Dysregulation of Wnt signaling in bone of type 2 diabetes mellitus and diabetic Charcot arthropathy.

BACKGROUND: Type 2 diabetes mellitus (T2DM) patients show a markedly higher fracture risk and impaired fracture healing when compared to non-diabetic patients. However in contrast to type 1 diabetes mellitus, bone mineral density in T2DM is known to be normal or even regionally elevated, also known as diabetic bone disease. Charcot arthropathy is a severe and challenging complication leading to bone destruction and mutilating bone deformities. Wnt signaling is involved in increasing bone mineral density, bone homeostasis and apoptotic processes. It has been shown that type 2 diabetes mellitus is strongly associated with gene variants of the Wnt signaling pathway, specifically polymorphisms of TCF7L2 (transcription factor 7 like 2), which is an effector transcription factor of this pathway. METHODS: Bone samples of 19 T2DM patients and 7 T2DM patients with additional Charcot arthropathy were compared to 19 non-diabetic controls. qPCR analysis for selected members of the Wnt-signaling pathway (WNT3A, WNT5A, catenin beta, TCF7L2) and bone gamma-carboxyglutamate (BGLAP, Osteocalcin) was performed and analyzed using the 2-ΔΔCt- Method. Statistical analysis comprised one-way analysis of variance (ANOVA). RESULTS: In T2DM patients who had developed Charcot arthropathy WNT3A and WNT5A gene expression was down-regulated by 89 and 58% compared to healthy controls (p < 0.0001). TCF7L2 gene expression showed a significant reduction by 63% (p < 0.0001) and 18% (p = 0.0136) in diabetic Charcot arthropathy. In all diabetic patients BGLAP (Osteocalcin) was significantly decreased by at least 59% (p = 0.0019). CONCLUSIONS: For the first time with this study downregulation of members of the Wnt-signaling pathway has been shown in the bone of diabetic patients with and without Charcot arthropathy. This may serve as future therapeutic target for this severe disease.

Effect of different orthotic concepts as first line treatment of plantar fasciitis.

BACKGROUND: Evaluation of the effectiveness of three different types of prefabricated foot orthotics in the treatment of plantar fasciitis. METHODS: Prospective, randomized head-to-head trial in 30 adults (21 women, 9 men) with plantar fasciitis without any anatomic alterations. Three different prefabricated orthotics were tested (thin, non supportive orthotic (NO); soft supportive foam orthotic (FO); foam covered rigid self-supporting plastic orthotic (PO)). The follow up was 3 weeks. Main outcome measures were maximum and average pain (VAS), duration of pain per day, walking distance and subjective comfort. RESULTS: There was no significant effect of NO on maximal pain and average pain. FO and PO had a significant effect on pain levels (p<0.05) whereas PO was superior concerning pain reduction and the time until the onset of effect (p<0.05). CONCLUSIONS: PO are superior regarding pain reduction and pain free time when compared to FO. NO did not demonstrate a significant effect in the test setup used.