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.

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.

Risk factors for the development of osteoporosis after spinal cord injury. A 12-month follow-up study.

UNLABELLED: Spinal cord injury (SCI) has been associated with a marked bone loss after injury and a consequent increased risk of osteoporosis. The evaluation of bone mineral density shortly after SCI is a simple and effective method for predicting the development of osteoporosis during the first year after SCI. INTRODUCTION: Spinal cord injury (SCI) has been associated with a marked bone loss after injury and a consequent increased risk of osteoporosis and fractures. The aim of this study was to analyze the factors associated with osteoporosis development short-term after SCI. METHODS: We included patients with complete recent SCI (<6 months) evaluating bone turnover markers (P1NP, bone ALP, and sCTx), 25-OH-vitamin D (25OHD) levels, and lumbar and femoral BMD (Lunar, Prodigy) at baseline, 6 and 12 months after SCI. The risk factors for osteoporosis analyzed included the following: age, gender, BMI, toxic habits, bone turnover markers, 25OHD levels, lumbar and femoral BMD, level, severity and type of SCI, and days-since-injury. Osteoporosis was defined according to WHO criteria. RESULTS: Thirty-five patients aged 35 ± 16 years were included, and 52 % developed osteoporosis during the 12-month follow-up. These latter patients had lower BMD values at femur and lumbar spine and higher bone turnover markers at baseline. On multivariate analysis, the principal factors related to osteoporosis development were as follows: total femur BMD <1 g/cm(2) (RR, 3.61; 95 % CI 1.30-10.06, p = 0.002) and lumbar BMD <1.2 g/cm(2) at baseline (0.97 probability of osteoporosis with both parameters under these values). Increased risk for osteoporosis was also associated with increased baseline values of bone ALP (>14 ng/mL) (RR 2.40; 95 % CI 1.10-5.23, p = 0.041) and P1NP (>140 ng/mL) (RR 3.08; 95 % CI 1.10-8.57, p = 0.017). CONCLUSIONS: The evaluation of BMD at the lumbar spine and femur short-term after SCI is a simple, effective method for predicting the development of osteoporosis during the first year after SCI. Our results also indicate the need to evaluate and treat these patients shortly after injury.

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)

Effect of glucocorticoid treatment on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover.

The aim of this study was to analyse the effect of glucocorticoid therapy (GCCT) on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover. 25 patients (8 M/17 F, aged 48±19yrs) recently initiating GCCT (≥7.5mg/day, ≤6months) were prospectively included. Bone turnover markers (bone formation: P1NP, osteocalcin [OC], bone ALP; bone resorption: sCTx) and Wnt antagonists (serum sclerostin and Dkk-1) were assessed in all patients (short-term and 12months after initiating GCCT). Bone mineral density (BMD) was performed to assess osteoporosis. The results were compared with 60 healthy controls. At short-term patients on GCCT showed a significant decrease in bone formation markers versus controls (P1NP: 19±9 vs. 43±16ng/mL, p<0.001; OC: 7.4±2.4 vs. 18.4±5.2ng/mL, p=0.001) and in Dkk-1 levels (24.5±20.1 vs. 36.8±13.7pmol/L, p=0.008) with similar sclerostin values (41.8±21.8 vs. 42.1±13.9pmol/L, p=0.950). Sclerostin correlated positively with GCCT doses (r=0.449, p=0.024) and lumbar BMD (r=0.424, p=0.035), and negatively with bone ALP (r=-0.398, p=0.049). A progressive decrease in Dkk-1 levels was observed at 12months, (19.1±14.9, p=0.001), whereas sclerostin increased compared to controls (48.9±11.6, p=0.045). In conclusion, the effect of GCCT on the serum levels of the Wnt signalling parameters differs depending on the antagonist evaluated. Whereas sclerostin values increased and showed a relationship with the dose and bone AP, Dkk-1 levels decreased throughout the study suggesting a counter-regulatory mechanism of this factor thereby reducing the deleterious effect of GCCT in the bone.

Factores relacionados con la respuesta inadecuada al tratamiento osteoformador (teriparatida/PTH 1-84) en pacientes con osteoporosis severa. Resultados preliminares / Factors related to bone forming inadequate response to treatment (teriparatide/PTH 1-84) in patients with severe osteoporosis. Preliminary results

El objetivo de este estudio ha sido analizar la evolución de la masa ósea a largo plazo tras tratamiento osteoformador (teriparatida o PTH 1-84) en pacientes con osteoporosis severa, y determinar la frecuencia y los factores relacionados con una respuesta inadecuada (RI) al tratamiento. Métodos: Se incluyeron 49 pacientes (46 mujeres:3 hombres) con una edad media de 69,5±11,1 años, tratados con teriparatida (41) o PTH1-84 (8) durante 18/24 meses (84% tenían fracturas vertebrales y 84% habían recibido tratamiento previamente). Se analizaron: factores de riesgo y causa de osteoporosis, fracturas y tratamiento antiosteoporótico previo. Se valoraron los marcadores de recambio óseo (MRO), los niveles de 25-OH vitamina D (25OHD) basal y a los 3, 6, 12 y 18/24 meses, radiografías de columna dorso-lumbar y densitometría ósea (DMO) previa, a los 12 y 18/24 meses. Se definió RI cuando el cambio de DMO lumbar era (AU)

The aim of this study was to evaluate the long-term bone mineral density (BMD) response rate to osteoanabolic treatment in patients with severe osteoporosis and the factors related to 'inadequate' response (IR). Methods: 49 patients (46F:3M) with a mean age of 69.5±11.1 years treated with teriparatide (41) or PTH1-84 (8) during 18/24months were included (84% had vertebral fractures and 84% had previously received bisphosphonates). Previous skeletal fractures and antiosteoporotic treatment, risk factors and cause of osteoporosis were recorded in all patients. Bone turnover markers (BTM) and 25-OH vitamin D (25OHD) levels were assessed before and at 3, 6, 12 and 18/24 months. Lumbar and femoral BMD and spinal X-ray were assessed at baseline and at 12 and 18/24 months. IR was defined by a lumbar BMD change (AU)

Spontaneous duodenal fistula due to hepatic hydatid cyst.

Communication of a hepatic hydatid cyst to the duodenum appears to be extremely rare. This is the first case described in the imaging literature of hepatic echinococcosis fistulized to the duodenum studied by computed tomography.

CT of primary bilateral adrenal lymphoma.

Two cases of bilateral primary adrenal lymphoma are presented. One case had a cystic appearance and the other a homogeneous density.

Spontaneous aortocaval fistula: CT findings with pathologic correlation.

We present a case of aortocaval fistula (ACF) secondary to spontaneous rupture of an atherosclerotic infrarenal aortic aneurysm into the inferior vena cava that was initially diagnosed with computed tomography (CT). This is believed to be the first report of this condition with CT demonstration of the exact site of fistula and CT-pathologic correlation. We retrospectively reviewed the CT findings of another two cases of ACF and the previous literature.