RESUMO
This study evaluated the cost-effectiveness of sequential treatment with romosozumab-to-alendronate compared to alendronate monotherapy and teriparatide-to-alendronate, in postmenopausal osteoporotic women from a Belgian healthcare perspective. Romosozumab-to-alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide-to-alendronate for osteoporotic women at high risk of fracture in Belgium. PURPOSE: This study aimed to evaluate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate compared to alendronate monotherapy and teriparatide followed by alendronate, in postmenopausal osteoporotic women at high risk of fracture, from a Belgian healthcare perspective. Romosozumab is reimbursed in Belgium since December 2021. METHODS: A Markov microsimulation model was used to evaluate the cost-effectiveness of romosozumab-to-alendronate compared to alendronate monotherapy and to teriparatide-to-alendronate over a lifetime horizon. Patients transition between five different health states every 6 months based on fracture risks or death. The model was populated with Belgium-specific epidemiological and cost data, where available. The fracture risk reduction of romosozumab treatment was collated from the ARCH study, and from a published network meta-analysis. Costs were included from a healthcare perspective (NIHDI). Cost-effectiveness was reported in terms of costs per quality-adjusted life year (QALY), reported in Euro () 2022. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed. RESULTS: Romosozumab-to-alendronate was associated with 0.12 additional QALYs at an additional cost of 2314 compared to alendronate monotherapy, resulting in an ICER of 19,978. Compared to teriparatide-to-alendronate, romosozumab-to-alendronate was found to be dominant, with higher QALYs and lower costs. The base-case results were robust to uncertainty in the input parameters when conducting the sensitivity analysis. CONCLUSION: Sequential treatment with romosozumab followed by alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide followed by alendronate for postmenopausal women with osteoporosis at high risk of fracture in Belgium.
Assuntos
Alendronato , Anticorpos Monoclonais , Conservadores da Densidade Óssea , Análise Custo-Benefício , Custos de Medicamentos , Cadeias de Markov , Osteoporose Pós-Menopausa , Fraturas por Osteoporose , Anos de Vida Ajustados por Qualidade de Vida , Teriparatida , Humanos , Feminino , Fraturas por Osteoporose/prevenção & controle , Fraturas por Osteoporose/economia , Fraturas por Osteoporose/epidemiologia , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/economia , Bélgica/epidemiologia , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/economia , Osteoporose Pós-Menopausa/complicações , Alendronato/uso terapêutico , Alendronato/economia , Alendronato/administração & dosagem , Teriparatida/uso terapêutico , Teriparatida/economia , Teriparatida/administração & dosagem , Idoso , Custos de Medicamentos/estatística & dados numéricos , Anticorpos Monoclonais/economia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Quimioterapia Combinada , Pessoa de Meia-Idade , Esquema de Medicação , Substituição de Medicamentos/economia , Substituição de Medicamentos/estatística & dados numéricosRESUMO
Post hoc analysis of FRAME and ARCH revealed that on-study nonvertebral and vertebral fractures by Month 12 were less common in women initially treated with romosozumab versus placebo or alendronate. Recurrent fracture risk was also lower in romosozumabtreated patients, and there were no fracturerelated complications. Results support continuing romosozumab treatment postfracture. PURPOSE: Post hoc analysis evaluating efficacy and safety of romosozumab, administered in the immediate postfracture period, in the FRAME and ARCH phase 3 trials. METHODS: In FRAME (NCT01575834) and ARCH (NCT01631214), postmenopausal women with osteoporosis were randomized 1:1 to romosozumab 210 mg monthly or comparator (FRAME, placebo; ARCH, alendronate 70 mg weekly) for 12 months, followed by antiresorptive therapy (FRAME, denosumab; ARCH, alendronate). In patients who experienced on-study nonvertebral or new/worsening vertebral fracture by Month 12, we report the following: fracture and treatmentemergent adverse event (TEAE) incidence through 36 months, bone mineral density changes (BMD), and romosozumab timing. Due to the sample sizes employed, meaningful statistical comparisons between treatments were not possible. RESULTS: Incidence of on-study nonvertebral and vertebral fractures by Month 12 was numerically lower in romosozumab- versus comparator-treated patients (FRAME, 1.6% and 0.5% versus 2.1% and 1.6%; ARCH, 3.4% and 3.3% versus 4.6% and 4.9%, respectively). In those who experienced on-study nonvertebral fracture by Month 12, recurrent nonvertebral and subsequent vertebral fracture incidences were numerically lower in patients initially treated with romosozumab versus comparator (FRAME, 3.6% [2/56] and 1.8% [1/56] versus 9.2% [7/76] and 3.9% [3/76]; ARCH, 10.0% [7/70] and 5.7% [4/70] versus 12.6% [12/95] and 8.4% [8/95], respectively). Among those with on-study vertebral fracture by Month 12, recurrent vertebral and subsequent nonvertebral fracture incidences were numerically lower with romosozumab versus comparator (FRAME, 0.0% [0/17] and 0.0% [0/17] versus 11.9% [7/59] and 8.5% [5/59]; ARCH, 9.0% [6/67] and 7.5% [5/67] versus 15.0% [15/100] and 16.0% [16/100], respectively). In patients with fracture by Month 12, no fracturerelated complications were reported in romosozumab-treated patients. BMD gains were numerically greater with romosozumab than comparators. CONCLUSION: Data suggest support for the efficacy and safety of continuing romosozumab treatment following fracture. TRIAL REGISTRATIONS: NCT01575834; NCT01631214.
Assuntos
Alendronato , Anticorpos Monoclonais , Conservadores da Densidade Óssea , Denosumab , Osteoporose Pós-Menopausa , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Feminino , Fraturas por Osteoporose/prevenção & controle , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/administração & dosagem , Fraturas da Coluna Vertebral/prevenção & controle , Fraturas da Coluna Vertebral/fisiopatologia , Idoso , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/fisiopatologia , Osteoporose Pós-Menopausa/complicações , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/administração & dosagem , Pessoa de Meia-Idade , Alendronato/uso terapêutico , Alendronato/administração & dosagem , Alendronato/efeitos adversos , Denosumab/uso terapêutico , Denosumab/efeitos adversos , Denosumab/administração & dosagem , Método Duplo-Cego , Densidade Óssea/efeitos dos fármacos , Idoso de 80 Anos ou mais , Esquema de Medicação , RecidivaRESUMO
BACKGROUND: The role of vitamin D in human physiology is a topic of great interest for the scientific community in the last decades. The common target for all clinicians is to improve its status in order to prevent several pathological conditions. METHODS: The aim of our study was to evaluate the safety and the efficacy of both calcifediol and cholecalciferol in combination with alendronate in osteoporotic women. A homogeneous population of 300 postmenopausal osteoporotic women was selected for this study. 150 women were administered with alendronate 70 mg combined with clacifediol 0.266 mg soft capsules monthly. The other half (other 150 women) were administered with alendronate 70 mg combined with cholecalciferol 25000 IU monthly. First follow-up was after 4 months and second follow-up after 12 months. RESULTS: No case of toxicity was detected throughout the study in any patient. In regards to increase of vitamin D serum level, after four months supplementation calcifediol is 1.29 fold more effective than cholecalciferol while after 12 months of supplementation calcifediol is 2.32 fold more effective compared to cholecalciferol. CONCLUSIONS: In our study calcifediol showed to be as safe as cholecalciferol and more effective than cholecalciferol in order to increase vitamin D serum level after four and 12 months of supplementation when supplementation is combined with alendronate 70 mg in osteoporotic women.
Assuntos
Alendronato , Conservadores da Densidade Óssea , Calcifediol , Colecalciferol , Osteoporose Pós-Menopausa , Humanos , Feminino , Alendronato/uso terapêutico , Alendronato/administração & dosagem , Alendronato/efeitos adversos , Colecalciferol/administração & dosagem , Colecalciferol/uso terapêutico , Colecalciferol/efeitos adversos , Estudos Transversais , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Idoso , Calcifediol/sangue , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/tratamento farmacológico , Quimioterapia Combinada , Resultado do Tratamento , Idoso de 80 Anos ou mais , CápsulasRESUMO
BACKGROUND: Low back pain (LBP) affects a significant proportion of the adult population. Potent anti-resorptive drugs such as intravenous zoledronic acid have been demonstrated to reduce Modic changes (MCs) upon magnetic resonance imaging (MRI) of the spine and concomitantly decrease associated LBP. It is uncertain whether oral alendronic acid has a similar effect. METHODS: 82 subjects were recruited in this case-control study. Treatment subjects (n = 41) received oral alendronic acid treatment for at least 1-year and were matched by gender and age (± 2) to control subjects (n = 41) not receiving any anti-osteoporotic medication. The prevalence, type, and extent of MCs were quantified upon T1 and T2-weighted MRIs of the lumbosacral spine. RESULTS: Treatment subjects received oral alendronic acid for 124.0 ± 62.1 weeks at the time of MRI assessment and exhibited a lower prevalence of MCs over the lumbosacral spine (18/41 vs. 30/41, p < 0.001) as compared to control subjects. Amongst both groups, type 2 MCs were predominant. Quantification of type 2 MCs in treatment subjects revealed a significant reduction in area (113 ± 106 mm2 vs. 231 ± 144 mm2, p < 0.01) and volume (453 ± 427 mm3 vs. 925 ± 575 mm3, p < 0.01) affected by type 2 MCs in comparison to matched controls. CONCLUSION: Oral alendronic acid may be useful in the treatment of MC-associated LBP in patients with concomitant osteoporosis.
Assuntos
Conservadores da Densidade Óssea , Dor Lombar , Vértebras Lombares , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Vértebras Lombares/diagnóstico por imagem , Estudos de Casos e Controles , Pessoa de Meia-Idade , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/administração & dosagem , Idoso , Dor Lombar/tratamento farmacológico , Dor Lombar/etiologia , Dor Lombar/diagnóstico por imagem , Alendronato/uso terapêutico , Alendronato/administração & dosagem , Fatores de Tempo , Adulto , Administração Oral , Fatores Etários , Resultado do Tratamento , Fatores SexuaisRESUMO
Background: Bisphosphonates are a class of medication commonly used to treat osteoporosis. Alendronate is recommended as the first-line treatment; however, long-term adherence (both treatment compliance and persistence) is poor. Alternative bisphosphonates are available, which can be given intravenously and have been shown to improve long-term adherence. However, the most clinically effective and cost-effective alternative bisphosphonate regimen remains unclear. What is the most cost-effective bisphosphonate in clinical trials may not be the most cost-effective or acceptable to patients in everyday clinical practice. Objectives: 1. Explore patient, clinician and stakeholder views, experiences and preferences of alendronate compared to alternative bisphosphonates. 2. Update and refine the 2016 systematic review and cost-effectiveness analysis of bisphosphonates, and estimate the value of further research into their benefits. 3. Undertake stakeholder/consensus engagement to identify important research questions and further rank research priorities. Methods: The study was conducted in two stages, stages 1A and 1B in parallel, followed by stage 2: ⢠Stage 1A - we elicited patient and healthcare experiences to understand their preferences of bisphosphonates for the treatment of osteoporosis. This was undertaken by performing a systematic review and framework synthesis of qualitative studies, followed by semistructured qualitative interviews with participants. ⢠Stage 1B - we updated and expanded the existing Health Technology Assessment systematic review and clinical and cost-effectiveness model, incorporating a more comprehensive review of treatment efficacy, safety, side effects, compliance and long-term persistence. ⢠Stage 2 - we identified and ranked further research questions that need to be answered about the effectiveness and acceptability of bisphosphonates. Results: Patients and healthcare professionals identified a number of challenges in adhering to bisphosphonate medication, balancing the potential for long-term risk reduction against the work involved in adhering to oral alendronate. Intravenous zoledronate treatment was generally more acceptable, with such regimens perceived to be more straightforward to engage in, although a portion of patients taking alendronate were satisfied with their current treatment. Intravenous zoledronate was found to be the most effective, with higher adherence rates compared to the other bisphosphonates, for reducing the risk of fragility fracture. However, oral bisphosphonates are more cost-effective than intravenous zoledronate due to the high cost of zoledronate administration in hospital. The importance of including patients and healthcare professionals when setting research priorities is recognised. Important areas for research were related to patient factors influencing treatment selection and effectiveness, how to optimise long-term care and the cost-effectiveness of delivering zoledronate in an alternative, non-hospital setting. Conclusions: Intravenous zoledronate treatment was generally more acceptable to patients and found to be the most effective bisphosphonate and with greater adherence; however, the cost-effectiveness relative to oral alendronate is limited by its higher zoledronate hospital administration costs. Future work: Further research is needed to support people to make decisions influencing treatment selection, effectiveness and optimal long-term care, together with the clinical and cost-effectiveness of intravenous zoledronate administered in a non-hospital (community) setting. Limitations: Lack of clarity and limitations in the many studies included in the systematic review may have under-interpreted some of the findings relating to effects of bisphosphonates. Trial registration: This trial is registered as ISRCTN10491361. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127550) and is published in full in Health Technology Assessment; Vol. 28, No. 21. See the NIHR Funding and Awards website for further award information.
Bisphosphonates are drug treatments commonly used to treat osteoporosis. Alendronate is the most used and is taken by mouth, weekly at a specific time of the week, which can be challenging. Less than one in four people continue this treatment beyond 2 years. Alternative bisphosphonates are available, which vary in frequency and how they are administered. The most acceptable and best value-for-money regimen is unclear. Our aim was to determine how effective alternative bisphosphonates are compared to alendronate at preventing fractures and whether reduction in fracture risk was achieved at a reasonable financial cost, but acceptable to patients. The study was conducted in two stages, stages 1A and 1B in parallel, followed by stage 2: Stage 1A: a review of the published evidence on patients' and doctors' views, experiences and preferences regarding different bisphosphonate treatment regimens, followed by interviews with patients and healthcare professionals. Stage 1B: an update of an existing study on how effective bisphosphonates are in preventing fragility fractures caused by osteoporosis and whether they are good value for money. Stage 2: identification of questions that need to be answered about the effectiveness and acceptability of bisphosphonate treatments. Taking bisphosphonate medication often involves quite a lot of effort by patients, particularly when taking alendronate tablets. A yearly infusion of zoledronate treatment was more acceptable, easier to engage with and the most effective treatment compared to alendronate. However, the cost of administering zoledronate in hospital made alendronate better value for money. Bisphosphonates are effective in reducing the risk of fracture, but 'continuing with treatment', particularly alendronate tablets, remains a challenge. A yearly infusion of zoledronate offers an acceptable and effective treatment, but further research is needed to support patients and healthcare professionals in making decisions about the various treatments, benefits and cost savings of administering zoledronate outside of hospital and in the community.
Assuntos
Alendronato , Conservadores da Densidade Óssea , Análise Custo-Benefício , Difosfonatos , Fraturas por Osteoporose , Humanos , Difosfonatos/uso terapêutico , Difosfonatos/administração & dosagem , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/administração & dosagem , Fraturas por Osteoporose/prevenção & controle , Alendronato/uso terapêutico , Alendronato/administração & dosagem , Alendronato/economia , Feminino , Osteoporose/tratamento farmacológico , Adesão à Medicação , Masculino , Idoso , Anos de Vida Ajustados por Qualidade de Vida , Avaliação da Tecnologia Biomédica , Pessoa de Meia-Idade , Ácido Zoledrônico/uso terapêutico , Ácido Zoledrônico/administração & dosagem , Pesquisa QualitativaRESUMO
This study demonstrated a large treatment gap in elderly subjects experiencing fragility fracture in Spanish primary care, a low treatment persistence among subjects who do receive treatment, and more than one-quarter having no follow-up visits post-fracture. These data highlight the need to improve secondary fracture prevention in primary care. PURPOSE: To describe osteoporosis (OP) treatment patterns and follow-up in subjects with fragility fracture seen in Spanish primary care (PC). METHODS: This observational, retrospective chart review included subjects aged ≥ 70 years listed in the centers' records (November 2018 to March 2020), with ≥ 1 fragility fracture and prior consultation for any reason; subjects who had participated in another study were excluded. Outcomes included OP treatments and follow-up visits post-fragility fracture. RESULTS: Of 665 subjects included, most (87%) were women; overall mean (SD) age, 82 years. Fewer than two thirds (61%) had received any prior OP treatment (women, 65%; men, 38%); of these, 38% had received > 1 treatment (women, 25%; men, 13%). Among treated subjects, the most frequent first-line treatments were alendronate (43%) and RANKL inhibitor denosumab (22%), with a higher discontinuation rate and shorter treatment duration observed for alendronate (discontinuation, 42% vs 16%; median treatment duration, 2.5 vs 2.1 years). Over one-quarter (26%) of subjects had no follow-up visits post-fragility fracture, with this gap higher in women than men (35% versus 25%). The most common schedule of follow-up visits was yearly (43% of subjects with a fragility fracture), followed by half-yearly (17%) and biennial (10%), with a similar trend in men and women. Most OP treatments were prescribed by PC physicians, other than teriparatide and zoledronate. CONCLUSIONS: Across Spanish PC, we observed a large gap in the treatment and follow-up of elderly subjects experiencing a fragility fracture. Our data highlights the urgent need to improve secondary fracture prevention in PC.
Assuntos
Conservadores da Densidade Óssea , Fraturas por Osteoporose , Atenção Primária à Saúde , Prevenção Secundária , Humanos , Feminino , Masculino , Idoso , Espanha/epidemiologia , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Atenção Primária à Saúde/estatística & dados numéricos , Conservadores da Densidade Óssea/uso terapêutico , Fraturas por Osteoporose/prevenção & controle , Fraturas por Osteoporose/epidemiologia , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Osteoporose/complicações , Alendronato/uso terapêutico , Alendronato/administração & dosagem , Denosumab/uso terapêuticoRESUMO
BACKGROUND: Low back pain is one of the most common symptoms of osteoporosis. The pain can seriously affect patients' mood and quality of life; it can also further aggravate bone loss, causing a serious social burden. Minodronate is an oral bisphosphonate that needs to be administered daily. It significantly reduces levels of bone turnover markers (BTMs) and rapidly improves symptoms of low back pain in patients with osteoporosis. Osteoporosis requires long-term treatment, and daily dosing reduces patient compliance. Minodronate has a better safety profile than other bisphosphonates. The objective of the trial is to explore the efficacy and safety of minodronate in the treatment of low back pain in postmenopausal osteoporosis patients. METHODS: This is a single-centre, randomized, open-label controlled trial with a 24-week duration. Seventy-two eligible patients will be randomly divided into 4 groups. Subjects will be randomized at a 1:1 ratio to receive either minodronate (1 mg/day) or alendronate (10 mg/day) every day; senior women (≥ 75 years old) and older women (< 75 years old) will be at a ratio of 1:2. The primary outcome is the time required for the visual analogue scale (VAS) score to decline by ≥ 10 from baseline. The secondary outcome is the changes in VAS scores from baseline, the frequency and dosage of rescue medication, BTMs, bone mineral density (BMD), and variations in upper gastrointestinal (GI) symptom scores from baseline (including heartburn, pain, and bloating). DISCUSSION: This study will provide objective evidence for the efficiency and safety of minodronate. Furthermore, it will be helpful to evaluate the quantitative relationship between BTMs and BMD in patients with osteoporosis under different ages. TRIAL REGISTRATION: This study protocol has been registered with ClinicalTrials.gov ID NCT05645289 ( https://clinicaltrials.gov/search?term=NCT05645289 ) on December 8, 2022. The registry name is Peking University Third Hospital. This study protocol was reviewed and approved by the Peking University Third Hospital Medical Science Research Ethics Committee (M2022465, 2022.08.09, V2.0). The results will be published in scientific peer-reviewed journals. TRIAL STATUS: The protocol was registered at ClinicalTrials.gov (registration number: NCT05645289). Recruitment has started in January 2023 and is still ongoing.
Assuntos
Conservadores da Densidade Óssea , Difosfonatos , Imidazóis , Dor Lombar , Osteoporose Pós-Menopausa , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Feminino , Osteoporose Pós-Menopausa/tratamento farmacológico , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/administração & dosagem , Idoso , Difosfonatos/uso terapêutico , Difosfonatos/efeitos adversos , Difosfonatos/administração & dosagem , Resultado do Tratamento , Dor Lombar/tratamento farmacológico , Pessoa de Meia-Idade , Imidazóis/uso terapêutico , Imidazóis/efeitos adversos , Imidazóis/administração & dosagem , Medição da Dor , Densidade Óssea/efeitos dos fármacos , Alendronato/uso terapêutico , Alendronato/efeitos adversos , Alendronato/administração & dosagemRESUMO
Systemic administration of alendronate is associated with various adverse reactions in clinical settings. To mitigate these side effects, poloxamer 407 (P-407) modified with cellulose was chosen to encapsulate alendronate. This drug-loaded system was then incorporated into a collagen/ß-tricalcium phosphate (ß-TCP) scaffold to create a localized drug delivery system. Nuclear magnetic resonance spectrum and rheological studies revealed hydrogen bonding between P-407 and cellulose as well as a competitive interaction with water that contributed to the delayed release of alendronate (ALN). Analysis of the degradation kinetics of P-407 and release kinetics of ALN indicated zero-order kinetics for the former and Fickian or quasi-Fickian diffusion for the latter. The addition of cellulose, particularly carboxymethyl cellulose (CMC), inhibited the degradation of P-407 and prolonged the release of ALN. The scaffold's structure increased the contact area of P-407 with the PBS buffer, thereby, influencing the release rate of ALN. Finally, biocompatibility testing demonstrated that the drug delivery system exhibited favorable cytocompatibility and hemocompatibility. Collectively, these findings suggest that the drug delivery system holds promise for implantation and bone healing applications.
Assuntos
Alendronato , Fosfatos de Cálcio , Colágeno , Poloxâmero , Alendronato/química , Alendronato/administração & dosagem , Fosfatos de Cálcio/química , Poloxâmero/química , Colágeno/química , Animais , Alicerces Teciduais/química , Humanos , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/química , Sistemas de Liberação de Medicamentos , Camundongos , Teste de Materiais , Preparações de Ação Retardada/química , Materiais Biocompatíveis/químicaRESUMO
Chronic myeloid leukemia is a hematological cancer, where disease relapse and drug resistance are caused by bone-hosted-residual leukemia cells. An innovative resolution is bone-homing and selective-active targeting of anticancer loaded-nanovectors. Herein, ivermectin (IVM) and methyl dihydrojasmonate (MDJ)-loaded nanostructured lipid carriers (IVM-NLC) were formulated then dually decorated by lactoferrin (Lf) and alendronate (Aln) to optimize (Aln/Lf/IVM-NLC) for active-targeting and bone-homing potential, respectively. Aln/Lf/IVM-NLC (1 mg) revealed nano-size (73.67 ± 0.06 nm), low-PDI (0.43 ± 0.06), sustained-release of IVM (62.75 % at 140-h) and MDJ (78.7 % at 48-h). Aln/Lf/IVM-NLC afforded substantial antileukemic-cytotoxicity on K562-cells (4.29-fold lower IC50), higher cellular uptake and nuclear fragmentation than IVM-NLC with acceptable cytocompatibility on oral-epithelial-cells (as normal cells). Aln/Lf/IVM-NLC effectively upregulated caspase-3 and BAX (4.53 and 15.9-fold higher than IVM-NLC, respectively). Bone homing studies verified higher hydroxyapatite affinity of Aln/Lf/IVM-NLC (1 mg; 22.88 ± 0.01 % at 3-h) and higher metaphyseal-binding (1.5-fold increase) than untargeted-NLC. Moreover, Aln/Lf/IVM-NLC-1 mg secured 1.35-fold higher in vivo bone localization than untargeted-NLC, with lower off-target distribution. Ex-vivo hemocompatibility and in-vivo biocompatibility of Aln/Lf/IVM-NLC (1 mg/mL) were established, with pronounced amelioration of hepatic and renal toxicity compared to higher Aln doses. The innovative Aln/Lf/IVM-NLC could serve as a promising nanovector for bone-homing, active-targeted leukemia therapy.
Assuntos
Alendronato , Portadores de Fármacos , Ivermectina , Lactoferrina , Humanos , Animais , Portadores de Fármacos/química , Lactoferrina/química , Lactoferrina/farmacologia , Lactoferrina/administração & dosagem , Alendronato/química , Alendronato/farmacologia , Alendronato/administração & dosagem , Ivermectina/química , Ivermectina/análogos & derivados , Ivermectina/farmacologia , Ivermectina/administração & dosagem , Ivermectina/farmacocinética , Células K562 , Nanopartículas/química , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Lipídeos/química , Apoptose/efeitos dos fármacosRESUMO
Introduction: Osteoporosis, characterized by dysregulation of osteoclastic bone resorption and osteoblastic bone formation, severely threatens human health during aging. However, there is still no good therapy for osteoporosis, so this direction requires our continuous attention, and there is an urgent need for new drugs to solve this problem. Methods: Traditional Chinese Medicine Salvia divinorum monomer pomolic acid (PA) could effectively inhibit osteoclastogenesis and ovariectomized osteoporosis. However, its poor solubility and lack of targeting severely limits its further application. A novel bone-targeting nanomedicine (PA@TLipo) has been developed to reconstruct the osteoporotic microenvironment by encapsulating pomolic acid in alendronate-functionalized liposomes. Through a series of operations such as synthesis, purification, encapsulation, and labeling, the PA@TLipo have been prepared. Moreover, the cytotoxicity, bone targeting and anti-osteoporosis effect was verified by cell and animal experiments. Results: In the aspect of targeting, the PA@TLipo can effectively aggregate on the bone tissue to reduce bone loss, and in terms of toxicity, PA@TLipo could increase the bone target ability in comparison to nontargeted liposome, thereby mitigating systemic cytotoxicity. Moreover, PA@TLipo inhibited osteoclast formation and bone resorption in vitro and reduced bone loss in ovariectomy-induced osteoporotic mice. Conclusion: In this study, a novel therapeutic agent was designed and constructed to treat osteoporosis, consisting of a liposome material as the drug pocket, PA as the anti-osteoporosis drug, and ALN as the bone-targeting molecule. And our study is the first to employ a bone-targeted delivery system to deliver PA for OVX-induced bone loss, providing an innovative solution for treating osteoporosis.
Assuntos
Alendronato , Lipossomos , Osteoporose , Animais , Lipossomos/química , Alendronato/química , Alendronato/farmacologia , Alendronato/administração & dosagem , Osteoporose/tratamento farmacológico , Feminino , Camundongos , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/química , Conservadores da Densidade Óssea/administração & dosagem , Osteoclastos/efeitos dos fármacos , Células RAW 264.7 , Humanos , Osso e Ossos/efeitos dos fármacos , Reabsorção Óssea/tratamento farmacológico , Homeostase/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , OvariectomiaRESUMO
Bone is one of the most prevalent sites of metastases in various epithelial malignancies, including breast cancer and this metastasis to bone often leads to severe skeletal complications in women due to its osteolytic nature. To address this, we devised a novel drug delivery approach using an Alendronate (ALN) functionalized self-assembled porous crystalsomes for concurrent targeting of Oleanolic acid (OA) and ALN (ALN + OA@NCs) to bone metastasis. Initially, the conjugation of both PEG-OA and OA-PEG-ALN with ALN and OA was achieved, and this conjugation was then self-assembled into porous crystalsomes (ALN + OA@NCs) by nanoemulsion crystallization. The reconstruction of a 3D single particle using transmission electron microscopy ensured the crystalline porous structure of ALN + OA@NCs, was well aligned with characteristic nanoparticle attributes including size distribution, polydispersity, and zeta potential. Further, ALN + OA@NCs showed enhanced efficacy in comparison to OA@NCs suggesting the cytotoxic roles of ALN towards cancer cells, followed by augmentation ROS generation (40.81%), mitochondrial membrane depolarization (57.20%), and induction of apoptosis (40.43%). We found that ALN + OA@NCs facilitated inhibiting osteoclastogenesis and bone resorption followed by inhibited osteolysis. In vivo activity of ALN + OA@NCs in the 4 T1 cell-induced tibia model rendered a reduced bone loss in the treated mice followed by restoring bone morphometric markers which were further corroborated bone-targeting effects of ALN + OA@NCs to reduce RANKL-stimulated osteoclastogenesis. Further, In vivo intravenous pharmacokinetics showed the improved therapeutic profile of the ALN + OA@NCs in comparison to the free drug, prolonging the levels of the drug in the systemic compartment by reducing the clearance culminating the higher accumulation at the tumor site. Our finding proposed that ALN + OA@NCs can effectively target and treat breast cancer metastasis to bone and its associated complications.
Assuntos
Alendronato , Neoplasias Ósseas , Nanopartículas , Osteólise , Tíbia , Alendronato/administração & dosagem , Alendronato/farmacocinética , Alendronato/química , Animais , Osteólise/prevenção & controle , Osteólise/tratamento farmacológico , Feminino , Nanopartículas/química , Nanopartículas/administração & dosagem , Tíbia/efeitos dos fármacos , Tíbia/patologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Porosidade , Linhagem Celular Tumoral , Humanos , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/farmacocinética , Ácido Oleanólico/administração & dosagem , Ácido Oleanólico/farmacocinética , Ácido Oleanólico/química , Ácido Oleanólico/análogos & derivados , Camundongos Endogâmicos BALB C , Camundongos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologiaRESUMO
The aim was to evaluate bone repair and gingival tissue repair in osteopenic rats. Fifteen female wistar rats were included; in all of them ovariectomy was realized to induce osteopenia; after 45 days, the animals were submitted to 2 surgical techinques 1) dental extraction of the upper central incisor with no socket preservation and 2) 5 mm cranial defect in the calvarium; 5 rats were included in the control group (G1) withput alendronate application; in the group 2 (G2) was used subcutenous alendronate (0.5 mg/kg) once for three weeks and then was realizd the both surgical techniques. In group 3 (G3), after ovariectomy was realized the both dental extraction and the calvarium defect and after that was realized the alendronate protocol. In each group, after six week was realized euthanasia and descriptive histological analysis of the surgical areas involved. In bone formation of the 5 mm cranial defect was observed with good progression in the 3 experimental models and no modification in quality of bone repair was observed. For the gingival tissue in the extraction socket, no differences were observed between G1 and G3. On other hand, in G2 a thinner and reduced gingival epithelium was found. Our results showed that alendronate was not an obstacle for bone repair; deficiencies in re-epithelialization of oral mucosa show the impact of alendronate before dental extraction.
El objetivo fue evaluar la reparación ósea y gingival en ratas con osteopenia. Quince ratas wistar hembras fueron incluidas; en todas ellas se realizo ovarectomia y fue realizada la inducción de osteopenia; después de 45 días, los animales fueron sometidos a dos técnicas quirúrgicas 1) extracciones dentales del incisivo central superior sin preservación alveolar y 2) creación de un defecto craneano de 5 mm en la calota; 5 animales fueron incluidos como grupo control (G1) sin la aplicación de alendronato; en el grupo 2 (G2) se utilizó alendronato subcutáneo (0,5 mg/kg) una vez a la semana durante 3 semanas. En el grupo 3 (G3), después de la ovarectomia se realizó la exodoncia y el defecto en el cráneo y después de ello se inicio el protocolo con alendronato. En cada grupo, después de seis semanas se realizó la eutanasia con descripción histológica de los hallazgos. En el hueso formado en el defecto craneano de 5 mm se observó una adecuada progresión de reparación en los 3 modelos experimentales y no se observó cambios importantes en el modelo de reparación. Para el tejido gingival en el sitio de extracción, no se observaron diferencias entre el grupo G1 y G3. Por otra parte, el G2 presentó un tejido mas delgado con reducción del epitelio gingival; nuestros resultados demuestran que el alendronato no fue un obstáculo en la reparación ósea; deficiencias en la re epitelización de la mucosa oral muestran el impacto del alendronato después de la exodoncia.
Assuntos
Animais , Feminino , Ratos , Doenças Ósseas Metabólicas/tratamento farmacológico , Regeneração Óssea/efeitos dos fármacos , Alendronato/administração & dosagem , Gengiva/efeitos dos fármacos , Osteonecrose/tratamento farmacológico , Osteoporose/tratamento farmacológico , Doenças Ósseas Metabólicas/complicações , Ovariectomia , Ratos Wistar , Difosfonatos/administração & dosagemRESUMO
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.
Assuntos
Animais , Masculino , Ratos , Osteogênese/fisiologia , Vitamina E/uso terapêutico , Alendronato/administração & dosagem , Osteoblastos , Vitamina E/administração & dosagem , Análise de Variância , Técnicas Histológicas , Ratos Wistar , Osso EsponjosoRESUMO
RESUMEN: El balance óseo está mediado por una regulación inmunoendócrina, siendo éste un complejo proceso. Entre las acciones llevadas a cabo para mantener la densidad y estructura del esqueleto son variadas las farmacoterapias utilizadas. Diversos estudios han demostrado que tanto Alendronato (AL) y Vitamina E (E) contribuyen a la inhibición de la reabsorción ósea. El objectivo de este trabajo fue estudiar el efecto de la administración combinada de (AL) por vía subcutánea y (E) se administró tres veces por semana también por vía subcutánea con una dosificación de 20 mg/kg de peso corporal. La fórmula farmacéutica fue de 0,5 mg/kg de peso corporal para AL, y 20 mg/kg de vitamina E. El efecto se evaluó en ratas machos Wistar (n=108), de 90 ± 20 g, divididas en 4 grupos. Se realizó la exodoncia de los primeros molares inferiores. La droga se inyectó en forma subcutánea en tiempos 0, 7, 15 y 30 días post cirugía. Las imágenes de las mandíbulas fueron adquiridas mediante radiovisiógrafo, en cada tiempo experimental y fueron analizadas con el Software Image ProPlus versión 4,1 de Media Cibernetics. Estudios estadísticos: no paramétrico: prueba de Kruskal-Wallis Resultados: El grupo C (que registró la media de intensidad más baja), se diferenció significativamente de los grupos E y A-E (p<0,001), no así del grupo que utilizó únicamente Al (p=0,070; p>0,05). Los grupos Al, E y el combinado Al-E no se diferenciaron significativamente entre sí (p>0,05 en todos los casos). Los datos evaluados sirven para mostrar una tendencia favorable en relación al efecto beneficioso de la combinación de AL y vitamina E.
ABSTRACT: The bone balance is mediated by an immunoendocrine regulation, this being a complex process. A number of pharmacotherapies are used among the actions taken to maintain the density and structure of the skeleton. Several studies have shown that both Alendronate (AL) and Vitamin E (E) contribute to the inhibition of bone resorption. Objective: To study the effect of combined administration of (LA) subcutaneously and (E) was administered three times per week also subcutaneously with a dosage of 20 mg / kg body weight. The pharmaceutical formulation was 0.5 mg / kg body weight for AL and 20 mg / kg vitamin E. The effect was evaluated in male Wistar rats (n = 108), 90 ± 20 g, divided into 4 groups. Extraction of the first lower molars was performed. The drug was injected subcutaneously at time 0, 7, 15 and 30 days post-surgery. The images of the jaws were acquired by radiovisiography, at each experimental time and were analyzed with Image ProPlus Software version 4.1 of Media Cibernetics. Statistical studies: non-parametric: Kruskal-Wallis test Group C (which recorded the lowest mean intensity) was significantly different from the E and AE groups (p <0.001), but not from the group that used only Al (P = 0.070, p> 0.05). The Al, E and combined Al-E groups did not differ significantly from each other (p> 0.05 in all cases). The data evaluated serve to show a favorable trend in relation to the beneficial effect of the combination of AL and vitamin E.
Assuntos
Animais , Ratos , Vitamina E/administração & dosagem , Remodelação Óssea/efeitos dos fármacos , Alendronato/administração & dosagem , Radiografia Dentária , Análise de Variância , Experimentação Animal , Difosfonatos/administração & dosagemRESUMO
Los tratamientos para osteoporosis se indican por tiempo variable dependiendo del tipo de droga, anabólica o anticatabólica, y de la gravedad de la enfermedad. Denosumab es un anticuerpo monoclonal totalmente humano que inhibe a RANK-L evitando de esa manera la interacción entre RANKL-RANK, con la consiguiente inhibición de la formación de los osteoclastos, su activación y sobrevida. Disminuye la resorción ósea cortical y trabecular. Su administración subcutánea de 60 mg cada 6 meses al cabo de 3 años ha demostrado reducción de la resorción ósea, incremento de la densidad mineral ósea y disminución de las fracturas vertebrales, no vertebrales y de cadera. Está indicado para el tratamiento de la osteoporosis con alto riesgo de fractura. Su mecanismo de acción es reversible. Se han descripto pérdida de la DMO y elevación de los marcadores de remodelado óseo postsuspensión. Una situación clínica grave son las fracturas vertebrales múltiples postsuspensión. Este evento es infrecuente y se lo atribuye a un rebote del remodelado óseo, postulándose se postula una predisposición especial, probablemente relacionada con microRNA. Se escriben dos mujeres con osteoporosis que presentaron este cuadro. Las fracturas ocurrieron entre 7 y 10 meses posteriores a la última dosis de denosumab. Registraron elevación de C-telopéptidos y disminución de la DMO conjuntamente con las fracturas vertebrales agudas en cascada. (AU)
The duration of osteoporosis treatments depends on the drug type, anabolic or anticatabolic, and the severity of the disease. Denosumab is a fully human monoclonal antibody that inactivates RANK-L, inhibiting the RANKL-RANK interaction . This inhibits osteoclast formation, activation, and survival. It also reduces cortical and trabecular bone resorption. Subcutaneous administration of 60 mg every 6 months for 3 years has reduced bone resorption, increased bone mineral density (BMD) and decreased vertebral, non-vertebral and hip fractures. It is indicated for the treatment of osteoporosis with high risk of fracture. Denosumab mechanism of action is reversible. After discontinuation, loss of BMD and elevation of bone turnover markers have been observed. In addition, multiple vertebral fractures after the suspension of the drug have been reported. These rebound-associated vertebral fractures are rare. A special genetic predisposition related to miRNA has been proposed. Two women with this clinical presentation are described. Fractures occurred between 7 and 10 months respectively after the last dose of denosumab. They presented with an increase in circulating C-telopeptid levels and a decrease inBMD with acute multiple vertebral fractures. (AU)
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Fraturas da Coluna Vertebral/tratamento farmacológico , Denosumab/efeitos adversos , Osteoporose/tratamento farmacológico , Qualidade de Vida , Menopausa , Biomarcadores , Densidade Óssea/efeitos dos fármacos , Cálcio/administração & dosagem , Fraturas da Coluna Vertebral/prevenção & controle , Charibdotoxina/análise , Citrato de Cálcio/administração & dosagem , Alendronato/administração & dosagem , MicroRNAs/metabolismo , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Ligante RANK/efeitos dos fármacos , Denosumab/administração & dosagem , Fumar Tabaco , Ácido Zoledrônico/administração & dosagem , Ácido Ibandrônico/administração & dosagem , Indapamida/administração & dosagemRESUMO
No disponible
Assuntos
Humanos , Cooperação e Adesão ao Tratamento , Osteoporose/tratamento farmacológico , Alendronato/administração & dosagem , Conservadores da Densidade Óssea/administração & dosagem , Ensaios Clínicos como Assunto , Fatores de Tempo , Alendronato/efeitos adversos , Gastroenteropatias/induzido quimicamente , Conservadores da Densidade Óssea/efeitos adversosRESUMO
No disponible
Assuntos
Humanos , Masculino , Feminino , Idoso , Guias de Prática Clínica como Assunto , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Conservadores da Densidade Óssea/administração & dosagem , Ácido Risedrônico/administração & dosagem , Alendronato/administração & dosagemRESUMO
Abstract This study aimed to evaluate the effect of two methods of local application of alendronate and parathyroid hormone (PTH) on bone repair and the systemic implications. A critically sized defect (5 mm) was created in the cranial region of twenty-five male Wistar rats, and the bone removed was particulated, and grafted back to the defect with different treatments. The animals were randomly divided into five groups: A1- bone graft immersion in alendronate solution (3 mg/kg) for 5 minutes; P1- bone graft immersion in PTH solution (20 µg); A2- weekly local applications of alendronate 1 mg/kg; P2- weekly local applications of PTH (20 µg); C- no drugs were used. The animals were euthanized 60 days after surgery. Cranial bone blocks were removed for histological, histomorphometric, and immunohistochemical analyses. MMP-2 and MMP-9 were used for immunolabeling. The kidneys, liver, and brain were also removed from all the rats for histological analysis. The data were submitted for statistical analysis with a level of significance of 0.05 (One-way ANOVA). The group C and group P2 presented a higher quantity of viable bone particles than the remaining groups. Groups A1, A2, and P1 presented with fewer viable bone particles than the control group, with a predominance of non-mineralized connective tissue. The histomorphometric analysis revealed no differences in relative bone area or MMP-2 or MMP-9 immunolabeling between the groups (p>0.05). Group A2 showed presence of fat in the liver consistent with hepatic steatosis. Changes in brain tissue were observed in groups A1 and P1.
Resumo Este estudo visou avaliar o efeito de dois métodos de aplicação local de alendronato e de paratormônio (PTH) no reparo ósseo e avaliar as implicações sistêmicas. Um defeito de tamanho crítico (5 mm) foi criado na calota craniana de vinte e cinco ratos Wistar machos, e o osso removido foi particulado e enxertado de volta no defeito com diferentes tratamentos. Os animais foram divididos aleatoriamente em cinco grupos: A1: imersão do enxerto ósseo em solução de alendronato (3 mg/kg) durante 5 min; P1- imersão do osso em solução de PTH (20 μg); A2- aplicações locais semanais de alendronato 1 mg/kg; P2- aplicações locais semanais de PTH 20 μg; C: não foram utilizados medicamentos. Os animais foram eutanasiados 60 dias após a cirurgia. Foram removidos os blocos ósseos envolvendo a região do defeito para realização das análises histológica, histomorfométrica e imuno-histoquímica. MMP2 e MMP9 foram as imunomarcações utilizadas. Os rins, fígado e cérebro também foram removidos de todos os ratos para análise histológica. Os dados foram submetidos à análise estatística com um nível de significância de 0,05 (One-way ANOVA). A análise histológica revelou que o grupo C e o grupo P2 apresentaram maior quantidade de partículas ósseas viáveis do que as apresentadas pelos demais grupos. Os grupos A1, A2 e P1 apresentaram menos partículas ósseas viáveis em comparação com o grupo controle com predominância de tecido conjuntivo não mineralizado. A análise histomorfométrica não revelou diferenças entres os grupos na área óssea relativa ou em MMP2 e MMP9 (p>0,05). O grupo A2 mostrou presença de gordura no fígado consistente com esteatose hepática. Alterações no tecido cerebral foram observadas nos grupos A1 e P1.
Assuntos
Animais , Masculino , Ratos , Osteogênese/efeitos dos fármacos , Hormônio Paratireóideo/farmacologia , Crânio/cirurgia , Crânio/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Alendronato/farmacologia , Cicatrização/efeitos dos fármacos , Reabsorção Óssea , Encéfalo/efeitos dos fármacos , Imuno-Histoquímica , Transplante Ósseo/métodos , Alendronato/administração & dosagem , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacosRESUMO
RESUMEN: Los bisfosfonatos son potentes inhibidores de la resorción ósea. El aceite de oliva (O) presenta propiedades anti-inflamatorias y anti-oxidantes. Estudiar el efecto del tratamiento combinado de alendronato (AL) y pamidronato (PA) por vía subcutánea y de O vía oral sobre la regeneración tisular de cavidades óseas neoformadas.: 54 ratas macho de la línea Wistar, se dividieron en 6 grupos. Grupo control (C), recibieron solución salina vía subcutánea. Grupo (AL) recibió 0,5 mg de AL/Kg de peso corporal de por vía subcutánea. Grupo (PA) recibió de igual manera que el grupo anterior. Grupo (O) fue tratado con aceite de oliva con la dieta, 50 g/ Kg de comida. Grupo (ALO) recibió tratamiento combinado con AL y O. Grupo (PAO) recibió de igual tratamiento. Los sacrificios para la toma de muestras fueron a los 15, 30, 60 y 90 días. Para los estudios histopatológicos los cortes fueron teñidos con HE y observados con microscopía óptica. Los estudios estadísticos se realizaron a través del análisis de la variancia. A los quince días las áreas de los osteocitos del grupo PA se diferencian significativamente sólo respecto al grupo AL. En cuanto a la Densidad trabecular se observa un incremento de tejido óseo en todos los grupos. O mejora cualitativamente la estructura del hueso trabecular y cortical, preservando la mineralización, el tamaño y la estructura de los cristales minerales Esto sugiere que O representa una opción terapéutica prometedora para la prevención y tratamiento de las patologías óseas.
ABSTRACT: Bisphosphonates are potent inhibitors of bone resorption. Olive oil (O) has anti-inflammatory and anti-oxidant properties. To study the effect of combined treatment with alendronate (AL) and pamidronate (PA) subcutaneously or orally, and on tissue regeneration of newly formed bone cavities, we divided 54 male Wistar rats into 6 groups. Control group (C) received saline subcutaneously. Group (AL) received 0.5 mg of AL / kg body weight subcutaneously. Group (PA) received the same as the previous group. (O) was treated with olive oil diet, 50 g / kg of food. Group (ALO) received combined treatment with AL and O. Group (PAO) received the same treatment. The animals were euthanized for sampling at 15, 30, 60 and 90 days. For histopathology sections were stained with HE and observed these with light microscopy. Statistical studies were performed by analysis of variance. Fifteen days osteocytes areas of the PA group were significantly different only for the AL group. As the density increased trabecular bone tissue was observed in all groups. O qualitatively improved the structure of trabecular and cortical bone mineralization while preserving the size and structure of the mineral crystals. This suggests that O represents a promising therapeutic option for prevention and treatment of bone diseases.
Assuntos
Animais , Masculino , Ratos , Implantes Dentários , Peri-Implantite , Ratos Wistar , Alendronato/administração & dosagem , Alendronato/uso terapêutico , Azeite de Oliva/uso terapêutico , Pamidronato/administração & dosagem , Pamidronato/uso terapêutico , HistologiaRESUMO
Estudios han demostrado que el aceite de oliva (O) con sus compuestos fenólicos tienen efectos positivos en diversos biomarcadores fisiológicos. Análisis previos han demostrado que los bisfosfonatos, son potentes inhibidores de la resorción ósea. Estudiar el efecto del tratamiento combinado de alendronato (AL) y pamidronato (PA) y de O sobre la regeneración ósea. Las fórmulas se dosificaron 0,5 mg/kg de peso para AL, y de 0,6 mg/kg de peso para PA. El O se administró en la dieta, 50 g/Kg. Cincuenta y cuatro ratas macho de la línea Wistar se dividieron en 6 grupos. El grupo control (C), recibió semanalmente 0,3 ml/100 g de solución salina vía subcutánea. El grupo (AL) recibió semanalmente por vía subcutánea en el miembro posterior izquierdo. El grupo (PA) se colocó igual que el grupo anterior. El grupo (O) fue tratado en la alimentación y en las áreas de la cirugía recibieron inyección subcutánea con solución fisiológica. El grupo (ALO) recibió tratamiento combinado con AL y O. El grupo (PAO) se trató igual al anterior. Se obtuvieron muestras de fémur en tiempos 15, 30, 60 y 90 días, que se incluyeron en solución fisiológica y mantenidos a -20 C. Los estudios estadísticos se realizaron a través del análisis de la variancia a dos y tres criterios de clasificación. Sólo el factor días influye significativamente sobre los valores. Las diferencias entre drogas no resultaron estadísticamente significativas. Tampoco se verificó interacción significativa entre los factores Droga y etapa. Los valores más elevados de fuerza de ruptura aplicada, se registraron a los 90 días. No se encontraron diferencias significativas en los ensayos biomecánicos, poniendo de manifiesto la acción sistémica de los fármacos. Estas acciones fueron benéficas al aumentar la rigidez.
Studies have shown that olive oil (O) with its phenolic compounds have positive effects on various physiological biomarkers. Previous analyzes have shown that bisphosphonates are potent inhibitors of bone resorption. The objective of this work was to study the effect of combined treatment with alendronate (AL) and pamidronate (PA) and O on bone regeneration. Formulas 0.5 mg/kg for AL dosed, and 0.6 mg/kg for PA. O was administered in the diet, 50 g/kg. Fifty-four male Wistar rats were divided into 6 groups. The control group (C) received weekly 0.3 mL/100 g of saline subcutaneously. Group (AL) received weekly subcutaneously in the left posterior limb. Group (PA) was placed as the previous group. Group (O) was treated in food and in the areas of surgery received subcutaneous injection with saline. The (ALO) group received combined treatment with Al and O. The group (PAO) was treated the same as before. Femur samples at times 15, 30, 60 and 90 days, were included in physiological solution and maintained at -20 °C were obtained. Statistical studies were conducted through analysis of variance to two and three classification criteria. The ANOVA showed that only days factor significantly influences the values of the variables (p <0.05). The differences between drugs were not statistically significant (p> 0.05). Nor was there significant drug interaction between factors and stage (p> 0.05) was verified. The highest values of force rupture applied occurred at 90 days. No significant differences were found in the biomechanical testing, demonstrating the systemic action of drugs. These actions were beneficial to increase rigidity.