[Evaluation of bone health in transgender people. Position of the Argentine Osteoporosis Society]. / Valoración de la densidad mineral ósea en personas transgénero. Posicionamiento de la Sociedad Argentina de Osteoporosis.

The Argentine Osteoporosis Society convened renowned specialists in the care of transgender people to prepare the first local position on the evaluation of bone health in this population. Law 26.743 on "Gender Identity" recognize all identities and guarantees free care throughout the health system. The impact of different gender affirmation treatments on bone mass has been topic of international debate. To date the evidence remains limited and different societies have issued suggestions and recommendations. For this reason, we believe it is relevant to mention our experience, capturing through this document a series of suggestions to be used in medical care.

La Sociedad Argentina de Osteoporosis convocó a especialistas reconocidos en la atención de personas transgénero para la elaboración del primer posicionamiento local sobre la evaluación de la salud ósea en esta población. La ley 26.743 de "Identidad de género" reconoce todas las identidades y garantiza su atención de manera gratuita en el sistema de salud. El impacto de los diferentes tratamientos de afirmación de género sobre la masa ósea ha sido tópico de debate internacional. Hasta la fecha la evidencia sigue siendo limitada y diferentes sociedades han emitido sugerencias y recomendaciones. Por tal motivo, creemos relevante mencionar nuestra experiencia plasmando mediante este documento una serie de sugerencias para ser utilizadas en la atención médica.

Fracturas vertebrales múltiples postsuspensión de denosumab: revisión del tema a partir de dos casos clínicos / Discontinuation of denosumab and multiple vertebral fractures: report of two cases and review of the literature

Los tratamientos para osteoporosis se indican por tiempo variable dependiendo del tipo de droga, anabólica o anticatabólica, y de la gravedad de la enfermedad. Denosumab es un anticuerpo monoclonal totalmente humano que inhibe a RANK-L evitando de esa manera la interacción entre RANKL-RANK, con la consiguiente inhibición de la formación de los osteoclastos, su activación y sobrevida. Disminuye la resorción ósea cortical y trabecular. Su administración subcutánea de 60 mg cada 6 meses al cabo de 3 años ha demostrado reducción de la resorción ósea, incremento de la densidad mineral ósea y disminución de las fracturas vertebrales, no vertebrales y de cadera. Está indicado para el tratamiento de la osteoporosis con alto riesgo de fractura. Su mecanismo de acción es reversible. Se han descripto pérdida de la DMO y elevación de los marcadores de remodelado óseo postsuspensión. Una situación clínica grave son las fracturas vertebrales múltiples postsuspensión. Este evento es infrecuente y se lo atribuye a un rebote del remodelado óseo, postulándose se postula una predisposición especial, probablemente relacionada con microRNA. Se escriben dos mujeres con osteoporosis que presentaron este cuadro. Las fracturas ocurrieron entre 7 y 10 meses posteriores a la última dosis de denosumab. Registraron elevación de C-telopéptidos y disminución de la DMO conjuntamente con las fracturas vertebrales agudas en cascada. (AU)

The duration of osteoporosis treatments depends on the drug type, anabolic or anticatabolic, and the severity of the disease. Denosumab is a fully human monoclonal antibody that inactivates RANK-L, inhibiting the RANKL-RANK interaction . This inhibits osteoclast formation, activation, and survival. It also reduces cortical and trabecular bone resorption. Subcutaneous administration of 60 mg every 6 months for 3 years has reduced bone resorption, increased bone mineral density (BMD) and decreased vertebral, non-vertebral and hip fractures. It is indicated for the treatment of osteoporosis with high risk of fracture. Denosumab mechanism of action is reversible. After discontinuation, loss of BMD and elevation of bone turnover markers have been observed. In addition, multiple vertebral fractures after the suspension of the drug have been reported. These rebound-associated vertebral fractures are rare. A special genetic predisposition related to miRNA has been proposed. Two women with this clinical presentation are described. Fractures occurred between 7 and 10 months respectively after the last dose of denosumab. They presented with an increase in circulating C-telopeptid levels and a decrease inBMD with acute multiple vertebral fractures. (AU)

Assessment of bone microarchitecture in postmenopausal women on long-term bisphosphonate therapy with atypical fractures of the femur.

Reports of atypical femoral fractures (AFFs) in patients receiving long- term bisphosphonate therapy have raised concerns regarding the genesis of this rare event. Using high-resolution peripheral quantitative computed tomography (HR-pQCT), we conducted a study to evaluate bone microarchitecture in patients who had suffered an AFF during long-term bisphosphonate treatment. The aim of our study was to evaluate if bone microarchitecture assessment could help explain the pathophysiology of these fractures. We compared bone volumetric density and microarchitectural parameters measured by HR-pQCT in the radius and tibia in 20 patients with AFFs with 35 postmenopausal women who had also received long-term bisphosphonate treatment but had not experienced AFFs, and with 54 treatment-naive postmenopausal women. Control groups were similar in age, body mass index (BMI), and bone mineral density (BMD). Mean age of the 20 patients with AFFs was 71 years, mean lumbar spine T-score was -2.2, and mean femoral neck T-score was -2. Mean time on bisphosphonate treatment was 10.9 years (range, 5-20 years). None of the patients had other conditions associated with AFFs such as rheumatoid arthritis, diabetes or glucocorticoid use. There were no statistically significant differences in any of the parameters measured by HR-pQCT between postmenopausal women with or without treatment history and with or without history of atypical fractures. We could not find any distinctive microarchitecture features in the peripheral skeleton of women who had suffered an atypical fracture of the femur while receiving bisphosphonate treatment. This suggests that risk of developing an atypical fracture is not related to bone microarchitecture deterioration. Our results indicate that there may be other individual factors predisposing to atypical fractures in patients treated with bisphosphonates, and that those are independent of bone microarchitecture. In the future, identification of those factors could help prevent and understand the complex physiopathology of these rare events.

Tratamiento con bisfosfonatos y fracturas atípicas / Treatment with bisphosphonates and atypical fractures

En los últimos veinticinco años los aminobisfosfonatos se han convertido en las drogas de elección para el tratamiento de la osteoporosis. Son potentes inhibidores de la actividad osteoclástica y reducen la incidencia de nuevas fracturas en pacientes con osteoporosis establecida, pero su prolongada vida media y sus efectos crónicos sobre la fisiología ósea son motivos de preocupación. Teóricamente, una prolongada inhibición del remodelado óseo podría traer aparejada graves efectos adversos, tales como la acumulación de microfracturas y, paradójicamente, la ocurrencia de nuevas fracturas atípicas. Pocos casos de estas infrecuentes fracturas han sido hasta ahora publicados en la literatura mundial. Todas ellas comparten algunas características comunes, además del tratamiento crónico con bisfosfonatos por osteoporosis. La más frecuente es la localización atípica de las mismas. La mayoría ocurren en una o ambas diáfisis femorales, pero también otros huesos pueden estar afectados, entre ellos sacro, isquión, costillas y rama pubiana. Las fracturas son atraumáticas o ante mínimos traumatismos, y en algunos casos fueron precedidas por un dolor prodrómico en la zona de la fractura. Todos los casos tuvieron evidencias bioquímicas o histomorfométricas de bajo recambio óseo. El objetivo de este trabajo es informar sobre tres nuevos casos de pacientes que cumplen con todos los criterios diagnósticos de esta nueva entidad, dos de ellos con fracturas de diáfisis femorales y el restante con fractura de pelvis.

In the last twenty five years aminobisphosphonates have became the drugs of choice for the treatment of osteoporosis. They strongly inhibit osteoclastic bone resorption and reduce the incidence of new fractures in patients with established osteoporosis, but their long half-life and their chronic effects on bone physiology are a matter of concern. Theoretically a harmful consequence of a prolonged inhibition of bone remodeling could be the microdamage accumulation, and paradoxically the occurrence of new and atypical fractures. Until now, few cases of these unusual fractures have been reported in the international literature. All these patients shared some common characteristics, apart from the chronic use of bisphosphonates for the treatment of osteoporosis. The more frequent is the atypical location of the fractures. Since the majority happened in one or both femoral shafts, others bones such as sacrum, ischium, ribs and pubic rami could be affected. The fractures were atraumatic or caused by minimal trauma and, in some cases, it was preceded by a prodromal pain in the affected area. All cases had biochemical or histomorphometric evidence of low bone turnover. The aim of this paper is to report three new cases of patients that fulfill with the diagnostic criteria of this new entity, two of them with femoral shaft fractures and the remainder with a pelvis one.

[Treatment with bisphosphonates and atypical fractures]. / Tratamiento con bisfosfonatos y fracturas atípicas.

In the last twenty five years aminobisphosphonates have became the drugs of choice for the treatment of osteoporosis. They strongly inhibit osteoclastic bone resorption and reduce the incidence of new fractures in patients with established osteoporosis, but their long half-life and their chronic effects on bone physiology are a matter of concern. Theoretically a harmful consequence of a prolonged inhibition of bone remodeling could be the microdamage accumulation, and paradoxically the occurrence of new and atypical fractures. Until now, few cases of these unusual fractures have been reported in the international literature. All these patients shared some common characteristics, apart from the chronic use of bisphosphonates for the treatment of osteoporosis. The more frequent is the atypical location of the fractures. Since the majority happened in one or both femoral shafts, others bones such as sacrum, ischium, ribs and pubic rami could be affected. The fractures were atraumatic or caused by minimal trauma and, in some cases, it was preceded by a prodromal pain in the affected area. All cases had biochemical or histomorphometric evidence of low bone turnover. The aim of this paper is to report three new cases of patients that fulfill with the diagnostic criteria of this new entity, two of them with femoral shaft fractures and the remainder with a pelvis one.

Densidad mineral ósea de raquis y cadera, y variables de resistencia ósea por DXA / Bone mineral density at the spine and hip, and bone resistance parameters calculated from DXA measurements

La densidad mineral ósea evaluada por DXA predice el riesgo de fractura de cadera. Los pacientes añosos, aún con densitometría normal pueden fracturarse. Esto indica que otras propiedades del hueso, participan en la resistencia ósea, como las características físicas del material y la geometría. Nuestro objetivo fue evaluar mujeres normales de la ciudad de Buenos Aires con las nuevas tecnologías DXA y medir los parámetros geométricos y arquitectónicos. Evaluamos 903 mujeres con equipo GE Lunar Prodigy. La edad media fue 55 ± 7.23 años y la talla 1.60 ± 0.06 m. Esta descendió progresivamente con la edad, siendo 1.54±0.05 m en las mayores de 70a. La DMO media de L1-L4, en mujeres jóvenes fue 1.16 ± 0.12 g/cm2, en cuello femoral, 0.93 ±0.1g/cm2, cuello superior 0.81 ± 0.13 g/cm2 y fémur total 0.95 ± 0.09 g/cm2. Los valores de DMO también descendieron progresivamente. La media de longitud del eje de cadera (HAL) fue 103.12 ±5.71 mm y mostró marcada correlación con la talla y no con edad. El momento de inercia de la sección cruzada (CSMI) correlacionó con la DMO. Las variables geométricas permanecieron estables con el tiempo, demostrando condicionamiento genético, en tanto las arquitectónicas se modificarían por el remodelado durante la vida. Nuestros datos demuestran que la mujer argentina presenta valores arquitectónicos y geométricos en fémur proximal similares a los descriptos en la literatura. La asociación de los mismos permitirá una mejor evaluación de los individuos en riesgo.

Elimination and clearance of pamidronate by haemodialysis.

Pamidronate (APD), a third-generation bisphosphonate, has proven to be useful in haemodialysis (HD) patients with ectopic calcifications and hypercalcaemia. Little is known about bisphosphonates clearance in patients undergoing HD. The authors' main objective was to study HD removal and clearance of APD. In total, 23 HD-requiring anuric end-stage renal disease (ESRD) adult individuals (12 men) aged 61.7 +/- 13 (mean +/- SD) years were admitted into the study. APD clearance and elimination were evaluated by (99m)Technetium APD (half-life 6 h). In total, 1 mg of labelled APD was injected via the arteriovenous graft prior to the start of HD. Blood samples were then drawn from the arterial (predialyser) and venous (postdialyser) lines of the extracorporeal circuit 2 h after the HD onset. In a subgroup of patients (n: 15) the dialysate was collected and quantified during the three initial HD hours. Venous APD concentrations (postdialyser) were 72 + 7% of arterial (predialyser) concentrations. Mean APD clearance was 69.3 + 16.6 mL/min, and mean APD extraction during dialysis session was 31.6 + 10.1%. In the present study involving HD-requiring anuric ESRD patients APD was successfully eliminated by HD. At the dose administered here none of the participants reported adverse events. APD is a potentially useful drug to be administered to HD-requiring ESRD patients, the understanding of its removal during HD as well as its dialytic clearance allows for a safer management of a drug that is usually eliminated by renal excretion.