Utilidad del trabecular bone score en sujetos adultos con osteogénesis imperfecta / Usefulness of the trabecular bone score in adult subjects with osteogenesis imperfecta

Objetivo: Analizar la utilidad del trabecular bone score (TBS) en adultos con osteogénesis imperfecta (OI) y su relación con variables clínicas, antropométricas y densitométricas, especialmente con la presencia de fracturas y la severidad de la enfermedad.Material y métodos: Estudio transversal realizado en 31 pacientes adultos con OI (edad 40.5±15.2 años, 68% mujeres, 87% tipo I). Se analizaron las características clínicas de los pacientes (fracturas, tipo de OI, IMC y tratamiento), la densidad mineral ósea (DMO) (mediante DXA), valorando la presencia de osteoporosis densitométrica, y los valores de TBS (TBS iNsight), estimando la presencia de microarquitectura degradada (valores <1.230). Los resultados se compararon entre los diferentes tipos de OI (I y III-IV) y con los de un grupo control de sujetos sanos.Resultados: La mayoría de los pacientes (29/31, 94%) tenían antecedentes de fracturas y el 29% recibía tratamiento antiosteoporótico. El 61% tenía una osteoporosis densitométrica y el 19% tenían una microarquitectura degradada. No se observaron diferencias en los valores del TBS según la gravedad de la OI (OI tipo I vs. III-IV: 1.297 vs. 1.339, p=n.s.); ningún paciente con OI tipo III-IV tenía TBS<1.230. Los valores de TBS se relacionaron con la edad (r=-0.6, p<0.01), la DMO lumbar (r=0.4, p=0.03) y el IMC (r=-0.5, p=0.01). Los pacientes con OI tenían valores más bajos de TBS y DMO que el grupo control en todas las localizaciones analizadas.Conclusión: El TBS es poco sensible en la valoración de la calidad ósea en la OI, pues ninguno de los pacientes con OI grave tenía una microarquitectura degradada y ésta sólo se observó en el 19% de los pacientes con OI a pesar de presentar una alta prevalencia de fracturas. (AU)

Resumen ejecutivo de las guías de práctica clínica en la osteoporosis posmenopáusica, glucocorticoidea y del varón (actualización 2022). Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM) / Executive summary clinical practice guideline of postmenopausal, glucocortcioid-induced and male osteoporosis (2022 update). Spanish Society for Bone and Mineral Metabolism Investigation (SEIOMM)

Esta versión actualizada de las guías de osteoporosis de la Sociedad Española de Investigación en Osteoporosis y Metabolismo Mineral (SEIOMM) incorpora la información más relevante publicada en los últimos 7años, desde las guías de 2015, con estudios de imagen, como la valoración de la fractura vertebral y el análisis del índice trabecular óseo. Además, los avances terapéuticos incluyen los nuevos fármacos anabólicos, los estudios comparativos de la eficacia de los fármacos y la terapia secuencial y combinada. Por ello se actualizan también las recomendaciones de los tratamientos (AU)

This updated version of the Spanish Society for Research in Osteoporosis and Mineral Metabolism (SEIOMM) osteoporosis guides incorporate the most relevant information published in the last 7years, since the 2015 guides, with imaging studies, such as vertebral fracture assessment and bone trabecular score analysis. In addition, therapeutic advances include new anabolic agents, comparative studies of drug efficacy, and sequential and combined therapy. Therefore, therapeutic algorithms are also updated (AU)

Health-related quality of life of X-linked hypophosphatemia in Spain.

BACKGROUND: Health-related quality of life (HRQoL) of patients with X-linked hypophosphatemia (XLH) is lower than that of both the general population and the patients with other chronic diseases, mainly due to diagnostic delay, treatment difficulties, poor psychosocial support, and problems with social integration. Early diagnosis and optimal treatment are paramount to control the disease in patients with XLH, avoid complications, and maintain or improve their HRQoL. We, therefore, analyzed the HRQoL of pediatric and adult patients with XLH treated with conventional therapy in Spain. RESULTS: We used several versions of the EuroQol-5 dimensions (EQ-5D) instrument according to the age of patients with XLH. Then we compared the HRQoL of patients to that of the general Spanish population. Children with XLH (n = 21) had moderate problems in walking about (61.9%), washing or dressing themselves (9.52%), and performing their usual activities (33.33%). They also felt moderate pain or discomfort (61.9%) and were moderately anxious or depressed (23.81%). Adults with XLH (n = 29) had lower HRQoL, with problems in walking (93%, with 3.45% unable to walk independently), some level of pain (86%, with 3.45% experiencing extreme pain), problems with their usual activities (80%) and self-care (> 50%), and reported symptoms of anxiety and/or depression (65%). There were important differences with the general Spanish population. CONCLUSIONS: XLH impacts negatively on physical functioning and HRQoL of patients. In Spanish patients with XLH, the HRQoL was reduced despite conventional treatment, clearly indicating the need to improve the therapeutic approach to this disorder.

X-linked hypophosphatemia (XLH) is a severe inherited disease. It is caused by loss of phosphorus by kidneys. As a result, blood level of phosphorus is low, affectingX-linked hypophosphatemia (XLH) is a severe inherited disease. It is caused by loss of phosphorus by kidneys. As a result, blood level of phosphorus is low, affecting bones and muscles. Patients can have growth retardation, short stature, rickets, limb deformities, pain and other health problems despite traditional treatment. Consequently, their quality of life can be very bad. However, a recently available new treatment (burosumab) can improve this quality of life. We studied the quality of life of children and adults with XLH treated with traditional treatment in Spain. Results showed that children had moderate problems, but adults reported moderate-to-severe problems in walking and performing their usual activities and self-care. Pain and anxiety and/or depression were very frequent. There were important differences with the general Spanish population. Moreover, we also found that XLH is associated to high healthcare cost and even higher socioeconomic cost. Our results highlight the need of improving the treatment of XLH.bones and muscles. Patients can have growth retardation, short stature, rickets, limb deformities, pain and other health problems despite traditional treatment. Consequently, their quality of life can be very bad. However, a recently available new treatment (burosumab) can improve this quality of life. We studied the quality of life of children and adults with XLH treated with traditional treatment in Spain. Results showed that children had moderate problems, but adults reported moderate-to-severe problems in walking and performing their usual activities and self-care. Pain and anxiety and/or depression were very frequent. There were important differences with the general Spanish population. Moreover, we also found that XLH is associated to high healthcare cost and even higher socioeconomic cost. Our results highlight the need of improving the treatment of XLH.

Efecto del tratamiento con denosumab durante 24 meses en individuos con lesión medular reciente con osteoporosis / Effect of 24-month denosumab treatment in individuals with recent spinal cord injury and osteoporosis

Introducción: El desarrollo de osteoporosis es una complicación frecuente tras una lesión medular (LM), especialmente bajo el nivel de la lesión. Sin embargo, su abordaje terapéutico continúa siendo incierto.Objetivo: Analizar la evolución de la densidad mineral ósea (DMO) y de los marcadores de remodelado óseo (MRO) en individuos con una LM reciente y osteoporosis asociada tratados con denosumab durante 24 meses.Métodos: Estudio prospectivo en el que se incluyeron pacientes con LM reciente y osteoporosis que recibieron tratamiento con denosumab durante 24 meses. A todos ellos se les realizó una analítica con determinación de MRO (PINP, CTX y FA ósea), 25-OH- vitamina D y una densitometría ósea en columna lumbar y fémur proximal basal y a los 12 y 24 meses.Resultados: Se incluyeron 13 pacientes (media de edad de 39±15 años) con LM reciente (con un tiempo medio de evolución de 15 meses) y osteoporosis. Todos los pacientes recibieron tratamiento con denosumab durante 24 meses. A los 12 meses de tratamiento con denosumab se observó un aumento significativo de la DMO en columna lumbar y fémur proximal, con un incremento adicional de los valores de DMO tras 24 meses de tratamiento, que fue del orden del 9,1% en columna lumbar, 4,4% en cuello de fémur y 5,3% en fémur total. Asimismo, los valores de los MRO disminuyeron de forma significativa durante los 24 meses de tratamiento. Ningún paciente presentó fracturas por fragilidad y no se observaron acontecimientos adversos relacionados con el tratamiento.Conclusiones: El tratamiento con denosumab durante 24 meses aumenta la DMO lumbar y femoral y disminuye los MRO en pacientes con LM reciente con osteoporosis. Denosumab parece ser una opción terapéutica prometedora en esta condición clínica. (AU)

Executive summary clinical practice guideline of postmenopausal, glucocortcioid-induced and male osteoporosis (2022 update). Spanish Society for Bone and Mineral Metabolism Investigation (SEIOMM).

This updated version of the Spanish Society for Research in Osteoporosis and Mineral Metabolism (SEIOMM) osteoporosis guides incorporate the most relevant information published in the last 7 years, since the 2015 guides, with imaging studies, such as vertebral fracture assessment and bone trabecular score analysis. In addition, therapeutic advances include new anabolic agents, comparative studies of drug efficacy, and sequential and combined therapy. Therefore, therapeutic algorithms are also updated.

Resumen ejecutivo de las Guías de práctica clínica en la osteoporosis postmenopáusica, glucocorticoidea y del varón (actualización 2022) / Executive summary clinical practice guideline of postmenopausal, glucocorticoid-induced, and male osteoporosis (2022 update)

Esta versión actualizada de la Guía de osteoporosis de la SEIOMM (Sociedad Española de Investigación en Osteoporosis y Metabolismo Mineral) incorpora la información más relevante publicada en los últimos 7 años, desde la Guía de 2015, con estudios de imagen, como la valoración de la fractura vertebral y el análisis del índice trabecular óseo. Además, los avances terapéuticos incluyen los nuevos fármacos anabólicos, los estudios comparativos de la eficacia de los fármacos y la terapia secuencial y combinada. Por ello se actualizan también las recomendaciones de los tratamientos. (AU)

Guías de práctica clínica en la osteoporosis postmenopáusica, glucocorticoidea y del varón (actualización 2022). Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM) / Clinical practice guidelines in postmenopausal, glucocorticoid and male osteoporosis (update 2022). Spanish Society for Bone and Mineral Metabolism Research (SEIOMM)

Esta actualización de las Guías incorpora la información más relevante aparecida durante los 7 años trascurridos desde la publicación de la versión anterior, especialmente en cuanto a procedimientos diagnósticos y opciones terapéuticas. Entre los primeros, merece la pena destacar la incorporación del TBS y la detección de fracturas vertebrales por densitometría. Entre los tratamientos, se consideran los nuevos fármacos anabólicos, los estudios comparativos de eficacia en osteoporosis grave, las pautas de actuación tras la suspensión de los antirresortivos y otros esquemas de tratamiento secuencial y combinado. Teniendo en cuenta todo ello, se actualizan los esquemas de tratamiento recomendados. (AU)

12ª Lección Jesús Culebras. La alimentación y la nutrición en los enfermos con cáncer de cabeza y cuello: un reto permanente / 12th "Jesús Culebras" Lesson. Feeding and nutrition in patients with head and neck cancer - A permanent challenge

Los enfermos con cáncer de cabeza y cuello son una población en riesgo nutricional permanente. El motivo es, además de la presencia del tumor, la localización del mismo, que afecta a todas las estructuras implicadas en la deglución. Los efectos secundarios de los tratamientos oncológicos que deben recibir en el transcurso de su enfermedad —cirugía, quimio-radioterapia, etc.— no hacen sino gravar más aun un estado nutricional ya de por sí precario. Por todo ello es imprescindible que, desde el diagnóstico de su enfermedad, estén supervisados por un equipo multidisciplinar con especialistas en dietética y nutrición (AU)

Head and neck cancer patients are a population at permanent nutritional risk. In addition to the presence of the tumour, the reason for this is the tumour's location, which affects all structures involved in the swallowing process. The side effects of the oncological treatments they must receive during the course of their illness—surgery, chemo-radiotherapy, etc.—only further burden an already precarious nutritional status. For all these reasons, it is essential that, from the diagnosis of their disease, a multidisciplinary team including specialists in dietetics and nutrition supervises them (AU)

Low serum osteocalcin levels are associated with diabetes mellitus in glucocorticoid treated patients.

Bone turnover markers are decreased in GC-treated subjects with DM. Decreased OC levels in GC-treated patients were associated with an increased risk of DM. These results suggest the involvement of OC in glucose homeostasis regulation in DM. INTRODUCTION: Osteocalcin (OC) is involved in the regulation of glucose homeostasis. Glucocorticoid (GC) treatment is associated with impaired osteoblast function, decreased OC levels, and the development and/or worsening of pre-existing diabetes mellitus (DM). Whether decreased OC levels in GC-treated subjects contribute to DM is not well known. The aim of this study was to analyse whether OC levels in GC-treated patients are associated with the presence of DM. METHODS: One hundred twenty-seven patients (aged 61.5 ± 17.9 years) on GC treatment were included. GC dose, treatment duration, presence of DM and bone formation (OC, bone ALP, PINP) and resorption markers (urinary NTX, serum CTX) were analysed. The cut-offs of each bone turnover marker (BTM) for the presence of DM were evaluated and optimised with the Youden index and included in the logistic regression analysis. RESULTS: Among the patients, 17.3% presented DM. No differences were observed in GC dose or duration or the presence of fractures. Diabetics showed lower levels of OC (7.57 ± 1.01 vs. 11.56 ± 1; p < 0.001), PINP (21.48 ± 1.01 vs. 28.39 ± 1; p = 0.0048), NTX (24.91 ± 1.01 vs. 31.7 ± 1; p = 0.036) and CTX (0.2 ± 1.01 vs. 0.3 ± 1; p = 0.0016). The discriminating BTM cut-offs for DM presence were < 9.25 ng/mL for OC, < 24 ng/mL for PINP, < 27.5 nMol/mM for NTX and < 0.25 ng/mL for CTX. In a multivariate logistic regression model adjusted for GC dose, BMI, age and the above four BTMs, only OC remained independently associated with DM presence. Thus, in a model adjusted for GC dose, BMI and age, OC was significantly associated with DM (OR: 6.1; 95%CI 1.87-19.89; p = 0.001). CONCLUSION: Decreased OC levels in GC-treated patients are associated with increased odds of DM, and only OC was independently associated with DM in a model including four BTMs.

Correction to: Prevalent vertebral fractures and minor vertebral deformities analyzed by vertebral fracture assessment (VFA) increases the risk of incident fractures in postmenopausal women: the FRODOS study.

Figure 1 as published in the original version of this article was unfortunately incomplete.

Prevalent vertebral fractures and minor vertebral deformities analyzed by vertebral fracture assessment (VFA) increases the risk of incident fractures in postmenopausal women: the FRODOS study.

The incidence of vertebral fractures (VF) by vertebral fracture assessment (VFA) was 6.6% in postmenopausal women (FRODOS cohort) after 4 years of follow-up, increasing with prevalent VF and minor vertebral deformities, age, lower bone mass, glucocorticoid use, and rheumatoid arthritis. This study supports the usefulness of VFA to identify VF. PURPOSE: Vertebral fracture assessment (VFA) is increasingly used to identify spine fractures, but few cohort studies have used this method in prevalence and incidence assessment. We previously reported the prevalence of vertebral fractures (VF) and minor vertebral deformities (MVD) by morphometric VFA in a population-based cohort of postmenopausal women (FRODOS study). Therefore, the aim of this study was to analyze the incidence of VF, the associated risk factors, and particularly the role of MVD in this cohort of subjects. METHODS: We performed a longitudinal analysis of 2510 women aged 59-70 years participating in the FRODOS prevalence study (2006-2009) with evaluable VFA 4 years later. VFA at baseline and in the present study was assessed by quantitative vertebral morphometry and by visual semiquantitative measurement. The multivariate Poisson regression model was performed, and relative risks with confidence interval of 95% were calculated for the incidence of VF. Bone mineral density (BMD) and an osteoporosis questionnaire were collected. RESULTS: Overall, the incidence of VF was 6.6%, increasing with prevalent VF (24.5%) and in women with prevalent MVD (17.7%). Age and low BMD were also associated risk factors as were the presence of rheumatoid arthritis and exposure to glucocorticoids and bisphosphonates. CONCLUSIONS: The presence of prevalent VF assessed by VFA is associated with further incident spinal fractures in postmenopausal women. In addition, having MVD confers an increased risk of new VF.

Direct costs of a home parenteral nutrition programme.

BACKGROUND & AIMS: Home parenteral nutrition (HPN) is a lifesaving treatment for people with chronic intestinal failure and its cost has been reported to be very high. The purpose of the present paper was to study the direct healthcare and non-healthcare costs associated with the HPN programme managed by a tertiary hospital. METHODS: Observational, retrospective study of all adult patients on HPN from 11.1.2014 to 10.31.2015 treated at Gregorio Marañón University Hospital (Madrid, Spain). An economic evaluation was undertaken to calculate the direct healthcare (HPN provision, outpatient monitoring and management of complications) and non-healthcare costs (transportation process) of the HPN programme. The variables were collected from medical records, the dispensary and the hospital's financial services. The unit costs were taken from official price lists. RESULTS: Thirty-two patients met the inclusion criteria. Total direct healthcare and non-healthcare costs amounted to €13,363.53 per patient (€124.02 per patient per day). The direct healthcare costs accounted for 98.32% of overall costs, while the non-healthcare costs accounted for the remaining 1.68%. HPN provision accounted for the majority of the costs (74.25%), followed by management of complications (21.85%) and outpatient monitoring (2.23%). CONCLUSIONS: The direct healthcare costs accounted for the majority of HPN expenditure, specifically HPN provision was the category with the highest percentage.

Utilidad del Trabecular Bone Score en la valoración del riesgo de fractura osteoporótica / Usefulness of the Trabecular Bone Score for assessing the risk of osteoporotic fracture

Introducción y objetivos. El Trabecular Bone Score (TBS) es una técnica de imagen que evalúa el estado de la microarquitectura trabecular. Resultados preliminares sugieren que, junto a la valoración de la densidad mineral ósea, podría mejorar la estimación del riesgo de fractura ostoporótica. El objetivo de este estudio fue analizar los valores de TBS y su relación con las características clínicas, densidad mineral ósea y antecedentes de fracturas en una cohorte de mujeres posmenopáusicas. Material y métodos. Analizamos 2.257 mujeres posmenopáusicas procedentes de la cohorte FRODOS, constituida para determinar los factores de riesgo de fractura osteoporótica mediante una encuesta clínica y densitometría ósea con morfometría vertebral. Se aplicó el TBS a las imágenes densitométricas. Valores de TBS ≤1,230 se consideraron indicativos de microarquitectura degradada. Se realizó una regresión lineal simple y múltiple para determinar los factores asociados con este índice. Resultados. El valor medio de TBS en L1-L4 fue de 1,203±0,121. El 55,3% de las mujeres presentaban valores de microarquitectura degradada. En el análisis de regresión lineal múltiple los factores asociados a los valores bajos de TBS fueron la edad, el peso, la altura, escala T de columna lumbar, tratamiento con glucocorticoides, presencia de diabetes tipo 2 y antecedentes de fractura por fragilidad. Conclusiones. El TBS mostró valores de microarquitectura degradada en las participantes de la cohorte FRODOS y se asoció a factores antropométricos, valor bajo de densidad mineral ósea, presencia de fracturas, antecedentes de diabetes mellitus tipo 2 y uso de glucocorticoides

Introduction and objectives. The trabecular bone score (TBS) is an imaging technique that assesses the condition of the trabecular microarchitecture. Preliminary results suggest that TBS, along with the bone mineral density assessment, could improve the calculation of the osteoporotic fracture risk. The aim of this study was to analyse TBS values and their relationship with the clinical characteristics, bone mineral density and history of fractures of a cohort of posmenopausal women. Material and methods. We analysed 2,257 posmenopausal women from the FRODOS cohort, which was created to determine the risk factors for osteoporotic fracture through a clinical survey and bone densitometry with vertebral morphometry. TBS was applied to the densitometry images. TBS values ≤1230 were considered indicative of degraded microarchitecture. We performed a simple and multiple linear regression to determine the factors associated with this index. Results. The mean TBS value in L1-L4 was 1.203±0.121. Some 55.3% of the women showed values indicating degraded microarchitecture. In the multiple linear regression analysis, the factors associated with low TBS values were age, weight, height, spinal T-score, glucocorticoid treatment, presence of type 2 diabetes and a history of fractures due to frailty. Conclusions. TBS showed microarchitecture degradation values in the participants of the FRODOS cohort and was associated with anthropometric factors, low bone mineral density values, the presence of fractures, a history of type 2 diabetes mellitus and the use of glucocorticoids

Usefulness of the Trabecular Bone Score for assessing the risk of osteoporotic fracture. / Utilidad del Trabecular Bone Score en la valoración del riesgo de fractura osteoporótica.

INTRODUCTION AND OBJECTIVES: The trabecular bone score (TBS) is an imaging technique that assesses the condition of the trabecular microarchitecture. Preliminary results suggest that TBS, along with the bone mineral density assessment, could improve the calculation of the osteoporotic fracture risk. The aim of this study was to analyse TBS values and their relationship with the clinical characteristics, bone mineral density and history of fractures of a cohort of posmenopausal women. MATERIAL AND METHODS: We analysed 2,257 posmenopausal women from the FRODOS cohort, which was created to determine the risk factors for osteoporotic fracture through a clinical survey and bone densitometry with vertebral morphometry. TBS was applied to the densitometry images. TBS values ≤1230 were considered indicative of degraded microarchitecture. We performed a simple and multiple linear regression to determine the factors associated with this index. RESULTS: The mean TBS value in L1-L4 was 1.203±0.121. Some 55.3% of the women showed values indicating degraded microarchitecture. In the multiple linear regression analysis, the factors associated with low TBS values were age, weight, height, spinal T-score, glucocorticoid treatment, presence of type 2 diabetes and a history of fractures due to frailty. CONCLUSIONS: TBS showed microarchitecture degradation values in the participants of the FRODOS cohort and was associated with anthropometric factors, low bone mineral density values, the presence of fractures, a history of type 2 diabetes mellitus and the use of glucocorticoids.

Analysis of the evolution of cortical and trabecular bone compartments in the proximal femur after spinal cord injury by 3D-DXA.

Marked trabecular and cortical bone loss was observed at the proximal femur short-term after spinal cord injury (SCI). 3D-DXA provided measurement of vBMD evolution at both femoral compartments and cortical thinning, thereby suggesting that this technique could be useful for bone analysis in these patients. INTRODUCTION: SCI is associated with a marked increase in bone loss and risk of osteoporosis development short-term after injury. 3D-DXA is a new imaging analysis technique providing 3D analysis of the cortical and trabecular bone from DXA scans. The aim of this study was to assess the evolution of trabecular macrostructure and cortical bone using 3D-DXA in patients with recent SCI followed over 12 months. METHODS: Sixteen males with recent SCI (< 3 months since injury) and without antiosteoporotic treatment were included. Clinical assessment, bone mineral density (BMD) measurements by DXA, and 3D-DXA evaluation at proximal femur (analyzing the integral, trabecular and cortical volumetric BMD [vBMD] and cortical thickness) were performed at baseline and at 6 and 12 months of follow-up. RESULTS: vBMD significantly decreased at integral, trabecular, and cortical compartments at 6 months (- 8.8, - 11.6, and - 2.4%), with a further decrease at 12 months, resulting in an overall decrease of - 16.6, - 21.9, and - 5.0%, respectively. Cortical thickness also decreased at 6 and 12 months (- 8.0 and - 11.4%), with the maximal decrease being observed during the first 6 months. The mean BMD losses by DXA at femoral neck and total femur were - 17.7 and - 21.1%, at 12 months, respectively. CONCLUSIONS: Marked trabecular and cortical bone loss was observed at the proximal femur short-term after SCI. 3D-DXA measured vBMD evolution at both femoral compartments and cortical thinning, providing better knowledge of their differential contributory role to bone strength and probably of the effect of therapy in these patients.

Effect of recent spinal cord injury on the OPG/RANKL system and its relationship with bone loss and the response to denosumab therapy.

There is marked bone loss after spinal cord injury (SCI); however, its pathogenesis and clinical management remain unclear. The increased circulating levels of receptor activator of nuclear factor kB ligand (RANKL) associated with bone loss shortly after SCI and the prevention of bone loss with denosumab treatment suggest a contributory role of RANKL in SCI-induced osteoporosis. INTRODUCTION: Bone turnover and bone loss are markedly increased shortly after SCI. However, the pathogenesis and clinical management of this process remain unclear, especially the role of the osteoprotegerin (OPG)/RANKL system in this disorder. The aim of this study was to analyze serum levels of OPG and RANKL in bone loss associated with recent SCI and the effect of denosumab treatment on these mediators. METHODS: Twenty-three males with recent complete SCI were prospectively included. Serum OPG and RANKL levels, bone turnover markers (PINP, bone ALP, CTX), and bone mineral density (BMD) were assessed at baseline, at 6 months of follow-up, prior to initiating denosumab, and 6 months after treatment. The results were compared with a healthy control group. RESULTS: At baseline, SCI patients showed higher RANKL levels vs. controls which were correlated with days-since-SCI and total hip BMD loss at 6 months. OPG levels were similar to controls at baseline. After denosumab treatment, OPG showed no changes, whereas RANKL levels became undetectable in 67% of patients. Patients with undetectable RANKL during treatment showed better response in femoral BMD and bone markers vs. patients with detectable RANKL at 6 months of denosumab. Increased parathormone (PTH) levels during treatment were negatively correlated with RANKL changes. CONCLUSIONS: RANKL levels are increased after SCI and related to BMD loss at the proximal femur, becoming undetectable after denosumab treatment. The effect of denosumab on preventing sublesional bone loss, especially in patients with undetectable levels during treatment, suggests a contributory role of RANKL in this process.

Comparison of total, free and bioavailable 25-OH vitamin D determinations to evaluate its biological activity in healthy adults: the LabOscat study.

Determination of different forms of 25-OHD (total, free and bioavailable) in healthy young women does not offer additional advantages over standard 25-OHDT for evaluating vitamin D deficiency. In these subjects 25-OHDT values <15 ng/ml would be more appropriate for defining this deficiency. INTRODUCTION: Determination of 25-OH vitamin D serum levels (25-OHD) constitutes the method of choice for evaluating vitamin D deficiency. However, vitamin D-binding protein (DBP) may modulate its bioavailability thereby affecting correct evaluation of 25-OHD status. We analysed the impact of the determination of 25-OHD (total, free and bioavailable) on the evaluation its biologic activity (estimated by serum PTH determination) in healthy young women. METHODS: 173 premenopausal women (aged 35-45 yrs.) were included. We analysed serum values of total 25-OHD (25-OHDT), DBP, albumin, PTH and bone formation (PINP,OC) and resorption (NTx,CTx) markers. Free(25-OHDF) and bioavailable (25-OHDB) serum 25-OHD levels were estimated by DBP and albumin determinations and also directly by ELISA (25-OHDF-2). We analysed threshold PTH values for the different forms of 25-OHD and the correlations and differences according to 25-OHDT levels <20 ng/ml. RESULTS: 62% of subjects had 25-OHD values <20 ng/ml and also had significantly lower 25-OHDF and 25-OHDB values, with no significant differences in bone markers and PTH values. The PTH threshold value was similar for all forms of 25-OHD (∼70 pg/ml). Women with PTH values >70 had lower 25-OHDT (15.4 ± 1.4 vs. 18.3 ± 2.7, p < 0.05) and 25OHDB values (1.7 ± 0.2 vs. 2.2 ± 0.09, p < 0.05). The different forms of 25OHD were significantly intercorrelated, with marginal correlations between PTH and 25-OHDT (r = -0.136, p = 0.082). CONCLUSIONS: Determination of different forms of 25-OHD in healthy young women does not offer additional advantages over standard 25-OHDT for evaluating vitamin D deficiency. In these subjects 25-OHDT values <15 ng/ml would be more appropriate for defining this deficiency.

Development of multiorganic calciphylaxis during teriparatide, vitamin D, and calcium treatment.

Non-uremic calciphylaxis is a severe rare disorder characterized by ischemic necrosis. Recently, three cases of cutaneous calciphylaxis have been described in the context of teriparatide treatment. We present a 51-year-old woman with alcoholic cirrhosis who developed multiorganic calciphylaxis shortly after starting teriparatide treatment associated with calcium and 25-hydroxyvitamin D supplements for severe osteoporosis. After lengthy care of the infectious complications and treatment with bisphosphonates and sodium thiosulfate progressive improvement was observed over a 3-year period. The time between the initiation of teriparatide and the development of calciphylaxis suggests that this agent may have been the triggering factor of this process. Nevertheless, other non-negligible risk factors for calciphylaxis such as alcoholic liver disease, obesity, and vitamin D treatment must also be considered in this patient. Considering the severity of this extremely rare clinical condition, better knowledge of the risk factors related to calciphylaxis development is mandatory.

Denosumab increases sublesional bone mass in osteoporotic individuals with recent spinal cord injury.

UNLABELLED: Osteoporosis is a frequent complication related to spinal cord injury (SCI), and data on osteoporosis treatment after SCI is scarce. Treatment with denosumab increases lumbar and femoral BMD and decreases bone turnover markers in individuals with recent SCI. This drug may be a promising therapeutic option in SCI-related osteoporosis. INTRODUCTION: Osteoporosis development is a frequent complication related to SCI, especially at the sublesional level. Nevertheless, data on osteoporosis treatment after SCI is scarce, particularly short term after injury, when the highest bone loss is produced. The aim of this study was to analyze the efficacy of denosumab in the treatment of SCI-related osteoporosis. METHODS: Fourteen individuals aged 39 ± 15 years with osteoporosis secondary to recent SCI (mean injury duration 15 ± 4 months) were treated with denosumab for 12 months. Bone turnover markers (BTMs) (PINP, bone ALP, sCTx), 25-hydroxyvitamin D (25OHD) levels and bone mineral density (BMD) at the lumbar spine (LS), total hip (TH), and femoral neck (FN) were assessed at baseline and at 12 months. All participants received calcium and vitamin D supplementation. RESULTS: At 12 months, SCI denosumab-treated participants showed a significant increase in BMD at TH (+2.4 ± 3.6 %, p = 0.042), FN (+3 ± 3.6 %, p = 0.006), and LS (+7.8 ± 3.7 %, p < 0.001) compared to baseline values. Denosumab treatment was associated with significant decreases in BTMs (bone ALP -42 %, p < 0.001; PINP -58 %, p < 0.001, sCTx -57 %, p = 0.002) at 12 months. BMD evolution was not related to BTM changes or 25OHD serum levels. No skeletal fractures or serious adverse events were observed during follow-up. CONCLUSIONS: Treatment with denosumab increases lumbar and femoral BMD and decreases bone turnover markers in individuals with recent SCI. This drug may be a promising therapeutic option in SCI-related osteoporosis.