Influence of non-osteoporotic treatments in patients on active anti-osteoporotic therapy: evidence from the OSTEOMED registry.

PURPOSE: To evaluate the effect of different non-osteoporotic drugs on the increase or decrease in the risk of incident fragility fractures (vertebral, humerus or hip) in a cohort of patients diagnosed with osteoporosis on active anti-osteoporotic therapy. METHODS: For this retrospective longitudinal study, baseline and follow-up data on prescribed non-osteoporotic treatments and the occurrence of vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression models. The drugs evaluated with a possible beneficial effect were thiazides and statins, while the drugs evaluated with a possible harmful effect were antiandrogens, aromatase inhibitors, proton pump inhibitors, selective serotonin reuptake inhibitors, benzodiazepines, GnRH agonists, thyroid hormones, and oral and inhaled corticosteroids. RESULTS: Logistic regression analyses indicated that no treatment significantly improved fracture risk, with the only treatments that significantly worsened fracture risk being letrozole (OR = 0.18, p-value = 0.03) and oral corticosteroids at doses ≤ 5 mg/day (OR = 0.16, p-value = 0.03) and > 5 mg/day (OR = 0.27, p-value = 0.04). CONCLUSION: The potential beneficial or detrimental effects of the different drugs evaluated on fracture risk are masked by treatment with anabolic or antiresorptive drugs that have a more potent action on bone metabolism, with two exceptions: letrozole and oral corticosteroids. These findings may have important clinical implications, as patients receiving these treatments are not fully protected by bisphosphonates, which may imply the need for more potent anti-osteoporotic drugs such as denosumab or teriparatide.

Comorbidity and osteoporotic fracture: approach through predictive modeling techniques using the OSTEOMED registry.

PURPOSE: To examine the response to anti-osteoporotic treatment, considered as incident fragility fractures after a minimum follow-up of 1 year, according to sex, age, and number of comorbidities of the patients. METHODS: For this retrospective observational study, data from baseline and follow-up visits on the number of comorbidities, prescribed anti-osteoporotic treatment and vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression and an artificial network model. RESULTS: Logistic regression showed that the probability of reducing fractures for each anti-osteoporotic treatment considered was independent of sex, age, and the number of comorbidities, increasing significantly only in males taking vitamin D (OR = 7.918), patients without comorbidities taking vitamin D (OR = 4.197) and patients with ≥ 3 comorbidities taking calcium (OR = 9.412). Logistic regression correctly classified 96% of patients (Hosmer-Lemeshow = 0.492) compared with the artificial neural network model, which correctly classified 95% of patients (AUC = 0.6). CONCLUSION: In general, sex, age and the number of comorbidities did not influence the likelihood that a given anti-osteoporotic treatment improved the risk of incident fragility fractures after 1 year, but this appeared to increase when patients had been treated with risedronate, strontium or teriparatide. The two models used classified patients similarly, but predicted differently in terms of the probability of improvement, with logistic regression being the better fit.

SNPs in bone-related miRNAs are associated with the osteoporotic phenotype.

Biogenesis and function of microRNAs can be influenced by genetic variants in the pri-miRNA sequences leading to phenotypic variability. This study aims to identify single nucleotide polymorphisms (SNPs) affecting the expression levels of bone-related mature microRNAs and thus, triggering an osteoporotic phenotype. An association analysis of SNPs located in pri-miRNA sequences with bone mineral density (BMD) was performed in the OSTEOMED2 cohort (n = 2183). Functional studies were performed for assessing the role of BMD-associated miRNAs in bone cells. Two SNPs, rs6430498 in the miR-3679 and rs12512664 in the miR-4274, were significantly associated with femoral neck BMD. Further, we measured these BMD-associated microRNAs in trabecular bone from osteoporotic hip fractures comparing to non-osteoporotic bone by qPCR. Both microRNAs were found overexpressed in fractured bone. Increased matrix mineralization was observed after miR-3679-3p inhibition in human osteoblastic cells. Finally, genotypes of rs6430498 and rs12512664 were correlated with expression levels of miR-3679 and miR-4274, respectively, in osteoblasts. In both cases, the allele that generated higher microRNA expression levels was associated with lower BMD values. In conclusion, two osteoblast-expressed microRNAs, miR-3679 and miR-4274, were associated with BMD; their overexpression could contribute to the osteoporotic phenotype. These findings open new areas for the study of bone disorders.

[Clinical usefulness of biochemical markers of bone turnover in early postmenopausal women: two years longitudinal study]. / Utilidad clínica de los marcadores bioquímicos de remodelado óseo en la mujer posmenopáusica reciente: estudio longitudinal a 2 años.

BACKGROUND AND OBJECTIVE: Many studies have been performed on the ability of bone turnover markers (BTM) for the prediction of bone loss and to assess the correlation of BTM with bone mineral density (BMD). However, the results from these studies have been mixed. The aim of this study was to assess the usefulness of BTM to predict bone loss and to analize the correlation of BTM with BMD in early postmenopausal women. SUBJECTS AND METHOD: 183 healthy women, aged 50 to 55 years, with natural menopause of 6 to 36 months were randomly selected. We measured bone alkaline phosphatase (BALP), intact osteocalcine (OC) and C-telopeptide (sCTx) in serum, and calcium, deoxipiridinoline (DPD) and N-telopeptide (NTx) in urine. Bone densitometry of the spine (L(2)-L(4)) was performed at the start of the study and two years later. Student t test, ANOVA, chi2 test and ROC curves were used for the statistical analysis. RESULTS: Bone markers, mainly OC and CTx, correlated with BMD and discriminated osteoporosis, osteopenia and normal bone mass (p < 0.001). According to the ROC curves, OC had a sensitivity of 77.8% and specificity of 80.6% for the diagnosis of osteoporosis and sCTx, 83.3% and 74.5%, respectively. Regarding the relation to bone loss, only sCTx showed difference between the lowest and the highest quartile (p = 0.042), but we did not find an association between high turnover and fast bone losers. CONCLUSIONS: Bone markers, mainly OC and sCTx, are useful for identification of osteoporotic and osteopenic early postmenopausal women. However, regarding the bone loss, only CTx has a weak predictive value.

Utilidad clínica de los marcadores bioquímicos de remodelado óseo en la mujer posmenopáusica reciente: estudio longitudinal a 2 años / Clinical usefulness of biochemical markers of bone turnover in early postmenopausal women: two years longitudinal study

FUNDAMENTO Y OBJETIVO: Los estudios sobre la capacidad de los marcadores del remodelado óseo (MRO) para la predicción de la pérdida ósea y sobre la correlación de los MRO con la densidad mineral ósea (DMO) han mostrado resultados dispares. Los objetivos del trabajo han sido evaluarla utilidad de los MRO para predecir la pérdida de masa ósea y estudiar la correlación entre los MRO y la DMO en las mujeres posmenopáusicas recientes. SUJETOS Y MÉTODO: Seleccionamos al azar a 183 mujeres sanas de 50-55 años, con menopausia natural en los últimos 6-36 meses. En suero analizamos fosfatasa alcalina ósea (FAO), osteocalcinaintacta (OC) y C-telopéptido (sCTx), y en orina, calcio, de oxipiridinolina (DPD) y N-telopéptido (NTx). Realizamos una densitometría ósea (L2-L4) basal y otra de control a los 2 años. El análisis estadístico se ha hecho mediante la t de Student, ANOVA, prueba de X2 y curvas ROC. RESULTADOS: Los MRO correlacionaron con la DMO y permitieron diferenciar entre osteoporosis, osteopenia y masa ósea normal, principalmente OC y sCTx (p < 0,001). Según las curvas ROC, la OC tuvo una sensibilidad del 77,8% y una especificidad del 80,6% para el diagnóstico de osteoporosis, mientras que la de sCTx, fue del 83,3 y el 74,5%, respectivamente. En cuanto ala relación con la pérdida ósea, solamente hubo diferencia entre el cuartil inferior y el superior de sCTx (p = 0,042). No encontramos asociación entre recambio óseo alto y pérdidas rápidas de masa ósea. CONCLUSIONES: Los MRO son de utilidad para la identificación de mujeres posmenopáusicas recientes con osteoporosis y osteopenia, principalmente OC y sCTx, pero respecto a la pérdida ósea tan sólo sCTx tiene un valor predictivo débil

BACKGROUND AND OBJECTIVE: Many studies have been performed on the ability of bone turnover markers (BTM) for the prediction of bone loss and to assess the correlation of BTM with bone mineral density (BMD). However, the results from these studies have been mixed. The aim of this study was to assess the usefulness of BTM to predict bone loss and to analize the correlation of BTM with BMD in early postmenopausal women. SUBJECTS AND METHOD: 183 healthy women, aged 50 to 55 years, with natural menopause of 6 to36 months were randomly selected. We measured bone alkaline phosphatase (BALP), intact osteocalcine(OC) and C-telopeptide (sCTx) in serum, and calcium, de oxipiridinoline (DPD) and N-telopeptide (NTx) in urine. Bone densitometry of the spine (L2-L4) was performed at the start of the study and two years later. Student t test, ANOVA, X2 test and ROC curves were used for the statistical analysis. RESULTS: Bone markers, mainly OC and CTx, correlated with BMD and discriminated osteoporosis, osteopenia and normal bone mass (p < 0.001). According to the ROC curves, OC had a sensitivity of 77.8% and specificity of 80.6% for the diagnosis of osteoporosis and sCTx,83.3% and 74.5%, respectively. Regarding the relation to bone loss, only sCTx showed difference between the lowest and the highest quartile (p = 0.042), but we did not find an association between high turnover and fast bone losers. CONCLUSIONS: Bone markers, mainly OC and sCTx, are useful for identification of osteoporoticand osteopenic early postmenopausal women. However, regarding the bone loss, only CTx has a weak predictive value

Péptido natriurético cerebral: una prueba de valor añadido a lahistoria clínica / Brain natriuretic peptide: a diagnostic test with added value to clinical history

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