Hypouricemia with hypercalciuria: Longitudinal study and review of the topic.

BACKGROUND AND OBJECTIVE: The association of hypouricemia and hypercalciuria is rare. In 1974 a new syndrome named Hypouricemia with hypercalciuria and decreased bone density was described. Afterwards, some cases with such association were published in which the fractional excretion of urate was higher than 20ml/100ml FGR. We have analyzed a series of children who were diagnosed with hypouricemia and hypercalciuria and who were monitored. The aim of this study was to determine whether our patients could be affected by the aforementioned syndrome or be carriers of a variant of idiopathic hypercalciuria. PATIENTS AND METHODS: Retrospective longitudinal study in which the medical records of eight patients (5V, 3M) diagnosed with hypouricemia and hypercalciuria in childhood. Clinical features at diagnosis, ultrasound and densitometric findings and selected biochemical variables were noted, with special emphasis on renal tubular handling of urate. Results were compared with 36 children with idiopathic hypercalciuria without hypouricemia (14V, 22M). RESULTS: In the hypouricemia group baseline urate levels were 1.9 (0.3) mg/dl (range: 1.5-2) and first day urine calcium/creatinine ratio 0.27 (0.05) mg/mg (range: 0.23-0.31). In all cases fractional urate excretion was less than 20ml/100ml FGR. The z-DMO values were less than -1 in 4/8 cases. At the last follow-up only three cases still had an elevated calcium/creatinine ratio and in all of them the urates levels was greater than 2mg/dl. The z-DMO value had improved in five cases and worsened in three others. In relation to the group without hypouricemia, no differences were observed between the various parameters studied including the z-DMO value, with the exception of fractional excretion and tubular urate reabsorption although plasmatic uric acid levels were still significantly lower. CONCLUSION: Our patients with hypercalciuria and hypouricemia would be affected by a variant of idiopathic hypercalciuria in which, due to an unknown cause, the proximal tubular reabsorption of urate is modestly reduced and improves over time. Hypouricemia with hypercalciuria and decreased bone density may not be a specific entity.

Hipouricemia con hipercalciuria. Estudio longitudinal y revisión del tema / Hypouricemia with hypercalciuria: Longitudinal study and review of the topic

Antecedentes y objetivo: La asociación de hipouricemia e hipercalciuria es poco frecuente. En 1974 se describió un nuevo síndrome nominado Hipouricemia con hipercalciuria y reducción de la densidad ósea. Posteriormente, se publicaron algunos casos con esa asociación en los que la excreción fraccional de urato era superior a 20/100ml FGR. Hemos analizado una serie de niños que fueron diagnosticados de hipouricemia e hipercalciuria y que fueron controlados evolutivamente. El objetivo del trabajo es intentar conocer si nuestros pacientes podrían estar afectos del síndrome antes mencionado o ser portadores de una variante de hipercalciuria idiopática. Pacientes y métodos: Estudio retrospectivo longitudinal en el que se estudiaron las historias clínicas de 8 pacientes (5V y 3M) diagnosticados de hipouricemia e hipercalciuria en la infancia. Se anotaron la clínica al diagnóstico, los hallazgos ecográficos y densitométricos, y determinadas variables bioquímicas, con especial hincapié en el manejo tubular renal del urato. Los resultados se compararon con los de 36 niños afectos de hipercalciuria idiopática sin hipouricemia (14V y 22M). Resultados: En el grupo con hipouricemia los niveles iniciales de uricemia fueron 1,9 (0,3) mg/dl (rango: 1,5-2) y los del cociente calcio/creatinina en primera orina del día, 0,27 (0,05) mg/mg (rango: 0,23-0,31). En todos los casos la excreción fraccional de urato fue inferior a 20ml/100ml FGR. Los valores de z-DMO fueron menores de −1 en 4/8 casos. En el último control, solo en 3 casos persistía el cociente calcio/creatinina elevado, y en todos la uricemia era superior a 2mg/dl. El valor de z-DMO había mejorado en 5 casos y empeorado en otros 3... (AU)

Background and objective: The association of hypouricemia and hypercalciuria is rare. In 1974 a new syndrome named Hypouricemia with hypercalciuria and decreased bone density was described. Afterwards, some cases with such association were published in which the fractional excretion of urate was higher than 20/100ml FGR. We have analyzed a series of children who were diagnosed with hypouricemia and hypercalciuria and who were monitored. The aim of this study was to determine whether our patients could be affected by the aforementioned syndrome or be carriers of a variant of idiopathic hypercalciuria. Patients and methods: Retrospective longitudinal study in which the medical records of eight patients (5V and 3M) diagnosed with hypouricemia and hypercalciuria in childhood. Clinical features at diagnosis, ultrasound and densitometric findings and selected biochemical variables were noted, with special emphasis on renal tubular handling of urate. Results were compared with 36 children with idiopathic hypercalciuria without hypouricemia (14V and 22M). Results: In the hypouricemia group baseline urate levels were 1.9 (0.3)mg/dl (range: 1.5-2) and first day urine calcium/creatinine ratio 0.27 (0.05)mg/mg (range: 0.23-0.31). In all cases fractional urate excretion was less than 20/100ml FGR. The z-DMO values were less than −1 in 4/8 cases. At the last follow-up only three cases still had an elevated calcium/creatinine ratio and in all of them the urates levels was greater than 2mg/dl. The z-DMO value had improved in five cases and worsened in three others. In relation to the group without hypouricemia, no differences were observed between the various parameters studied including the z-DMO value, with the exception of fractional excretion and tubular urate reabsorption although plasmatic uric acid levels were still significantly lower... (AU)

Manejo de la osteoporosis en el paciente con enfermedad renal crónica (Estudio ERCOS): un desafío en la asistencia nefrológica / Osteoporosis management in patients with chronic kidney disease (ERCOS Study): A challenge in nephrological care

La valoración del riesgo de fractura del paciente con enfermedad renal crónica (ERC) ha sido incluida en el complejo Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBD) en guías nefrológicas internacionales y nacionales, sugiriéndose por primera vez la evaluación de la densidad mineral ósea (DMO) si los resultados pueden condicionar la toma de decisiones terapéuticas. Sin embargo, existe muy poca información en práctica clínica real en esta población. El objetivo principal del estudio ERC-Osteoporosis (ERCOS) es describir el perfil de los pacientes con ERC G3-5D con osteoporosis (OP) y/o fracturas por fragilidad atendidos en consultas especializadas de nefrología, reumatología y medicina interna en España. Participaron 15 centros y se incluyeron 162 pacientes (siendo en su mayoría mujeres [71,2%] posmenopáusicas [98,3%]) con una mediana de edad de 77 años. La mediana del filtrado glomerular estimado (FGe) fue de 36ml/min/1,73m2 y el 38% de pacientes incluidos estaban en diálisis. Destacamos la elevada frecuencia de fracturas por fragilidad prevalentes ([37,7%), principalmente vertebrales [52,5%] y de cadera 24,6%]), el antecedente desproporcionado de pacientes con enfermedad glomerular en comparación con series puramente nefrológicas (corticoides) y el infratratamiento para la prevención de fracturas, fundamentalmente en consultas nefrológicas. Este estudio supone una inmediata llamada a la acción con la difusión de las nuevas guías clínicas, más proactivas, y subraya la necesidad de homogeneizar el enfoque asistencial/terapéutico multidisciplinar coordinado de estos pacientes de un modo eficiente para evitar las actuales discrepancias y el nihilismo terapéutico. (AU)

Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBD) complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results will impact treatment decisions. However, there is very little information on actual clinical practice in this population. The main objective of the ERC-Osteoporosis (ERCOS) study is to describe the profile of patients with CKD G3-5D with osteoporosis (OP) and/or fragility fractures treated in specialized nephrology, rheumatology and internal medicine clinics in Spain. Fifteen centers participated and 162 patients (mostly women [71.2%] postmenopausal [98.3%]) with a median age of 77 years were included. Mean estimated glomerular filtration rate (eGFR) was 36ml/min/1.73m2 and 38% of the included patients were on dialysis. We highlight the high frequency of prevalent fragility fractures ([37.7%], mainly vertebral [52.5%] and hip [24.6%]), the disproportionate history of patients with glomerular disease compared to purely nephrological series (corticosteroids) and undertreatment for fracture prevention, especially in nephrology consultations. This study is an immediate call to action with the dissemination of the new, more proactive, clinical guidelines, and underlines the need to standardize a coordinated and efficient multidisciplinary care/therapeutic approach to these patients to avoid current discrepancies and therapeutic nihilism. (AU)

Osteoporosis management in patients with chronic kidney disease (ERCOS Study): A challenge in nephrological care.

Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the CKD-MBD ("Chronic Kidney Disease-Mineral and Bone Disorders") complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results can influence therapeutic decision-making. However, there is very little information on actual clinical practice in this population. The main objective of the ERCOS (ERC-Osteoporosis) study is to describe the profile of patients with CKD G3-5D with osteoporosis (OP) and/or fragility fractures treated in specialized nephrology, rheumatology and internal medicine clinics in Spain. Fifteen centers participated and 162 patients (mostly women [71.2%] postmenopausal [98.3%]) with a median age of 77 years were included. Mean estimated glomerular filtration rate (eGFR) was 36 mL/min/1.73 m2 and 38% of the included patients were on dialysis. We highlight the high frequency of prevalent fragility fractures [37.7%), mainly vertebral (52.5%) and hip (24.6%)], the disproportionate history of patients with glomerular disease compared to purely nephrological series (corticosteroids) and undertreatment for fracture prevention, especially in nephrology consultations. This study is an immediate call to action with the dissemination of the new, more proactive, clinical guidelines, and underlines the need to standardize a coordinated and multidisciplinary care/therapeutic approach to these patients in an efficient way to avoid current discrepancies and therapeutic nihilism.

Why do patients with urinary diversions have an increased risk of bone fracture? A systematic review on risk factors for osteoporosis and bone mineral density loss in this group of patients.

INTRODUCTION: Patients undergoing radical cystectomy with urinary diversions (UD) are at increased risk of bone fractures compared to the general population. Although a loss of bone mineral density (BMD) has been described in patients with UD, we still do not know with certainty why these patients follow this tendency. OBJECTIVE: We performed a systematic review of the available literature to analyze the prevalence of osteoporosis and bone alterations in patients with ileal UD and the possible associated risk factors. EVIDENCE ACQUISITION: We systematically searched PubMed® and Cochrane Library for original articles published before December 2022 according to PRISMA guidelines. EVIDENCE SYNTHESIS: A total of 394 publications were identified. We selected 12 studies that met the inclusion criteria with 496 patients included. Six of the twelve studies showed decreased BMD values. Prevalence of osteoporosis was specified in three articles, with values ranging ​​from 0% to 36%. Risk factors such as age, sex, body mass index, metabolic acidosis and renal function appear to have an impact on bone tissue reduction, while type of UD, follow-up, 25-hydroxyvitamin D and parathormone had less evidence or contradictory data. The heterogeneity of the studies analyzed could led to interpretation bias. CONCLUSIONS: UD are associated with multiple risk factors for osteoporosis and bone fractures. Identifying patients at highest risk and establishing diagnostic protocols in routine clinical practice are essential to reduce the risk of fractures and the resulting complications.

Whole-hand and regional bone mineral density involvement in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by symmetric polyarthritis that can lead to joint deformity, disability, and osteoporosis. We aimed to evaluate whole hand and regional BMD in RA patients compared to controls. In addition, we evaluated the BMD of dominant versus non-dominant hands in healthy subjects. We included adult female and male RA patients and control subjects matched by age, sex, and BMI. BMD (g/cm2) was measured by DXA in lumbar spine (LS), whole hand, and three regions of interest: carpus, metacarpal bones, and phalanges. Results: 44 control subjects (49.5±11.8 y) and 60 with RA (52.7±12.7 y) were included. Significant lower BMD in RA patients was found in LS (-8.7%), dominant whole hand (-9.5%), carpus, metacarpal bones, and phalanges, and non-dominant whole hand (-8.7%), metacarpal bones, and phalanges compared to controls. A significant positive correlation was found between LS and whole-hand BMD (dominant r=.63, non-dominant r=.67). Finally, the whole hand, metacarpal bones, and carpus BMD measurements were significantly higher in the dominant hand compared to the non-dominant hand without differences in the phalangeal ROI. In conclusion, hand BMD was significantly lower in RA patients compared to control subjects and there was a significant correlation with LS BMD. We demonstrated that BMD measurements of the whole-hand, and different ROI (carpus, metacarpal bones, and phalanges) by DXA would be an easily reproducible technique to evaluate bone loss. In addition, the whole hand, metacarpal bones and carpus BMD measurements were significantly higher in the dominant hand compared to the non-dominant hand without differences in the phalanges.

Whole-hand and regional bone mineral density involvement in rheumatoid arthritis / Compromiso de la densidad mineral ósea de la mano completa y regional en la artritis reumatoide

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by symmetric polyarthritis that can lead to joint deformity, disability, and osteoporosis. We aimed to evaluate whole hand and regional BMD in RA patients compared to controls. In addition, we evaluated the BMD of dominant versus non-dominant hands in healthy subjects. We included adult female and male RA patients and control subjects matched by age, sex, and BMI. BMD (g/cm2) was measured by DXA in lumbar spine (LS), whole hand, and three regions of interest: carpus, metacarpal bones, and phalanges. Results: 44 control subjects (49.5±11.8 y) and 60 with RA (52.7±12.7 y) were included. Significant lower BMD in RA patients was found in LS (−8.7%), dominant whole hand (−9.5%), carpus, metacarpal bones, and phalanges, and non-dominant whole hand (−8.7%), metacarpal bones, and phalanges compared to controls. A significant positive correlation was found between LS and whole-hand BMD (dominant r=.63, non-dominant r=.67). Finally, the whole hand, metacarpal bones, and carpus BMD measurements were significantly higher in the dominant hand compared to the non-dominant hand without differences in the phalangeal ROI. In conclusion, hand BMD was significantly lower in RA patients compared to control subjects and there was a significant correlation with LS BMD. We demonstrated that BMD measurements of the whole-hand, and different ROI (carpus, metacarpal bones, and phalanges) by DXA would be an easily reproducible technique to evaluate bone loss. In addition, the whole hand, metacarpal bones and carpus BMD measurements were significantly higher in the dominant hand compared to the non-dominant hand without differences in the phalanges.(AU)

La artritis reumatoide (AR) es una enfermedad autoinmune crónica caracterizada por poliartritis simétrica que puede provocar deformidad e incapacidad articular y osteoporosis. Nuestro objetivo fue evaluar la DMO de manos completa y por regiones en los pacientes con AR en comparación con los controles. Se incluyeron pacientes adultos de ambos sexos con AR, y sujetos controles de edad, sexo e IMC similar. La DMO se midió por DXA en columna lumbar (CL), manos completas y 3 regiones de interés: carpo, metacarpianos y falanges. Resultados: se incluyeron 44 sujetos control (49,5±11,8 años) y 60 con AR (52,7±12,7 años). Se encontró una DMO significativamente más baja en los pacientes con AR en CL (−8,7%), mano completa dominante (−9,5%) y mano completa no dominante (−8,7%) en comparación con los sujetos controles. Se encontró una correlación positiva significativa entre la CL y la DMO de la mano completa (dominante, r=0,63; no dominante, r=0,67). Finalmente, la DMO de la mano completa, los huesos metacarpianos y el carpo fueron significativamente más altos en la mano dominante en comparación con la mano no dominante sin diferencias en la región de las falanges. En conclusión, la DMO de la mano fue significativamente menor en los pacientes con AR en comparación con los sujetos controles, y hubo una correlación significativa con la DMO de la CL. Demostramos que las mediciones de la DMO de toda la mano y diferentes ROI (carpo, huesos metacarpianos y falanges) por DXA serían una técnica fácilmente reproducible para evaluar la pérdida ósea. Además, la DMO de la mano completa, los huesos metacarpianos y el carpo fueron significativamente más altos en la mano dominante en comparación con la mano no dominante.(AU)

Bone modification of the college american football player: longitudinal study / Modificaciones óseas del jugador de futbol americano universitario: estudio longitudinal

The purpose of this study was to know the bone changes of college football (FA)players. A total of 39 male FA players participated, ranging in age from 18 to 25 years old. They were grouped according to each playing position they play in the team such as: Linemen (n = 15), players of great skills (n = 7), players of skill (n = 13) and quarterbacks (n = 4). For the assessment of BMD (g/cm2) a Double X-ray Bone Densitometry (DXA) was used. The results of this study showed a significant decrease (p<.05) of BMD in head and legs, in contrast, the CMO showed an increase in legs, however, in the pelvic region showed a significant decrease (p<.05). In conclusion, significant changes were found for BMD and CMO in the head, leg and pelvis regions in college AF players over a one-year span of competition (AU)

El propósito de este estudio fue conocer los cambios óseos de los jugadores de futbol americano (FA) universitario. Participaron un total de 39 jugadores de FA masculino, con rangos de edad de 18 a 25 años. Se agruparon acorde a cada posición de juego que desempeñan en el equipo como: Linieros (n=15), jugadores de grandes habilidades (n=7), jugadores de habilidad (n=13) y mariscales de campo (n=4). Para la valoración de DMO (g/cm2) se utilizó un Densitometría Ósea Doble de Rayos X (DXA). Los resultados de este estudio mostraron una disminución significativa (p<.05) de DMO en cabeza y piernas, en cambio, el CMO mostró un aumento en piernas, sin embargo, en la región de pelvis mostro una disminución significativa (p<.05). En conclusión, se encontraron cambios significativos para la DMO y CMO en las regiones de cabeza, piernas y pelvis en los jugadores de FA universitario en un lapso de un año de competencia (AU)

Asociación de la gamma glutamil transferasa con la presencia y progresión de calcificaciones aórticas abdominales y con cambios en densidad mineral ósea / Association of gamma glutamyl transferase in the presence and progression of abdominal aortic calcifications and changes to bone mineral density

Introducción y objetivo: la calcificación aórtica abdominal (CAA) es predictora de eventos cardiovasculares. El objetivo de este trabajo fue valorar la asociación de la gamma glutamil transferasa (GGT) con presencia y progresión de CAA y los cambios en densidad mineral ósea (DMO) en columna lumbar y cuello femoral. Material y métodos: se seleccionaron 326 hombres y mujeres mayores de 50 años que realizaron un cuestionario, dos radiografías laterales dorso-lumbares y DMO, repitiendo a los 4 años las mismas pruebas y un estudio analítico. Resultados: la presencia y progresión de CAA (nuevas o mayor severidad) fue inferior en el cuartil 1 (Q1) de GGT respecto a los otros cuartiles (40 % vs. 58 %, p = 0,021; 24 % vs. 44 %, p = 0,022). Comparado con Q1, el análisis de regresión logística ajustado por confusores mostró que los Q2 y Q4 se asociaron con aumentos en la presencia de CAA [odds ratio (OR) = 2,53, intervalo de confianza del 95 % (IC 96 %) = (1,22-5,25) y OR = 3,04, IC 95 % = (1,36-6,77)] y Q2, Q3 y Q4 se asociaron con aumentos en progresión de CAA [OR = 2,24, IC 95 % = (1,07-4,67); OR = 2,35, IC 95 % = (1,09-5,07) y OR = 3,47, IC 95 % = (1,56-7,70)]. El análisis multivariante por sexos mostró que tanto en hombres como mujeres el Q4 de GGT se asoció con progresión de CAA [OR = 3,27, IC 95 % = (1,14-9,36) y OR = 3,26, IC 95 % = (1,03-10,29) respectivamente] y en mujeres con mayores pérdidas de DMO a nivel lumbar. No hubo efecto con respecto a la prevalencia de CAA. Conclusiones: valores elevados de GGT podrían ser un indicador de presencia y progresión de CAA en población mayor de 50 años. De forma separada por sexo, los mayores niveles de GGT se asociaron con progresión de CAA, siendo un marcador pronóstico de daño cardiovascular.(AU)

Introduction and objective: abdominal aortic calcification (AAC) is a predictor of cardiovascular events. This study aimedto assess the association of gamma glutamyl transferase (GGT) in the presence and progression of AAC, as well as changesto bone mineral density (BMD) in the lumbar spine and femoral neck.Materials and methods: a total of 326 men and women over 50 years of age were selected for this study. They completeda questionnaire, underwent two lateral dorso-lumbar spine X-rays, and BMD measurements. The same tests and 1 analyticalassessment were repeated after 4 years.Results: the presence and progression of AAC (new occurrences or increased severity) were lower in GGT quartile 1 (Q1)compared with the other quartiles (40 % vs 58 %; p = 0.021; 24 % vs 44 %; p = 0.022). Compared with Q1, the confound -ers-adjusted logistic regression analysis showed that Q2 and Q4 were associated with more presence of AAC [odds ratio(OR), 2.53; 95 % confidence interval (95 % CI), 1.22-5.25 and OR, 3.04; 95 % CI, 1.36-6.77]. Additionally, Q2, Q3, and Q4were associated with more AAC progression [OR, 2.24; 95 % CI, 1.07-4.67; OR, 2.35; 95 % CI, 1.09-5.07; and OR, 3.47;95 % CI, 1.56-7.70]. The gender-stratified multivariate analysis revealed that in both men and women, the Q4 of GGT wasassociated with AAC progression [OR, 3.27; 95 % CI, 1.14-9.36, and OR, 3.26; 95 % CI, 1.03-10.29, respectively], and inwomen alone, with greater lumbar BMD losses. There were no effects regarding the prevalence of AAC.Conclusions: elevated GGT levels could serve as an indicator of the presence and progression of AAC in individuals olderthan 50 years. When analyzed separately by gender, higher GGT levels were associated with AAC progression, which actedas a prognostic marker for cardiovascular disease.(AU)

Bone mineral density and growth changes in patients with distal renal tubular acidosis after two-years treatment with a new alkalizing drug (ADV7103) / Cambios en la densidad mineral ósea y en el crecimiento en pacientes con acidosis tubular renal distal tras dos años de tratamiento con un nuevo fármaco alcalinizante (ADV7103)

Background and objectives: ADV7103 is a new prolonged-release treatment for distal renal tubular acidosis (dRTA), containing potassium citrate and potassium bicarbonate. Since acidosis may affect bone mineral contents, the effects of ADV7103 on bone mineral density (BMD) and growth in patients with dRTA over 24 months were evaluated. Patients and methods: Thirty patients (24 paediatric patients and 6 adults) were included in an open-label extension study after a phase II/III trial. BMD, measured by densitometry, was assessed at baseline and at 24 months. Growth was evaluated throughout the study. Plasma bicarbonate, parathyroid hormone, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, bone alkaline phosphatase, calciuria and citraturia, were also determined. Safety and treatment compliance were evaluated as well. Results: After 24 months of treatment with ADV7103, mean spine BMD z-score values significantly increased as compared with baseline (p=0.024). In adults, spine and whole-body densitometry z-scores showed a significant correlation with plasma bicarbonate levels (rS=0.82 and rS=0.97, respectively, p<0.005). There was an increase>0.5 units in z-scores for height and weight in 18% and 36% of the paediatric patients, respectively. With treatment, plasma bicarbonate concentration and calciuria at the different visits were normal in 69–86% and 93–96% patients, respectively. Only nine treatment-related gastrointestinal AEs of mild/moderate severity, were reported in five patients. Conclusions: Two years of ADV7103 treatment improved growth and increased spine BMD. These results suggest that control of acidosis by ADV7103 treatment improves bone parameters. (AU)

Antecedentes y objetivo: El ADV7103 es un nuevo tratamiento de liberación prolongada para la acidosis tubular renal distal (ATRd), que contiene citrato potásico y bicarbonato potásico. Dado que la acidosis puede afectar al contenido mineral óseo, se ha evaluado el efecto de dicho medicamento a lo largo de 24 meses sobre la densidad mineral ósea (DMO) y el crecimiento en pacientes con ATRd. Pacientes y métodos: Se incluyeron treinta pacientes (24 pediátricos y seis adultos) en un estudio abierto de extensión tras un ensayo clínico de fase II/III. La DMO medida por densitometría se midió al inicio del estudio y los 24 meses. El crecimiento se evaluó a lo largo del estudio. Adicionalmente, se determinaron el bicarbonato plasmático, la parathormona, 25 hidroxivitamina D, 1,25 dihidroxivitamina D, fosfatasa alcalina ósea, calciuria y citraturia. La seguridad y el cumplimento terapéutico también fueron evaluados. Resultados: Tras 24 meses de tratamiento con ADV7103 la media del z-score de DMO de columna aumentó significativamente frente al valor basal (p = 0,024). En los adultos el z-score de la densitometría de columna y corporal total mostró una correlación significativa con los valores de bicarbonato plasmático (rS = 0,82 y rS = 0,97, respectivamente, p < 0,005). Se registró un incremento > 0,5 unidades de z-score para altura y peso en el 18 y 36%, respectivamente, de los pacientes pediátricos. Con el tratamiento, la concentración plasmática de bicarbonato y la calciuria fueron normales en las diferentes visitas en un 69-86% y un 93-96% de los pacientes, respectivamente. Solamente se notificaron nueve eventos adversos gastrointestinales relacionados con el tratamiento, todos de intensidad leve/moderada en cinco pacientes. Conclusiones: Dos años de tratamiento con ADV7103 mejoraron el crecimiento y la DMO de columna. Estos resultados sugieren que el control de la acidosis con dicho tratamiento provoca una mejora de parámetros óseos. (AU)

Alimentación basada en plantas y su efecto sobre la salud ósea: del mito a la evidencia Plant-based diets and its effects on bone health: from myth to evidence

Resumen Introducción: la alimentación es uno de los factores modificables más importantes que participa en la salud ósea. Contribuye a ésta, una adecuada ingesta de calcio, vitamina D y proteínas, como así también otros nutrientes. A la alimentación basada en plantas (ABP) se le ha atribuido importantes beneficios para la salud en general, pero mal planificada podría tener efectos deletéreos sobre la salud ósea. Materiales y método: revisión narrativa con búsqueda en el sistema digital de recopilación de información biomédica PubMed cuyo objetivo fue analizar la evidencia científica disponible en la actualidad sobre el efecto de la ABP sobre la salud ósea. Resultados: dentro de los patrones de consumo de la ABP, los veganos que exhiben un consumo de calcio inferior a 525 mg/día presentan mayor riesgo de fractura por fragilidad ósea [incidencia de fractura: 1.37 (IC95%: 1,07; 1,74)]. En cambio, el papel de la hiperhomocisteinemia (HHcy) secundaria al déficit de vitamina B12 y riesgo de fractura continúa siendo controvertido en esta población. Si bien, in vitro la HHcy puede incrementar la actividad de los osteoclastos, en estudios clínicos no se observaron diferencias estadísticamente significativas en los niveles de crosslaps sérico (marcador de resorción ósea) en los consumidores de ABP (vegetarianos) comparados con los omnívoros. Conclusión: una ABP bien planificada, óptima y adecuada, que cubra los requerimientos diarios de calcio, vitamina D, vitamina B12 y proteínas aportará importantes beneficios para la salud general sin afectar la salud ósea en particular, aunque se requiere de futuros estudios para una mejor comprensión de su efecto sobre aspectos específicos del sistema musculo esquelético.

Abstract Introduction: diet is one of the most significant and modifiable factors involved in bone health, as an appropriate intake of calcium, vitamin D and proteins, as well as other nutrients, contributes to this. Significant overall health benefits have been attributed to plant-based diets (PBD); however, poorly planned PBD could have detrimental effects on bone health. Materials and Method: a narrative review through a search in the digital biomedical data collection system PubMed whose objective was to analyze currently available scientific evidence about the effects of PBD on bone health. Results: within the PBD intake patterns, vegans exhibiting calcium intakes below 525mg/day are at a higher risk of fracture due to bone fragility [incidence of fracture: 1.37 (95% CI: 1.07; 1.74)]. In contrast, the role of hyperhomocysteinemia (HHcy) secondary to vitamin B12 deficiency and fracture risk remains controversial in this population. While in vitro HHcy osteoclast activity may increase, in clinical studies no statistically significant differences in serum crosslaps levels (bone resorption marker) were observed in PBD consumers (vegetarians) when compared to omnivores. Conclusion: a well-planned, optimal and adequate PBD, covering daily calcium, vitamin D, vitamin B12 and proteins requirements, will provide significant benefits to the overall health condition without affecting bone health in particular, although future studies are required in order to better understand its effects on specific aspects of the musculoskeletal system.

Threshold based on bone mineral density for therapeutic decision-making in postmenopausal women and men over 50 years old under glucocorticoid therapy.

INTRODUCTION AND AIM: T-score bone mineral density (BMD) thresholds may influence guidance for treatment in patients under glucocorticoid (GC) therapy. Different BMD thresholds have been described but there is no international consensus. The aim of this study was to find a threshold to help in treatment decision-making in the population under GC therapy. METHODS: A working group representing three scientific societies from Argentina was convened. The first team was formed by specialists with expertise in glucocorticoid-induced osteoporosis (GIO) who voted according to summary of evidence. The second team was constituted by a methodology group who coordinated and supervised each stage. We conducted two systematic reviews to synthesize the evidence. The first included trials of drugs used in GIO to analyze the BMD cut-off used as inclusion criteria. In the second, we analyzed the evidence regarding the densitometric thresholds to discriminate between fractured and non-fractured patients under GC treatment. RESULTS: In the first review, 31 articles were included for qualitative synthesis and more than 90% of the trials included patients regardless of their densitometric T-score or range of osteopenia. In the second review, 4 articles were included and more than 80% of the T-scores were in the range -1.6 to -2.0. The summary of findings was analyzed and put to a vote. CONCLUSIONS: With more than 80% agreement of the voting expert panel, a T-score≤-1.7 was considered the most appropriate for treatment in postmenopausal women and men over 50 years of age under GC therapy. This study could help in treatment decision-making in patients under GC therapy without fractures but other fracture risk factors should certainly be considered.

Threshold based on bone mineral density for therapeutic decision-making in postmenopausal women and men over 50 years old under glucocorticoid therapy / Umbral densitométrico de densidad mineral ósea para considerar tratamiento en pacientes mujeres posmenopáusicas y hombres mayores de 50 años en tratamiento con glucocorticoids

Introduction and aim: T-score bone mineral density (BMD) thresholds may influence guidance for treatment in patients under glucocorticoid (GC) therapy. Different BMD thresholds have been described but there is no international consensus. The aim of this study was to find a threshold to help in treatment decision-making in the population under GC therapy. Methods: A working group representing three scientific societies from Argentina was convened. The first team was formed by specialists with expertise in glucocorticoid-induced osteoporosis (GIO) who voted according to summary of evidence. The second team was constituted by a methodology group who coordinated and supervised each stage. We conducted two systematic reviews to synthesize the evidence. The first included trials of drugs used in GIO to analyze the BMD cut-off used as inclusion criteria. In the second, we analyzed the evidence regarding the densitometric thresholds to discriminate between fractured and non-fractured patients under GC treatment. Results: In the first review, 31 articles were included for qualitative synthesis and more than 90% of the trials included patients regardless of their densitometric T-score or range of osteopenia. In the second review, 4 articles were included and more than 80% of the T-scores were in the range −1.6 to −2.0. The summary of findings was analyzed and put to a vote. Conclusions: With more than 80% agreement of the voting expert panel, a T-score≤−1.7 was considered the most appropriate for treatment in postmenopausal women and men over 50 years of age under GC therapy. This study could help in treatment decision-making in patients under GC therapy without fractures but other fracture risk factors should certainly be considered.(AU)

Introducción y objetivo: Los umbrales del T-score de densidad mineral ósea (DMO) podrían influir en el tratamiento de pacientes bajo terapia con glucocorticoides (GC). Se han descrito diferentes umbrales, pero no existe un consenso internacional. El objetivo de este trabajo fue encontrar un umbral que ayude en la decisión terapéutica en la población bajo tratamiento con GC. Métodos: Se convocó un grupo de trabajo en representación de tres sociedades científicas de Argentina. El primer equipo estuvo formado por especialistas con experiencia en osteoporosis inducida por glucocorticoides (OIG), quienes estuvieron a cargo de la votación basada en la evidencia. El segundo equipo estuvo a cargo de la metodología coordinando y supervisando cada etapa. Realizamos dos revisiones sistemáticas: la primera incluyó ensayos de fármacos utilizados en OIG para analizar el T-score considerado como criterio de inclusión. En la segunda, analizamos la evidencia sobre umbrales densitométricos para la discriminación de pacientes fracturados y no fracturados bajo tratamiento con GC. Resultados: En la primera revisión se incluyeron 31 artículos donde se halló que más de 90% de los ensayos incluyeron pacientes independientemente del T-score o en el rango de osteopenia. En la segunda revisión se incluyeron cuatro artículos donde observamos que más de 80% de los valores de T-score se encontraban entre -1,6 y -2,0. Conclusiones: Con un acuerdo superior a 80% del panel de expertos, un T-score ≤ -1,7 se consideró el más adecuado para el tratamiento en mujeres posmenopáusicas y hombres mayores de 50 años bajo tratamiento con GC. Este estudio podría ayudar en la decisión terapéutica en pacientes bajo tratamiento con GC sin fracturas, pero ciertamente deberían considerarse otros factores de riesgos de fracturas complementarios.(AU)

Ingesta de calcio y densidad mineral ósea en adolescentes chilenos con desarrollo puberal completo

Introducción: La cantidad diaria recomendada (RDA) de calcio en adolescentes es de 1.300 mg/día. La última Encuesta Nacional de Consumo Alimentario de Chile, mostró que la mediana de ingesta total de calcio fue menos de la mitad de la RDA. Una ingesta insuficiente de calcio puede impactar negativamente la mineralización ósea. Objetivo: Determinar el efecto de la ingesta de calcio y estado nutricional sobre la densidad mineral ósea (DMO) de adolescentes con desarrollo puberal completo. Métodos: Estudio de corte transversal. Participaron n= 79 adolescentes de ambos sexos de entre 17 y 18 años elegidos al azar, aparentemente sanos, estadio Tanner 5 e IMC-1 DE). Según estado nutricional, no hubo diferencias significativas en la ingesta de nutrientes, pero sí en la DMO. En media, la DMO estandarizada (puntaje Z) fue normal para ambos sexos (>-1 DE); los adolescentes con obesidad presentaron una DMO estandarizada significativamente mayor que los adolescentes de peso normal (1,05±0,85 vs 0.33±0,86; P= 0,04). La ingesta de calcio no se relacionó con la masa ósea total ni con la DMO estandarizada. Conclusión: En adolescentes con desarrollo puberal completo no hubo relación entre la ingesta de calcio y los niveles de mineralización ósea. Sí hubo relación entre mineralización ósea y estado nutricional, siendo mayor la DMO en los individuos con obesidad.

Background: In adolescents, the recommended daily intake (RDI) of calcium is 1,300 mg. In Chile, the latest National Survey of Food Consumption showed that the median total calcium intake was less than half of the RDI. An adequate intake of calcium in adolescence negatively affects BMD. Aim: To determine the association of calcium intake and nutritional status with bone mineral density (BMD) in male and female adolescents with completed pubertal development (Tanner 5). Methods: Cross-sectional study in a random sample of 79 male and female adolescents, ages 17-18. Participants were healthy, Tanner stage 5, and BMI −1 SD. BMD was higher in obese participants compared to normal-weight adolescents (1.05±0.85 vs 0.33±0.86; P= 0.04), although no differences in nutrients and food intake. Calcium intake was unrelated to total bone mass and unstandardized BMD. Conclusions: In our sample of adolescents with complete pubertal development, there was no relationship between calcium intake and bone mineralization levels. There was a significant relationship between bone mineralization and nutritional status, with BMD being higher in adolescents with obesity.

Estudios de asociación de genoma completo (GWAS) versus validación funcional: reto de la era post-GWAS / Genome-wide association studies (GWAS) versus functional validation: challenge of the post-GWAS era

En los últimos años se han dedicado muchos esfuerzos a la determinación de variantes y genes que pueden ser impor-tantes en la determinación de la densidad mineral ósea (DMO) y, a su vez, en diversas patologías óseas. Para conseguiresto, la aproximación que ha presentado mayores éxitos ha sido la de los estudios de asociación de genoma completo(GWAS). En particular, en la investigación sobre la biología ósea, se han publicado más de 50 grandes GWAS o metaa-nálisis de GWAS identificando más de 500 loci genéticos asociados con diferentes parámetros óseos como son la DMO,la resistencia ósea y el riesgo de fractura. Si bien el descubrimiento de las variantes asociadas es un aspecto esencial,es igualmente importante la validación funcional de dichas variantes para dilucidar su efecto y la relación causal quetienen con la enfermedad genética. Al tratarse de un aspecto mucho más lento y tedioso, se ha convertido en el nuevoreto de esta era post-GWAS. Entre los genes que ya se han abordado se incluyen varios de la vía de WNT y en especialel gen SOST, que juega un papel muy importante tanto en la determinación de la DMO poblacional como en enferme-dades monogénicas con elevada masa ósea y que ha dado lugar a un nuevo tratamiento contra la osteoporosis. En estarevisión recogemos los principales estudios GWAS con relación a fenotipos del hueso, así como algunos ejemplos devalidaciones funcionales para analizar las asociaciones encontradas en los mismos.(AU)

Efecto de diferentes esquemas de terapia de deprivación androgénica sobre la densidad mineral ósea de pacientes con cáncer de próstata / Effect of different schemes of androgen deprivation therapy on bone mass density in prostate cancer patients

Objetivos: Evaluar aspectos del metabolismo óseo basal en pacientes con cáncer de próstata y el efecto, en práctica clínica habitual, de diferentes esquemas de tratamiento (intermitente o continuo) con agonistas de la hormona liberadora de hormona luteinizante (LH-RH) y del denosumab en la evolución de la densidad mineral ósea (DMO).MétodosEstudio observacional retrospectivo de una cohorte de pacientes con cáncer de próstata en tratamiento con agonistas LH-RH, valorados en el servicio de reumatología de un hospital de tercer nivel. Se recogieron datos demográficos, índice de FRAX, esquema de tratamiento LH-RH, tratamiento de osteoporosis, datos de laboratorio y de DMO. Se usaron modelos de regresión lineal de efecto mixto analizando la interacción de los esquemas de tratamiento LH-RH, denosumab y la evolución de DMO.ResultadosSe incluyeron 83 pacientes (73±8años). Evaluación basal: el 16% de los pacientes presentaron osteoporosis densitométrica y además un 27% un riesgo elevado de fractura (FRAX). El 80% tenían niveles de vitaminaD <30ng/l. La pauta intermitente de agonistas LH-RH y los niveles elevados de vitaminaD se asociaron a mejor DMO basal. No se detectó asociación entre la evolución de la DMO y las pautas de tratamiento de agonistas LH-RH, pero sí se encontró una correlación positiva con denosumab.ConclusionesUna elevada proporción de pacientes presentaban un alto riesgo de fractura o niveles insuficientes de vitaminaD no detectados previamente. El estudio tanto del metabolismo óseo como del riesgo de fractura son convenientes en estos pacientes. En práctica clínica habitual el efecto sobre la DMO del denosumab se detecta a corto plazo, mientras que el del esquema intermitente con agonistas LH-RH es menos evidente. (AU)

Objectives: To evaluate the aspects of the basal bone health status in prostate cancer patients. Furthermore, to evaluate in a real-world setting the effect of different schemes (intermittent or continuous) of androgen deprivation therapy (ADT) and the effect of denosumab in bone mass density (BMD).MethodsObservational, retrospective study of a cohort of prostate cancer patients in treatment with luteinizing hormone-releasing hormone (LH-RH) agonists, evaluated in the rheumatology department of a tertiary center. Demographics, FRAX score, LH-RH treatment scheme, osteoporosis treatment, laboratory data and BMD were collected. Mixed effect regression models to analyze the interaction between LH-RH treatment scheme, denosumab and BMD evolution were used.ResultsEighty-three patients (mean age 71±8years) were included. At the basal evaluation, 16% of patients presented densitometric osteoporosis and 27% of patients presented high fracture risk. Eighty percent of patients had inadequate vitaminD levels. VitaminD >30ng/mL was correlated with higher T-scores. There was no association between LH-RH treatment scheme and BMD evolution, however there was a positive association with denosumab.ConclusionA high proportion of patients presented elevated fracture risk or inadequate vitaminD levels, not previously recognized. Bone health assessment and fracture risk evaluation are convenient in these patients. In a real-world setting, the effect of denosumab in BMD is detected, however the effect of intermittent LH-RH schema treatment is less evident. (AU)

Evaluación de los factores relacionados con la aparición de nuevas fracturas por fragilidad: un estudio de casos y controles / Evaluation of factors related to the occurrence of new fragility fractures: A case–control study

Introducción: Las fracturas por fragilidad (FF) son frecuentes en pacientes osteoporóticos. Existen una serie de factores de riesgo y variables clínicas, que podrían predecir su aparición. Material y método: Se realizó un estudio observacional retrospectivo de casos y controles. Los casos estuvieron definidos por la presencia de una FF (326 participantes) y los controles por pacientes de similares características sin FF (629 participantes). Resultados: Ciertos factores aumentan el riesgo de FF, como un diagnóstico previo de DM tipo 2 (OR: 2,001), las elevaciones de 1ng/mL del CTX (OR: 1,88), tener antecedentes parentales de fractura de cadera (OR: 1,667), el aumento en 5 años en la edad (OR: 1,39) y los incrementos de 1kg/m2 del IMC (OR: 1,041). Por el contrario, otros factores evaluados disminuyen ese riesgo, como mantener unos niveles de 25(OH)D≥30ng/mL (OR: 0,686) y una T-score≥−2,5 (OR: 0,642). Conclusiones: Niveles de 25(OH)D≥30ng/mL y una T-score en el cuello femoral≥−2,5 son factores protectores de las FF, mientras que el diagnóstico previo de DM tipo 2, un CTX elevado, el antecedente parental de fractura de cadera, un incremento de 1kg/m2 del IMC y el aumento de la edad en 5 años serían predisponentes a padecer FF.(AU)

Introduction: Fragility fractures (FF) are frequent in osteoporotic patients. There are a series of risk factors and clinical variables that could predict their appearance. Material and method: A retrospective observational study of cases and controls was carried out. Cases were defined by the presence of FF (326 participants) and controls by patients with similar characteristics without FF (629 participants). Results: Certain factors increase the risk of FF, such as a previous diagnosis of type 2 DM (OR: 2.001), 1ng/mL elevations of CTX (OR: 1.88), having a parental history of hip fracture (OR: 1.667), 5-year increase in age (OR: 1.39), and 1kg/m2 increases in BMI (OR: 1.041). In contrast, other factors evaluated decreased this risk, such as maintaining 25(OH)D levels≥30ng/mL (OR: 0.686) and a T-score≥−2.5 (OR: 0.642). Conclusions: Levels of 25(OH)D≥30ng/mL and a T-score at the femoral neck≥−2.5 are protective factors for FF, while a previous diagnosis of type 2 DM, an elevated CTX, a parental history of hip fracture, an increase of 1kg/m2 in BMI and an increase in age by 5 years would be predisposing to FF.(AU)

[Translated article] Evaluation of factors related to the occurrence of new fragility fractures: A case–control study / Evaluación de los factores relacionados con la aparición de nuevas fracturas por fragilidad: un estudio de casos y controles

Introduction: Fragility fractures (FF) are frequent in osteoporotic patients. There are a series of risk factors and clinical variables that could predict their appearance. Material and method: A retrospective observational study of cases and controls was carried out. Cases were defined by the presence of FF (326 participants) and controls by patients with similar characteristics without FF (629 participants). Results: Certain factors increase the risk of FF, such as a previous diagnosis of type 2 DM (OR: 2.001), 1ng/mL elevations of CTX (OR: 1.88), having a parental history of hip fracture (OR: 1.667), 5-year increase in age (OR: 1.39), and 1kg/m2 increases in BMI (OR: 1.041). In contrast, other factors evaluated decreased this risk, such as maintaining 25(OH)D levels≥30ng/mL (OR: 0.686) and a T-score≥−2.5 (OR: 0.642). Conclusions: Levels of 25(OH)D≥30ng/mL and a T-score at the femoral neck≥−2.5 are protective factors for FF, while a previous diagnosis of type 2 DM, an elevated CTX, a parental history of hip fracture, an increase of 1kg/m2 in BMI and an increase in age by 5 years would be predisposing to FF.(AU)

Introducción: Las fracturas por fragilidad (FF) son frecuentes en pacientes osteoporóticos. Existen una serie de factores de riesgo y variables clínicas, que podrían predecir su aparición. Material y método: Se realizó un estudio observacional retrospectivo de casos y controles. Los casos estuvieron definidos por la presencia de una FF (326 participantes) y los controles por pacientes de similares características sin FF (629 participantes). Resultados: Ciertos factores aumentan el riesgo de FF, como un diagnóstico previo de DM tipo 2 (OR: 2,001), las elevaciones de 1ng/mL del CTX (OR: 1,88), tener antecedentes parentales de fractura de cadera (OR: 1,667), el aumento en 5 años en la edad (OR: 1,39) y los incrementos de 1kg/m2 del IMC (OR: 1,041). Por el contrario, otros factores evaluados disminuyen ese riesgo, como mantener unos niveles de 25(OH)D≥30ng/mL (OR: 0,686) y una T-score≥−2,5 (OR: 0,642). Conclusiones: Niveles de 25(OH)D≥30ng/mL y una T-score en el cuello femoral≥−2,5 son factores protectores de las FF, mientras que el diagnóstico previo de DM tipo 2, un CTX elevado, el antecedente parental de fractura de cadera, un incremento de 1kg/m2 del IMC y el aumento de la edad en 5 años serían predisponentes a padecer FF.(AU)

Bone mineral density and growth changes in patients with distal renal tubular acidosis after two-years treatment with a new alkalizing drug (ADV7103).

BACKGROUND AND OBJECTIVES: ADV7103 is a new prolonged-release treatment for distal renal tubular acidosis (dRTA), containing potassium citrate and potassium bicarbonate. Since acidosis may affect bone mineral contents, the effects of ADV7103 on bone mineral density (BMD) and growth in patients with dRTA over 24 months were evaluated. PATIENTS AND METHODS: Thirty patients (24 paediatric patients and 6 adults) were included in an open-label extension study after a phase II/III trial. BMD, measured by densitometry, was assessed at baseline and at 24 months. Growth was evaluated throughout the study. Plasma bicarbonate, parathyroid hormone, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, bone alkaline phosphatase, calciuria and citraturia, were also determined. Safety and treatment compliance were evaluated as well. RESULTS: After 24 months of treatment with ADV7103, mean spine BMD z-score values significantly increased as compared with baseline (p=0.024). In adults, spine and whole-body densitometry z-scores showed a significant correlation with plasma bicarbonate levels (rS=0.82 and rS=0.97, respectively, p<0.005). There was an increase>0.5 units in z-scores for height and weight in 18% and 36% of the paediatric patients, respectively. With treatment, plasma bicarbonate concentration and calciuria at the different visits were normal in 69-86% and 93-96% patients, respectively. Only nine treatment-related gastrointestinal AEs of mild/moderate severity, were reported in five patients. CONCLUSIONS: Two years of ADV7103 treatment improved growth and increased spine BMD. These results suggest that control of acidosis by ADV7103 treatment improves bone parameters.

[Translated article] Evaluation of factors related to the occurrence of new fragility fractures: A case-control study.

INTRODUCTION: Fragility fractures (FF) are frequent in osteoporotic patients. There are a series of risk factors and clinical variables that could predict their appearance. MATERIAL AND METHOD: A retrospective observational study of cases and controls was carried out. Cases were defined by the presence of FF (326 participants) and controls by patients with similar characteristics without FF (629 participants). RESULTS: Certain factors increase the risk of FF, such as a previous diagnosis of type 2 DM (OR: 2.001), 1ng/mL elevations of CTX (OR: 1.88), having a parental history of hip fracture (OR: 1.667), 5-year increase in age (OR: 1.39), and 1kg/m2 increases in BMI (OR: 1.041). In contrast, other factors evaluated decreased this risk, such as maintaining 25(OH)D levels≥30ng/mL (OR: 0.686) and a T-score≥-2.5 (OR: 0.642). CONCLUSIONS: Levels of 25(OH)D≥30ng/mL and a T-score at the femoral neck≥-2.5 are protective factors for FF, while a previous diagnosis of type 2 DM, an elevated CTX, a parental history of hip fracture, an increase of 1kg/m2 in BMI and an increase in age by 5 years would be predisposing to FF.