Vertebral fracture risk in glucocorticoid-induced osteoporosis: the role of hypogonadism and corticosteroid boluses

Objective: The aim of this study was to identify the risk factors associated with fragility fracture (FF) development in glucocorticoid (GC)-treated patients. Methods: 127 patients (aged 62±18 years, 63% women) on GC-treatment (mean dose 14.5±14.1 mg/day and duration 47.7±69 months) were included. The clinical data collected included bone metabolism study (including gonadal axis), GC-treatment, disease activity, dual-energy X-ray absorptiometry analysis (evaluating densitometric osteoporosis (OP) and trabecular bone score (TBS) degraded microarchitecture values (DMA)), X-ray (assessing vertebral fractures (VF)), FRAX risk (GC-adjusted) and previous FF. Results: 17% of the patients had VF, 28% FF (VF and/or non-VF), 29% OP and 52% DMA. Patients with VF received more GC boluses (57.1% vs 29.5%, p=0.03), were older (68±13 vs 60±19 years, p=0.02), postmenopausal (100% vs 67%, p=0.02), had low testosterone levels (57% vs 11%, p=0.02), lower TBS values (1.119±0.03 vs 1.237±0.013, p100, p=0.01) and having received GC boluses (OR 3.45; 95% CI 1.04 to 12.15, p=0.01) were the main factors related to VF. Hypogonadism (OR 7.03; 95% CI 1.47 to 38.37, p=0.01) and FRAX >20 (OR 7.08; 95% CI 1.28 to 53.71, p=0.02) were factors related to FF. Conclusion: Hypogonadism is the principal risk factor for developing fractures in GC-treated men and women, whereas receiving GC boluses is a major factor for VF. These results indicate the importance of evaluating the gonadal axis in these patients

Reference intervals for bone turnover markers in Spanish premenopausal women

BACKGROUND: The aims of this study were to establish robust reference intervals and to investigate the factors influencing bone turnover markers (BTMs) in healthy premenopausal Spanish women. METHODS: A total of 184 women (35-45 years) from 13 centers in Catalonia were analyzed. Blood and second void urine samples were collected between 8 a.m. and 10 a.m. after an overnight fast. Serum procollagen type I amino-terminal propeptide (PINP) and serum cross-linked C-terminal telopeptide of type I collagen (CTX-I) were measured by two automated assays (Roche and IDS), bone alkaline phosphatase (bone ALP) by ELISA, osteocalcin (OC) by IRMA and urinary NTX-I by ELISA. PTH and 25-hydroxyvitamin D (25OHD) levels were measured. All participants completed a questionnaire on lifestyle factors. RESULTS: Reference intervals were: PINP: 22.7-63.1 and 21.8-65.5 μg/L, bone ALP: 6.0-13.6 μg/L, OC: 8.0-23.0 μg/L, CTX-I: 137-484 and 109-544 ng/L and NTX-I: 19.6-68.9 nM/mM. Oral contraceptive pills (OCPs) influenced PINP (p=0.007), and low body mass index (BMI) was associated with higher BTMs except for bone ALP. Women under 40 had higher median values of most BTMs. CTX-I was influenced by calcium intake (p=0.010) and PTH (p=0.007). 25OHD levels did not influence BTMs. Concordance between the two automated assays for PINP and particularly CTX-I was poor. CONCLUSIONS: Robust reference intervals for BTMs in a Southern European country are provided. The effects of OCPs and BMI on their levels are significant, whilst serum 25OHD levels did not influence BTMs. Age, calcium intake, BMI and PTH influenced CTX-I. The two automated assays for measuring PINP and CTX-I are not interchangeable

Early changes in biochemical markers of bone formation during teriparatide therapy correlate with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis

Summary: Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. Introduction: To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. Methods: A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 μg/day, n = 45) and risedronate (35 mg/week, n = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. Results: PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. Conclusions: Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients

High incidence of clinical fragility fractures in postmenopausal women with rheumatoid arthritis. A case-control study.

Objectives: To estimate the incidence of clinical fragility fractures in postmenopausal women with rheumatoid arthritis (RA) and analyze risk factors for fracture. Methods: Incidence of clinical fragility fractures in 330 postmenopausal women with RA was compared to that of a control population of 660 age-matched postmenopausal Spanish women. Clinical fractures during the previous five years were recorded. We analyzed associations with risk factors for fracture in both populations and with disease-related variables in RA patients. Results: Median age of RA patients was 64 years; median RA duration was eight years. Sixty-nine percent were in remission or on low activity. Eighty-five percent had received glucocorticoids (GCs); 85 %, methotrexate; and 40 %, ≥1 biologic DMARD. Fifty-four patients and 47 controls had ≥1 major osteoporotic fracture (MOF). Incidence of MOFs was 3.55 per 100 patient-year in patients and 0.72 in controls (HR: 2.6). Risk factors for MOFs in RA patients were age, previous fracture, parental hip fracture, years since menopause, BMD, erosions, disease activity and disability, and cumulative dose of GCs. Previous fracture in RA patients was a strong risk for MOFs (HR: 10.37). Conclusion: Of every 100 postmenopausal Spanish women with RA, 3-4 have a MOF per year. This is more than double that of the general population. A previous fracture poses a high risk for a new fracture. Other classic risk factors for fracture, RA disease activity and disability, and the cumulative dose of GCs are associated with fracture development

Osteodistrofia de la cirrosis biliar primaria

[spa] La cirrosis biliar primaria es una enfermedad hepática que se manifiesta por un patrón clínico, bioquímico e histológico de colestasis crónica. Su curso puede complicarse con el desarrollo de una patología metabólica ósea cuyo tipo, frecuencia y mecanismos patogenéticos no están bien establecidos. Esta tesis se ha realizado con el fin de analizar la prevalencia y tipo de enfermedad metabólica ósea que se asocia a la cirrosis biliar primaria (CBP) e investigar los factores que influyen en su desarrollo. 1) PACIENTES Y MÉTODOS Se han estudiado 20 pacientes con CBP (18M, 2 V) con una edad media de 48.6 +/- 10.6 años. A todos ellos se ha practicado: estudio del grado de colestasis biológica y de la función hepatocelular, además de determinaciones bioquímicas y hormonales (25-hidroxivitamina D; 1,25 dihidroxivitamina D y parathormona N-terminal) del metabolismo mineral. En 16 pacientes se determinó la capacidad de absorción intestinal de calcio. A todos los pacientes se practicaron radiografías de la columna vertebral y biopsia ósea, por vía transilíaca, tras doble "marcaje" con tetraciclinas, para análisis histomorfométrico en especimen óseo no decalcificado. El estudio histomorfométrico se realizó mediante el método semiautomático y se analizaron parámetros estáticos y dinámicos. 2) RESULTADOS Siete pacientes tenían una osteoporosis al presentar una reducción del volumen trabecular. Tres de ellos tenían asociado un trastorno moderado de la mineralización ósea que no cumplía criterios de osteomalacia. Quince pacientes (5 con osteoporosis) tenían una disminución del grado de formación ósea y en 19 casos la reabsorción ósea era normal o estaba disminuida. Los pacientes con osteoporosis tenían una duración de la CBP más prolongada (5.4 +/- 2.8) que los pacientes sin osteoporosis (2.0 +/- 2.1 a p= 0.07). Además, la osteoporosis fue significativamente más frecuente en las mujeres postmenopáusicas, ya que 6 de los 7 pacientes con osteoporosis (86%) pero sólo 3 de los 11 sin osteoporosis (27%) eran mujeres postmenopaúsicas (p= 0.02). Por otro lado, los pacientes con osteoporosis tenían con mayor frecuencia una malabsorción intestinal de calcio (80%) que los pacientes sin osteoporosis (18%) (p= 0.03). Aunque la severidad de la colestasis no se relacionó con la presencia de osteoporosis, sí se halló una relación lineal inversa entre la absorción intestinal de calcio y la concentración plasmática de sales biliares (r= -0.55, p < 0.05) y el nivel sérico de la fosfatasa alcalina (r= -0.5, p < 0.05). Cuatro pacientes, dos de ellos con trastornos de la mineralización ósea, tenían niveles séricos bajos de 25-hidroxivitamina D. Sin embargo, los niveles séricos del metabolitos 1,25-dihidroxivitamina D fueron normales en todos los casos. 3) CONCLUSIONES Los resultados de este estudio indican que: 1.- La osteoporosis es la enfermedad metabólica ósea que comúnmente se asocia a la cirrosis biliar primaria. Su prevalencia fue del 35% en nuestra serie analizada. 2.- Los pacientes con cirrosis biliar primaria de nuestro medio no desarrollan una osteomalacia, aunque no es infrecuente que presenten un trastorno moderado de la mineralización ósea. Un 15% de los pacientes desarrollaron este trastorno. 3.- La osteoporosis asociada a la cirrosis biliar primaria es de bajo "turnover" óseo y su base fisiopatológica es un déficit de la formación ósea. El 71% de los pacientes con osteoporosis tenían un déficit de la formación ósea, alteración que también presentaba el 83% de los pacientes sin osteoporosis. Ello permite sugerir que un elevado porcentaje de pacientes con cirrosis biliar primaria y masa ósea normal están en alto riesgo de desarrollar una osteoporosis. 4,- Los factores de riesgo implicados en el desarrollo de osteoporosis en la cirrosis biliar primaria son: duración de la hepatopatía, estado postmenopáusico y malabsorción intestinal de calcio. 5,- El desarrollo de un trastorno moderado de la mineralización ósea es más frecuente en los pacientes con déficit de 2S-hidroxivitamina D. Sin embargo, el "status" deficitario de vitamina D no es exclusivo de los pacientes con trastorno de la mineralización ósea

Crowned dens syndrome. It's never too late to diagnose

El síndrome de Crowned Dens fue descrito por primera vez en 1985 y se trata de una manifestación poco frecuente. Los síntomas asociados pueden ir desde un dolor cervical agudo, hasta rigidez cervical e incluso fiebre. En algunos pacientes es asintomático. Por lo tanto es un síndrome de difícil diagnóstico. En este artículo se trata de un caso clínico de una mujer de 69 años de edad.

Factores relacionados con la respuesta inadecuada al tratamiento osteoformador (teriparatida/PTH 1–84) en pacientes con osteoporosis severa. Resultados preliminares

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 <3% at 18/24 months. Results: 29% of patients showed IR to therapy. No significant differences were observed in age, baseline BMD and BTM and 25OHD levels between patients with or without IR. 92% of IR patients had been previously treated with bisphosphonates (vs 79%, p=0.34) during 7±4.8 years (vs 4.9±4.2 years, p=0.19). No significant differences were observed between groups in the magnitude of changes in BTM throughout the study. Conclusions: 29% of patients with severe osteoporosis presented IR to osteoanabolic therapy. Although no predictive factors related to this finding were identified, previous prolonged therapy with bisphosphonates may play a role.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 <3% a los 18/24 meses. Resultados: 29% de los pacientes presentaron RI al tratamiento. No se observaron diferencias en la edad, DMO basal, valores de 25OHD y/o MRO entre los pacientes con y sin RI. El 92% de pacientes con RI había seguido tratamiento previo con bisfosfonatos (vs. el 79% de los pacientes sin RI, p=0,34) durante 7±4,8 años (vs. 4,9±4,2 años, p=0,19). No se observaron diferencias significativas en la evolución de los MRO tras iniciar el tratamiento entre ambos grupos de pacientes. Conclusión: El 29% de los pacientes con osteoporosis grave presenta una RI al tratamiento osteoformador. Aunque no se han identificado factores predictores de este tipo de respuesta, es posible que el tratamiento prolongado previo con bisfosfonatos pueda estar relacionado con este hallazgo

Pain, quality of life, and safety outcomes of Kyphoplasty for vertebral compression fractures: report of a task force of the American Society for Bone and Mineral Research

The relative efficacy and harms of balloon kyphoplasty (BK) for treating vertebral compression fractures (VCF) are uncertain. We searched multiple electronic databases to March 2016 for randomized and quasi‐randomized controlled trials comparing BK with control treatment (nonsurgical management [NSM], percutaneous vertebroplasty [PV], KIVA VCF treatment system [Benvenue Medical, Inc., Santa Clara, CA, USA], vertebral body stenting, or other) in adults with VCF. Outcomes included back pain, back disability, quality of life, new VCF, and adverse events (AEs). One reviewer extracted data, a second checked accuracy, and two rated risk of bias (ROB). Mean differences and 95% confidence intervals (CIs) were calculated using inverse‐variance models. Risk ratios of new VCF and AE were calculated using Mantel‐Haenszel models. Ten unique trials enrolled 1837 participants (age range, 61 to 76 years; 74% female), all rated as having high or uncertain ROB. Versus NSM, BK was associated with greater reductions in pain, back‐related disability, and better quality of life (k = 1 trial) that appeared to lessen over time, but were less than minimally clinically important differences. Risk of new VCF at 3 and 12 months was not significantly different (k = 2 trials). Risk of any AE was increased at 1 month (RR = 1.73; 95% CI, 1.36 to 2.21). There were no significant differences between BK and PV in back pain, back disability, quality of life, risk of new VCF, or any AE (k = 1 to 3 trials). Limitations included lack of a BK versus sham comparison, availability of only one RCT of BK versus NSM, and lack of study blinding. Individuals with painful VCF experienced symptomatic improvement compared with baseline with all interventions. The clinical importance of the greater improvements with BK versus NSM is unclear, may be due to placebo effect, and may not counterbalance short‐term AE risks. Outcomes appeared similar between BK and other surgical interventions. Well‐conducted randomized trials comparing BK with sham would help resolve remaining uncertainty about the relative benefits and harms of BK

Clinical evolution of sacral stress fractures: influence of additional pelvic fractures

To evaluate the clinical evolution of sacral stress fractures in relation to the scintigraphic pattern and the presence of additional pelvic fractures. METHODS--This was a retrospective study of 14 patients with sacral fractures. RESULTS--Six patients had additional pelvic fractures. Four bone scintigraphic patterns were found. The resolution of symptoms was longer in patients with associated pelvic fractures (30 weeks v three weeks). No relation was found between the bone scintigraphic pattern and the time of evolution. CONCLUSION--Associated pelvic fractures delay the resolution of symptoms in patients with sacral fractures, regardless of scintigraphic pattern

Clinical evolution of sacral stress fractures: influence of additional pelvic fractures

To evaluate the clinical evolution of sacral stress fractures in relation to the scintigraphic pattern and the presence of additional pelvic fractures. METHODS--This was a retrospective study of 14 patients with sacral fractures. RESULTS--Six patients had additional pelvic fractures. Four bone scintigraphic patterns were found. The resolution of symptoms was longer in patients with associated pelvic fractures (30 weeks v three weeks). No relation was found between the bone scintigraphic pattern and the time of evolution. CONCLUSION--Associated pelvic fractures delay the resolution of symptoms in patients with sacral fractures, regardless of scintigraphic pattern