No abstract

Background Heterotopic ossification (HO) affects the majority of combat-related lower extremity wounds involving severe fracture and amputation. Defining the timing of early osteogenic-related genes may help identify candidate prophylactic agents and guide the timing of prophylactic therapy after blast and other combat-related extremity injuries. Questions/purposes Using a recently developed animal model of combat-related HO, we sought to determine (1) the timing of early chondrogenesis, cartilage formation, and radiographic ectopic bone development; and (2) the early cartilage and bone-related gene and protein patterns in traumatized soft tissue. Methods We used an established rat HO model consisting of blast exposure, controlled femur fracture, crush injury, and transfemoral amputation through the zone of injury. Postoperatively, rats were euthanized on Days 3 to 28. We assessed evidence of early ectopic bone formation by micro-CT and histology and performed proteomic and gene expression analysis. Results All rats showed radiographic evidence of HO within 28 days. Key chondrogenic (collagen type I alpha 1 [COL1a1], p = 0.016) and osteogenic-related genes (RuntThis work was supported by CDMRP (W81XWH-14-2-0010; PI-JAF) and BUMED (602115HP.3720.001.A1014; PI-JAF). Some of the authors are employees of the US Government. This work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that ''Copyright protection under this title is not available for any work of the United States Government.'' Title 17 U.S.C. §101 defined a US Government work as a work prepared by a military service member or employees of the US Government as part of that person's official duties. The opinions or assertions contained in this paper are the private views of the authors and are not to be construed as reflecting the views, policy or positions of the Department of the Navy, Department of Defense nor the US Government. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research 1 editors and board members are on file with the publication and can be viewed on request. Clinical Orthopaedics and Related Research 1 neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA-approval status, of any drug or device prior to clinical use. Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research. This work performed at the Naval Medical Research Center, Silver Spring, MD, USA. Conclusions We found that genes that regulate early chondrogenic and osteogenic signaling and bone development (COL1a1, RUNX-2, OCN, PHEX, and POU5F1) are induced early during the tissue reparative/healing phase in a rat model simulating a combat-related extremity injury. Clinical Relevance The ability to correlate molecular events with histologic and morphologic changes will assist re...

Background Case reports suggest that there is an increased risk of subtrochanteric femur fracture after femoral neck fixation with cannulated screws when the distal-most screw is placed distal to the lesser trochanter. However, to our knowledge, there are no biomechanical data supporting this observation. Questions/purposes (1) Is there an increased risk of subtrochanteric femur fracture after femoral neck fixation with cannulated screws in normal density and osteoporotic Sawbones when the distal-most screw is started distal to the lesser trochanter? (2) Does the screw starting point position after femoral neck fixation with cannulated screws affect load to failure when normal density and osteoporotic Sawbones are loaded through their mechanical axis? Methods Normal density and osteoporotic Sawbones femora were instrumented with three cannulated screws in a triangular apex distal configuration with the distal-most screw starting either proximal to, at, or distal to the level of the lesser trochanter. Specimens were loaded along the mechanical axis to failure. The fracture location and ultimate load to failure were compared between groups. Results The screw start point distal to the lesser trochanter resulted in a greater proportion of subtrochanteric femur fractures compared with screw start points at or proximal to the lesser trochanter in the subset of osteoporotic specimens (three of 10 specimens versus 0 of 20 specimens; p = 0.030). No subtrochanteric femur fractures were observed in the normal density specimens. Load to failure was lower when the distal-most screw was started distal to the lesser trochanter than when it was started at or proximal to the lesser trochanter (normal density subset 13,502 ± 1980 N versus 14,675 ±1528 N; osteoporotic subset 8946 ± 1509 N versus 10,026 ± 1256 N; linear regression coefficient 1127 N [95% CI 298 to 1956 N]; adjusted r2 = 0.71; p = 0.009). Conclusions A screw start point distal to the lesser trochanter was associated with subtrochanteric femur fractures in the osteoporotic subset. Additionally, there was decreased load to failure when the distal-most screw was started distal to the lesser trochanter. Clinical Relevance These data suggest that avoiding a screw start point distal to the level of the lesser trochanter in femoral neck fracture fixation may decrease the risk of catastrophic subtrochanteric femur fractures, especially in patients with osteoporosis. However, it should be noted that a more overall varus screw alignment could theoretically compromise the ability to achieve compression across the fracture, with attendant implications with regard to fracture union in the acute setting.