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Article in Chinese | WPRIM | ID: wpr-928342


OBJECTIVE@#To investigate the effect of intra-articular berberine injection on the structural remodeling of subchondral bone plate and osteoprotegerin/receptor activator of nuclear factor kappa-B ligand(OPG/RANKL) system expression in rabbits with osteoarthritis(OA).@*METHODS@#Forty 12-month-old male rabbits with an average of(2.73±0.18) kg of body weight, underwent left anterior cruciate ligament transection(ACLT), and were divided into berberine group and placebo groups after operation, 20 rabbits in each group. The berberine group received intra-articular injection of 100 μmol/L berberine 0.3 ml every week for 6 weeks. In placebo group, the same dose of 0.9% sodium chloride injection was injected into the left knee joint cavity every week for 6 weeks. Another 20 12-month-old male rabbits, weighing (2.68±0.18) kg, underwent sham operation on the left knee joint without intra-articular injection intervention (sham operation group). On the last day of the sixth week after operation, three groups of animals were sacrificed to obtain knee joint specimens. The femoral medial condyle samples were obtained for histological evaluation of cartilage and subchondral bone, Mankin scoring system was used to evaluate articular cartilage structure. Image-Pro Plus(IPP) software was used to evaluate subchondral bone plate bone volume(BV), bone volume/total volume(BV/TV), trabecular circumference(TC), mean trabecular thickness (Tb.Th). Real-time quantitative reverse transcription polymerization Enzyme chain reaction(reverse transcription-polymerase chain reaction, RT-PCR) was used to detect the mRNA expression levels of OPG and RANKL in subchondral bone tissue at 6 weeks after operation.@*RESULTS@#The cartilage structure evaluation showed that the surface of cartilage tissue in the sham operation group was smooth and flat, and the safranin coloration was full in the full thickness of the cartilage;the cartilage tissue in the berberine group showed uneven surface layer, and the staining of safranin O was mildly decreased;the surface layer fibrosis was seen in placebo group, Safranin O faded significantly. The Mankin score in the berberine group was lower than that in placebo group(P<0.01), but higher than that in sham operation group(P<0.01). The structural evaluation of subchondral bone plate showed that the trabecular bone in sham-operated group was densely arranged;after berberine intervention, the trabeculae were closely arranged;the subchondral bone trabeculae in placebo group were relatively sparse, and the distance between trabeculae was wider. Subchondral bone plate IPP software evaluation showed that BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), while lower than the sham operation group (P<0.01). PCR test results showed that the expression of OPG mRNA in the berberine group was significantly higher than that in placebo group(P<0.01), and OPG mRNA in the berberine group was lower than that in sham operation group (P<0.01). There was no significant difference in mRNA expression of RANKL among three groups(P>0.05);the ratio of OPG/RANKL in berberine group was higher than that in placebo group(P<0.01), but lower than that in sham operation group(P<0.01).@*CONCLUSION@#Intra-articular injection of berberine can effectively inhibit the resorption of subchondral bone in the early stage of OA and delay the development of the disease. The specific mechanism may be that berberine maintains the balance of OPG/RANKL system by up-regulating the expression of OPG gene in subchondral bone.

Animals , Berberine/therapeutic use , Bone Density Conservation Agents/therapeutic use , Bone Plates , Cartilage, Articular , Humans , Ligands , Male , NF-kappa B/metabolism , Osteoarthritis/metabolism , Osteoprotegerin/metabolism , RNA, Messenger/therapeutic use , Rabbits
Medicina (B.Aires) ; 81(5): 749-753, oct. 2021. graf
Article in English | LILACS | ID: biblio-1351046


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.

Humans , Female , Teriparatide/therapeutic use , Bone Density Conservation Agents/therapeutic use , Bone Density , Retrospective Studies , Denosumab/therapeutic use
Arch. endocrinol. metab. (Online) ; 64(4): 331-336, July-Aug. 2020. graf
Article in English | LILACS | ID: biblio-1131117


ABSTRACT Osteoporosis is a systemic skeletal disease characterized by reduced bone mass and deterioration of bone tissue microarchitecture leading to an increased risk of fractures. Fragility fractures, especially hip fractures, are associated with a significant reduction in the physical function and quality of life of affected patients, as well as increased mortality, leading to a major financial impact on health care. Many drugs have been registered for the treatment of osteoporosis and very recently, a new anabolic agent, romosozumab, has been approved in some countries. Despite the expansion of efficacious antiresorptive and anabolic therapies in recent years, a concomitant increase in concerns have been raised by physicians, patients and the lay press about the potential for adverse events, especially atypical femoral fractures (AFF) following prolonged use of bisphosphonates. Whatever the mechanism(s) may be, direct or indirect, linking prolonged bisphosphonate use to atypical femoral fractures, this adverse event is very rare in comparison to the magnitude of risk reduction of typical osteoporotic fractures. An estimated 162 osteoporosis-related fractures are prevented for each atypical femoral fracture associated with an anti-resorptive medication. Until a risk calculator for predicting risk of atypical fractures, becomes available in clinical practice, and we view this as an unlikely scenario, it is up to the physician to consider continuing or discontinuing bisphosphonate use after the critical 3-5 year period of treatment with zoledronic acid or alendronate, but close monitoring for the residual bone effects overtime should be planned. For other bisphosphonates, in which no residual effects are expected, drug holiday is usually not applied.

Humans , Female , Osteoporosis, Postmenopausal , Diphosphonates/therapeutic use , Quality of Life , Alendronate , Bone Density Conservation Agents/therapeutic use
Article in Portuguese | LILACS, ColecionaSUS, CONASS, SES-GO | ID: biblio-1118551


Tecnologia: Denosumabe e bifosfonados. Indicação: tratamento de osteoporose para prevenção de fraturas. Pergunta: O denosumabe é mais eficaz e seguro que os bifosfonados orais para tratamento da osteoporose e prevenção de fraturas secundárias à osteoporose? Métodos: Levantamento bibliográfico realizado na PUBMED seguindo estratégia de busca predefinida. Avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta AMSTAR (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foram selecionadas e incluídas 3 revisões sistemáticas, com pontuação de 9 a 11 no AMSTAR. Conclusão: Denosumabe tem menor risco relativo que alendronato e risedronato de sódio para fraturas vertebrais e maior efeito sobre densidade óssea mineral femoral, com risco similar de outros tipos de fratura e eventos adversos (infecções, transtornos cardiovasculares, óbito por infecção, morte cardiovascular ou por qualquer causa). Denosumabe evita 0,00154 fraturas, previne 0,00025 institucionalizações (ou cuidados permanentes de enfermagem no domicílio) e promove um ganho de 0,0018 anos de vida a mais que o alendronato de sódio por paciente tratado. Denosumabe é um pouco mais eficaz e tão seguro quanto os bifosfonados, mas a diferença de eficácia é mínima

Technology: Denosumab and bisphosphonates. Indication: osteoporosis treatment for fracture prevention. Question: Denosumab is more effective and safer than oral bisphosphonates for treating osteoporosis and preventing fractures related to osteoporosis? Methods: Bibliographic search was performed on PUBMED, following predefined search strategies. Evaluation of the methodological quality of systematic reviews was carried out using the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool. Results: We selected and included 3 systematic reviews. Their scores ranged from 9 to 11 on AMSTAR. Conclusion: Denosumab has a lower relative risk than sodium alendronate and risedronate for vertebral fractures and greater effect on femoral mineral bone density, with a similar risk for non-vertebral fractures and adverse events (infections, cardiovascular disorders, death caused by infection, cardiovascular death or any cause mortality). Denosumab avoids 0.00154 fractures, prevents 0.00025 nursing home/ residential care admissions and get 0.0018 years of life gained per treated patient more than sodium alendronate. Denosumab is slightly more effective and as safe as bisphosphonates, but the effectiveness difference is minimal

Humans , Osteoporosis/drug therapy , Alendronate/therapeutic use , Bone Density Conservation Agents/therapeutic use , Osteoporotic Fractures/prevention & control , Risedronic Acid/therapeutic use , Denosumab/therapeutic use , Treatment Outcome , Alendronate/adverse effects , Evidence-Based Medicine , Risedronic Acid/adverse effects , Denosumab/adverse effects
J. bras. nefrol ; 41(2): 304-305, Apr.-June 2019. graf
Article in English | LILACS | ID: biblio-1012531


Abstract Mineral bone disorder is a common feature of chronic kidney disease. Lion face syndrome is rare complication of severe hyperparathyroidism in end-stage renal disease patients, which has been less commonly reported due to dialysis and medical treatment advances in the last decade. The early recognition of the characteristic facial deformity is crucial to prompt management and prevent severe disfigurement. The authors present a rare case of severe hyperparathyroidism presenting with lion face syndrome and bone fractures.

Resumo O distúrbio mineral e ósseo é uma característica comum da doença renal crônica. A síndrome da face leonina é uma complicação rara do hiperparatireoidismo grave em pacientes com doença renal terminal, que tem sido menos relatada devido aos avanços na diálise e tratamento médico na última década. O reconhecimento precoce da deformidade facial característica é crucial para estimular o tratamento precoce e prevenir a desfiguração severa. Os autores apresentam um caso raro de hiperparatireoidismo grave, apresentando síndrome da face leonina e fraturas ósseas.

Humans , Female , Adult , Chronic Kidney Disease-Mineral and Bone Disorder/complications , Hyperostosis Frontalis Interna/diagnosis , Hyperostosis Frontalis Interna/etiology , Kidney Failure, Chronic/complications , Postoperative Complications/drug therapy , Bone Density , Hyperostosis Frontalis Interna/surgery , Ergocalciferols/therapeutic use , Calcium/therapeutic use , Parathyroidectomy/adverse effects , Renal Dialysis , Treatment Outcome , Teriparatide/therapeutic use , Fractures, Bone/diagnosis , Bone Density Conservation Agents/therapeutic use , Hypocalcemia/etiology , Hypocalcemia/drug therapy
Acta ortop. mex ; 33(2): 63-66, mar.-abr. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1248636


Resumen: Introducción: La osteogénesis imperfecta (OI) es un grupo heterogéneo de enfermedades hereditarias, las cuales cursan con la presencia de fragilidad ósea, fracturas frecuentes, deformidades óseas y talla baja. El tratamiento con bifosfonatos en los pacientes con diagnóstico de OI ha demostrado un decremento en la frecuencia de fracturas, así como una mejoría en la densidad ósea vertebral. Existe poca evidencia sobre la calidad de vida en pacientes con OI posterior al tratamiento con bifosfonatos. ¿Los bifosfonatos mejoran la calidad de vida de los pacientes con OI? Material y métodos: Se trata de un ensayo prospectivo, de intervención deliberada, ensayo clínico autocontrolado. Nueve pacientes que se encontraban entre las edades de dos y 13 años con diagnóstico de OI fueron tratados con ácido zolendrónico. Se realizó una medición de la calidad de vida en los pacientes previa y posteriormente. Para la medición de la calidad de vida de los pacientes utilizamos la encuesta de calidad de vida PedsQL 4.0 que fue aplicada tanto a los niños como a los padres. Resultados: En la encuesta de calidad de vida efectuada a los padres se observó un incremento en las cuatro dimensiones evaluadas. En la encuesta realizada a los niños se apreció un aumento en dos dimensiones. El número de fracturas disminuyó posterior al tratamiento. Conclusiones: Existe una correlación entre la disminución del número de fracturas y la percepción que tienen tanto los padres como los niños en la calidad de vida posterior al tratamiento con bifosfonatos.

Abstract: Introduction: Osteogenesis imperfeta (OI) is defined as a heterogeneous group of hereditary diseases, which present with the presence of bone fragility, frequent fractures, bone deformities and short stature. Treatment with biphosfonates in patients with diagnosis of OI has shown a decrease in the frecuency of fractures, as well as an improvement in vertebral bone density. There is little evidence on quality of life in patients diagnosed with OI treated with bisphosphonates, Therefore this study evaluated the quality of life of patients diagnosed with OI after treatment with bisphosphonates. Material and methods: It is a prospective, deliberate intervention, self-controlled clinical trial. Nine patients with ages between two and thirteen ages and diagnosed with OI were treated with Zolendronic, a quality of life measurement was performed in the patients before and after the application. For measuring the quality of life in the patients we used the PedsQL 4.0 quality of life survey that was applied to both children and parents. Results: In the quality of life survey performed on the parents, an increase was observed in the four dimensions evaluated. In the survey made on the children two dimensions showed a significant increase. The number of fractures decreased after the treatment. Conclusions: There is a correlation between the decrease in the number of fractures and the perception that both parents and children have in the quality of life after treatment with bisphosphonates.

Humans , Child, Preschool , Child , Adolescent , Osteogenesis Imperfecta/complications , Osteogenesis Imperfecta/drug therapy , Quality of Life , Diphosphonates/therapeutic use , Bone Density Conservation Agents/therapeutic use , Prospective Studies
Braz. oral res. (Online) ; 33: e086, 2019. tab, graf
Article in English | LILACS | ID: biblio-1019605


Abstract Treatment of patients with bisphosphonate usage is a significant concern for oral surgeons because it interferes with jaw bone turnover and regeneration. In case of adverse effects manifesting related to bisphosphonate use, oral surgeons are usually treating and keep the patient's symptoms under control. In this study, we aimed to investigate a new treatment protocol for medication-related osteonecrosis of the jaw (MRONJ). This treatment protocol consisted of administering human parathyroid hormone (hPTH) loaded chitosan microspheres which were prepared by ionotropic gelation method or/and the prepared microspheres were suspended in a poloxamer gel. After in-vitro optimization studies, the efficacy of the chosen formulations was evaluated in-vivo studies. Zoledronic acid was administered daily to forty-eight adult female Sprague-Dawley rats, divided into four experimental groups, at a daily concentration of 0.11 mg/kg over three weeks to induce the MRONJ model. At the end of this period, maxillary left molar teeth were extracted. In the first group, the subjects received no treatment. In the negative control group, poloxamer hydrogel containing empty microspheres were immediately applied to the soft tissues surrounding the extraction socket. The treatment group-1 was treated with local injections of poloxamer hydrogel containing hPTH. The treatment group-2 was treated with a single local injection of poloxamer hydrogel containing hPTH-loaded chitosan microspheres. Both treatment groups received a total of 7 µg of hPTH at the end of the treatment protocol. Our study demonstrates successful attenuation of MRONJ through a local drug delivery system combined with hPTH, as opposed to previously attempted treatment strategies.

Humans , Animals , Female , Parathyroid Hormone/pharmacology , Chitosan/pharmacology , Bone Density Conservation Agents/pharmacology , Maxilla/drug effects , Parathyroid Hormone/therapeutic use , Rats, Sprague-Dawley , Poloxamer/administration & dosage , Poloxamer/chemistry , Models, Animal , Delayed-Action Preparations , Chitosan/therapeutic use , Bone Density Conservation Agents/adverse effects , Bone Density Conservation Agents/therapeutic use , Bisphosphonate-Associated Osteonecrosis of the Jaw , Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy , Zoledronic Acid/adverse effects , Maxilla/pathology , Microspheres
Braz. oral res. (Online) ; 33: e050, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011654


Abstract The present study aimed to investigate the use of platelet-rich plasma (PRP) on tooth extraction sites in rats treated with bisphosphonates. Thirty Albinus Wistar male rats were administered 0.035 mg/kg zoledronic acid intravenously for 8 weeks, divided into four administrations with a 2-week interval between each application, after which their upper right central incisors were extracted to induce the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). The samples were divided into the following two groups: Group 1 (G1) underwent marginal resection of BRONJ followed by the use of PRP, while Group 2 (G2) underwent resection of BRONJ but without the use of PRP. The treatment groups were evaluated after 14, 28, and 42 days. Clinical, microtomographic, microscopic, and immunohistochemical (IHC) evaluations were performed. Microtomography results revealed no significant difference between the groups (p <0.05) in any time period. Histomorphometric analysis showed increased bone formation over time for both groups (p < 0.001). G1 demonstrated a greater amount of new bone formation than G2 at 28 and 42 days (p < 0.001), with G1 presenting greater vascularization and a slightly higher VEGF expression. For both groups, RANKL/OPG expression levels were sufficient as a parameter for indicating the rate of bone remodeling in a previously treated area of osteonecrosis groups. Taken together, our findings indicated that the use of PRP improves the resolution process of BRONJ.

Animals , Male , Rats , Diphosphonates/therapeutic use , Bone Density Conservation Agents/therapeutic use , Platelet-Rich Plasma , Bisphosphonate-Associated Osteonecrosis of the Jaw/therapy , Osteoclasts/drug effects , Tooth Extraction/adverse effects , Wound Healing , Rats, Wistar , Disease Models, Animal , Bisphosphonate-Associated Osteonecrosis of the Jaw/physiopathology , Bisphosphonate-Associated Osteonecrosis of the Jaw/pathology
Arch. endocrinol. metab. (Online) ; 62(1): 125-128, Jan.-Feb. 2018.
Article in English | LILACS | ID: biblio-887627


SUMMARY Hypercalcemia can be hazardous during pregnancy, most cases being due to primary hyperparathyroidism. We report a case of hypercalcemia with suppressed PTH levels necessitating treatment with bisphosphonates during pregnancy. A 38-year-old woman at the 26th week gestation was admitted because of symptomatic hypercalcemia. She did not take any medication that could influence her calcium levels. Physical examination was unremarkable. Laboratory tests on admission were: calcium 12.7 mg/dL (8.5-10.5 mg/dL), phosphorus 1.8 mg/dL (2.5-4.5 mg/dL) and PTH on 3 consecutive tests 1.2, 1.3 and 1.2 pg/mL (15-65 pg/mL). Her 24h urine calcium was 900 mg, 25-OH-D 40 ng/mL (30-58 ng/mL) and 1,25-OH-D 99 pg/mL (80-146 for women in the third trimester). Abdominal ultrasound revealed multiple hypervascular liver lesions consistent with hemangiomas by MRI. Breast and neck ultrasound were normal, and chest CT revealed few non-significant 0.3-0.7 cm pulmonary nodules with no change after an interval of 3 months. She was treated with isotonic saline, loop diuretics and calcitonin. Despite this treatment, calcium levels remained high (14.1 mg/dL), and pamidronate was initiated. On 35th week gestation, she underwent a cesarean section complicated by hypocalcemia of the newborn. Eight weeks after delivery, her calcium levels are 9.4 mg/dL and PTH 18 mg/dL. According to the extensive workup and the post-partum normalization of PTH and calcium levels, we conclude that excessive secretion of placental PTHrP was the cause of hypercalcemia in this patient. No significant adverse effect of bisphosphonate on the mother or baby were seen at the short term follow up.

Humans , Female , Pregnancy , Adult , Pregnancy Complications/drug therapy , Diphosphonates/therapeutic use , Bone Density Conservation Agents/therapeutic use , Hypercalcemia/drug therapy , Parathyroid Hormone/blood , Pregnancy Complications/blood , Hypercalcemia/blood
Braz. j. med. biol. res ; 51(8): e7440, 2018. graf
Article in English | LILACS | ID: biblio-951737


Considering that osteoarthritis (OA) is the most prevalent joint disease worldwide, multiple pharmacological treatments have been proposed to alter the articular structure with potential benefit in the progression of the disease. The so-called disease-modifying OA drugs have been frequently investigated but conclusive findings are rare. Strontium ranelate (SrRan) is a drug usually prescribed to treat osteoporosis, with proven effects in decreasing the risk of fractures and possible effect in reducing the progression of OA. The objective of this review was to demonstrate the current panorama of knowledge on the use of SrRan in clinical and experimental models, clarifying its mechanisms of action and describing possible anti-nociceptive and anti-inflammatory effects. The systematic review was based on the PRISMA statement and included articles that are indexed in scientific databases. Fifteen studies were included: seven pre-clinical and eight clinical studies. Despite the limited number of studies, the results suggest a positive effect of SrRan in patients with OA, through changes in functional capacity and reduction of progression of morphological parameters and joint degradation, with moderate quality of evidence for those clinical outcomes. Novel studies are necessary to elucidate the molecular targets of SrRan, focusing on anti-inflammatory effects and histological changes promoted by SrRan, which seemed to reduce the progression of OA in the experimental and clinical studies.

Humans , Animals , Osteoarthritis/drug therapy , Thiophenes/therapeutic use , Bone Density Conservation Agents/therapeutic use , Thiophenes/pharmacology , Bone Resorption/drug therapy , Cartilage, Articular/drug effects , Bone Remodeling/drug effects , Disease Progression , Arthralgia/drug therapy , Bone Density Conservation Agents/pharmacology
Actual. osteol ; 13(3): 198-206, Sept - DIc. 2017. graf, tab
Article in Spanish | LILACS | ID: biblio-1117027


La osteoporosis afecta al 6-7% de la población masculina. Es alta la proporción de pacientes con fracturas sin diagnóstico previo de esta enfermedad. La mortalidad luego de una fractura es mayor en hombres que en población femenina; a pesar de esto, la mayoría de los pacientes no reciben tratamiento. Los fármacos aprobados, en nuestro medio, para tratar la osteoporosis masculina son: bifosfonatos, teriparatida y ranelato de estroncio. El objetivo de este estudio fue evaluar el efecto del ranelato de estroncio sobre la densidad mineral ósea en hombres después de 1 año de tratamiento. Se incluyeron los registros de 20 hombres de 67,8±3,0 años, tratados con ranelato de estroncio (2 g/día) durante 1 año. Todos los pacientes presentaban un T-score inferior a -2,5 en cadera o columna vertebral o un T-score inferior a -2,0 y factores de riesgo de fractura. No hubo modificación de parámetros de laboratorio luego del tratamiento (calcemia, calciuria, fósforo sérico, parathormona, 25(OH)vitamina D, fosfatasa alcalina y desoxipiridinolina) en relación a los basales. Luego del tratamiento con ranelato de estroncio se observó incremento de la densidad mineral ósea en columna lumbar: 0,953±0,029 versus 0,997±0,030 g/cm2 (p=0,0068), cuello femoral: 0,734±0,013 versus 0,764±0,016 g/cm2 (p=0,0084) y cadera total: 0,821±0,02 versus 0,834±0,02 g/cm2 (p=0,0419). Conclusión: el tratamiento con ranelato de estroncio produjo un incremento significativo de la densidad mineral ósea en columna lumbar y fémur proximal en hombres con osteoporosis. (AU)

Osteoporosis affects 6-7% of the male population. The proportion of patients with fragility fractures but without diagnosis of the disease is high. Mortality after hip fracture is higher in men than in women; in spite of this, most patients are left without treatment for osteoporosis. Drugs approved, for the treatment of osteoporosis in our country are bisphosphonates, teriparatide, and strontium ranelate (SrR). The objective of this study was to evaluate the effect of SrR on axial BMD in men after one year of treatment. We obtained pertinent data from medical registries of 20 men aged 67,8±3,0 years, treated with oral SrR (2 g/day) for 12 months. All patients had a T-score below -2,5 at the hip or the lumbar spine, or a T-score below -2,0 and one or more risk factors for fracture. The levels of serum calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, or PTH, or urinary calcium and desoxipyridinoline remained unchanged following SrR administration. After treatment with SrR there were significant increases in BMD at the lumbar spine: 0,953±0,029 versus 0,997±0,030 g/cm2 (p=0,0068), femoral neck: 0,734±0,013 versus 0,764±0,016 g/cm2 (p=0.0084), and total hip: 0,821±0,02 versus 0,834±0,02 g/cm2 (p=0,0419). Conclusion: in osteoporotic men, treatment with SrR significantly increases BMD in the lumbar spine and the proximal femur. (AU)

Humans , Male , Aged , Osteoporosis/drug therapy , Strontium/chemistry , Bone Diseases, Metabolic/drug therapy , Bone Density/drug effects , Organometallic Compounds , Osteoporosis/diagnosis , Argentina , Strontium/administration & dosage , Testosterone/therapeutic use , Thiophenes , Vitamin D/administration & dosage , Bone Diseases, Metabolic/metabolism , Bone Diseases, Metabolic/blood , Body Mass Index , Sex Factors , Calcium/administration & dosage , Retrospective Studies , Risk Factors , Bone Density Conservation Agents/therapeutic use , Osteoporotic Fractures , Hypogonadism/complications
Acta cir. bras ; 32(9): 781-795, Sept. 2017. graf
Article in English | LILACS | ID: biblio-886237


Abstract Purpose: To performed a histomorphometric and radiological study to evaluate the effects of alendronate sodium administered locally in mandibular bone defects created in rabbits. Methods: Two circular defects 5 mm in diameter were created bilaterally in the mandibular corpus of 20 New Zealand rabbits (i.e., four defects per animal). Each defect received one of four treatments: no treatment (EC group), alendronate irrigation (AL group), autogenous bone grafting (AG group), or alendronate irrigation with autogenous bone grafting (AL+AG group). Histomorphometric and radiological assessments were conducted at 4 and 8 weeks after surgery. Results: Between-group comparisons of the new bone area, the value of the AL+AG group was significantly lower thanthe remaining three groups at 4 weeks postoperatively. In all groups, the new bone area was significantly larger at 8 weeks than at 4 weeks. The residual graft area at 4 and 8 weeks was significantly higher in the AL+AG group than in the AG group, although it was significantly smaller at 8 weeks than at 4 weeks in both these groups. Conclusion: The use of alendronate sodium in conjunction with autogenous bone grafting improves the osteoconductive properties of the graft, enhances graft retention in the defect, and improves ossification.

Animals , Male , Female , Rats , Bone Regeneration/drug effects , Fracture Healing/drug effects , Alendronate/therapeutic use , Fractures, Bone/drug therapy , Bone Density Conservation Agents/therapeutic use , Disease Models, Animal , Fractures, Bone/pathology , Fractures, Bone/diagnostic imaging
Actual. osteol ; 13(2): 136-156, Mayo - Ago. 2017. ilus, tab
Article in Spanish | LILACS | ID: biblio-1118080


La osteoporosis es una enfermedad en constante crecimiento y que afecta a más de 200 millones de personas a nivel mundial. Nuestras recomendaciones son guías para el diagnóstico, la prevención y tratamiento, pero no normas para las decisiones clínicas en casos individuales. El médico debe adaptarlas a situaciones en la práctica clínica cotidiana, incorporando factores personales que trascienden los límites de estas guías y hacen al saber y al arte de la práctica médica. Como todo conocimiento científico, deben ser actualizadas periódicamente a medida que se adquieran nuevas, mejores y más efectivas herramientas diagnósticas y terapéuticas. (AU)

Osteoporosis is an evolving disease which affects over 200 million people worldwide. Our recommendations are guidelines for its diagnosis, prevention and treatment, but they do not constitute standards for clinical decisions in individual cases. The physician must adapt them to individual special situations, incorporating personal factors that transcend the limits of these guidelines and are dependent on the knowledge and art of the practice of Medicine. These guidelines should be reviewed and updated periodically as new, better and more effective diagnostic and therapeutic tools become available. (AU)

Humans , Osteoporosis/prevention & control , Practice Guidelines as Topic , Osteoporosis/diagnosis , Osteoporosis/drug therapy , Practice Patterns, Physicians'/trends , Bone Density Conservation Agents/therapeutic use , Clinical Decision-Making
Rev. bras. reumatol ; 57(3): 254-263, May-June 2017. graf
Article in English | LILACS | ID: biblio-899421


ABSTRACT Bisphosphonates are considered first-line agents in the treatment of postmenopausal osteoporosis based on extensive experience of use, safety, and proven efficacy in reducing vertebral, non-vertebral and femur fractures. However, post-marketing reports based on the treatment of millions of patients/year over lengthy periods of time have revealed the occurrence of initially unexpected adverse effects, such as osteonecrosis of the jaw and atypical femoral fracture, leading to the restriction of treatment duration with bisphosphonates by global regulatory agencies. However, despite the association between these effects and bisphosphonates, this risk should be analyzed in the context of osteoporosis treatment, alongside the benefit of preventing osteoporotic fractures and their clinical consequences. Therefore, we consider it plausible to discuss the restriction to the use of bisphosphonates, possible indications for prolonged treatment and alternative therapies following the suspension of this drug class for patients with persistent high risk of fracture after initial treatment, especially considering the problems of public health funding in Brazil and the shortage of drugs provided by the government. Thus, to standardize the treatment of osteoporosis in the public health care system, we aim to develop a proposal for a scientifically-based pharmacological treatment for postmenopausal osteoporosis, establishing criteria for indication and allowing the rational use of each pharmacological agent. We discuss the duration of the initial bisphosphonate treatment, the therapeutic options for refractory patients and potential indications of other classes of drugs as first-choice treatment in the sphere of public health, in which assessing risk and cost effectiveness is a priority.

RESUMO Com base na vasta experiência de uso, segurança e eficácia comprovada na redução de fraturas vertebrais, não vertebrais e femorais, os bisfosfonatos são considerados agentes de primeira linha no tratamento da osteoporose pós-menopáusica. No entanto, os relatos pós-venda baseados no tratamento de milhões de pacientes/ano durante períodos prolongados de tempo revelaram a ocorrência de efeitos adversos inicialmente inesperados, como osteonecrose da mandíbula e fratura atípica do fêmur. Isso levou as agências reguladoras globais a restringirem a duração do tratamento com bisfosfonatos. No entanto, apesar da associação entre esses efeitos e os bisfosfonatos, esse risco deve ser analisado no contexto do tratamento da osteoporose, paralelamente ao benefício na prevenção de fraturas osteoporóticas e suas consequências clínicas. Portanto, considera-se plausível discutir a restrição ao uso dos bisfosfonatos, possíveis indicações para o tratamento prolongado e terapias opcionais após a suspensão dessa classe de fármaco para pacientes com alto risco persistente de fratura após o tratamento inicial, especialmente se considerarmos os problemas financeiros de saúde pública no Brasil e a escassez de fármacos fornecidos pelo governo. Assim, para padronizar o tratamento da osteoporose no sistema público de saúde pretende-se desenvolver uma proposta de tratamento farmacológico cientificamente fundamentada para a osteoporose pós-menopáusica, estabelecer critérios de indicação e permitir o uso racional de cada agente farmacológico. Discutem-se a duração do tratamento inicial com bisfosfonatos, as opções terapêuticas para pacientes refratários e potenciais indicações de outras classes de medicamentos como tratamento de primeira linha na esfera da saúde pública, em que a avaliação do risco e custo-efetividade é uma prioridade.

Humans , Osteoporosis, Postmenopausal/drug therapy , Diphosphonates/therapeutic use , Bone Density Conservation Agents/therapeutic use , Clinical Decision-Making/methods , Algorithms , Brazil , Osteoporosis, Postmenopausal/complications , Osteoporosis, Postmenopausal/economics , Risk Factors , Cost-Benefit Analysis , Diphosphonates/economics , Bone Density Conservation Agents/economics , Osteoporotic Fractures/economics , Osteoporotic Fractures/chemically induced , Osteoporotic Fractures/prevention & control , Bisphosphonate-Associated Osteonecrosis of the Jaw/economics , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , National Health Programs
Rev. cuba. endocrinol ; 28(1): 1-10, Jan.-Apr. 2017. ilus, tab
Article in Spanish | LILACS | ID: biblio-901008


Introducción: el tratamiento con bisfosfonatos es efectivo para prevenir las fracturas por fragilidad. Objetivos: describir la respuesta ósea al tratamiento con bisfosfonatos en mujeres de edad mediana con osteoporosis, y factores clínicos relacionados con ella. Métodos: estudio retrospectivo que incluyó el total de mujeres con edades entre 40-59 años con osteoporosis atendidas en la Clínica de Climaterio y Osteoporosis entre 2005 y 2010, que cumplieron tratamiento con alendronato de sodio (70 mg/sem) o ibandronato de sodio (150 mg/mensual) por más de 1 año, y que se realizaran densitometrías anuales. Se consideró respuesta ósea favorable (no pérdida de la densidad mineral ósea, ni nuevas fracturas); y no favorable (si hubo pérdida de la densidad mineral ósea y/o nueva fractura). Como factores asociados se destacan: la edad, el color de piel, los antecedentes familiares y personales de osteoporosis, el tabaquismo, el tiempo de vida reproductiva, la etapa del climaterio y el tipo de bisfosfonatos. Se utilizó distribución de frecuencias promedio y desviación estándar, y para identificar asociación prueba U Mann Whitney con (p< 0,05) para significación estadística. Resultados: utilizaron alendronato 53 pacientes, tres ibandronato y en 12 alendronato+ibandronato. El 98,5 por ciento mantuvo tratamiento entre 3 y 5 años. El 86,7 por ciento (59/68) tuvo respuesta favorable, y como factores relacionados: ausencia de familiares con osteoporosis, la lactancia materna y recibir alendronato; la respuesta no favorable se dio en 9/68, y ocurrió en mujeres con tabaquismo, que tenían familiares con osteoporosis y que recibieron ibandronato (8/9). Conclusiones: se confirma utilidad del alendronato para preservar la masa ósea en columna lumbar(AU)

Introduction: treatment with bisphosphonates is effective to prevent bone fractures due to fragility. Objectives: to describe the bone response to bisphosphonate treatment in middle aged women with osteoporosis and some clinical factors related to it. Methods: retrospective study covering the total number of women aged 40-59 years with osteoporosis, who were seen at the climaterium and osteoporosis clinic from 2005 to 2010 and treated with alendromate (70 mg a week) or ibandronate (150 mg a month) for over a year and who underwent annual densitometries. Bone response was considered as favorable when there was no loss of bone mineral density nor new fractures, and unfavorable when there was loss of bone mineral density and/or new fractures occurred. The most important associated factors were age, race, family and personal history of osteoporosis, smoking, time of reproductive life, the phase of climaterium and the type of bisphosphonates taken. Average frequency distribution and standard deviation were used along with U Mann Whitney test with (p< 0.05) for statistical significance to establish associations. Results: alendronate was taken by 53 patients, ibandronate by three and the combination of alendronate and ibandronate by 12 patients. In the sample 98.5 percent adhered to treatment for 3 to 5 years. Favorable bone response was seen in 86.7 percent (59 out of 68) and the related factors were no family history of osteoporosis, breastfeeding and taking alendronate. Unfavorable response was seen in 9 out of 68 and occurred in smoking women who had family history of osteoporosis and took ibandronate (8 out of 9). Conclusions: usefulness of alendronate is confirmed to preserve bone mass in lumbar column(AU)

Humans , Female , Adult , Middle Aged , Climacteric , Densitometry/adverse effects , Diphosphonates/therapeutic use , Bone Density Conservation Agents/therapeutic use , Retrospective Studies , Data Interpretation, Statistical
Actual. osteol ; 13(1): 9-16, Ene - Abr. 2017. tab
Article in Spanish | LILACS | ID: biblio-1118618


Tanto el ranelato de estroncio (RSr) como el denosumab (Dmab) son eficaces en el tratamiento de la osteoporosis (OP) posmenopáusica (PM). El efecto de cada fármaco por separado sobre la densidad mineral ósea (DMO) ha sido estudiado recientemente. Con ambas drogas se observó, al año de tratamiento, un aumento significativo de la DMO en columna lumbar (CL), cuello femoral (CF) y cadera total (CT). En este trabajo comparamos la respuesta densitométrica al año de tratamiento con una y otra droga. Utilizamos los registros de 425 pacientes PMOP tratadas con Dmab y 441 tratadas con RSr. En cada paciente analizamos el porcentaje de cambio; se clasificaron como respondedoras aquellas que mostraron un cambio ≥3%. Adicionalmente se comparó la respuesta en pacientes no previamente tratadas con bifosfonatos (BF-naïve) en comparación con pacientes que habían recibido previamente un BF. Al analizar el grupo completo para Dmab, el porcentaje de pacientes respondedoras fue de 68,4% en CL, 63,3% en CF y 49,3% en CT. Por otro lado, en el grupo de pacientes tratadas con RSr, el porcentaje de respondedoras (53,8% en CL, 40,0% en CF y 35,6% en CT) fue estadísticamente menor. Cuando comparamos la respuesta entre las pacientes BF-naïve que recibieron RSr o Dmab, el Dmab indujo mayor respuesta en CL y CF que el grupo RSr, sin diferencias en CT. Cuando se analizaron los subgrupos BF-previo, las tratadas con Dmab mostraron mayor respuesta en todas las regiones. Conclusión: en pacientes con OP-PM, el tratamiento con Dmab produjo mayores incrementos densitométricos que el RSr, siendo el porcentaje de pacientes respondedoras mayor con Dmab que con RSr. (AU)

Both strontium ranelate (SrR) and denosumab (Dmab) are effective in the treatment of postmenopausal osteoporosis (PMOP). The effect of each drug on bone mineral density (BMD) has been studied separately by us. With both treatments, there was a significant increase after one year of treatment at the lumbar spine (LS) and hip. In this paper we compared the densitometric response after one year of treatment with both drugs used separately. We used the clinical records of 425 PM patients treated with Dmab and 441 treated with SrR. For each patient we analyzed the percentage of change; those who showed a change ≥3% were classified as responders. Additionally, the response was compared in patients not previously treated with bisphosphonates (BP-naïve) compared to patients who had previously received a BP. When analyzing the complete group for Dmab, the percentage of "responders" was 65.2% at the LS, 62.9% at the femoral neck (FN) and 47.4% at the total hip (TH). On the other hand, in the group of patients treated with SrR the percentage of responders (53.8% at the LS, 40.0% at the FN and 35.6% at the TH) was statistically lower. When comparing the response between in BF-naïve patients receiving RSr or Dmab, Dmab induced a greater response at the LS and FN than the RSr group, with no statistical differences at the TH. When the subgroups with prior BP treatment were analyzed, those treated with Dmab showed greater response in all regions. Conclusion: in patients with PMOP treatment with Dmab produced greater densitometric increments than SrR, and the percentage of responders was higher with Dmab than with SrR. (AU)

Humans , Female , Middle Aged , Aged , Aged, 80 and over , Strontium/therapeutic use , Osteoporosis, Postmenopausal/drug therapy , Denosumab/therapeutic use , Phosphates/blood , Strontium/administration & dosage , Strontium/chemistry , Vitamin D/administration & dosage , Biomarkers , Bone Density/drug effects , Fractures, Stress/prevention & control , Osteocalcin/blood , Osteoporosis, Postmenopausal/blood , Calcium/administration & dosage , Calcium/blood , Retrospective Studies , Teriparatide/therapeutic use , Densitometry , Diphosphonates/therapeutic use , Alkaline Phosphatase/blood , Bone Density Conservation Agents/therapeutic use , Femur Neck/drug effects , Denosumab/administration & dosage , Treatment Adherence and Compliance , Hip , Lumbosacral Region
Actual. osteol ; 13(1): 58-66, Ene - Abr. 2017. ilus
Article in English | LILACS | ID: biblio-1118913


Connexins (Cxs) are a family of transmembrane proteins that form gap junctions and hemi-channels, which mediate cell-cell communication between neighboring cells and the respective extracellular milieu in different tissues. Most tissues and cell types throughout the body express one or more Cx proteins, highlighting its importance in regulating cell growth, differentiation, adhesion, migration, cell death and others. Moreover, Cx can propagate intracellular signals through its C-terminus domain, and thus function beyond a mere channel. Cx43 is the most highly expressed and most well studied Cx in bone and musculoskeletal tissues, although Cx40, Cx45, Cx46 and more recently, the Cx37 have been described in bone tissue, along with Cx26, Cx32 and Cx39 in other musculoskeletal tissues. Here, we discuss the basic structure of gap junctions and the role of the Cxs in musculoskeletal tissue, with special focus on Cx37. (AU)

Las conexinas (Cxs) son una familia de proteínas transmembrana que forman uniones en hendidura y hemicanales encargados de mediar la comunicación entre células vecinas y el respectivo medio extracelular en diferentes tejidos. La mayoría de los tejidos y células expresan una o más proteínas conexina, jugando un papel importante en la regulación de la proliferación celular, diferenciación, adhesión, migración y muerte celular, entre otras funciones. Además de actuar como un canal, las conexinas pueden propagar señales intracelulares a través del dominio C-terminal. La Cx43 es la conexina mas expresada y mejor estudiada en el tejido óseo y el músculo, aunque las Cx40, Cx45, Cx46, y mas recientemente Cx37, son también detectadas en el hueso. A su vez la expresión de la Cx26, Cx32 y Cx39 ha sido observada en otros tejidos músculoesqueléticos. En este manuscrito describimos la estructura básica de las uniones tipo gap y el papel que las Cxs, y en especial la Cx37, tienen en tejidos músculo-esqueléticos. (AU)

Humans , Bone and Bones/metabolism , Bone Resorption/prevention & control , Connexins/physiology , Osteoblasts/metabolism , Osteocytes/metabolism , Tendons/metabolism , Signal Transduction/physiology , Cartilage/metabolism , Cell Communication/physiology , Cell Physiological Phenomena , Gap Junctions/drug effects , Gap Junctions/physiology , Connexin 43/physiology , Muscle, Skeletal/metabolism , Bone Density Conservation Agents/therapeutic use , Ligaments/metabolism , Anti-Arrhythmia Agents/adverse effects
Medicina (B.Aires) ; 77(1): 46-60, feb. 2017. ilus, tab
Article in Spanish | LILACS | ID: biblio-841633


La osteoporosis es una enfermedad en constante crecimiento y que afecta a más de 200 millones de personas en todo el mundo. Nuestras recomendaciones son guías para el diagnóstico, la prevención y tratamiento, pero no normas para las decisiones clínicas en casos individuales. El médico debe adaptarlas a situaciones en la práctica clínica cotidiana, incorporando factores personales que trascienden los límites de estas guías y hacen al saber y al arte de la práctica médica. Como todo conocimiento científico, deben ser actualizadas periódicamente a medida que se adquieran nuevas, mejores y más efectivas herramientas diagnósticas y terapéuticas.

Osteoporosis is an evolving disease which affects over 200 million people worldwide. Our recommendations are guidelines for its diagnosis, prevention and treatment, but they do not constitute standards for clinical decisions in individual cases. The physician must adapt them to individual special situations, incorporating personal factors that transcend the limits of these guidelines and are dependent on the knowledge and art of the practice of Medicine. These guidelines should be reviewed and updated periodically as new, better and more effective diagnostic and therapeutic tools become available.

Humans , Osteoporosis/diagnosis , Osteoporosis/prevention & control , Osteoporosis/drug therapy , Fractures, Bone/etiology , Argentina , Risk Factors , Fractures, Bone/prevention & control , Bone Density Conservation Agents/therapeutic use
Braz. j. med. biol. res ; 50(9): e6314, 2017. graf
Article in English | LILACS | ID: biblio-888989


Strontium ranelate (SrRan) is a drug usually prescribed to treat osteoporosis, with proven effects of decreasing the risk of fractures and an indication of reducing the progression of osteoarthritis (OA). This study aimed to investigate the effects of SrRan as either a prophylactic or a treatment drug, using an OA rat model to assess pain behavior. A monoiodoacetate (MIA)-induced knee joint OA model in Wistar rats was used. Thirty Wistar rats (both sexes, 60 days old) were distributed in five groups of 6 rats each: the control group, that received no intervention; a prophylactic group, that received oral administration of 25 mg·kg-1·day-1 of SrRan for 28 days before induction of OA; a group treated with 25 mg·kg-1·day-1 of SrRan for 28 days after OA induction; a group treated with 50 mg·kg-1·day-1 during 28 days after OA induction; and a group that received oral saline for 28 days after induction. The assessment of pain behavior was performed considering articular incapacitation (weight-bearing test), mechanical hyperalgesia (Randall Selitto test) and motor activity (rotarod test), on days 0, 7, 14, 21, and 28. This experiment did not yield a significant difference when comparing the group that received SrRan prophylactically with the groups treated with 25 or 50 mg·kg-1·day-1 and the group that received oral saline. Thus, SrRan did not provide analgesia in either treated rats or as a prophylactic drug with the tested doses. Higher doses should be tested further to achieve possible significant results.

Animals , Male , Rats , Bone Density Conservation Agents/therapeutic use , Hyperalgesia/drug therapy , Osteoarthritis, Knee/drug therapy , Thiophenes/therapeutic use , Disease Models, Animal , Rats, Wistar