3D cell culture studies more accurately represent the complex in vivo mechanical environment of human bone and are, thus, superior to 2D studies when testing the efficacy of osteoporosis therapies. As such, the objective of this study was to use a 3D model to investigate the effect of sclerostin antibodies. Sclerostin is a protein, which inhibits osteoblasts and is downregulated under mechanical stimulation. It is not yet known how expression of sclerostin mediates the site-specific and temporal changes in mineralisation. To address this, we developed a 3D cellular niche of MC3T3 osteoblasts encapsulated within gelatin and applied mechanical loading to the constructs using a custom-designed compression bioreactor system (0.5% strain at 0.5 Hz, 1 hr/day) (VizStim) under continuous perfusion of cell culture media. Osteoblasts were pretreated with estrogen for 14 days, followed by estrogen withdrawal (EW) to simulate postmenopausal conditions. 3D constructs were successfully fabricated and actin staining revealed the formation of dendritic cells under both static and stimulated conditions indicative of osteocyte-like cells. Under static conditions, estrogen treatment enhanced production of calcium by osteoblasts when compared to the same cells cultured under estrogen deficient conditions. Overall, preliminary results propose a link between mechanical stimulation, estrogen deficiency and mineral production by osteoblasts. Ongoing studies are comparing the static and stimulated groups after a longer culture period of 21 days using sclerostin antibodies. This research aims to deliver further understanding of the mechanical regulation of bone formation, and will inform novel approaches for regeneration of bone tissue and treatment of osteoporosis.

Hip fractures accounts to about 86000 cases per annum in UK. AP and Lateral radiographs form an essential investigation in planning the management of these fractures. Recently it has been suggested that lateral view doesn't provide any additional information in majority of the cases. We looked retrospectively at 25 consecutive radiographs with intracapsular and extracapsular fracture neck of femur each presenting to our department between May 2010 and January 2011. These radiographs were put on the CD in 2 folders as AP and Lateral. It was reviewed by 2 Observers who suggested their preferred treatment. The results were compared for the intra observer agreement to assess the necessity of the lateral view of the radiographs. We also compared the treatment options with the gold standard and looked at the interobserver agreement. Of the 50 set of radiographs that were reviewed, Observer 1 had disagreed with himself on one occasion (98%agreement) compared to the Observer 2 who had two disagreements (96% agreement). When analyzing the intracapsular fractures, we found 100% agreement of OBSERVER 1 with himself when proposing treatment on AP and Lateral View. Whereas, OBSERVER 2 had only one disagreement. It gave us a Free marginal kappa value of more than 0.70 indicating excellent agreement. One difference doesn't have any statistical significance. In the extracapsular fractures, Kappa values ranged from 0.413 to 0.88. OBSERVER 1 did change his opinion after reviewing the lateral view but generally had good outcome (K=0.88). Whereas, the opinion of OBSERVER 2 was unaffected by the Lateral view. The X-ray diagnoses by OBSERVER 1 and OBSERVER 2 had only moderate agreement (K=0.52 (AP) and 0.57 (Lat). Comparing the observer opinion to the gold standard (operation performed) showed moderate agreement both on AP and Lateral view (OBSERVER 1 AP and Lat both K=0.64, OBSERVER 2 AP and Lat both K=0.41). The Lateral view failed to change the opinion of the observers (K > 0.7) but there was moderate to excellent agreement between the observers and observer vs operation (The Gold Standard) with kappa value of more than 0.52. We feel that the Lateral view doesn't make any difference in most of the cases as shown by a good intra-observer agreement. However, we cannot completely rule out their importance and they should be performed in occult fractures, pathological fractures, fractures extending into the shaft, young patients, and on the request of physician.