Calcium and vitamin D supplementation in the management of osteoporosis. What is the advisable dose of vitamin D?

Los fundamentos fisiopatológicos que justifican la suplementación con calcio y vitamina D en la osteoporosis se sustancian en una amplia evidencia científica que se ha obtenido a través de varios ensayos clínicos aleatorizados y posteriores meta‐análisis que han demostrado una reducción del riesgo de fracturas osteoporóticas estadísticamente significativa y clínicamente relevante. Esta evidencia ha conducido a su recomendación por parte de varias sociedades científicas interesadas en el manejo de la osteoporosis. Con el fin de optimizar la eficacia y el balance beneficio/riesgo de estos, el calcio y la vitamina D deben administrarse conjuntamente con los fármacos que se prescriban para el tratamiento de la osteoporosis, pues en todos estos estudios de referencia se ha utilizado calcio y vitamina D tanto en la rama que recibe el fármaco como la del placebo. La sal de calcio mayormente utilizada es el carbonato y el metabolito de la vitamina D, el colecalciferol o vitamina D 3. No existe consenso ni evidencia científica concluyente sobre cuál es la dosis a emplear en la deficiencia de vitamina D asociada a osteoporosis. No obstante, la tendencia ha sido siempre a ir aumentando estas cantidades, desde las 400 UI que se recomendaban hace unos 30 años a las 2.000 UI diarias de la actualidad. Revisaremos en este artículo cuales son las recomendaciones que se realizan por medio de las guías clínicas, al recoger éstas la evidencia científica disponible.The pathophysiological foundations justifying calcium and vitamin D supplements in osteoporosis are supported by extensive scientific evidence that has been obtained through several randomized clinical trials and subsequent meta‐analyzes that have shown a statistically significant and clinically relevant reduction in the risk of osteoporotic fractures. This evidence has led to its recommendation by several scientific societies interested in the management of osteoporosis. In order to optimize the efficacy and the benefit/risk balance of these, calcium and vitamin D should be administered together with the drugs that are prescribed for the treatment of osteoporosis, since calcium and vitamin D have been used in all these reference studies, both in the arm that receives the drug and also in the placebo arm. The most commonly used calcium salt is carbonate and the metabolite of vitamin D, cholecalciferol or vitamin D 3. There is no consensus or conclusive scientific evidence on the dose to be used in vitamin D deficiency associated with osteoporosis. However, the trend has always been to increase these amounts, from the 400 IU recommended 30 years ago to the 2,000 IU daily today. We will review in this article which recommendations are made by means of the clinical guidelines, as they collect the available scientific evidence

Hipercalcemia y enfermedades autoinmunes

La hipercalcemia es un trastorno hidroelectrolítico muy frecuente en la práctica clínica diaria. Se define como la presencia de una concentración sérica de calcio superior a 2 desviaciones típicas del valor medio del laboratorio, el cual habitualmente es 10,6 mg/dL1. (extracto

Valoración de la capacidad predictiva de la calculadora Garvan del riesgo de fractura a 10 años en una población española

Introduction: Several calculation tools or scales have been developed in recent years to assess the risk of fracture due to long-term fragility. The Garvan calculator has not been validated in the Spanish population. This study aims to observe their predictive capacity in a population sample of the Canary Islands and, therefore, of the Spanish population. Material and Methods: We included 121 patients who were followed up for 10 years in our consultations. All were assessed the risk of fracture using the Garvan calculator and based on the data obtained in the first visit. Results: Of the 121 patients, 30 suffered at least one osteoporotic fracture over the 10-year follow-up period. The group of patients with fractures had on the Garvan scale an average risk value to suffer any fracturing fracture of 27%, compared to 13% of those who did not suffer fracture (p<0.001). The area under the corresponding ROC curve was 0.718 (CI-95% = 0.613 ; 0.824). Based on this, the estimated optimal cut-off point to consider a high risk fracture was 18.5%. This value corresponded to a sensitivity of 0.67 (CI-95% = 0.47 ; 0.83) and a specificity of 0.67 (CI-95% = 0.56 ; 0.77). Conclusions: Our results show that the Garvan scale adequately predicts the risk of 10-year osteoporotic fracture in our population. A value lower than 18.5% would allow us to establish a low fracture risk and could be used as a screening tool.Introducción: En los últimos años se han desarrollado varias herramientas de cálculo o escalas para valorar el riesgo de fractura por fragilidad a largo plazo. La calculadora Garvan no ha sido validada en la población española. El objetivo de este estudio fue observar su capacidad predictiva en una muestra de la población canaria y, por tanto, de la española. Material y métodos: Se incluyó a 121 pacientes a los que se les realizó un seguimiento de 10 años en nuestras consultas. A todos se les valoró el riesgo de fractura usando la calculadora Garvan y basándonos en los datos obtenidos en la primera visita realizada. Resultados: De los 121 pacientes, 30 sufrieron al menos una fractura osteoporótica a lo largo de los 10 años de seguimiento. El grupo de pacientes fracturados tenían en la escala Garvan un valor medio de riesgo de sufrir cualquier fractura por fragilidad de 27%, frente al 13% de aquellos que no sufrieron fractura (p<0,001). El área bajo la correspondiente curva ROC fue de 0,718 (IC-95% = 0,613 ; 0,824). En base a ella, se estimó que el punto de corte óptimo para considerar un alto riesgo de fractura por fragilidad fue 18,5%. A este valor le correspondió una sensibilidad de 0,67 (IC-95% = 0,47 ; 0,83) y una especificidad de 0,67 (IC-95% = 0,56 ; 0,77). Conclusiones: Nuestros resultados muestran que la escala Garvan predice adecuadamente el riesgo de fractura osteoporótica a 10 años en nuestra población. Un valor inferior a 18,5% permitiría establecer un riesgo de fractura bajo, pudiendo ser utilizada como herramienta de cribado

Bone metabolism and clinical study of 44 patients with bisphosphonate-related osteonecrosis of the jaws

Osteonecrosis of the jaws is a clinical entity described and linked to treatment with bisphosphonates in 2003. Its real incidence is unknown and it could increase due to the large number of patients treated with these drugs, and its cumulative effect on the bone. State of the art knowledge regarding its etiopathogeny, clinical course and suitable treatments is limited. Objectives: To study the clinical characteristics of 44 patients with bisphosphonate-related osteonecrosis of the jaws and the state of their bone mineral metabolism: bone remodeling state, prevalence of fractures, bone mineral density study, and assessment of the different treatment strategies. Design of the Study: Observational. Information was gathered prospectively through interviews, clinical examinations, additional tests and review of medical records. Results: We studied 16 men and 28 women with a mean age of 64.7 years. Breast cancer was the most frequent underlying disease. Zoledronate was used in 82% of the cases and in the non-oncology group of patients; alendronate was the most frequently used bisphosphonate. The mean duration of the zoledronate and alendronate treatments was 25 months and 88 months respectively. The lower jaw was the most frequent location, and previous exodontias- among the triggering factors known-were the most closely linked to its onset. We found considerable osteoblastic activity in patients suffering from neoplasia, with artifacts present in their bone densitometry and a high percentage of vertebral fractures. Conclusions: According to our results, osteonecrosis of the jaws affects elderly patients. We found a direct relationship between the duration of exposure and the accumulated dose. Other relevant factors are: Poor oral and dental health, corticoids, diabetes and teeth extractions. In essence, it is a clinical diagnosis. Prevention is the best strategy to handle this clinical entity

Multiple vertebral fractures after suspension of denosumab. A series of 56 cases

Background: Denosumab is a monoclonal antibody approved for the treatment of postmenopausal osteoporosis. The withdrawal of denosumab produces an abrupt loss of bone mineral density and may cause multiple vertebral fractures (MVF). Objective: The objective of this study is to study the clinical, biochemical, and densitometric characteristics in a large series of postmenopausal women who suffered MVF after denosumab withdrawal. Likewise, we try to identify those factors related to the presence of a greater number of vertebral fractures (VF). Patients and methods: Fifty-six patients (54 women) who suffered MVF after receiving denosumab at least for three consecutive years and abruptly suspended it. A clinical examination was carried out. Biochemical bone remodelling markers (BBRM) and bone densitometry at the lumbar spine and proximal femur were measured. VF were diagnosed by magnetic resonance imaging MRI, X-ray, or both at dorsal and lumbar spine. Results: Fifty-six patients presented a total of 192 VF. 41 patients (73.2%) had not previously suffered VF. After discontinuation of the drug, a statistically significant increase in the BBRM was observed. In the multivariate analysis, only the time that denosumab was previously received was associated with the presence of a greater number of VF (P = .04). Conclusions: We present the series with the largest number of patients collected to date. 56 patients accumulated 192 new VF. After the suspension of denosumab and the production of MVF, there was an increase in the serum values of the BBRM. The time of denosumab use was the only parameter associated with a greater number of fractures

Influence of non-osteoporotic treatments in patients on active anti-osteoporotic therapy: evidence from the OSTEOMED registry

Producción CientíficaPurpose To evaluate the effect of different non-osteoporotic drugs on the increase or decrease in the risk of incident fragility fractures (vertebral, humerus or hip) in a cohort of patients diagnosed with osteoporosis on active anti-osteoporotic therapy. Methods For this retrospective longitudinal study, baseline and follow-up data on prescribed non-osteoporotic treatments and the occurrence of vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression models. The drugs evaluated with a possible beneficial effect were thiazides and statins, while the drugs evaluated with a possible harmful effect were antiandrogens, aromatase inhibitors, proton pump inhibitors, selective serotonin reuptake inhibitors, benzodiazepines, GnRH agonists, thyroid hormones, and oral and inhaled corticosteroids. Results Logistic regression analyses indicated that no treatment significantly improved fracture risk, with the only treatments that significantly worsened fracture risk being letrozole (OR = 0.18, p-value = 0.03) and oral corticosteroids at doses ≤ 5 mg/ day (OR = 0.16, p-value = 0.03) and > 5 mg/day (OR = 0.27, p-value = 0.04). Conclusion The potential beneficial or detrimental effects of the different drugs evaluated on fracture risk are masked by treatment with anabolic or antiresorptive drugs that have a more potent action on bone metabolism, with two exceptions: letrozole and oral corticosteroids. These findings may have important clinical implications, as patients receiving these treat- ments are not fully protected by bisphosphonates, which may imply the need for more potent anti-osteoporotic drugs such as denosumab or teriparatide.Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCL

Timing of surgery for hip fracture and in-hospital mortality: a retrospective population-based cohort study in the Spanish National Health System

<p>Abstract</p> <p>Background</p> <p>While the benefits or otherwise of early hip fracture repair is a long-running controversy with studies showing contradictory results, this practice is being adopted as a quality indicator in several health care organizations. The aim of this study is to analyze the association between early hip fracture repair and in-hospital mortality in elderly people attending public hospitals in the Spanish National Health System and, additionally, to explore factors associated with the decision to perform early hip fracture repair.</p> <p>Methods</p> <p>A cohort of 56,500 patients of 60-years-old and over, hospitalized for hip fracture during the period 2002 to 2005 in all the public hospitals in 8 Spanish regions, were followed up using administrative databases to identify the time to surgical repair and in-hospital mortality. We used a multivariate logistic regression model to analyze the relationship between the timing of surgery (< 2 days from admission) and in-hospital mortality, controlling for several confounding factors.</p> <p>Results</p> <p>Early surgery was performed on 25% of the patients. In the unadjusted analysis early surgery showed an absolute difference in risk of mortality of 0.57 (from 4.42% to 3.85%). However, patients undergoing delayed surgery were older and had higher comorbidity and severity of illness. Timeliness for surgery was not found to be related to in-hospital mortality once confounding factors such as age, sex, chronic comorbidities as well as the severity of illness were controlled for in the multivariate analysis.</p> <p>Conclusions</p> <p>Older age, male gender, higher chronic comorbidity and higher severity measured by the Risk Mortality Index were associated with higher mortality, but the time to surgery was not.</p

Cholecalciferol or Calcifediol in the Management of Vitamin D Deficiency

Vitamin D deficiency is a global health problem due to its high prevalence and its negative consequences on musculoskeletal and extra-skeletal health. In our comparative review of the two exogenous vitamin D supplementation options most used in our care setting, we found that cholecalciferol has more scientific evidence with positive results than calcifediol in musculoskeletal diseases and that it is the form of vitamin D of choice in the most accepted and internationally recognized clinical guidelines on the management of osteoporosis. Cholecalciferol, unlike calcifediol, guarantees an exact dosage in IU (International Units) of vitamin D and has pharmacokinetic properties that allow either daily or even weekly, fortnightly, or monthly administration in its equivalent doses, which can facilitate adherence to treatment. Regardless of the pattern of administration, cholecalciferol may be more likely to achieve serum levels of 25(OH)D (25-hydroxy-vitamin D) of 30&ndash;50 ng/mL, an interval considered optimal for maximum benefit at the lowest risk. In summary, the form of vitamin D of choice for exogenous supplementation should be cholecalciferol, with calcifediol reserved for patients with liver failure or severe intestinal malabsorption syndromes