Alan L. Jones

Recombinant human BMP-2 and allograft compared with autogenous bone graft for reconstruction of diaphyseal tibial fractures with cortical defects : A randomized, controlled trial

BACKGROUND Currently, the treatment of diaphyseal tibial fractures associated with substantial bone loss often involves autogenous bone-grafting as part of a staged reconstruction. Although this technique results in high healing rates, the donor-site morbidity and potentially limited supply of suitable autogenous bone in some patients are commonly recognized drawbacks. The purpose of the present study was to investigate the benefit and safety of the osteoinductive protein recombinant human bone morphogenetic protein-2 (rhBMP-2) when implanted on an absorbable collagen sponge in combination with freeze-dried cancellous allograft. METHODS Adult patients with a tibial diaphyseal fracture and a residual cortical defect were randomly assigned to receive either autogenous bone graft or allograft (cancellous bone chips) for staged reconstruction of the tibial defect. Patients in the allograft group also received an onlay application of rhBMP-2 on an absorbable collagen sponge. The clinical evaluation of fracture-healing included an assessment of pain with full weight-bearing and fracture-site tenderness. The Short Musculoskeletal Function Assessment (SMFA) was administered before and after treatment. Radiographs were used to document union, the presence of extracortical bridging callus, and incorporation of the bone-graft material. RESULTS Fifteen patients were enrolled in each group. The mean length of the defect was 4 cm (range, 1 to 7 cm). Ten patients in the autograft group and thirteen patients in the rhBMP-2/allograft group had healing without further intervention. The mean estimated blood loss was significantly less in the rhBMP-2/allograft group. Improvement in the SMFA scores was comparable between the groups. No patient in the rhBMP-2/allograft group had development of antibodies to BMP-2; one patient had development of transient antibodies to bovine type-I collagen. CONCLUSIONS The present study suggests that rhBMP-2/allograft is safe and as effective as traditional autogenous bone-grafting for the treatment of tibial fractures associated with extensive traumatic diaphyseal bone loss. LEVEL OF EVIDENCE Therapeutic Level II. See Instructions to Authors for a complete description of levels of evidence.

A prospective evaluation of the clinical utility of the lower-extremity injury-severity scores

Background: High-energy trauma to the lower extremity presents challenges with regard to reconstruction and rehabilitation. Failed efforts at limb salvage are associated with increased patient mortality and high hospital costs. Lower-extremity injury-severity scoring systems were developed to assist the surgical team with the initial decision to amputate or salvage a limb. The purpose of the present study was to prospectively evaluate the clinical utility of five lower-extremity injury-severity scoring systems. Methods: Five hundred and fifty-six high-energy lower-extremity injuries were prospectively evaluated with use of five injury-severity scoring systems for lower-extremity trauma designed to assist in the decision-making process for the care of patients with such injuries. Four hundred and seven limbs remained in the salvage pathway six months after the injury. The sensitivity, specificity, and area under the receiver operating characteristic curve were calculated for the Mangled Extremity Severity Score (MESS); the Limb Salvage Index (LSI); the Predictive Salvage Index (PSI); the Nerve Injury, Ischemia, Soft-Tissue Injury, Skeletal Injury, Shock, and Age of Patient Score (NISSSA); and the Hannover Fracture Scale-97 (HFS-97) for ischemic and nonischemic limbs. The scores were analyzed in two ways: including and excluding limbs that required immediate amputation. Results: The analysis did not validate the clinical utility of any of the lower-extremity injury-severity scores. The high specificity of the scores in all of the patient subgroups did confirm that low scores could be used to predict limb-salvage potential. The converse, however, was not true. The low sensitivity of the indices failed to support the validity of the scores as predictors of amputation. Conclusions: Lower-extremity injury-severity scores at or above the amputation threshold should be cautiously used by a surgeon who must decide the fate of a lower extremity with a high-energy injury.

Long-term persistence of disability following severe lower-limb trauma : Results of a seven-year follow-up

BACKGROUND A recent study demonstrated that patients treated with amputation and those treated with reconstruction had comparable functional outcomes at two years following limb-threatening trauma. The present study was designed to determine whether those outcomes improved after two years, and whether differences according to the type of treatment emerged. METHODS Three hundred and ninety-seven patients who had undergone amputation or reconstruction of the lower extremity were interviewed by telephone at an average of eighty-four months after the injury. Functional outcomes were assessed with use of the physical and psychosocial subscores of the Sickness Impact Profile (SIP) and were compared with similar scores obtained at twenty-four months. RESULTS On the average, physical and psychosocial functioning deteriorated between twenty-four and eighty-four months after the injury. At eighty-four months, one-half of the patients had a physical SIP subscore of > or = 10 points, which is indicative of substantial disability, and only 34.5% had a score typical of a general population of similar age and gender. There were few significant differences in the outcomes according to the type of treatment, with two exceptions. Compared with patients treated with reconstruction for a tibial shaft fracture, those with only a severe soft-tissue injury of the leg were 3.1 times more likely to have a physical SIP subscore of 5 points (p < 0.05) and those treated with a through-the-knee amputation were 11.5 times more likely to have a physical subscore of 5 points (p < 0.05). There were no significant differences in the psychosocial outcomes according to treatment group. Patient characteristics that were significantly associated with poorer outcomes included older age, female gender, nonwhite race, lower education level, living in a poor household, current or previous smoking, low self-efficacy, poor self-reported health status before the injury, and involvement with the legal system in an effort to obtain disability payments. Except for age, predictors of poor outcome were similar at twenty-four and eighty-four months after the injury. CONCLUSIONS The results confirm previous conclusions that reconstruction for the treatment of injuries below the distal part of the femur typically results in functional outcomes equivalent to those of amputation. Regardless of the treatment option, however, long-term functional outcomes are poor. Priority should be given to efforts to improve post-acute-care services that address secondary conditions that compromise optimal recovery.

Impact of Smoking on Fracture Healing and Risk of Complications in Limb-threatening Open Tibia Fractures

Objectives: Current data show smoking is associated with a number of complications of the fracture healing process. A concern, however, is the potential confounding effect of covariates associated with smoking. The present study is the first to prospectively examine time to union, as well as major complications of the fracture healing process, while adjusting for potential confounders. Setting: Eight Level I trauma centers. Patients: Patients with unilateral open tibia fractures were divided into 3 baseline smoking categories: never smoked (n = 81), previous smoker (n = 82), and current smoker (n = 105). Outcome Measure: Time to fracture healing, diagnosis of infection, and osteomyelitis. Methods: Survival and logistic analyses were used to study differences in time to fracture healing and the likelihood of developing complications, respectively. Multivariate models were used to adjust for injury severity, treatment variations, and patient characteristics Results: After adjusting for covariates, current and previous smokers were 37% (P = 0.01) and 32% (P = 0.04) less likely to achieve union than nonsmokers, respectively. Current smokers were more than twice as likely to develop an infection (P = 0.05) and 3.7 times as likely to develop osteomyelitis (P = 0.01). Previous smokers were 2.8 times as likely to develop osteomyelitis (P = 0.07), but were at no greater risk for other types of infection. Conclusion: Smoking places the patient at risk for increased time to union and complications. Previous smoking history also appears to increase the risk of osteomyelitis and increased time to union. The results highlight the need for orthopaedic surgeons to encourage their patients to enter a smoking cessation programs.

Effect of Recombinant Human Bone Morphogenetic Protein‐2 on Fracture Healing in a Goat Tibial Fracture Model

Bone morphogenetic proteins (BMPs) are considered to have important regulatory roles in skeletal embryogenesis and bone healing. Recombinant human BMPs (rhBMPs) have been shown to heal critical size defects and promote spinal fusion. We studied the effects of rhBMP‐2 in an absorbable collagen sponge (ACS) on bone healing in a large animal tibial fracture model. Bilateral closed tibial fractures were created in 16 skeletally mature goats and reduced and stabilized using external fixation. In each animal, one tibia received the study device (0.86 mg of rhBMP‐2/ACS or buffer/ACS), and the contralateral fracture served as control. The device was implanted as a folded onlay or wrapped circumferentially around the fracture. Six weeks following fracture, the animals were sacrificed and the tibiae harvested for torsional testing and histomorphologic evaluation. Radiographs indicated increased callus at 3 weeks in the rhBMP‐2/ACS treated tibiae. At 6 weeks, the rhBMP‐2/ACS wrapped fractures had superior radiographic healing scores compared with buffer groups and controls. The rhBMP‐2/ACS produced a significant increase in torsional toughness (p = 0.02), and trends of increased torsional strength and stiffness (p = 0.09) compared with fracture controls. The device placed in a wrapped fashion around the fracture produced significantly tougher callus (p = 0.02) compared with the onlay application. Total callus new bone volume was significantly increased (p = 0.02) in the rhBMP‐2/ACS fractures compared with buffer groups and controls regardless of the method of device application. The rhBMP‐2/ACS did not alter the timing of onset of periosteal/endosteal callus formation compared with controls. Neither the mineral apposition rates nor bone formation rates were affected by rhBMP‐2/ACS treatment. The increased callus volume associated with rhBMP‐2 treatment produced only moderate increases in strength and stiffness.

Damage control orthopaedics: evolving concepts in the treatment of patients who have sustained orthopaedic trauma.

In some groups of polytrauma patients, particularly those with chest injuries, head injuries, and those with mangled extremities, early total care of major bone fractures may be potentially harmful. Delaying all orthopaedic surgery, however, is also not always the best approach. In these situations, damage control orthopaedics, which emphasizes the stabilization and control of the injury rather than repair will add little additional physiologic insult to the patient and is a treatment option that should be considered.

Recombinant human bone morphogenetic protein-2 in open tibial fractures. A subgroup analysis of data combined from two prospective randomized studies.

BACKGROUND The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) to improve the healing of open tibial shaft fractures has been the focus of two prospective clinical studies. The objective of the current study was to perform a subgroup analysis of the combined data from these studies. METHODS Two prospective, randomized clinical studies were conducted. A total of 510 patients with open tibial fractures were randomized to receive the control treatment (intramedullary nail fixation and routine soft-tissue management) or the control treatment and an absorbable collagen sponge impregnated with one of two concentrations of rhBMP-2. The rhBMP-2 implant was placed over the fracture at the time of definitive wound closure. For the purpose of this analysis, only the control treatment and the Food and Drug Administration-approved concentration of rhBMP-2 (1.50 mg/mL) were compared. Patients who anticipated receiving planned bone-grafting as part of a staged treatment were excluded from enrollment. RESULTS Fifty-nine trauma centers in twelve countries participated, and patients were followed for twelve months postoperatively. Two subgroups were analyzed: (1) the 131 patients with a Gustilo-Anderson type-IIIA or IIIB open tibial fracture and (2) the 113 patients treated with reamed intramedullary nailing. The first subgroup demonstrated significant improvements in the rhBMP-2 group, with fewer bone-grafting procedures (p = 0.0005), fewer patients requiring invasive secondary interventions (p = 0.0065), and a lower rate of infection (p = 0.0234), compared with the control group. The second subgroup analysis of fractures treated with reamed intramedullary nailing demonstrated no significant difference between the control and the rhBMP-2 groups. CONCLUSIONS The addition of rhBMP-2 to the treatment of type-III open tibial fractures can significantly reduce the frequency of bone-grafting procedures and other secondary interventions. This analysis establishes the clinical efficacy of rhBMP-2 combined with an absorbable collagen sponge implant for the treatment of these severe fractures.

Pelvic ring disruptions: Prediction of associated injuries, transfusion requirement, pelvic arteriography, complications, and mortality

Objective To determine if age, fracture pattern, systolic blood pressure on arrival, base deficit, or the Revised Trauma Score is predictive of mortality, transfusion requirements, use of pelvic arteriography, later complications, or injuries associated with the pelvic ring disruption. Study Design Retrospective review of a prospectively collected database. Methods All closed pelvic ring disruptions seen between November 1, 1997 and November 30, 1999 were included. Predictive variables and outcome variables were recorded for each patient. Statistical analysis was used to determine if the above variables were predictive. Results Shock on arrival and the Revised Trauma Score were significantly associated with mortality, transfusion requirement, Injury Severity Score, and all the Abbreviated Injury Scores except the one for skin. In addition, the Revised Trauma Score was significantly associated with the use of pelvic arteriography and predicted more complications than did shock on arrival. Age was significantly associated with transfusion requirement, Injury Severity Score, the chest and skin Abbreviated Injury Scores, use of arteriography, and death. The mortality rate among patients who presented in shock was 57 percent. A Revised Trauma Score of less than 11 predicted mortality with a sensitivity and specificity of 58 percent and 92 percent, respectively. Shock on arrival predicted mortality with a sensitivity and specificity of 27 percent and 96 percent, respectively. Age greater than sixty years predicted mortality with a sensitivity and specificity of 26 percent and 91 percent, respectively. In our analysis of the fracture patterns, we were unable to demonstrate consistent, meaningful links between specific fracture classes and the outcome variables. Conclusions Shock on arrival and the Revised Trauma Score are useful predictors of mortality and transfusion requirements, Injury Severity Score, and Abbreviated Injury Scores for the head and neck, face, chest, abdomen, and extremities. In addition, the Revised Trauma Score predicts the use of pelvic arteriography and later complications. Age predicted transfusion requirement, Injury Severity Score, the chest and skin Abbreviated Injury Scores, use of arteriography, and death.

Health-care costs associated with amputation or reconstruction of a limb-threatening injury

BACKGROUND Recent reports have suggested that functional outcomes are similar following either amputation or reconstruction of a severely injured lower extremity. The goal of this study was to compare two-year direct health-care costs and projected lifetime health-care costs associated with these two treatment pathways. METHODS Two-year health-care costs were estimated for 545 patients with a unilateral limb-threatening lower-extremity injury treated at one of eight level-I trauma centers. Included in the calculation were costs related to (1) the initial hospitalization, (2) all rehospitalizations for acute care related to the limb injury, (3) inpatient rehabilitation, (4) outpatient doctor visits, (5) outpatient physical and occupational therapy, and (6) purchase and maintenance of prosthetic devices. All dollar figures were inflated to constant 2002 dollars with use of the medical service Consumer Price Index. To estimate projected lifetime costs, the number of expected life years was multiplied by an estimate of future annual health-care costs and added to an estimate of future costs associated with the purchase and maintenance of prosthetic devices. RESULTS When costs associated with rehospitalizations and post-acute care were added to the cost of the initial hospitalization, the two-year costs for reconstruction and amputation were similar. When prosthesis-related costs were added, there was a substantial difference between the two groups (

Functional Outcomes Following Trauma-Related Lower-Extremity Amputation

81,316 for patients treated with reconstruction and