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)

Vitamin D Endocrine System and COVID-19: Treatment with Calcifediol.

The COVID-19 pandemic is the greatest challenge facing modern medicine and public health systems. The viral evolution of SARS-CoV-2, with the emergence of new variants with in-creased infectious potential, is a cause for concern. In addition, vaccination coverage remains in-sufficient worldwide. Therefore, there is a need to develop new therapeutic options, and/or to optimize the repositioning of drugs approved for other indications for COVID-19. This may include the use of calcifediol, the prohormone of the vitamin D endocrine system (VDES) as it may have potential useful effects for the treatment of COVID-19. We review the aspects associating COVID-19 with VDES and the potential use of calcifediol in COVID-19. VDES/VDR stimulation may enhance innate antiviral effector mechanisms, facilitating the induction of antimicrobial peptides/autophagy, with a critical modulatory role in the subsequent host reactive hyperinflammatory phase during COVID-19: By decreasing the cytokine/chemokine storm, regulating the renin-angiotensin-bradykinin system (RAAS), modulating neutrophil activity and maintaining the integrity of the pulmonary epithelial barrier, stimulating epithelial repair, and directly and indirectly decreasing the increased coagulability and prothrombotic tendency associated with severe COVID-19 and its complications. Available evidence suggests that VDES/VDR stimulation, while maintaining optimal serum 25OHD status, in patients with SARS-CoV-2 infection may significantly reduce the risk of acute respiratory distress syndrome (ARDS) and severe COVID-19, with possible beneficial effects on the need for mechanical ventilation and/or intensive care unit (ICU) admission, as well as deaths in the course of the disease. The pharmacokinetic and functional characteristics of calcifediol give it superiority in rapidly optimizing 25OHD levels in COVID-19. A pilot study and several observational intervention studies using high doses of calcifediol (0.532 mg on day 1 and 0.266 mg on days 3, 7, 14, 21, and 28) dramatically decreased the need for ICU admission and the mortality rate. We, therefore, propose to use calcifediol at the doses described for the rapid correction of 25OHD deficiency in all patients in the early stages of COVID-19, in association, if necessary, with the new oral antiviral agents.

Vitamin D: Before, during and after Pregnancy: Effect on Neonates and Children.

A worldwide high prevalence of vitamin D (VD) deficiency has become of growing concern because of potential adverse effects on human health, including pregnant women and their offsprings. Beyond its classical function as a regulator of calcium and phosphate metabolism, together with its fundamental role in bone health in every stage of life, its deficiency has been associated to multiple adverse health effects. The classic effects of VD deficiency in pregnancy and neonates have been late hypocalcemia and nutritional rickets. Nevertheless, recent studies have linked VD to fertility and 25(OH)D with several clinical conditions in pregnancy: preeclampsia, gestational diabetes, higher incidence of cesarean section and preterm birth, while in infants, the clinical conditions are low birth weight, lower bone mass and possible relationship with the development of such diseases as bronchiolitis, asthma, type 1 diabetes, multiple sclerosis and autism included as VD non-classical actions. The supplementation with Vitamin D and achievement of optimal levels reduce maternal-fetal and newborn complications. Supplementation in children with VD deficiency reduces the risk of respiratory infections and possibly autoimmune diseases and autism. This review emphasizes the roles of Vitamin D deficiency and the consequences of intervention from preconception to infancy.

The relationship between 25(OH) vitamin D levels and COVID-19 onset and disease course in Spanish patients.

OBJECTIVE: Currently, there are no definitive data on the relationship between low levels of vitamin D in the blood and a more severe disease course, in terms of the need for hospital admission, intensive care unit (ICU) stay, and mortality, in patients with coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to study the association between levels of circulating 25-hydroxyvitamin D (25(OH)D) and adverse clinical outcomes linked to SARS-CoV-2 infection. We further aimed to observe the incidence of low, below-average, and normal levels of 25(OH)D in patients hospitalized for COVID-19 between March 12, 2020, and May 20, 2020, and assess whether these values differed between these patients and a normal population. Finally, we determined whether the need for transfer to the intensive care unit (ICU) and the mortality rate were related to low levels of 25(OH)D. STUDY DESIGN: Retrospective observational study. SETTING: Quironsalud Hospitals in Madrid, Spain. PARTICIPANTS: We analyzed 1549 patients (mean age, 70 years; range, 21-104 years); 835 were male (53.9 %; mean age, 73.02 years), and 714 were female (46.1 %; mean age, 68.05 years). Subsequently, infected patients admitted to the ICU (n = 112) and those with a fatal outcome (n = 324) were analyzed. PROCEDURES: Serum concentrations of 25(OH)D were measured by electrochemiluminescence. RESULTS: More hospitalized patients (66 %, n = 1017) had low baseline levels of 25(OH)D (<20 ng/mL) than normal individuals (45 %) (p < 0.001). An analysis by age group revealed that COVID-19 patients between the ages of 20 and 80 years old had significantly lower vitamin D levels than those of the normal population (p < 0.001). Patients admitted to the ICU tended to have lower levels of 25(OH)D than other inpatients (p < 0.001); if we stratified patients by 25(OH)D levels, we observed that the rate of ICU admission was higher among patients with vitamin D deficiency (p < 0.001), indicating that higher vitamin D levels are associated with a lower risk of ICU admission due to COVID-19. ICU admission was related to sex (higher rates in men, p < 0.001) and age (p < 0.001). When using a logistic regression model, we found that vitamin D levels continued to show a statistically significant relationship with ICU admission rates, even when adjusting for sex and age. Therefore, the relationship found between vitamin D levels and the risk of ICU admission was independent of patient age and sex in both groups. Deceased patients (n = 324 tended to have lower levels of 25 (OH)D that normal population of the same age (p < 0.001). CONCLUSION: Vitamin D deficiency in patients with COVID-19 is correlated with an increased risk of hospital admission and the need for critical care. We found no clear relationship between vitamin D levels and mortality.

Vitamina d, sus acciones "no clásicas" y su utilidad en la pandemia del covid-19 / Vitamin d, its "non-classic" actions and it utility in the covid-19 pandemic

RESUMEN El descubrimiento de que la síntesis de 1,25 vitamina D no fue solo renal, la enzima 1 alfa hidroxilasa se encuentra en numerosos tejidos del organismo, además de la evidencia de que la asociación entre el déficit de vitamina D y la presencia de enfermedades no óseas (cáncer, esclerosis múltiple, enfermedades autoinmunes, etc.) nos ofrece la posibilidad de intentar prevenir estas afecciones. Los estudios de suplementación contra placebo no han dado resultados positivos para algunas afecciones, aunque algunos de esos trials se realizaron en población "suficiente" y no "deficiente" de vitamina D. Sin embargo, otros metaanálisis han demostrado prevención en los grupos suplementados con déficit para algunas patologías (infecciones respiratorias, prediabetes). Además, existe evidencia de efecto antiviral de la misma. La acción antiinfecciosa e inmunomoduladora que ejerce y su efecto sobre el sistema renina angiotensina, estimulando la enzima convertidora de angiotensina 2 (que es el receptor virus del SARS-CoV), permiten sospechar, actualmente, que con niveles elevados podría ser más difícil, o menos grave, la infección por COVID-19. La suplementación con vitamina D es conveniente para prevenir enfermedades en sujetos con déficit, pero en medio de la grave pandemia 2020 administrarla, aún sin tener un dosaje previo en las poblaciones de mayor riesgo, podría disminuir la chance de esta enfermedad.

ABSTRACT The discovery that the synthesis of 1-25-vitamin D is not only renal and that the enzyme 1 alpha hydroxylase is found in numerous tissues of the body, together with the evidence of the association between vitamin D deficiency and the presence of non-bone diseases (cancer, multiple sclerosis, autoimmune diseases, etc.), gives us the possibility of trying to prevent these conditions. Placebo-controlled supplementation studies have not provided positive results for certain conditions, but some of these trials have been carried out on populations with "sufficient" and not "deficient" vitamin D levels. However, other meta-analyses have shown prevention of some conditions (respiratory infections, prediabetes) in groups of patients with deficiencies who were given supplements. There is also evidence of antiviral effect of vitamin D. Its anti-infective and immunomodulatory action and its effect upon the renin-angiotensin system, stimulating the angiotensin-converting enzyme 2 (the SARS-CoV virus receptor), nowadays allow us to think that, in high levels, COVID-19 infection could be less likely or serious. Vitamin D supplementation is adequate for preventing diseases in patients with deficiencies; administering vitamin D within the 2020 pandemic, even without having tested it in high-risk populations, could diminish the incidence of this disease.

El suplemento con altas dosis de vitaminaD podría representar una alternativa promisoria para prevenir o tratar la infección por COVID-19 / Vitamin D high doses supplementation could represent a promising alternative to prevent or treat COVID-19 infection

Si bien carecemos de suficiente evidencia que justifique suplementar con vitaminaD en la prevención y/o tratamiento de la infección por COVID-19, a la fecha resulta cada vez más factible que esta hipótesis sea válida. Dos mecanismos básicos generales deberían ser considerados. Uno sería la acción antiinfecciosa e inmunomoduladora que ejerce mejorando las barreras intercelulares por estímulo de la inmunidad innata, así también por modulación de la inmunidad adaptativa. También, la vitaminaD reduce la producción de citoquinas inflamatorias como IL-2 e interferón gamma (INF-γ). Más recientemente se han demostrado múltiples efectos pleiotrópicos sobre las acciones de la vitaminaD a nivel antiinflamatorio e inmunomodulador. Esto explica resultados positivos en estudios con influenza, coronavirus y otras infecciones respiratorias. Se ha descrito relación inversa entre niveles séricos de vitaminaD y prevalencia de patología infecciosa respiratoria. De interés, otro abordaje mecanístico responde a considerar la inhibición del sistema renina-angiotensina-aldosterona, que se exacerba en la infección por COVID-19 debido a que el virus se une a la enzima ECA2, quedando disponible más angiotensinaII para causar daño. La vitaminaD inhibe mediadores del SRAA -presente en todas las células del organismo-, y al inhibir la actividad ECA y aumentar la ECA2, disminuye los niveles de angiotensinaII. Presentamos estudios con propuestas de dosis recomendadas de vitaminaD, y aunque no quede concretada una única guía, los posibles beneficios son promisorios. Finalmente, el propósito de la presente revisión es compartir esta idea con profesionales de la salud para encender el debate y llamar a la reflexión crítica, de modo tal que se pueda contribuir con el emprendimiento de diseños clínicos adecuados para validar los beneficios de utilizar altas dosis de vitaminaD en beneficio de la salud pública, sobre todo en tiempos de esta emergencia por COVID-19

Although we lack enough evidence to justify supplementing with vitaminD in the prevention and treatment of COVID-19 infection, it is increasingly feasible that this hypothesis is valid. Two general underlying mechanisms should be considered. One would be the anti-infectious and immunomodulatory action that it exerts by improving intercellular barriers by stimulating innate immunity, as well as by modulating adaptive immunity. Also, vitaminD reduces the production of inflammatory cytokines, such as IL-2 and interferon-gamma (INF-γ). More recently, multiple pleiotropic effects have been demonstrated on the actions of vitaminD at the anti-inflammatory and immunomodulatory level with positive results in studies with influenza, coronavirus, and other respiratory infections. An inverse relationship between serum vitaminD levels and the prevalence of the respiratory infectious disease has been described. Of interest, another mechanistic approach responds to considering the inhibition of the renin-angiotensin-aldosterone system (RAAS), which is exacerbated in COVID-19 infection because the virus binds to the enzyme ACE2, making more angiotensinII available to cause damage. VitaminD inhibits mediators of RAAS - present in all cells of the body - and by inhibiting ACE activity and increasing ACE2, it lowers angiotensinII levels. We present studies with proposals for recommended doses of vitaminD, and although a single guideline is not specified, the possible benefits are promising. Finally, the purpose of this review is to share this idea with health professionals to ignite the debate and call for critical reflection, so that it can contribute to the undertaking of more and better clinical designs to validate the benefits of using high doses of vitaminD for the benefit of public health and especially in times of crisis for COVID-19

Vitamin D high doses supplementation could represent a promising alternative to prevent or treat COVID-19 infection. / El suplemento con altas dosis de vitaminaD podría representar una alternativa promisoria para prevenir o tratar la infección por COVID-19.

Although we lack enough evidence to justify supplementing with vitaminD in the prevention and treatment of COVID-19 infection, it is increasingly feasible that this hypothesis is valid. Two general underlying mechanisms should be considered. One would be the anti-infectious and immunomodulatory action that it exerts by improving intercellular barriers by stimulating innate immunity, as well as by modulating adaptive immunity. Also, vitaminD reduces the production of inflammatory cytokines, such as IL-2 and interferon-gamma (INF-γ). More recently, multiple pleiotropic effects have been demonstrated on the actions of vitaminD at the anti-inflammatory and immunomodulatory level with positive results in studies with influenza, coronavirus, and other respiratory infections. An inverse relationship between serum vitaminD levels and the prevalence of the respiratory infectious disease has been described. Of interest, another mechanistic approach responds to considering the inhibition of the renin-angiotensin-aldosterone system (RAAS), which is exacerbated in COVID-19 infection because the virus binds to the enzyme ACE2, making more angiotensinII available to cause damage. VitaminD inhibits mediators of RAAS - present in all cells of the body - and by inhibiting ACE activity and increasing ACE2, it lowers angiotensinII levels. We present studies with proposals for recommended doses of vitaminD, and although a single guideline is not specified, the possible benefits are promising. Finally, the purpose of this review is to share this idea with health professionals to ignite the debate and call for critical reflection, so that it can contribute to the undertaking of more and better clinical designs to validate the benefits of using high doses of vitaminD for the benefit of public health and especially in times of crisis for COVID-19.

Osteonecrosis de los maxilares asociada a medicamentos (ONMM): guía redactada por expertos invitados por la Asociación Argentina de Osteología y Metabolismo Mineral y por la Sociedad Argentina de Osteoporosis / Medication-related osteonecrosis of the jaw (MRONJ): guideline prepared by experts invited by the Argentine Association of Osteology and Mineral Metabolism, and the Argentine Society for Osteoporosis

La osteonecrosis maxilar asociada a medicamentos (ONMM=MRONJ como se conoce en la literatura en inglés) se define como un área ósea expuesta al medio bucal con más de ocho semanas de permanencia, en pacientes tratados con antirresortivos y/o antiangiogénicos y sin antecedentes de radioterapia en cabeza y cuello. Las fracturas ocasionan una morbimortalidad significativa y los antirresortivos son drogas eficaces y seguras para prevenirlas. Se utilizan principalmente en osteoporosis, pero también en enfermedades oncológicas como mieloma múltiple o metástasis óseas de tumores sólidos. La posología varía según el contexto clínico, siendo mayor la dosis y frecuencia de administración en oncología. Los antirresortivos actualmente más utilizados son los bifosfonatos (BF) y el denosumab (Dmab). Si bien los BF persisten largo tiempo en el tejido óseo, el Dmab tiene un mecanismo de acción reversible y su suspensión abrupta conlleva importante pérdida de masa ósea y riesgo aumentado de fracturas vertebrales múltiples. Ninguna droga puede ser suspendida ni espaciada sin autorización médica, dado que no es de competencia del odontólogo. El diagnóstico presuntivo de ONMM debe ser confirmado clínicamente por un odontólogo, quien solicitará imágenes radiológicas para establecer el estadio de la lesión. La anamnesis correcta permite establecer un diagnóstico diferencial entre ONMM, osteomielitis y osteorradionecrosis. La presentación clínica es variable y puede mostrar distintos estadios. La mayoría de los casos están precedidos por un procedimiento quirúrgico odontológico. Suele ser asintomática, aunque puede haber dolor si se localiza cerca de una estructura neuronal. La localización es variable: 62,3% se produce en el maxilar inferior. La incidencia de ONMM es baja, en un rango de 0,001 a 0,01% y tiene relación con las dosis y el tiempo de administración. La remoción de caries, la operatoria dental, la endodoncia y la rehabilitación protética fija o removible no se asocian a riesgo de ONMM. Con menos de 3 años de tratamiento antirresortivo se pueden efectuar terapéuticas quirúrgicas como exodoncias, apicectomías, cistectomías, tratamientos periodontales de raspaje y alisado subgingival sin riesgo. Con más de 3 años se aconseja evitar la realización de exodoncias y manipulación de tejido óseo. Ante la necesidad de realizar un procedimiento odontológico, no hay evidencia que avale que la suspensión transitoria del tratamiento antirresortivo pueda reducir el riesgo. Tampoco la medición de marcadores de remodelado óseo aporta datos de utilidad. Existen pocos datos en la literatura sobre la colocación de implantes dentales en pacientes que reciben drogas antirresortivas en dosis bajas; si bien existe ONMM asociada, su incidencia sería baja. Antes de iniciar un tratamiento antirresortivo se recomienda realizar interconsulta con el odontólogo para evaluar potenciales necesidades quirúrgicas. Quienes reciben antirresortivos deben realizar controles orales periódicos (semestrales) y, ante cualquier síntoma compatible con un estadio incipiente de ONMM, deben consultar a su odontólogo. El trabajo conjunto del médico y el odontólogo puede prevenir la aparición de la ONMM, un evento infrecuente, pero que puede generar elevada morbilidad en los pacientes. La comunicación fluida entre profesionales tenderá a evitar no solo la incertidumbre y desconfianza de los pacientes, sino también que se produzcan lesiones con la consecuente necesidad de tratamientos de mayor complejidad. (AU)

Medication-Related Osteonecrosis of the Jaw (MRONJ) is defined as a bone area exposed to the oral environment lasting more than eight weeks, in patients treated with antiresorptive and/or antiangiogenic drugs and without a history radiation therapy to the head and neck. Fractures cause significant morbidity and mortality, and antiresorptives are effective and safe drugs to prevent them. They are used to treat not only osteoporosis but also oncological diseases such as multiple myeloma or bone metastases from solid tumors. The dosage varies according to the clinical context; doses and frequencies of administration are higher in oncology. The most commonly used antiresorptive medications are bisphosphonates (BP) and denosumab (Dmab). Whereas BP persist for a long time in bone tissue, Dmab has a reversible mechanism of action and its discontinuation leads to significant loss of bone mass and an increased risk of multiple vertebral fractures. No drug can be suspended or spaced without medical authorization. Dentists should not take decisions about antiresorptive prescription. The presumptive diagnosis of MRONJ must be clinically confirmed by a dentist, who will order radiological studies to establish the stage of the injury. The correct anamnesis helps differentiate MRONJ from osteomyelitis and osteoradionecrosis. Clinical presentation is variable and can present different stages. Most of the cases are preceded by a dental surgical procedure. Usually MRONJ is asymptomatic although patients may feel pain if it is located near a neuronal structure. The location is variable: 62.3% occurs in the lower jaw. The incidence of MRONJ is low, in the range of 0.001 to 0.01%, and is related to the dose and time of administration. Caries removal, dental surgery, endodontics, fixed or removable prosthetic rehabilitation are not associated with risk of MRONJ. With less than 3 years of antiresorptive treatment, surgical therapies such as extractions, apicectomies, cystectomies, periodontal scaling treatments and subgingival smoothing can be performed without risk. With more than 3 years, it is advisable to avoid performing extractions and manipulating bone tissue. Given the need to perform a dental procedure, there is no evidence to support that the temporary suspension of antiresorptive treatment can reduce the risk. Nor does the measurement of bone turnover markers provide useful information. There are few data in the literature on the placement of dental implants in patients receiving antiresorptive drugs at low doses; although there might be an associated risk of MRONJ, its incidence appears to be low. Before starting antiresorptive treatment, consultation with the dentist is recommended to evaluate potential surgical needs. Patients receiving treatment with antiresorptive agents should undergo periodic oral controls (every six months) and in the event of any symptoms compatible with an early MRONJ stage, they should consult their dentists. The collaboration between physician and dentist can prevent the appearance of MRONJ, that is an infrequent event, but can generate high morbidity in patients. Fluid communication between professionals will tend to avoid, not only the uncertainty and distrust of patients, but also the occurrence of injuries needing complex treatments. (AU)

Miopatía por estatinas y vitamina D / Statin-Related Myopathy and Vitamin D

Las estatinas son fármacos habitualmente seguros y bien tolerados, muy eficaces para la prevención de trastornos cardiovasculares. La presencia de mialgias, poco frecuente, pero con incidencia dispar en diversos reportes, es una de las causas de abandono de su uso. También las distintas denominaciones (mialgia, miopatía, rabdomiólisis) y la subjetividad de cada paciente para referirlas han creado confusión en el tema. Se ha comenzado a reportar asociación entre niveles de vitamina D sérica disminuida y mayor riesgo de miopatía, por un lado, y trabajos donde pacientes que las abandonaban a causa de mialgias, con deficiencia de vitamina D, pueden tolerarlas una vez que se suplementa la vitamina hasta valores deseables. La presencia de polimorfismos en genes de enzimas que metabolizan o transportan a las estatinas es otro factor claramente relacionado con miopatía. Es posible que el déficit de vitamina D deba ser considerado un factor de riesgo para desarrollar miopatía por estatinas, como lo serían también la administración simultánea de fármacos que se metabolizan por la misma vía de citocromo P450, o la presencia de los polimorfismos mencionados. En conclusión, el hallazgo de tener deficiencia de vitamina D se asocia a miopatía por estatinas, o que es un factor de riego para desarrollarla, abre nuevas perspectivas para un gran número de pacientes que abandonan este tratamiento debido a esta patología. (AU)

Statins are usually safe and well tolerated drugs, very effective for preventing cardiovascular complications. The rare presence of myalgia, with different incidence as reported by several studies, is one of the causes of lack of drug compliance. Also the different symptoms referred (myalgia, myopathy, rhabdomyolysis) and the lack of objetivity of each patient when referring to the symptoms, have created confusion in this matter. Associations between decreased vitamin D levels and increased risk of myopathy has been reported. Indeed, studies describing patients with vitamin D deficiency who are not compliant due to myalgia show that they become tolerant to the drugs once the vitamin is supplemented to desirable values. The presence of gene polymorphisms for enzymes that metabolize or transport statins is another factor clearly related to myopathy. Therefore, we should consider vitamin D deficiency and other conditions such as the simultaneous administration of drugs that are metabolized by the same cytochrome P450 pathway, or the presence of mentioned polymorphisms as a risk factor for developing myopathy due to statins. In conclusion, the finding that vitamin D deficiency is associated with statin myopathy, or is a risk factor its develpoment, opens new perspectives for a large number of patients who leave this treatment due to this condition. (AU)

Incidentalomas paratiroideos: un nuevo diagnóstico, un nuevo problema. Prevalencia en Argentina / Parathyroid incidentaloma: a new diagnosis, a new problem. Prevalence in Argentina

Los incidentalomas paratiroideos (IP) fueron descriptos como hallazgos intraquirúrgicos y luego en estudios ecográficos de tiroides. Escasos estudios se han realizado, por lo que su incidencia no es clara. Más aún, la presencia de una imagen hipoecogénica en topografía paratiroidea puede también ser tejido tiroideo o linfático. Se evaluaron retrospectivamente las historias clínicas de 7 años buscando los pacientes en los que se diagnosticó un IP durante una ecografía tiroidea. Se diagnosticó IP en 24 pacientes (4,0% del total). Tenían hipotiroidismo autoinmune 21 pacientes y nódulos tiroideos 3 pacientes. En 10 casos la lesión fue única y en 14 eran 2 o más. En la evolución se repitió la ecografía en 13 pacientes, hallando imágenes similares a la primera en todas. La calcemia y la PTH fueron normales en 23 pacientes, pero en una de ellas, con una imagen de 6 mm, hubo PTH levemente elevada con calcemia normal, que luego se elevó, y se diagnosticó adenoma paratiroideo. El hallazgo de IP parece cada vez más frecuente; nuestra incidencia del 4% como imágenes compatibles (sin confirmar la naturaleza paratiroidea) es más alta que las escasas publicaciones existentes sobre el tema. Es posible que muchas no presenten cambios ni ecográficos ni de laboratorio, pero otros casos, como el hallado en una de nuestras 24 pacientes, pueden ser un estadio inicial de hiperparatiroidismo primario, por lo que el seguimiento es aconsejable.

Parathyroid incidentalomas (PI) were first described as intraoperative findings and then in ultrasound thyroid scan studies. Few studies have been performed to investigate this, so their incidence is unclear. Moreover, the presence of a hypo-echogenic image in parathy- roid topography may also be thyroid or lymphatic tissue. A retrospective evaluation was performed on the seven-year clinical records of patients in whom a PI was diagnosed during a thyroid ultrasound scan. PI was diagnosed in 24 patients (4.0%). Twenty one patients had autoimmune hypothyroidism and 3 patients had thyroid nodules. In 10 cases the lesion was unique, and in 14 cases there were two or more lesions. During follow-up, ultrasound was repeated in 13 patients, and all showe findings. Serum calcium and PTH were normal in 23 patients, but in one of them, with an image of a lesion of 6 mm, PTH was slightly elevated, with normal serum calcium. Later, hypercalcaemia was detected and a parathyroid adenoma was diagnosed. The incidence of PI seems to be increasing, with our rate of 4% of compatible images (without confirming the parathyroid origin of the lesion) is higher than that reported in the few existing publications on the subject. Many patients with PI may not present with biochemical abnormalities, but as our experience shows, these lesions may represent the first stage of primary hyperparathyroidism; therefore careful follow-up is advisable.

Evaluación de la respuesta densitométrica en pacientes con osteoporosis posmenopáusica tratadas con ranelato de estroncio o denosumab / Densitometric response in postmenopausal osteoporosis treated with strontium ranelate or denosumab

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)

Insulin resistance and familial history of breast cancer

Objetivo: Analizar si la resistencia a la insulina (IR) se asocia a un riesgo incrementado de cáncer de mama (CM). No se ha encontrado hasta el momento los principales genes de CM familiar de bajo a moderado riesgo. Nuestra hipótesis es que se relacionan con la IR. Para evaluarla estudiamos la relación de la IR con la historia familiar de CM de bajo a moderado riesgo (AF+CM). Pacientes y método: Se estudió a 846 mujeres sanas, premenopáusicas, con edades entre 18 y 50 años, IMC 18-39,9, sin (NOC) y con (OC) obesidad central (perímetro de cintura >= 88 cm), con (AF+CM) y sin (AF­CM) antecedentes familiares de CM. De las 494 mujeres NOC, 108 tenían AF+CM y 386 no los tenían; y de 352 mujeres OC, 103 tenían AF+CM y 249 no los tenían. Resultados: Las mujeres NOC con AF+CM presentaron mayor frecuencia de IR (HOMA > 2,5 o insulina posprandial > 60 µUI/ml) (odds ratio [OR] = 4,26; intervalo de confianza [IC] del 95%, 2,04-8,83; p = 200 mg/dl) (OR = 1,78; IC del 95%, 1,09-2,90; p = 0,01), triglicéridos (TG) elevados (>= 150 mg/dl) (OR = 3,23; IC del 95%, 2,32-4,49; p 3,2) (OR = 4,45; IC del 95%, 1,80-10,98; p 36,5 cm (OR = 4,25; IC del 95%, 1,76-10,27; p 36,5 cm (OR = 2,08; IC del 95%, 1,28-3,39; p = 0,01). En ambos grupos las glucemias basales y posprandiales y la frecuencia de acrocordones resultaron significativamente más elevadas en AF+CM. Conclusiones: Describimos una asociación entre la historia familiar de CM de bajo y moderado riesgo y el síndrome de resistencia a la insulina hasta el momento no descrita (AU)

Objective: Insulin resistance has been linked to an increased risk of breast cancer. The main genes involved in low- to moderate-risk familial breast cancer remain to be identified. To test the hypothesis that there may be a genetic influence in insulin resistance, the present study analyzed the association of a familial history of breast cancer (low-to-moderate risk, defined as having a positive familial history of breast cancer) with insulin resistance. Patients and method: We studied 846 healthy premenopausal women with no central obesity (NCO) (waist circumference = 88 cm), aged 18-50 years, body mass index 18-39.9, with and without a familial history of breast cancer. There were 494 women with NCO (108 with a positive familial history and 386 without) and 352 women with CO (103 with a positive familial history and 249 without). Results: NCO women with a positive familial history for breast cancer showed a significantly higher frequency of insulin resistance (HOMA > 2.5 or postprandial insulin > 60 µUI/ml) [OR = 4.26 (95% CI, 2.04-8.83), p 36.5 cm [OR = 4.25 (95% CI, 1.76-10.27), p 36.5 cm [OR = 2.08 (95% CI, 1.28-3.39), p = 0.01]. In both groups basal and postprandial glycemia and the frequency of acrochordons were significantly higher in women with a positive familial history for breast cancer. Conclusions: We describe a previously unreported association in women between a family history of low-to-moderate risk of breast cancer and insulin resistance syndrome (AU)