RESUMO
Several drugs are available for the treatment of osteoporosis in postmenopausal women. Over the last decades, most patients requiring pharmacological intervention were offered antiresorptive drugs as first-line therapy, while anabolic agents were considered a last resource for those with therapeutic failure. However, recent randomized trials in patients with severe osteoporosis have shown that anabolic agents reduce fractures to a greater extent than antiresorptive medications. Additionally, evidence indicates that increases in bone mineral density (BMD) are maximized when patients are treated with anabolic agents first, followed by antiresorptive therapy. This evidence is key, considering that greater increases in BMD during osteoporosis treatment are associated with a more pronounced reduction in fracture risk. Thus, international guidelines have recently proposed an individualized approach to osteoporosis treatment based on fracture risk stratification, in which the stratification risk has been refined to include a category of patients at very high risk of fracture who should be managed with anabolic agents as first-line therapy. In this document, the Brazilian Society of Endocrinology and Metabolism and the Brazilian Association of Bone Assessment and Metabolism propose the definition of very high risk of osteoporotic fracture in postmenopausal women, for whom anabolic agents should be considered as first-line therapy. This document also reviews the factors associated with increased fracture risk, trials comparing anabolic versus antiresorptive agents, efficacy of anabolic agents in patients who are treatment naïve versus those previously treated with antiresorptive agents, and safety of anabolic agents.
Assuntos
Anabolizantes , Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Osteoporose , Fraturas por Osteoporose , Humanos , Feminino , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Anabolizantes/uso terapêutico , Brasil , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Fraturas por Osteoporose/tratamento farmacológico , Densidade ÓsseaRESUMO
Osteoporosis is characterized by the loss of bone mass, deterioration of the bone microarchitecture, and an increased risk of fractures; these later complications are associated with significant morbidity and mortality. The asymptomatic and progressive nature of osteoporosis underscores the importance of identifying this entity in early stages. Despite the various treatments available, the prevention of the disease represents the most important aspect of management. An adequate intake of calcium and vitamin D as well as a healthy lifestyle is the basis for maintaining bone health. When osteoporosis is diagnosed, the choice of medications must be individualized considering characteristics of the patient and the risk of fractures. In this article, we review the main causes of osteoporosis, when and how to start treatment, and appropriate therapy and monitoring.
Assuntos
Fraturas Ósseas/epidemiologia , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Deficiência de Vitamina D/tratamento farmacológico , Anabolizantes/uso terapêutico , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Cálcio da Dieta/uso terapêutico , Feminino , Fraturas Ósseas/etiologia , Glucocorticoides/efeitos adversos , Estilo de Vida Saudável , Humanos , Masculino , Osteoporose/induzido quimicamente , Fatores Sexuais , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicaçõesRESUMO
La suplementación con calcio reduciría, sola o asociada a otra medicación para osteoporosis, la pérdida de masa ósea y el riesgo de fracturas. Sin embargo, su tasa de adherencia es baja debido a la poca tolerancia. Objetivo: comparar la tasa de absorción neta de calcio entre dos formulaciones distintas de carbonato de calcio (500 mg): comprimidos vs. mousse. Material y métodos: 11 pruebas fueron realizadas en mujeres posmenopáusicas de 58,9±3 años. El diseño fue exploratorio abierto, aleatorizado, prospectivo cruzado de fase 4. Intervención: las participantes fueron aleatorizadas en dos grupos para recibir las dos formulaciones previa suplementación con vitamina D3. La tasa de absorción neta de calcio fue estudiada por la prueba de inhibición de hormona paratiroidea (PTH). Se obtuvieron muestras de sangre: basal y en la 1a, 2a y 3a hora posadministración del calcio asignado, y de orina de 2 horas basal y al final de la prueba. Determinaciones bioquímicas: calcio, fósforo, albúmina, 25-hidroxivitamina D y hormona paratiroidea intacta y calciuria. Análisis estadístico: método de los trapecios para calcular el área bajo la curva (AUC) de la concentración de calcio en el tiempo (R Development Core Team (2008). http://www.Rp-project.org) y Anova con dos términos de error para evaluar el efecto secuencia, período y formulación. Resultados: la mayor inhibición de PTH se observó a dos horas de la toma de ambas formulaciones (comprimidos -39,2% vs. mousse -38,0%; p=ns), con similar AUC0-3 h (comprimidos 3,35; IC 95%: 3,32; 3,37 vs. mousse 3,36; IC 95%: 3,33; 3,38). Cuando analizamos tolerancia y preferencias no se observaron diferencias estadísticamente significativas entre ambas formulaciones. Conclusión: el carbonato de calcio en mousse mostró similar tasa de absorción intestinal, preferencia y tolerancia gastrointestinal que en comprimido. (AU)
Calcium supplementation, administered alone or in combination with a specific medication for osteoporosis, would reduce bone mass loss and fracture risk in postmenopausal women. However, the adherence rate to calcium supplements is low, mainly due to low tolerance. Objective: comparisson of net calcium absorption rate between two different pharmaceutical formulations of calcium carbonate (PFCa) in postmenopausal women. Materials and Methods: 11 tests were performed in postmenopausal women aged 58.9±3 yrs. Design: Comparative, randomized, prospective, open-label exploratory crossover study of calcium mousse versus calcium pills. Intervention: Participants were randomized in 2 groups to receive the 2 different PFCa (500mg): pills vs. mousse, with previous vitamin D3 supplementation. The parathyroid hormone (PTH) inhibition test and the area-under-thecurve (AUC) of calcium were analyzed. Blood samples were taken at baseline and 1, 2 and 3 hrs after intake of the assigned PFCa. Urine samples (2hs) were obtained at -baseline, after 2hs of PFCa intake and at the end of the test. Biochemical Determinations: Serum: calcium, phosphorus, albumin, 25-hydroxyvitamin D, and intact PTH. In urine: calcium. Statistical Analysis: The trapezoid rule was applied to assess AUC in time (R Development Core Team (2008). http://www.Rp-project.org). An ANOVA model with 2 error terms was used to assess the effect of sequence, period, and formulation. Results: The highest inhibition PTH rates were observed after 2 hrs of PFCa (pills -39.2% vs. mousse -38.0%; p=ns). The AUC0-3hrs for both PFCa was similar (pills 3.35; 95%CI: 3.32; 3.37 vs. mousse 3.36; 95%CI: 3.33; 3.38). No statistically significant differences were observed when we analyze tolerance and predilection. Conclusion: The calcium carbonate in mousse showed an adequate rate of intestinal absorption, similarly predilection and gastrointestinal tolerance than the pill presentation. (AU)
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Carbonato de Cálcio/farmacocinética , Osteoporose Pós-Menopausa/prevenção & controle , Cálcio/farmacocinética , Hormônio Paratireóideo/análise , Acloridria , Calcitriol/farmacocinética , Carbonato de Cálcio/administração & dosagem , Carbonato de Cálcio/uso terapêutico , Índice de Massa Corporal , Densidade Óssea , Avaliação Nutricional , Osteoporose Pós-Menopausa/dietoterapia , Osteoporose Pós-Menopausa/tratamento farmacológico , Programas de Rastreamento , Cálcio/deficiência , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/sangue , Colecalciferol/administração & dosagem , Colecalciferol/efeitos adversos , Estudos Cross-Over , Citrato de Cálcio/uso terapêutico , Fraturas Ósseas/prevenção & controle , Estrogênios/deficiência , Absorção Gastrointestinal/efeitos dos fármacos , Cooperação e Adesão ao Tratamento , Anabolizantes/uso terapêuticoRESUMO
BACKGROUND: There is evidence of hypertensive effects caused by anabolic androgenic steroids (AAS). A single exercise session promotes the acute reduction of blood pressure, but the effects of AAS on this phenomenon are unknown. OBJECTIVES: To investigate the post-exercise blood pressure response in androgenic-anabolic steroid users. METHODS: Thirteen AAS users (23.9±4.3 years old) and sixteen controls (22.1±4.5 years old) performed a session of aerobic exercise. Heart rate and blood pressure were assessed before exercise and during a 60min post-exercise resting period. Repeated ANOVA measures were used to determine differences between the groups. RESULTS: While the control group had a significant reduction in post-exercise systolic blood pressure of up to 13.9±11.6mmHg at 40min, this phenomenon was limited among AAS users who reached a maximum of 6.2±11.5mmHg at 60min. The between groups comparison revealed significant higher post-exercise hypotension (PEH) for the control group at 30min (-12.9±14.1mmHg versus -2.9±7.6mmHg), 40min (-13.9±11.6mmHg versus -2.5±8.3mmHg), 50min (-13.9±13.9mmHg versus -5.0±7.9mmHg) and 60min (-12.5±12.8mmHg versus -6.2±11.5mmHg). There was no significant diastolic PEH in any of the groups. CONCLUSIONS: This study demonstrated impaired systolic post-exercise hypotension as a new adverse effect of AAS usage.
Assuntos
Anabolizantes/uso terapêutico , Androgênios/uso terapêutico , Hipotensão Pós-Exercício/prevenção & controle , Hipotensão Pós-Exercício/fisiopatologia , Congêneres da Testosterona/uso terapêutico , Adulto , Anabolizantes/farmacologia , Androgênios/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Estudos de Casos e Controles , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Sístole/efeitos dos fármacos , Sístole/fisiologia , Congêneres da Testosterona/farmacologia , Adulto JovemAssuntos
Conservadores da Densidade Óssea/uso terapêutico , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Osteoporose/tratamento farmacológico , Anabolizantes/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/ultraestrutura , Ensaios Clínicos como Assunto , Humanos , Osteoporose/patologia , Teriparatida/uso terapêutico , Tiofenos/uso terapêutico , Resultado do Tratamento , Ácido Zoledrônico/uso terapêuticoRESUMO
Type 1 diabetes mellitus (T1DM) is associated with several skeletal alterations, particularly in conditions of poor glycaemic control. Insulin therapy is the major conservative treatment for T1DM; however, the effects of this hormone on bone markers of T1DM rats are limited, and the regulatory mechanisms remain elusive. Therefore, the evaluation of molecular and non-molecular parameters in a chronic animal model of T1DM-induced bone loss, treated with and without insulin, may help in elucidating the insulin mechanisms. Male Wistar rats were assigned into three groups: control, T1DM (T1DM rats induced with streptozotocin [STZ] at 40 mg/kg intravenously) and T1DM plus insulin therapy (T1DMI). After 8 weeks, we evaluated the serum biochemical, tibia histomorphometric and biomechanical parameters, as well as the gene expression of the receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and osteocalcin (OC) of femur mRNA. Compared with T1DM, the T1DMI group showed less bone loss, which was revealed by the increased trabecular width (TbWi, p < 0.001) and trabecular bone area (BAr, p < 0.01), reduced trabecular separation (TbSp, p < 0.01) and increased Young's modulus (p < 0.05). Moreover, molecular analyses indicated that the expression of OPG and OC was up-regulated (p < 0.001 and p < 0.05, respectively). In summary, the up-regulation of OPG and OC in the T1DMI group supports an anabolic effect of insulin, which was demonstrated by the maintenance of bone architecture and flexibility. These results suggest that insulin therapy may prevent T1DM-induced bone loss via the effects on the bone formation.
Assuntos
Anabolizantes/farmacologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina/farmacologia , Osteocalcina/metabolismo , Osteoprotegerina/metabolismo , Anabolizantes/uso terapêutico , Animais , Densidade Óssea/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Fêmur/metabolismo , Insulina/uso terapêutico , Masculino , Ligante RANK/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Tíbia/patologia , Regulação para CimaRESUMO
BACKGROUND:: Hip fracture occurs predominantly in older people, many of whom are frail and undernourished. After hip fracture surgery and rehabilitation, most patients experience a decline in mobility and function. Anabolic steroids, the synthetic derivatives of the male hormone testosterone, have been used in combination with exercise to improve muscle mass and strength in athletes. They may have similar effects in older people who are recovering from hip fracture. OBJECTIVES:: To examine the effects (primarily in terms of functional outcome and adverse events) of anabolic steroids after surgical treatment of hip fracture in older people. METHODS:: Search methods: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialized Register (10 September 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2013 Issue 8), MEDLINE (1946 to August Week 4 2013), EMBASE (1974 to 2013 Week 36), trial registers, conference proceedings, and reference lists of relevant articles. The search was run in September 2013.Selection criteria: Randomized controlled trials of anabolic steroids given after hip fracture surgery, in inpatient or outpatient settings, to improve physical functioning in older patients with hip fracture.Data collection and analysis: Two review authors independently selected trials (based on predefined inclusion criteria), extracted data and assessed each study's risk of bias. A third review author moderated disagreements. Only very limited pooling of data was possible. The primary outcomes were function (for example, independence in mobility and activities of daily living) and adverse events, including mortality. MAIN RESULTS:: We screened 1290 records and found only three trials involving 154 female participants, all of whom were aged above 65 years and had had hip fracture surgery. All studies had methodological shortcomings that placed them at high or unclear risk of bias. Because of this high risk of bias, imprecise results and likelihood of publication bias, we judged the quality of the evidence for all primary outcomes to be very low.These trials tested two comparisons. One trial had three groups and contributed data to both comparisons. None of the trials reported on patient acceptability of the intervention.Two very different trials compared anabolic steroid versus control (no anabolic steroid or placebo). One trial compared anabolic steroid injections (given weekly until discharge from hospital or four weeks, whichever came first) versus placebo injections in 29 "frail elderly females". This found very low quality evidence of little difference between the two groups in the numbers discharged to a higher level of care or dead (one person in the control group died) (8/15 versus 10/14; risk ratio (RR) 0.75, 95% confidence interval (CI) 0.42 to 1.33; P = 0.32), time to independent mobilization or individual adverse events. The second trial compared anabolic steroid injections (every three weeks for six months) and daily protein supplementation versus daily protein supplementation alone in 40 "lean elderly women" who were followed up for one year after surgery. This trial provided very low quality evidence that anabolic steroid may result in less dependency, assessed in terms of being either dependent in at least two functions or dead (one person in the control group died) at six and 12 months, but the result was also compatible with no difference or an increase in dependency (dependent in at least two levels of function or dead at 12 months: 1/17 versus 5/19; RR 0.22, 95% CI 0.03 to 1.73; P = 0.15). The trial found no evidence of between-group differences in individual adverse events.Two trials compared anabolic steroids combined with another nutritional intervention ('steroid plus') versus control (no 'steroid plus'). One trial compared anabolic steroid injections every three weeks for 12 months in combination with daily supplement of vitamin D and calcium versus calcium only in 63 women who were living independently at home. The other trial compared anabolic steroid injections every three weeks for six months and daily protein supplementation versus control in 40 "lean elderly women". Both trials found some evidence of better function in the steroid plus group. One trial reported greater independence, higher Harris hip scores and gait speeds in the steroid plus group at 12 months. The second trial found fewer participants in the anabolic steroid group were either dependent in at least two functions, including bathing, or dead at six and 12 months (one person in the control group died) (1/17 versus 7/18; RR 0.15, 95% CI 0.02 to 1.10; P = 0.06). Pooled mortality data (2/51 versus 3/51) from the two trials showed no evidence of a difference between the two groups at one year. Similarly, there was no evidence of between-group differences in individual adverse events. Three participants in the steroid group of one trial reported side effects of hoarseness and increased facial hair. The other trial reported better quality of life in the steroid plus group. AUTHORS' CONCLUSIONS:: The available evidence is insufficient to draw conclusions on the effects, primarily in terms of functional outcome and adverse events, of anabolic steroids, either separately or in combination with nutritional supplements, after surgical treatment of hip fracture in older people. Given that the available data points to the potential for more promising outcomes with a combined anabolic steroid and nutritional supplement intervention, we suggest that future research should focus on evaluating this combination.
Assuntos
Anabolizantes/uso terapêutico , Fraturas do Quadril/tratamento farmacológico , Idoso , Feminino , Idoso Fragilizado , Fraturas do Quadril/reabilitação , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
ABSTRACT BACKGROUND: Hip fracture occurs predominantly in older people, many of whom are frail and undernourished. After hip fracture surgery and rehabilitation, most patients experience a decline in mobility and function. Anabolic steroids, the synthetic derivatives of the male hormone testosterone, have been used in combination with exercise to improve muscle mass and strength in athletes. They may have similar effects in older people who are recovering from hip fracture. OBJECTIVES: To examine the effects (primarily in terms of functional outcome and adverse events) of anabolic steroids after surgical treatment of hip fracture in older people. METHODS: Search methods: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialized Register (10 September 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2013 Issue 8), MEDLINE (1946 to August Week 4 2013), EMBASE (1974 to 2013 Week 36), trial registers, conference proceedings, and reference lists of relevant articles. The search was run in September 2013. Selection criteria: Randomized controlled trials of anabolic steroids given after hip fracture surgery, in inpatient or outpatient settings, to improve physical functioning in older patients with hip fracture. Data collection and analysis: Two review authors independently selected trials (based on predefined inclusion criteria), extracted data and assessed each study's risk of bias. A third review author moderated disagreements. Only very limited pooling of data was possible. The primary outcomes were function (for example, independence in mobility and activities of daily living) and adverse events, including mortality. MAIN RESULTS: We screened 1290 records and found only three trials involving 154 female participants, all of whom were aged above 65 years and had had hip fracture surgery. All studies had methodological shortcomings that placed them at high or unclear risk of bias. Because of this high risk of bias, imprecise results and likelihood of publication bias, we judged the quality of the evidence for all primary outcomes to be very low. These trials tested two comparisons. One trial had three groups and contributed data to both comparisons. None of the trials reported on patient acceptability of the intervention. Two very different trials compared anabolic steroid versus control (no anabolic steroid or placebo). One trial compared anabolic steroid injections (given weekly until discharge from hospital or four weeks, whichever came first) versus placebo injections in 29 "frail elderly females". This found very low quality evidence of little difference between the two groups in the numbers discharged to a higher level of care or dead (one person in the control group died) (8/15 versus 10/14; risk ratio (RR) 0.75, 95% confidence interval (CI) 0.42 to 1.33; P = 0.32), time to independent mobilization or individual adverse events. The second trial compared anabolic steroid injections (every three weeks for six months) and daily protein supplementation versus daily protein supplementation alone in 40 "lean elderly women" who were followed up for one year after surgery. This trial provided very low quality evidence that anabolic steroid may result in less dependency, assessed in terms of being either dependent in at least two functions or dead (one person in the control group died) at six and 12 months, but the result was also compatible with no difference or an increase in dependency (dependent in at least two levels of function or dead at 12 months: 1/17 versus 5/19; RR 0.22, 95% CI 0.03 to 1.73; P = 0.15). The trial found no evidence of between-group differences in individual adverse events. Two trials compared anabolic steroids combined with another nutritional intervention ('steroid plus') versus control (no 'steroid plus'). One trial compared anabolic steroid injections every three weeks for 12 months in combination with daily supplement of vitamin D and calcium versus calcium only in 63 women who were living independently at home. The other trial compared anabolic steroid injections every three weeks for six months and daily protein supplementation versus control in 40 "lean elderly women". Both trials found some evidence of better function in the steroid plus group. One trial reported greater independence, higher Harris hip scores and gait speeds in the steroid plus group at 12 months. The second trial found fewer participants in the anabolic steroid group were either dependent in at least two functions, including bathing, or dead at six and 12 months (one person in the control group died) (1/17 versus 7/18; RR 0.15, 95% CI 0.02 to 1.10; P = 0.06). Pooled mortality data (2/51 versus 3/51) from the two trials showed no evidence of a difference between the two groups at one year. Similarly, there was no evidence of between-group differences in individual adverse events. Three participants in the steroid group of one trial reported side effects of hoarseness and increased facial hair. The other trial reported better quality of life in the steroid plus group. AUTHORS' CONCLUSIONS: The available evidence is insufficient to draw conclusions on the effects, primarily in terms of functional outcome and adverse events, of anabolic steroids, either separately or in combination with nutritional supplements, after surgical treatment of hip fracture in older people. Given that the available data points to the potential for more promising outcomes with a combined anabolic steroid and nutritional supplement intervention, we suggest that future research should focus on evaluating this combination.
Assuntos
Humanos , Feminino , Idoso , Fraturas do Quadril/tratamento farmacológico , Anabolizantes/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Idoso Fragilizado , Fraturas do Quadril/reabilitaçãoRESUMO
The aim of this study was to describe a case of pathology of the testicle after long-term anabolic steroid treatment in a Thoroughbread horse. Were study an equine Thoroughbread with cryptorchidism from Venezuela, male of 5 years old. With history of lameness chronic and subfertility. Necropsy was performed and samples of testicle tissue were collected. The tissue samples were fixed in formalin and processed by conventional H&E techniques. Additionally, the special staining procedure of Tricromico de Gomory and Blue VonKossa were also carried out. Samples of blood and urine were recollected for toxicological by competitive ELISA. The left testicle was diameter testicle 6cm. and cryptorchidism (testicle right). Macroscopic were observed bilateral fibrosis parenchyma testicle and atrophic. The histological study revealed atrophy of seminiferous tubules and interstitial fibrosis increases in collagen fibres in the lamina propria of seminiferous tubules and testicular interstitium. Lamina propria surrounding atrophic tubules was thickened by an increase in collagen type IV and elastic fibres and by proliferation of bizarre myoid cells. Basal lamina was also thickened but had decreased for collagen type IV. Special stain Tricromico of Gomory (+) showed fibrosis interstitium severed and VonKossa (-) no evidence mineral. Toxicological studies allowed the detection of boldenona and dexamethasone generic in blood and urine samples. To conclude, we detected the presence of pathology of the testicle associated a after long-term anabolic steroid treatment in a Thoroughbred horse.