Cortical thickness mapping to identify focal osteoporosis in patients with hip fracture.

BACKGROUND: Individuals with osteoporosis are predisposed to hip fracture during trips, stumbles or falls, but half of all hip fractures occur in those without generalised osteoporosis. By analysing ordinary clinical CT scans using a novel cortical thickness mapping technique, we discovered patches of markedly thinner bone at fracture-prone regions in the femurs of women with acute hip fracture compared with controls. METHODS: We analysed CT scans from 75 female volunteers with acute fracture and 75 age- and sex-matched controls. We classified the fracture location as femoral neck or trochanteric before creating bone thickness maps of the outer 'cortical' shell of the intact contra-lateral hip. After registration of each bone to an average femur shape and statistical parametric mapping, we were able to visualise and quantify statistically significant foci of thinner cortical bone associated with each fracture type, assuming good symmetry of bone structure between the intact and fractured hip. The technique allowed us to pinpoint systematic differences and display the results on a 3D average femur shape model. FINDINGS: The cortex was generally thinner in femoral neck fracture cases than controls. More striking were several discrete patches of statistically significant thinner bone of up to 30%, which coincided with common sites of fracture initiation (femoral neck or trochanteric). INTERPRETATION: Femoral neck fracture patients had a thumbnail-sized patch of focal osteoporosis at the upper head-neck junction. This region coincided with a weak part of the femur, prone to both spontaneous 'tensile' fractures of the femoral neck, and as a site of crack initiation when falling sideways. Current hip fracture prevention strategies are based on case finding: they involve clinical risk factor estimation to determine the need for single-plane bone density measurement within a standard region of interest (ROI) of the femoral neck. The precise sites of focal osteoporosis that we have identified are overlooked by current 2D bone densitometry methods

Proteomic analysis of the extracellular matrix in idiopathic pes equinovarus

Abstract Idiopathic pes equinovarus is a congenital deformity of the foot and lower leg defined as a fixation of the foot in adduction, supination, and varus. Although the pathogenesis of clubfoot remains unclear, it has been suggested that fibroblasts and growth factors are involved. To directly analyze the protein composition of the extracellular matrix in contracted tissue of patients with clubfoot. A total of 13 infants with idiopathic clubfoot treated with the Ponseti method were included in the present study. Tissue samples were obtained from patients undergoing surgery for relapsed clubfeet. Contracted tissues were obtained from the medial aspect of the talonavicular joint. Protein was extracted after digestion and delipidation using zip-tip C18. Individual collagenous fractions were detected using a chemiluminescent assay. Amino acid analysis of tissue samples revealed a predominance of collagens, namely collagen types I, III, and VI. The high content of glycine and h-proline suggests a predominance of collagens I and III. A total of 19 extracellular matrix proteins were identified. The major result of the present study was the observation that the extracellular matrix in clubfoot is composed of an additional 16 proteins, including collagens V, VI, and XII, as well as the previously described collagen types I and III and transforming growth factor b. The characterization of the general protein composition of the extracellular matrix in various regions of clubfoot may help in understanding the pathogenesis of this anomaly and, thus, contribute to the development of more efficacious therapeutic approaches

Cortical Thickness Colour Mapping using ordinary clinical CT data.

<p>Femora and pelvis from an 84-year-old osteoporotic female who sustained a fracture without falling. She felt her right hip break as she placed her right foot on a low step. Femoral neck BMD was 0.46 g/cm2, T score −3.3. From the Arthritis Research UK FEMCO study (07/H0305/61).</p

Details of thinner patches of femoral cortex in hip fracture.

<p>Details of thinner patches of femoral cortex in hip fracture.</p

Approximate orientation of the focally thin (red) zone during the different phases of gait.

<p>Right femur (a) toe-off, (b) single leg stance and (c) heel strike. A slightly modified stance position (b) conferred the greatest risk of spontaneous femoral neck fracture in the laboratory simulations of Cristofolini et al <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038466#pone.0038466-Cristofolini1" target="_blank">[3]</a>. The focally thin patch we identified coincides with a region of high tensile stress during simulations of spontaneous fracture.</p