Temporal and spatial expression of bone morphogenetic protein-2, -4, and -7 during distraction osteogenesis in rabbits

The Ilizarov method of limb lengthening makes use of the fact that osteogenesis is induced at an osteotomy site when distraction is applied. It is unknown at present how the mechanical forces created by distraction are translated into biological signals. Because bone morphogenetic proteins (BMPs) are potent inducers of osteogenesis in many experimental systems, they are obvious candidates for playing a role in this process. In this study, we investigated the temporal and spatial expression of BMP-2, -4, and -7 proteins during distraction osteogenesis using immunohistochemistry. An osteotomy was performed on the right tibiae of white New Zealand rabbits. After a delay of 7 days, distraction was started at a rate of 0.25 mm/12 h for 3 weeks, followed by a 3 week consolidation phase. Each week after osteotomy one rabbit was killed for immunohistochemical studies. Staining for BMP-2, -4, and -7 was evident before distraction was applied and was mainly localized to mesenchymal cells and osteoblastic cells in the periosteal region. After distraction was started, the typical fibrous interzone developed between the osteotomy fragments, where both intramembranous and endochondral ossification were noted. In this area, cells resembling fibroblasts and chondrocytes, but not mature osteoblasts, showed intense staining for all three BMPs. This high level of expression was maintained during the entire distraction phase and then gradually disappeared during the consolidation phase. These results are compatible with the hypothesis that BMPs play an important role in the signaling pathways that link the mechanical forces created by distraction to biological responses. (Bone 27:453-459; 2000

Low-value clinical practices in injury care: a scoping review and expert consultation survey

BACKGROUND: Tests and treatments that are not supported by evidence and could expose patients to unnecessary harm, referred to here as low-value clinical practices, consume up to 30% of healthcare resources. Choosing Wisely and other organisations have published lists of clinical practices to be avoided. However, few apply to injury and most are based uniquely on expert consensus. We aimed to identify low-value clinical practices in acute injury care. METHODS: We conducted a scoping review targeting articles, reviews and guidelines that identified low-value clinical practices specific to injury populations. Thirty-six experts rated clinical practices on a 5-point Likert scale from clearly low-value to clearly beneficial. Clinical practices reported as low-value by at least one level I, II or III study and considered clearly or potentially low-value by at least 75% of experts were retained as candidates for low-value injury care. RESULTS: Of 50,695 citations, 815 studies were included and led to the identification of 150 clinical practices. Of these 63 were considered candidates for low-value injury care; 33 in the emergency room, 9 in trauma surgery, 15 in the intensive care unit and 5 in orthopaedics. We also identified 87 'grey zone' practices, which did not meet our criteria for low-value care. CONCLUSIONS: We identified 63 low-value clinical practices in acute injury care that are supported by empirical evidence and expert opinion. Conditional on future research, they represent potential targets for guidelines, overuse metrics and de-implementation interventions. We also identified 87 'grey zone' practices, which may be interesting targets for value-based decision-making. Our study represents an important step towards the de-implementation of low-value clinical practices in injury care. LEVEL OF EVIDENCE: III