecto similar en los marcadores bioquímicos después de un año de tratamiento. La DMO aumentó significativamente en la cadera total y mostró una tendencia similar en columna lumbar con denosumab, sin diferencias entre ambos tratamientos.
Assuntos
Conservadores da Densidade Óssea , Teriparatida , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Feminino , Humanos , Estudos Retrospectivos , Teriparatida/uso terapêuticoRESUMO
Abstract Anabolic drugs are the treatment of choice for osteoporotic patients with very high risk of fractures. Post anabolic treatment with an antiresorptive drug maintains the bone mineral density (BMD) gained. The recommendations regarding the ideal antiresorptive drug are not precise. The aim of this paper is to compare the usefulness of zoledronate and denosumab in a group of 28 women with very high risk of fractures. All of them completed at least one year of treatment with teripatide and latter 14 received zolendronate and 14 denosumab for another year. We retrospectively review their biochemical and densitometric changes. Both treat ment groups experienced a reduction in bone turnover markers of the same magnitude at the end of the second year. In Lumbar Spine BMD increase of 3.96 ± 8.56% Median (Me) 2.54 p = 0.21 in zolendronate group and 3.55 ± 5.36% (Me 5.14) p = 0.07 in denosumab group. Femoral Neck BMD changed -0.09 ± 6.50% (Me 0.29) p = 0.85 in zolendronate group, and - 3.41 ± 5.08% (Me 5.35) p = 0.59 in denosumab group, with no difference between both groups. In Total Hip BMD an increase of 0.55 ± 4.20% (Me 0.43) p = 0.70 in zoledronate group, and 4.53 ± 5.13% (Me 0.64) p = 0.04 with denosumab. We conclude that both antiresortive treatments have a similar effect in biochemical markers after one year of treatment. BMD increase significantly in total hip and changed with a trend toward in lumbar spine with denosumab, but without differences between both groups of treatment.
Resumen Los anabólicos son el tratamiento de elección en la osteoporosis con muy alto riesgo de fracturas. Después del tratamiento anabólico un fármaco antirresortivo mantiene la densidad mineral ósea (DMO) ganada. Las reco mendaciones sobre el fármaco antirresortivo ideal no son precisas. El objetivo de este trabajo es comparar la utilidad de zoledronato y denosumab en un grupo de 28 mujeres con muy alto riesgo de fracturas. Todas ellas completaron al menos un año de tratamiento con teripatide y luego 14 recibieron zolendronato y 14 denosumab durante un año. Revisamos retrospectivamente sus cambios bioquímicos y densitométricos. Ambos grupos de tratamiento experimentaron una reducción de los marcadores de recambio óseo de la misma magnitud al final del segundo año. En columna lumbar la DMO aumentó 3.96 ± 8.56% Mediana (Me) 2.54, p = 0.21 en el grupo zolendronato y 3.55 ± 5.36% (Me 5.14) p = 0.07 en el grupo denosumab. La DMO del cuello femoral cambió -0.09 ± 6.50% (Me 0.29) p = 0.85 en el grupo zolendronato y - 3.41 ± 5.08% (Me 5.35) p = 0.59 en el grupo de denosumab, sin diferencias entre ambos grupos. En la Cadera Total la DMO aumentó 0.55 ± 4.20% (Me 0.43) p = 0.70 con zoledronato y 4.53 ± 5.13% (Me 0.64) p = 0.04 con denosumab. Concluimos que ambos tratamien tos antiresortivos tuvieron un efecto similar en los marcadores bioquímicos después de un año de tratamiento. La DMO aumentó significativamente en la cadera total y mostró una tendencia similar en columna lumbar con denosumab, sin diferencias entre ambos tratamientos.
Assuntos
Humanos , Feminino , Teriparatida/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea , Estudos Retrospectivos , Denosumab/uso terapêuticoRESUMO
Considering the lack of studies determining the real TPTD efficacy in individuals who develop MRONJ, our objective was to combine the available data on MRONJ cases treated with TPTD. The findings demonstrated that TPTD in combination with another therapy, especially antibiotic therapy, can be considered an effective protocol for MRONJ. PURPOSE: To integrate the data published on the effect of teriparatide (TPTD) therapy on cases of medication-related osteonecrosis of the jaws (MRONJ) into a comprehensive analysis of clinical features. METHODS: An electronic search was undertaken in six databases. Descriptive analyses of clinicodemographic data of MRONJ were carried out. Poisson regression was also run to evaluate predictors of total resolution of MRONJ treated with TPTD. RESULTS: Twenty-six publications comprising 111 cases were included. Most reported cases affected female individuals (82.0%) with a mean age of 76.54 years. Osteoporosis (76.5%) represented the main reason for using antiresorptive drugs, with bisphosphonates (98.1%) as the most frequently reported. Comorbidities were commonly present. The most related trigger factor of MRONJ was dental extraction (61.7%). Mandible (75.8%) was the most commonly affected site, with a mean evolution time of 5 months. MRONJ stage 2 (61.3%) was the most prevalent. Regarding TPTD treatment, in 45.1% cases, TPTD was used alone, with the total resolution being observed in 59.5% of the individuals. Associated therapy (54.9%) included surgery, antibiotic therapy, and laser therapy. Mean follow-up was 8.7 months. Poisson regression demonstrated that individuals with MRONJ stage 1 were 1.21 times more likely to present total resolution of osteonecrosis than individuals with MRONJ stage 3 (CI = 1.02-1.43; p < 0.023). Individuals who had undergone treatment with TPTD in association with another therapeutic modality were 1.21 times more likely to present total resolution of osteonecrosis than those who had undergone treatment with TPTD alone (CI = 1.40-1.39; p < 0.010). CONCLUSION: TPTD in combination with another therapy, especially antibiotic therapy, should be considered an effective therapeutic modality for MRONJ.
Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Idoso , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos , Feminino , Humanos , Arcada Osseodentária , Teriparatida/uso terapêuticoRESUMO
BACKGROUND: This article presents evidence and recommendations regarding the efficacy and safety of the approved and available therapies in Mexico to treat severe or established osteoporosis with the aim of developing a position regarding therapeutics in this stage of the disease, according to the descriptive cards of the National Drug Formulary of the National General Health Council of Mexico. METHODS: We performed a systematic and narrative review of the evidence of teriparatide and denosumab, from their pharmacological profile, effectiveness, and safety derived from clinical trials, as well as an analysis of the general recommendations of the national and international clinical practice guidelines. RESULTS: The evidence establishes that teriparatide and denosumab belong to different therapeutic classes, with biologically opposed mechanisms of action and indications of use, which are clearly differentiated in their respective national codes, therefore these drugs cannot be substitutable or interchangeable in severe osteoporosis therapy. Both represent the best options currently available for this stage of the disease; being similar in their efficacy in preventing new vertebral fragility fractures, with an RR of .35 (CI 95%; .22-.55) for teriparatide, and .32 (CI 95%: .26-.41) for denosumab. The absolute risk reduction is higher with teriparatide 9.3% (21 months) compared with denosumab at 4.8% (36 months). CONCLUSIONS: Our results agree with the recommendations available in national and international clinical practice guidelines, with both therapies proposed as a sequential, but not a substitute, treatment.
RESUMO
O objetivo do presente estudo foi investigar a ação da associação de medicação sistêmica (bifosfonato oral) e teriparatida como medicação local funcionalizando as superfícies dos implantes. Para a realização deste projeto, o mesmo foi divido em 2 etapas. A primeira etapa consistiu na determinação do melhor protocolo para a funcionalização de implantes com teriparatida, a partir da técnica layer by layer. Ainda nesta etapa, foram realizados testes físicos e in vitro (culturas de células) a fim de avaliar as propriedades da superfície funcionalizada, quanto à melhora nas respostas osteogênicas. A segunda etapa consistiu na realização de experimentos in vivo para avaliar o efeito desta superfície funcionalizada durante o reparo periimplantar. Para isso, 96 ratas Wistar, adultas jovens foram divididas em seis grandes grupos: 1. Grupo SHAM (n=16), no qual os animais foram submetidos à ovariectomia fictícia e dieta balanceada. 2. Grupo SHAM/SM (n=16), no qual os animais receberam dieta de cafeteria. 3. Grupo OVX (n=16), no qual os animais foram submetidos a cirurgia de ovariectomia e não receberam tratamento medicamentoso. 4. Grupo OVX/SM (n=16), no qual os animais foram submetidos à cirurgia ovariectomia e receberam dieta de cafeteria. 5. Grupo OVX/RIS (n=16), no qual os animais foram submetidos à cirurgia de ovariectomia e tratados com risedronato de sódio. 6. Grupo OVX/SM/RIS (n=16), no qual os animais foram submetidos à cirurgia de ovariectomia e à dieta de cafeteria associada ao tratamento medicamentoso com risedronato de sódio. Em cada grande grupo há dois subgrupos: A- implantes convencionais e B- implantes funcionalizados com teriparatida. No dia 0 foi realizada a ovariectomia ou cirurgia fictícia. Passados 30 dias foi iniciado o tratamento medicamentoso com risedronato de sódio. Após 30 dias do início do tratamento medicamentoso, os animais foram submetidos à exodontia do primeiro molar superior direito, em seguida receberam os implantes na região onde foi realizada a exodontia. Aos 28 dias após a instalação dos implantes, os animais foram submetidos à eutanásia para mensuração do torque de remoção. Os dados foram submetidos ao teste de homocedasticidade (Shapiro Wilk). Houve a confirmação de distribuição normal dos dados amostrais e na sequência, foi realizado o teste paramétrico ANOVA One Way, seguido do pós teste de Tukey, com o nível de significância de 5% (p< 0,05). Os implantes funcionalizados apresentaram os maiores valores de torque de remoção em todos os grupos experimentais. A associação sistêmica entre o risedronato de sódio e teriparatida de forma tópica fez com que o grupo OVX/SM/RIS teriparatida obtivesse o maior torque de remoção quando comparado aos demais grupos. Com isso, conclui-se que o desempenho clínico dos implantes funcionalizados com teriparatida foi favorável, no entanto, quando associado à administração sistêmica de risedronato de sódio, os resultados se tornam mais promissores(AU)
The objective of this study was to investigate the action of the association of systemic medication (oral biphosphonate) and teriparatide as local medication functionalized to the surfaces of implants. For the execution of this project, it was divided in 2 stages. The first stage consisted in determining the best protocol for the functionalization of implants with teriparatide, based on the layer by layer technique. Still in this stage, physical and in vitro tests (cell cultures) were performed in order to evaluate the properties of the functionalized surface, regarding the improvement in osteogenic responses. The second stage consisted in conducting in vivo experiments to evaluate the effect of this surface functionalized during the peri-implant repair. For this, 96 Wistar rats, young adults were divided into six large groups: 1. SHAM Group (n=16), where the animals underwent sham surgery and balanced diet. 2. SHAM/SM Group (n=16), in which the animals received a cafeteria diet. 3) Group OVX (n=16), in which the animals underwent ovariectomy without drug treatment. 4. Group OVX/SM (n=16), in which the animals underwent ovariectomy and received a cafeteria diet. 5. Group OVX/SM/RIS (n=16), in which the animals underwent ovariectomy surgery and cafeteria diet associated with drug treatment with sodium risedronate. 6. Group OVX/RIS (n=16), in which the animals underwent ovariectomy and were treated with sodium risedronate. In each large group there are two subgroups: A- conventional implants and B- implants functionalized with teriparatide. After 30 days of beginning the drug treatment, the animals were submitted to bilateral first molar exodontia, then received the implants in the region where the exodontia was performed. At 28 days after installation of the implants, the animals were euthanized to measure the removal torque. The data were submitted to the homoscedasticity test (Shapiro Wilk). There was confirmation of normal distribution of the sample data and in the sequence, the parametric test ANOVA One Way was performed, followed by Tukey's post-test, with the significance level of 5% (p< 0.05). The functionalized implants had the highest removal torque values in all experimental groups. The systemic association between sodium risedronate and teriparatide topically resulted in the OVX/SM/RIS teriparatide group obtaining the highest removal torque when compared to the other groups. Thus, it is concluded that the clinical performance of implants functionalized with teriparatida was favorable, however, when associated with systemic administration of sodium risedronate, the results become more promising(AU)
Assuntos
Animais , Ratos , Osteoporose , Implantes Dentários , Teriparatida , Regeneração Óssea , TorqueRESUMO
PURPOSE: Teriparatide is used to treat patients with established osteoporosis but is often reserved for patients who have inadequate response to antiresorptive therapy. Biosimilar teriparatide, which is believed to have efficacy and safety similar to the originator product, is now available in Colombia. However, little is known about patients' preferences for originator biologic and biosimilar treatments. Our objective was to quantify the relative importance that patients in Colombia place on features of injectable osteoporosis treatments including whether the treatment is an originator biologic or a biosimilar. PATIENTS AND METHODS: We used a discrete choice experiment (DCE) to elicit preferences of patients with osteoporosis treatment devices in Colombia. The survey was completed by 200 respondents at high risk of fracture, with or without teriparatide experience. Each treatment alternative within the DCE was characterized by five attributes: type of medicine (originator biologic, biosimilar), needle length, angle of injection, how to measure the medicine dose, and how long the medicine can be left unrefrigerated. A random parameters logit regression was used to estimate preferences and conditional relative attribute importance, while controlling for preference heterogeneity. RESULTS: A total of 200 patients (mean age = 58.3 years) completed the survey. Most were female (84.5%) and married (54.5%); 50.5% had secondary education or less, 21% had current teriparatide exposure. The attribute with the highest conditional relative importance estimate (standard error) was biologic versus biosimilar (10 [1.11]), followed by needle length (8.06 [1.11]), dose measurement (6.38 [0.87]), refrigeration (3.81 [1.18]), and angle of injection (1.30 [0.66]). Unobserved preference heterogeneity was present and controlled for in the analyses. CONCLUSION: Despite the availability of biosimilar teriparatide in Colombia, patients expressed a strong preference for an originator biologic osteoporosis medicine over a biosimilar osteoporosis medicine, when the efficacy, safety, and cost of the two options were assumed to be the same.
RESUMO
BACKGROUND: Osteoporosis is a major healthcare concern in Latin America. Factors such as changing demographics, fragmented healthcare systems, and financial considerations may result in a huge increase in the burden of osteoporosis in this region. The aim of this article is to describe the baseline clinical characteristics and fracture history of patients who are prescribed teriparatide in normal clinical practice in Latin America. METHODS: We conducted a prospective, multinational, observational study (the Asia and Latin America Fracture Observational Study [ALAFOS]) in 20 countries worldwide to assess the incidence of fractures in postmenopausal women with osteoporosis receiving teriparatide as a part of routine clinical practice in a real-world setting. In this subregional analysis of the ALAFOS study, we report the clinical characteristics, fracture history, risk factors for osteoporosis, comorbidities, previous osteoporosis therapies and health-related quality of life measures at baseline for patients from the four participant Latin American countries: Argentina, Brazil, Colombia, and Mexico. RESULTS: The Latin America subregional cohort included 546 postmenopausal women (mean [SD] age: 71.0 [10.1] years; range: 40-94 years), constituting 18% of the ALAFOS total population. The baseline mean (SD) bone mineral density T-scores were - 3.02 (1.23) at the lumbar spine and - 2.31 (0.96) at the femoral neck; 62.8% of patients had a history of low trauma fracture after the age of 40 years and 39.7% of patients had experienced ≥1 fall in the past year. Osteoporosis medications were used by 70.9% of patients before initiating teriparatide. The median (Q1, Q3) EQ-5D-5 L Visual Analog Scale (VAS) scores for perceived health status at baseline was 70 (50, 80). The mean (SD) worst back pain numeric rating scale score for the overall Latin American cohort was 4.3 (3.4) at baseline. CONCLUSIONS: This baseline analysis of the Latin America subregion of the ALAFOS study indicates that patients who are prescribed teriparatide in the four participant countries had severe osteoporosis and high prevalence of fractures. They also had back pain and poor health-related quality of life. The proportions of patients with severe or extreme problems on the EQ-5D-5 L individual domains were lower than those in the overall ALAFOS study population.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/epidemiologia , Pós-Menopausa , Teriparatida/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Argentina/epidemiologia , Dor nas Costas/tratamento farmacológico , Densidade Óssea , Brasil/epidemiologia , Colômbia/epidemiologia , Comorbidade , Feminino , Glucocorticoides/uso terapêutico , Humanos , América Latina , México/epidemiologia , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Osteoporose/etiologia , Fraturas por Osteoporose/etiologia , Medição da Dor , Prevalência , Estudos Prospectivos , Qualidade de Vida , História Reprodutiva , Fatores de Risco , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Escala Visual AnalógicaRESUMO
INTRODUCTION: Bisphosphonates have been the gold standard in the management of osteoporosis. Its antiresorptive effect has reduced the incidence of fractures due to bone fragility, as well as its impact on public health. We present the clinical case of a patient in prolonged treatment with bisphosphonates and atypical bilateral femur fracture. CASE REPORT: A 65-year-old female who presented a fall from her own height, on treatment with risedronate for seven years, and a history of systemic arterial hypertension and hypercholesterolemia, both with medical treatment. Diagnosed with bilateral atypical femoral fracture, treated with closed reduction internal fixation (CRIF) with intramedullary nailing, application of calcium citrate and teriparatide. DISCUSSION: Multiple studies indicate that the benefit of using bisphosphonates for osteoporosis is higher than the risk of presenting atypical fractures.
INTRODUCCIÓN: Los bifosfonatos han sido de gran utilidad en el manejo de la osteoporosis. Su efecto antirresortivo ha disminuido la incidencia de fracturas por fragilidad ósea, así como, su impacto en salud pública. Presentamos el caso clínico de una usuaria en tratamiento prolongado con bifosfonatos y fractura atípica de fémur bilateral. CASO CLÍNICO: Femenino de 65 años, presenta caía de su plano de sustentación, en tratamiento con risedronato desde hace siete años y antecedente de hipertensión arterial sistémica e hipercolesterolemia, ambas con manejo médico. Diagnosticada con fractura bilateral de fémur, tratada con enclavado centro-medular, citrato de calcio y teriparatida. DISCUSIÓN: Múltiples estudios refieren que el beneficio del uso de bifosfonatos en la prevención del riesgo de fracturas es mayor, aunque exista la posibilidad de presentar fracturas atípicas.
Assuntos
Conservadores da Densidade Óssea , Fraturas do Fêmur , Osteoporose , Idoso , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos , Feminino , Fraturas do Fêmur/etiologia , Humanos , Osteoporose/tratamento farmacológico , TeriparatidaRESUMO
OBJECTIVE: To systematically evaluate the effects of bone anabolic therapies (BATs) - specifically, drug therapy with teriparatide, abaloparatide or romosozumab - on fractures, bone mineral density (BMD), and bone metabolites in postmenopausal osteoporosis. METHODS: Six computerized engines were searched through to November 2018. We selected randomized controlled trials (RCTs) evaluating the effect of BATs on postmenopausal osteoporosis and with at least 6 months of follow-up. Controls were placebo, no treatment, or bisphosphonates. Primary outcomes were vertebral and non-vertebral fractures. Secondary outcomes were: BMD determined by dual energy X-ray absorptiometry at total hip, lumbar spine, and femoral neck; N-terminal propeptide of type I procollagen (PINP); C-terminal telopeptide of type I collagen (CTX); and severe adverse events (SAE). We followed the PRISMA guidelines for reporting, and used version 2 of the Cochrane risk-of-bias tool. Frequentist network meta-analyses were performed per outcome. Effects for dichotomous and continuous outcomes were expressed as relative risks and mean differences and their 95% confidence intervals. We used p-scores to rank best treatments per outcome. RESULTS: Sixteen RCTs (nâ¯=â¯18,940) were evaluated. Mean ages ranged between 61 and 74 years, and follow-up times between 6 and 30 months. Four RCTs (nâ¯=â¯971) excluded patients with previous fractures. In contrast to placebo/no treatment, all BATs significantly reduced the risk of vertebral fractures, but no intervention significantly reduced the risk of non-vertebral fractures; abaloparatide ranked better than other interventions for both fracture types (p-scores: 0.95, and 0.89, respectively). All BATs significantly increased BMD at all locations in comparison with placebo/no treatment; romosozumab consistently ranked better than other interventions at all BMD locations (p-scores >0.86). Teriparatide ranked better than other interventions for increasing PINP. No differences in SAE were observed among treatments. CONCLUSIONS: Abaloparatide, romosozumab, and teriparatide are the best treatments, respectively, to reduce vertebral/non-vertebral fractures, increase BMD, and increase bone formation.