Bisphosphonates play an important role in the treatment of catabolic bone diseases such as osteoporosis. In addition to their anti-resorptive activity exerted by their proapoptotic effect on osteoclasts, recent data suggest that nitrogen-containing bisphosphonates (N-BP) may also promote osteogenic differentiation by an unknown mechanism. Similar bone-anabolic effects have been attributed to cholesterol-lowering statins, which represent another class of mevalonate pathway inhibitors besides N-BP, suggesting a common mode of action. In vascular endothelial cells statins were recently shown to activate the Mek5/Erk5 mitogen-activated protein kinase cascade, which plays an important role in cellular differentiation, apoptosis or inflammatory processes. Here we evaluated whether N-BPs may also target the Mek5/Erk5 pathway and analysed the consequence of Erk5 activation on bone-relevant gene expression, calcification and osteoblast differentiation. We show that N-BP dose-dependently activate Erk5 in primary human endothelial cells and osteoblasts. The mechanism likely involves farnesyldiphosphate synthase (FDPS) inhibition and subsequent inactivation of the small GTPase Cdc42 since siRNA-mediated knockdown of both genes could reproduce N-BP-induced ERK5 activation. ERK5 activation resulted in regulation of several bone-relevant genes and was required for calcification and osteoblastic differentiation of mesenchymal stems cells as evident by the lack of alkaline phosphatase induction and alizarin-red staining observed upon Erk5 knockdown or upon differentiation initiation in presence of a pharmacological Erk5 inhibitor.Background/Aims
Methods and Results
The relationship between radiologic union and clinical outcome in thoracoscopic scoliosis surgery is not clear, as apparent non-union does not always correspond to a poor clinical result. Our aim was to evaluate CT fusion rates 2yrs after thoracoscopic surgery, and explore the relationship between fusion scores and; (i) rod diameter, (ii) graft type, (iii) fusion level, (iv) implant failure, and (v) lateral position in disc space. Between 2000 and 2006 a cohort of 44 patients had thoracoscopic scoliosis correction. Discectomies were performed and defect was packed with either autograft (n=14) or allograft (n=30). Instrumentation consisted of either 4.5mm (n=24) or 5.5mm (n=20) single titanium anterior rod and vertebral body screws. Fusion quality and implant integrity were evaluated 2yr following surgery using low-dose CT. At each disc space, left, right and mid-sagittal CT reconstructions were generated and graded using the Sucato 4-point scale (Sucato, 2004) which is based on calculated percentage of fusion across disc space. Fusion scores were measured for 259 disc spaces in 44 patients. Rod diameter had a strong effect on fusion score, with a mean score of 2.12±0.74 for 4.5mm Ti rod, decreasing to 1.41+0.55 for 5.5mm Ti rod, and to 1.09+0.36 for 5.5mm Ti-alloy rod. Mean fusion scores for autograft and allograft subgroups were 2.13±0.72 and 2.14±0.74 respectively. Fusion scores were highest in the middle of implant construct, dropping off by 20–30% toward the ends. Fusion scores adjacent to the rod (2.19±0.72) were significantly higher than on the contralateral side of the disc (1.24±0.85). Levels where rod fracture occurred (n=11) had lower fusion scores than those without fracture (1.09±0.67 vs 1.76±0.80). Levels where top screw pullout occurred (n=6) had lower CT fusion scores than those without (1.25±0.60 vs 1.83±0.76). Rod diameter (larger), intervertebral level (proximal or distal), lateral position in disc (further from rod) and rod fracture or screw pullout all reduce fusion scores, while graft type does not affect scores. The assumed link between higher fusion score and better clinical outcome must be treated with caution, because rod fractures did not necessarily occur in patients with lower fusion scores. It is possible that with a stiffer rod, less bony fusion mass is required for a stable construct. We propose that moderate fusion scores secure successful clinical outcomes in thoracoscopic scoliosis surgery.
Luk (Luk et al. Spine vol 23(21) 2303-2307 1998) has shown that in posterior surgery, the correction achieved can be predicted by fulcrum bending films. The relevance to anterior correction has been disputed, as this commonly involves shortening the spine by the removal of intervertebral discs. The aim of the study was to see whether the pre-operative bending angle reflected the degree of correction achieved. 91 patients with a structural thoracic curve had an anterior endoscopic correction using a single rod. The mean age was 16.1 years. (range 10-46) The majority of curves were Lenke type 1 (79%) or Type 2 (8%). In all cases disc clearance and bone grafting were performed. All had pre-operative fulcrum bending films. The mean Cobb angle achieved at the pre-operative bending film was compared with the post-operative correction at 2 months. The FBCI (Fulcrum Bending Correction Index) and correction rates were also calculated. The FBCI is calculated by dividing the correction rate by the fulcrum flexibility and expressed as a percentage. It takes into account the pre-operative flexibility of the curve.Introduction
Method
1. To evaluate how radiological parameters change during the first 3 years following anterior endoscopic surgery. 2. To report complications encountered in this period. Between April 2000 and June 2006,106 patients underwent an anterior endoscopic instrumented fusion. There were 95 females and 11 males. Average age was 16.1 years (range 10-46). 103 (97%) had right-sided idiopathic curves. The majority were Lenke type 1 (79%). Patients were assessed at 3, 6, 12, 24, and 36 months. 83 patients had 1 year follow-up, 69 had 2 years or more. The following were investigated; the structural curve, instrumented curve, non-structural curves, skeletal age at operation and sagittal profile (T5-T12).Purpose
Methods
Radiographic parameters have been shown to have a poor correlation with clinical outcome after open scoliosis procedures. However this has not been previously addressed after endoscopic surgery. The purpose of our study was to examine prospectively the relationship between curve correction and clinical outcome for endoscopic scoliosis surgery. We studied 50 consecutive patients who underwent endoscopic instrumentation, with a minimum follow-up of two years. All patients were assessed pre-operatively and at 24 months post-operatively. Radiological parameters were measured from plain standing radiographs including the coronal Cobb angle, sagittal alignment, coronal alignment and shoulder elevation. Clinical outcome was assessed using the Scoliosis Research Society Outcomes Instrument (SRS-24). Correlation between radiological parameters and SRS-24 scores were determined using the Pearson correlation coefficient.Introduction
Methods
There was a positive correlation between instrumented Cobb angle and total SRS-24 score (p=0.03, r2=0.085) and between curve correction and total SRS-24 score (p=0.04, r2=0.081). No correlation was found between coronal alignment, sagittal alignment, shoulder elevation or size of rib hump and the SRS-24 scores (p>
0.05).