Bone effects of epidural and intra-articular glucocorticoids: a systematic literature review / Efectos óseos de los glucocorticoides epidurales e intraarticulares: revisión sistemática de la literatura

Osteoporosis and vertebral and non-vertebral fractures are common in glucocorticoids (GC) treated patients. Oral GC treatment leads to bone loss, particularly of trabecular bone. The benefits of GC used in rheumatological and traumatological disorders are known but they would have possible negative effects on bone. This systematic review aimed to evaluate the effects of epidural steroid injections (ESI), and intra-articular and intramuscular GC administration on bone mineral density (BMD) and fragility fractures. A systematic review of Medline/PubMed, Cochrane, and LILACS up to November 2020 was conducted. Meta-analyses, systematic reviews, randomized and non-randomized controlled trials, and prospective and retrospective studies comparing the effect of ESI, intra-articular or intramuscular GC used compared to a control group or baseline measurements were included. Results: A total of 8272 individuals were included among the 13 selected articles (10 about ESI and 3 about intra-articular GC; no article was found evaluating intramuscular GC). Only a few studies showed a negative effect of ESI on bone in the qualitative analysis considering osteopenia and osteoporosis in lumbar spine, femoral neck and total hip and BMD as surrogate outcomes. On the other hand, the qualitative analysis showed that most studies found an increased risk of fragility fracture. However, only two studies could be included in the quantitative analysis, in which there were no differences between patients exposed to ESI versus controls in all evaluated regions. In conclusion, there was insufficient evidence to suggest that ESI and intra-articular GC, unlike oral GC, negatively affect bone mass. Longitudinal studies are needed to obtain more knowledge regarding the effect of ESI or intra-articular GC on BMD and fragility fractures. (AU)

La osteoporosis y las fracturas vertebrales y no vertebrales son comunes en pacientes tratados con glucocorticoides (GC). El tratamiento oral con GC conduce a la pérdida ósea, particularmente del hueso trabecular. Los beneficios de los GC utilizados en patologías reumatológicas y traumatológicas son conocidos, pero tendrían posibles efectos negativos sobre el hueso. Esta revisión sistemática tuvo como objetivo evaluar los efectos de las inyecciones epidurales de esteroides (ESI), GC intraarticulares e intramusculares sobre la densidad mineral ósea (DMO) y las fracturas por fragilidad. Se realizó una revisión sistemática de Medline/PubMed, Cochrane y LILACS hasta noviembre de 2020. Se incluyeron metanálisis, revisiones sistemáticas, ensayos controlados aleatorizados y no aleatorizados, estudios prospectivos y retrospectivos que compararon el efecto de ESI, GC intraarticular o intramuscular utilizado en comparación con un grupo de control o mediciones iniciales. Resultados: Se incluyeron un total de 8272 individuos entre los 13 artículos seleccionados (10 sobre ESI y 3 sobre GC intraarticular; no se encontró ningún artículo que evaluara GC intramuscular). Solo unos pocos estudios mostraron un efecto negativo del ESI sobre el hueso en el análisis cualitativo considerando la osteopenia y la osteoporosis en la columna lumbar, el cuello femoral y la cadera total y la DMO como un resultado indirecto. Por otro lado, el análisis cualitativo mostró que la mayoría de los estudios encontraron un mayor riesgo de fractura por fragilidad. Sin embargo, solo dos estudios pudieron incluirse en el análisis cuantitativo, en los que no hubo diferencias entre los pacientes expuestos a ESI versus los controles en todas las regiones evaluadas. En conclusión, no hallamos datos suficientes para sugerir que la ESI y los GC intraarticulares, a diferencia de los GC orales, afectan negativamente a la pérdida ósea. Se necesitan estudios longitudinales para obtener más conocimiento sobre el efecto de ESI o GC intraarticular en la DMO y las fracturas por fragilidad. (AU)

Argentine Guidelines for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Postmenopausal Women and Men Aged 50 Years and Older.

OBJECTIVE: The aim of this study was to provide an evidence-based framework to guide health care professionals treating patients under glucocorticoid (GC) therapy and develop guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis (GIO) in postmenopausal women and men aged ≥50 years. METHODS: An expert panel on bone diseases designed a series of clinically meaningful questions following the PICO (Population, Intervention, Comparator, and Outcome) structure. Using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology, we made a systematic literature review, extracted and summarized the effect estimates, and graded the quality of the evidence. The expert panel voted each PICO question and made recommendations after reaching an agreement of at least 70%. RESULTS: Seventeen recommendations (9 strong and 8 conditional) and 8 general principles were developed for postmenopausal women and men aged ≥50 years under GC treatment. Bone mineral density (BMD), occurrence of fragility fractures, probability of fracture at 10 years by Fracture Risk Assessment Tool, and other screening factors for low BMD are recommended for patient evaluation and stratification according to fragility fracture risk. The treatment of patients under GC therapy should include counseling on lifestyle habits and strict control of comorbidities. The goal of GIO treatment is the nonoccurrence of new fragility fractures as well as to increase or maintain BMD in certain clinical situations. This was considered for the therapeutic approach in different clinical scenarios. CONCLUSIONS: This GIO guideline provides evidence-based guidance for health care providers treating patients.

Romosozumab improves lumbar spine bone mass and bone strength parameters relative to alendronate in postmenopausal women: results from the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial.

The Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial (NCT01631214; https://clinicaltrials.gov/ct2/show/NCT01631214) showed that romosozumab for 1 year followed by alendronate led to larger areal bone mineral density (aBMD) gains and superior fracture risk reduction versus alendronate alone. aBMD correlates with bone strength but does not capture all determinants of bone strength that might be differentially affected by various osteoporosis therapeutic agents. We therefore used quantitative computed tomography (QCT) and finite element analysis (FEA) to assess changes in lumbar spine volumetric bone mineral density (vBMD), bone volume, bone mineral content (BMC), and bone strength with romosozumab versus alendronate in a subset of ARCH patients. In ARCH, 4093 postmenopausal women with severe osteoporosis received monthly romosozumab 210 mg sc or weekly oral alendronate 70 mg for 12 months, followed by open-label weekly oral alendronate 70 mg for ≥12 months. Of these, 90 (49 romosozumab, 41 alendronate) enrolled in the QCT/FEA imaging substudy. QCT scans at baseline and at months 6, 12, and 24 were assessed to determine changes in integral (total), cortical, and trabecular lumbar spine vBMD and corresponding bone strength by FEA. Additional outcomes assessed include changes in aBMD, bone volume, and BMC. Romosozumab caused greater gains in lumbar spine integral, cortical, and trabecular vBMD and BMC than alendronate at months 6 and 12, with the greater gains maintained upon transition to alendronate through month 24. These improvements were accompanied by significantly greater increases in FEA bone strength (p < 0.001 at all time points). Most newly formed bone was accrued in the cortical compartment, with romosozumab showing larger absolute BMC gains than alendronate (p < 0.001 at all time points). In conclusion, romosozumab significantly improved bone mass and bone strength parameters at the lumbar spine compared with alendronate. These results are consistent with greater vertebral fracture risk reduction observed with romosozumab versus alendronate in ARCH and provide insights into structural determinants of this differential treatment effect. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Postmenopausal women with sarcopenia have higher prevalence of falls and vertebral fractures / Las mujeres postmenopáusicas con sarcopenia tienen mayor prevalencia de caídas y fracturas vertebrales

Abstract Recently, a new consensus of the European Working Group on Sarcopenia in Older People (EWSOP2) recommended new cut-off points for the diagnosis of sarcopenia. The aim of the present manuscript was to assess the prevalence of sarcopenia in postmenopausal women and its relationship with bone mineral density, falls and fragility fractures according to EWGSOP2. In this cross-sectional study, 250 ambulatory postmenopausal women over 60 years of age were included. Lumbar spine and hip bone mineral density (BMD) and whole-body composition were assessed by dual-energy X-ray absorptiometry (DXA). Muscle strength was evaluated by handgrip dynamometry and physical performance by a 4-m walk gait speed and five-repetition sit-to-stand test. Sarcopenia was defined according to EWGSOP2 as low muscle strength (handgrip) and low muscle mass (appendicular skeletal muscle mass index by DXA). A sarcopenia prevalence of 4% was found in the whole group increasing with age being 12.5% in ≥ 80year-old. A higher percentage of falls, prevalence of osteoporosis and vertebral fractures were found in the sarcopenic group. Sarcopenia increased 6.0-fold the likelihood of having a fragility fracture. Women with sarcopenia had significantly lower femoral neck BMD and higher frequency of falls and vertebral fractures. According to our results, identifying patients with sarcopenia might be a useful tool to detect adults at higher risk of falls and fractures.

Resumen Recientemente el grupo de trabajo europeo sobre sarcopenia en adultos mayores (EWGSOP2) recomendó nuevos criterios y valores de referencia para el diagnóstico de sarcopenia. El objetivo del presente trabajo fue evaluar la prevalencia de sarcopenia en mujeres postmenopáusicas en nuestro medio y su relación con densidad mineral ósea, caídas y fracturas por fragilidad. Este es un estudio de diseño transversal en el cual se incluyeron un total de 250 mujeres ambulatorias mayores de 60 años. La densidad mineral ósea (DMO) de columna lumbar y cadera y la composición corporal fueron evaluados por absorciometría dual de rayos X (DXA). La fuerza fue evaluada por dinamometría de puño; para el rendimiento físico se utilizó caminata de 4 m y la prueba de levantarse y sentarse de una silla (5 repeticiones). La sarcopenia se definió de acuerdo a EWGSOP2 como baja fuerza muscular (dinamometría) y baja masa muscular (índice de masa muscular esquelética por DXA). El 4% de las mujeres cumplía con los criterios de sarcopenia siendo aún mayor en aquellas ≥ 80 años. Las mujeres con sarcopenia presentaron significativamente mayor frecuencia de caídas, osteoporosis y fracturas vertebrales. El riesgo de fracturas por fragilidad se vio incrementado 6 veces en las mujeres con sarcopenia. El diagnóstico de sarcopenia podría considerarse una herramienta útil para identificar a aquellos adultos con riesgo incrementado de caídas y fracturas.

Postmenopausal women with sarcopenia have higher prevalence of falls and vertebral fractures.

Recently, a new consensus of the European Working Group on Sarcopenia in Older People (EWSOP2) recommended new cut-off points for the diagnosis of sarcopenia. The aim of the present manuscript was to assess the prevalence of sarcopenia in postmenopausal women and its relationship with bone mineral density, falls and fragility fractures according to EWGSOP2. In this cross-sectional study, 250 ambulatory postmenopausal women over 60 years of age were included. Lumbar spine and hip bone mineral density (BMD) and whole-body composition were assessed by dual-energy X-ray absorptiometry (DXA). Muscle strength was evaluated by handgrip dynamometry and physical performance by a 4-m walk gait speed and five-repetition sit-to-stand test. Sarcopenia was defined according to EWGSOP2 as low muscle strength (handgrip) and low muscle mass (appendicular skeletal muscle mass index by DXA). A sarcopenia prevalence of 4% was found in the whole group increasing with age being 12.5% in = 80- year-old. A higher percentage of falls, prevalence of osteoporosis and vertebral fractures were found in the sarcopenic group. Sarcopenia increased 6.0-fold the likelihood of having a fragility fracture. Women with sarcopenia had significantly lower femoral neck BMD and higher frequency of falls and vertebral fractures. According to our results, identifying patients with sarcopenia might be a useful tool to detect adults at higher risk of falls and fractures.

Recientemente el grupo de trabajo europeo sobre sarcopenia en adultos mayores (EWGSOP2) recomendó nuevos criterios y valores de referencia para el diagnóstico de sarcopenia. El objetivo del presente trabajo fue evaluar la prevalencia de sarcopenia en mujeres postmenopáusicas en nuestro medio y su relación con densidad mineral ósea, caídas y fracturas por fragilidad. Este es un estudio de diseño transversal en el cual se incluyeron un total de 250 mujeres ambulatorias mayores de 60 años. La densidad mineral ósea (DMO) de columna lumbar y cadera y la composición corporal fueron evaluados por absorciometría dual de rayos X (DXA). La fuerza fue evaluada por dinamometría de puño; para el rendimiento físico se utilizó caminata de 4 m y la prueba de levantarse y sentarse de una silla (5 repeticiones). La sarcopenia se definió de acuerdo a EWGSOP2 como baja fuerza muscular (dinamometría) y baja masa muscular (índice de masa muscular esquelética por DXA). El 4% de las mujeres cumplía con los criterios de sarcopenia siendo aún mayor en aquellas = 80 años. Las mujeres con sarcopenia presentaron significativamente mayor frecuencia de caídas, osteoporosis y fracturas vertebrales. El riesgo de fracturas por fragilidad se vio incrementado 6 veces en las mujeres con sarcopenia. El diagnóstico de sarcopenia podría considerarse una herramienta útil para identificar a aquellos adultos con riesgo incrementado de caídas y fracturas.

Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial.

BACKGROUND: Previous bisphosphonate treatment attenuates the bone-forming effect of teriparatide. We compared the effects of 12 months of romosozumab (AMG 785), a sclerostin monoclonal antibody, versus teriparatide on bone mineral density (BMD) in women with postmenopausal osteoporosis transitioning from bisphosphonate therapy. METHODS: This randomised, phase 3, open-label, active-controlled study was done at 46 sites in North America, Latin America, and Europe. We enrolled women (aged ≥55 to ≤90 years) with postmenopausal osteoporosis who had taken an oral bisphosphonate for at least 3 years before screening and alendronate the year before screening; an areal BMD T score of -2·5 or lower at the total hip, femoral neck, or lumbar spine; and a history of fracture. Patients were randomly assigned (1:1) via an interactive voice response system to receive subcutaneous romosozumab (210 mg once monthly) or subcutaneous teriparatide (20 µg once daily). The primary endpoint was percentage change from baseline in areal BMD by dual-energy x-ray absorptiometry at the total hip through month 12 (mean of months 6 and 12), which used a linear mixed effects model for repeated measures and represented the mean treatment effect at months 6 and 12. All randomised patients with a baseline measurement and at least one post-baseline measurement were included in the efficacy analysis. This trial is registered with ClinicalTrials.gov, number NCT01796301. FINDINGS: Between Jan 31, 2013, and April 29, 2014, 436 patients were randomly assigned to romosozumab (n=218) or teriparatide (n=218). 206 patients in the romosozumab group and 209 in the teriparatide group were included in the primary efficacy analysis. Through 12 months, the mean percentage change from baseline in total hip areal BMD was 2·6% (95% CI 2·2 to 3·0) in the romosozumab group and -0·6% (-1·0 to -0·2) in the teriparatide group; difference 3·2% (95% CI 2·7 to 3·8; p<0·0001). The frequency of adverse events was generally balanced between treatment groups. The most frequently reported adverse events were nasopharyngitis (28 [13%] of 218 in the romosozumab group vs 22 [10%] of 214 in the teriparatide group), hypercalcaemia (two [<1%] vs 22 [10%]), and arthralgia (22 [10%] vs 13 [6%]). Serious adverse events were reported in 17 (8%) patients on romosozumab and in 23 (11%) on teriparatide; none were judged treatment related. There were six (3%) patients in the romosozumab group compared with 12 (6%) in the teriparatide group with adverse events leading to investigational product withdrawal. INTERPRETATION: Transition to a bone-forming agent is common practice in patients treated with bisphosphonates, such as those who fracture while on therapy. In such patients, romosozumab led to gains in hip BMD that were not observed with teriparatide. These data could inform clinical decisions for patients at high risk of fracture. FUNDING: Amgen, Astellas, and UCB Pharma.

Impaired Bone Microarchitecture Improves After One Year On Gluten-Free Diet: A Prospective Longitudinal HRpQCT Study in Women With Celiac Disease.

We have recently identified a significant deterioration of bone microarchitecture in premenopausal women with newly diagnosed celiac disease (CD) using high-resolution peripheral quantitative computed tomography (HRpQCT). The aim of this work was to assess changes in bone microarchitecture after 1 year on a gluten-free diet (GFD) in a cohort of premenopausal women. We prospectively enrolled 31 consecutive females at diagnosis of CD; 26 of them were reassessed 1 year after GFD. They all underwent HRpQCT scans of distal radius and tibia, areal BMD by DXA, and biochemical tests (bone-specific parameters and CD serology) at both time points. Secondary, we compared 1-year results with those of a control group of healthy premenopausal women of similar age and BMI in order to assess whether the microarchitectural parameters of treated CD patients had reached the values expected for their age. Compared with baseline, the trabecular compartment in the distal radius and tibia improved significantly (trabecular density, trabecular/bone volume fraction [BV/TV] [p < 0.0001], and trabecular thickness [p = 0.0004]). Trabecular number remained stable in both regions. Cortical density increased only in the tibia (p = 0.0004). Cortical thickness decreased significantly in both sites (radius: p = 0.03; tibia: p = 0.05). DXA increased in all regions (lumbar spine [LS], p = 0.01; femoral neck [FN], p = 0.009; ultradistal [UD] radius, p = 0.001). Most parameters continued to be significantly lower than those of healthy controls. This prospective HRpQCT study showed that most trabecular parameters altered at CD diagnosis improved significantly by specific treatment (GFD) and calcium and vitamin D supplementation. However, there were still significant differences with a control group of women of similar age and BMI. In the prospective follow-up of this group of patients we expect to be able to assess whether bone microarchitecture attains levels expected for their age. © 2016 American Society for Bone and Mineral Research.

Eficácia e segurança da associação de sulfato de glucosamina e sulfato de condroitina no tratamento sintomático da osteoartrite de joelho / Efficacy and safety of the association of glucosamine sulfate and chondroitin sulfate in the treatment of symptomatic knee osteoarthritis

Objetivos: Avaliar a eficácia e a segurança da associação glucosamina e condroitina (GC) no tratamento da osteoartrite (OA) de joelho. Métodos: Ensaio clínico, randomizado, duplo-cego, controlado por placebo. Pacientes portadores de OA de joelho com índice algofuncional total de Lequesne (Leqt) entre 5 e 13 pontos e graus 2 ou 3 de Kellgren-Lawrence foram aleatorizados para receber a associação de sulfato de glucosamina (1,5 g) e sulfato de condroitina (1,2g) ou placebo durante 12 semanas, sendo acompanhados por 12 semanas adicionais. Empregou-se paracetamol como medicamento de resgate. Resultados: Observou-se redução de Leqt médio nos dois grupos de tratamento, de maior magnitude no grupo GC. A diferença se tornou evidente após quatro semanas, aumentando no decorrer do tratamento, embora sem atingir significância estatística (p = 0,1643 na população com intenção de tratar [ITT] e p = 0,0681 na população por protocolo [PP]). A quantidade de paracetamol consumido foi significativamente maior no grupo placebo nas populações ITT (p = 0,0394) e PP (p = 0,0257). Durante o seguimento, Leqt médio mostrou valores inferiores no grupo GC (p = 0,1061 e p = 0,0494 nas populações ITT e PP, respectivamente). Leqt começou a aumentar logo após o final do tratamento apenas no grupo placebo, observando-se redução adicional de seu valor médio no grupo GC, evidenciando o efeito terapêutico residual da associação. Os grupos foram semelhantes quanto aos eventos adversos relatados. Conclusão: Os resultados foram consistentes quanto à efetividade da associação GC. A associação se mostrou segura e bem tolerada.

[Starting an insulin regimen with insulin lispro mix 25 versus glargine insulin for type 2 diabetes]. / Régimen con insulina lispro mix 25 versus insulina glargina para la diabetes tipo 2.

Information on starting insulin regimens in specific populations with type 2 diabetes (T2D) is limited. This analysis compared efficacy and safety of two starter insulin regimens: insulin lispro mix 25 (LM25) and basal insulin glargine (GL) in patients from Argentina. This post-hoc analysis evaluated 193 insulin-naïve patients who participated in the DURABLE trial 24-week initiation phase. Patients 30-79 years with T2D inadequately controlled (HbA1c > 7.0%) with = 2 oral antihyperglycemic medications (OAMs), were randomized to add LM25 (25% insulin lispro, 75% insulin lispro protamine suspension) twice daily or GL (basal insulin glargine) once daily to pre-study OAMs. Primary efficacy was measured by HbA1c at 24-week endpoint. Secondary measures included: proportion of patients achieving HbA1c = 6.5% and = 7.0%, body weight change, self-monitored blood glucose (BG) values, and hypoglycemia rates. LM25 demonstrated greater HbA1c reduction (- 2.4% ± 0.16 vs. -2.0% ± 0.16, P = 0.002), a higher proportion of patients achieving HbA1c = 7.0% (P = 0.012), and lower BG levels after the morning (P = 0.028) and evening (P = 0.011) meals, and at 3:00AM (P = 0.005) compared with GL. Fasting BG and proportion of patients achieving HbA1c = 6.5% were similar between groups. Both groups increased body weight, although the gain was higher at endpoint with LM25 (6.35 kg vs. 4.23 kg, P < 0.001). No differences in hypoglycemia rates were observed between groups, and no serious adverse events were reported for either group. In this subgroup from Argentina, LM25 demonstrated greater improvement in glucose control with similar risk of hypoglycemia and more weight gain than GL.

Régimen con insulina lispro mix 25 versus insulina glargina para la diabetes tipo 2 / Starting an insulin regimen with insulin lispro mix 25 versus glargine insulin for type 2 diabetes

La información sobre el inicio de regímenes de insulina en poblaciones específicas con diabetes tipo 2 (DT2) es limitada. Se comparó eficacia y seguridad de dos regímenes de inicio: insulina lispro mix 25 (LM25) e insulina glargina basal (GL). Se evaluaron 193 pacientes no tratados previamente con insulina, en la fase de iniciación de 24 semanas del ensayo DURABLE; edades: 30-79 años, DT2 controlada inadecuadamente (HbA1c > 7.0%) con = 2 medicaciones orales antidiabéticas (MOAs), aleatorizados para LM25 (25% de insulina lispro, 75% de insulina lispro protamina en suspensión) dos veces/día, o GL (insulina glargina basal) una vez/ día, a las MOAs previas. La eficacia primaria se midió por HbA1c a las 24 semanas. Se midió eficacia secundaria por: proporción de pacientes que alcanzaron HbA1c= 6.5% y= 7.0%, cambio en peso corporal, valores de automonitoreo glucémico e índices de hipoglucemia. LM25 demostró mayor reducción de la HbA1c (- 2.4% ± 0.16 vs. -2.0% ± 0.16, P = 0.002), mayor proporción de pacientes alcanzaron HbA1c= 7.0% (P = 0.012) y niveles de glucemia menores después del desayuno (P = 0.028) y de la cena (P = 0.011), y a las 3 a.m. (P = 0.005) comparada con GL. La glucemia en ayunas (GA) y la proporción de pacientes que alcanzaron una HbA1c= 6.5% fueron similares. En ambos grupos hubo aumento del peso corporal, mayor en la valoración final con LM25 (6.35 kg vs. 4.23 kg, P < 0.001). No hubieron diferencias en índices de hipoglucemia entre grupos, ni eventos adversos serios en ninguno. Con LM25 fue mejor el control de glucosa, riesgo de hipoglucemia similar y mayor aumento de peso que GL.

Information on starting insulin regimens in specific populations with type 2 diabetes (T2D) is limited. This analysis compared efficacy and safety of two starter insulin regimens: insulin lispro mix 25 (LM25) and basal insulin glargine (GL) in patients from Argentina. This post-hoc analysis evaluated 193 insulin-naïve patients who participated in the DURABLE trial 24-week initiation phase. Patients 30-79 years with T2D inadequately controlled (HbA1c > 7.0%) with = 2 oral antihyperglycemic medications (OAMs), were randomized to add LM25 (25% insulin lispro, 75% insulin lispro protamine suspension) twice daily or GL (basal insulin glargine) once daily to pre-study OAMs. Primary efficacy was measured by HbA1c at 24-week endpoint. Secondary measures included: proportion of patients achieving HbA1c= 6.5% and= 7.0%, body weight change, self-monitored blood glucose (BG) values, and hypoglycemia rates. LM25 demonstrated greater HbA1c reduction (- 2.4% ± 0.16 vs. -2.0% ± 0.16, P = 0.002), a higher proportion of patients achieving HbA1c= 7.0% (P = 0.012), and lower BG levels after the morning (P = 0.028) and evening (P = 0.011) meals, and at 3:00AM (P = 0.005) compared with GL. Fasting BG and proportion of patients achieving HbA1c= 6.5% were similar between groups. Both groups increased body weight, although the gain was higher at endpoint with LM25 (6.35 kg vs. 4.23 kg, P < 0.001). No differences in hypoglycemia rates were observed between groups, and no serious adverse events were reported for either group. In this subgroup from Argentina, LM25 demonstrated greater improvement in glucose control with similar risk of hypoglycemia and more weight gain than GL.

Régimen con insulina lispro mix 25 versus insulina glargina para la diabetes tipo 2 / Starting an insulin regimen with insulin lispro mix 25 versus glargine insulin for type 2 diabetes

La información sobre el inicio de regímenes de insulina en poblaciones específicas con diabetes tipo 2 (DT2) es limitada. Se comparó eficacia y seguridad de dos regímenes de inicio: insulina lispro mix 25 (LM25) e insulina glargina basal (GL). Se evaluaron 193 pacientes no tratados previamente con insulina, en la fase de iniciación de 24 semanas del ensayo DURABLE; edades: 30-79 años, DT2 controlada inadecuadamente (HbA1c > 7.0%) con = 2 medicaciones orales antidiabéticas (MOAs), aleatorizados para LM25 (25% de insulina lispro, 75% de insulina lispro protamina en suspensión) dos veces/día, o GL (insulina glargina basal) una vez/ día, a las MOAs previas. La eficacia primaria se midió por HbA1c a las 24 semanas. Se midió eficacia secundaria por: proporción de pacientes que alcanzaron HbA1c= 6.5% y= 7.0%, cambio en peso corporal, valores de automonitoreo glucémico e índices de hipoglucemia. LM25 demostró mayor reducción de la HbA1c (- 2.4% ± 0.16 vs. -2.0% ± 0.16, P = 0.002), mayor proporción de pacientes alcanzaron HbA1c= 7.0% (P = 0.012) y niveles de glucemia menores después del desayuno (P = 0.028) y de la cena (P = 0.011), y a las 3 a.m. (P = 0.005) comparada con GL. La glucemia en ayunas (GA) y la proporción de pacientes que alcanzaron una HbA1c= 6.5% fueron similares. En ambos grupos hubo aumento del peso corporal, mayor en la valoración final con LM25 (6.35 kg vs. 4.23 kg, P < 0.001). No hubieron diferencias en índices de hipoglucemia entre grupos, ni eventos adversos serios en ninguno. Con LM25 fue mejor el control de glucosa, riesgo de hipoglucemia similar y mayor aumento de peso que GL.(AU)

Information on starting insulin regimens in specific populations with type 2 diabetes (T2D) is limited. This analysis compared efficacy and safety of two starter insulin regimens: insulin lispro mix 25 (LM25) and basal insulin glargine (GL) in patients from Argentina. This post-hoc analysis evaluated 193 insulin-na´ve patients who participated in the DURABLE trial 24-week initiation phase. Patients 30-79 years with T2D inadequately controlled (HbA1c > 7.0%) with = 2 oral antihyperglycemic medications (OAMs), were randomized to add LM25 (25% insulin lispro, 75% insulin lispro protamine suspension) twice daily or GL (basal insulin glargine) once daily to pre-study OAMs. Primary efficacy was measured by HbA1c at 24-week endpoint. Secondary measures included: proportion of patients achieving HbA1c= 6.5% and= 7.0%, body weight change, self-monitored blood glucose (BG) values, and hypoglycemia rates. LM25 demonstrated greater HbA1c reduction (- 2.4% ± 0.16 vs. -2.0% ± 0.16, P = 0.002), a higher proportion of patients achieving HbA1c= 7.0% (P = 0.012), and lower BG levels after the morning (P = 0.028) and evening (P = 0.011) meals, and at 3:00AM (P = 0.005) compared with GL. Fasting BG and proportion of patients achieving HbA1c= 6.5% were similar between groups. Both groups increased body weight, although the gain was higher at endpoint with LM25 (6.35 kg vs. 4.23 kg, P < 0.001). No differences in hypoglycemia rates were observed between groups, and no serious adverse events were reported for either group. In this subgroup from Argentina, LM25 demonstrated greater improvement in glucose control with similar risk of hypoglycemia and more weight gain than GL.(AU)

Denosumab: What's new?

Denosumab is the first fully human monoclonal antibody that inhibits the formation, function, and survival of osteoclasts by blocking the interaction of receptor activator of nuclear factor-κB (RANK) ligand with its osteoclastic receptor RANK. Clinical studies have shown that the decreased bone resorption and increased bone mineral density resulting from the use of denosumab 60 mg twice yearly entail significant risk reduction of vertebral, hip, and nonvertebral fractures in women with postmenopausal osteoporosis, with an acceptable rate of side effects so far. Following its approval by the US Food and Drug Administration and the European Medicines Agency, a number of clinical trials with denosumab are ongoing to demonstrate its value for other indications and to further characterize its effects on immunomodulation. Denosumab offers a new choice for the treatment of postmenopausal osteoporosis in patients at high risk for fracture.

Parathyroid hormone (1-84) and teriparatide in the treatment of postmenopausal osteoporosis.

Osteoporosis-related fractures are a major public health problem worldwide. Antiresorptive drugs, which work principally by suppressing bone resorption, are the established therapeutic approach for the prevention of fragility fractures in patients with osteoporosis. Parathyroid hormone and its analogs represent a new class of agents with anabolic effects on the skeleton. The results of double-blind, randomized, placebo-controlled trials have shown that both the full length, 84 amino acid parathyroid hormone and teriparatide, the parathyroid hormone fragment (1-34) increase bone mineral density and reduce the risk of fracture when administered intermittently to postmenopausal osteoporotic women. Therefore, these drugs should be considered an alternative therapy in postmenopausal osteoporosis.

Fenofibrate of gemfibrozil for treatment of types IIa and IIb primary hyperlipoproteinemia: a randomized, double-blind, crossover study.

OBJECTIVE: To compare the hypolipidemic effects of gemfibrozil and micronized fenofibrate in patients with primary hyperlipoproteinemia, phenotypes IIa and IIb, with emphasis on their cholesterol-lowering effectiveness. METHODS: A randomized, double-blind, double-dummy, crossover study was performed to assess the effects of gemfibrozil (900 mg) and micronized fenofibrate (200 mg), administered once daily, to 21 patients (45 to 70 years old)-16 with type IIa and 5 with type IIb primary hyperlipidemia. The two treatment periods lasted 6 weeks each; the run-in and washout periods were 4 weeks. RESULTS: Both drugs significantly reduced total cholesterol, calculated low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein B, and fibrinogen (P<0.01 for all calculations, except P<0.05 for fibrinogen with gemfibrozil therapy) and increased high-density lipoprotein (HDL) cholesterol (P<0.01). Neither drug affected Lp(a) lipoprotein, whereas uric acid was reduced only by fenofibrate (P<0.01). The percentage decrease in total cholesterol and LDL cholesterol was greater with fenofibrate than with gemfibrozil (-22% versus -15%, P<0.02; and -27% versus -16%, P<0.02, respectively). In contrast, reductions in levels of triglycerides (-54% versus -46.5%), apolipoprotein B, and fibrinogen, as well as the increase in HDL (+9% for both drugs), showed no significant difference between treatments. Separate analysis of patients with type IIb hyperlipoproteinemia showed essentially the same plasma lipid changes as for the overall group, but with greater modifications in triglyceride and HDL concentrations. CONCLUSION: Fenofibrate and gemfibrozil induced similar variations from baseline values in triglycerides, HDL cholesterol, apolipoprotein B, and fibrinogen, but the decreases in total and LDL cholesterol levels were greater with fenofibrate, in this group of patients with primary hyperlipidemia.