A severe myopathy case in aged patient treated with high statin dosage.

Statins (S) are widely used drugs for cardiovascular prevention however their utilization may cause a various grade of muscle toxicity. Sometime S discontinuation alone is not sufficient to revert muscle injury and this can evolve in serious inflammatory muscle disease. In this case immunosuppressive medications are required to achieve remission. This case report describes a patient who developed rhabdomyolysis after recent S treatment initiation and the diagnostic work up have lead to the diagnosis of necrotizing autoimmune myopathy (NAM). We believe that the clinical case described here is a useful report of this rare toxicity and we aim to highlight the importance of its prompt recognition and treatment.

The relationship between inhibitors of the Wnt signalling pathway (sclerostin and Dickkopf-1) and carotid intima-media thickness in postmenopausal women with type 2 diabetes mellitus.

The aim of the study was to investigate the association of the extracellular inhibitors of Wnt/ß-catenin signalling sclerostin and Dickkopf-1 (Dkk-1) with carotid intima-media thickness (CIMT) in type 2 diabetes mellitus (T2DM). We performed a cross-sectional study including 40 T2DM postmenopausal women and 40 healthy controls. CIMT was measured by B-mode ultrasound. Serum sclerostin and Dkk-1 were measured by solid-phase enzyme-linked immunosorbent assay (ELISA). Serum sclerostin and Dkk-1 concentrations were significantly higher in T2DM group than in controls. There was a significant negative correlation between sclerostin and Dkk-1 and CIMT in T2DM (p = 0.0063 and p = 0.0017, respectively). After adjustment for potential confounders, associations remained significant only for sclerostin. These data suggest that sclerostin, an established modulator of the canonical Wnt signalling, may protect against progression of vascular complications in diabetic patients, possibly by attenuating upregulation of ß-catenin activity in the vascular cells.

Sclerostin levels associated with inhibition of the Wnt/ß-catenin signaling and reduced bone turnover in type 2 diabetes mellitus.

CONTEXT: Patients with type 2 diabetes (T2DM) have low bone turnover, poor bone quality, and circulating levels of sclerostin significantly higher than non-T2DM controls. There are no data on the possible association of sclerostin with ß-catenin, a key component of the Wnt/ß-catenin canonical signaling. OBJECTIVES: The aim of the study was to evaluate the circulating ß-catenin levels in T2DM patients and to analyze their relationship with sclerostin and bone turnover markers. DESIGN: This was a cross-sectional study. SETTING AND PATIENTS: The study was conducted at a clinical research center. Forty T2DM postmenopausal women were studied and compared with 40 healthy controls. Bone status was assessed by dual-energy x-ray absorptiometry measurements (bone mineral density) and by measuring bone alkaline phosphatase and carboxy-terminal telopeptide of type 1 collagen. Sclerostin and ß-catenin were evaluated by an immunoenzymetric assay. RESULTS: Consistent with previous reports in T2DM subjects, we found sclerostin levels higher and bone turnover markers lower than controls. In our cohort of T2DM patients, ß-catenin levels are significantly lower than in controls (median 1.22 pg/ml, 25th to 75th percentiles 0.50-2.80; and median 4.25 pg/ml, 25th to 75th percentiles 2.20-7.62, respectively; P=0.0002). ß-Catenin correlated negatively with sclerostin (P<0.0001) and positively with bone alkaline phosphatase (P=0.0030) only in T2DM patients and negatively with age in both groups. Eight of the 40 T2DM patients had vertebral fractures. CONCLUSIONS: These results show for the first time that T2DM patients have serum concentrations of ß-catenin lower than controls. The negative association of ß-catenin with sclerostin suggests a biological effect of increased sclerostin on the Wnt signaling, which appears impaired in T2DM.