Are OPG and RANKL involved in human fracture healing?

Human fracture healing is a complex interaction of several cytokines that regulate osteoblast and osteoclast activity. By monitoring OPG (osteoprotegerin) and sRANKL we aimed to possibly predict normal or impaired fracture healing. In 64 patients with a fracture of a long bone serum level of sRANKL and OPG were evaluated with respect to bony union (n=57) or pseudarthrosis (n=7). Measurements were carried out at admission and at 1, 2, 4, 6, 8, 12, 24, and 48 weeks after the injury. Patients' serum levels were compared to 33 healthy controls. Fracture hematoma contained significantly higher sRANKL and OPG concentrations compared to patients serum (p=0.005, p=0.028). OPG level in fracture hematoma was higher compared to the unions serum level (p=0.028). sRANKL was decreased in unions during the observation period. In non-unions sRANKL and OPG levels showed a variable course, with no statistical significance. This is the first study to document the course of OPG and sRANKL in normal and delayed human fracture healing emphasizing its local and systemic involvement. We provide evidence of strongly enhanced OPG levels in patients with a long bone fracture compared to healthy controls. Further, levels of free sRANKL were decreased during regular fracture repair.

Primary anterior cruciate ligament reconstruction in athletes: a 5-year follow up comparing patellar tendon versus hamstring tendon autograft.

INTRODUCTION: ACL reconstruction with quadruple hamstring graft (HT) as well as bone-patellar tendon-bone autograft (PT) is a frequent procedure in athletes after ACL rupture. Both techniques are reported to provide for satisfying results but only few articles compare both techniques. MATERIAL AND METHODS: Prospective evaluation was performed on 96 patients with isolated ACL rupture undergoing reconstruction with a HT or PT autograft by a single surgeon at our institution. Long time follow-up after five years included the IKDC and KOOS evaluation form as well as clinical assessment (ROM, Lachmann testing, KT-2000). RESULTS: Comparing both methods revealed no significant differences regarding IKDC and KOOS. The KT-2000 arthrometer testing showed a slightly increased mean laxity in the HT group. There were no differences regarding harvest side symptoms comparing HT and PT as well as one and two incision technique. Kneeling pain was significantly less common after HT autograft. HT as well as PT autograft achieve equally good clinical results in athletes at five year follow-up with no significant difference regarding knee stability. Although no difference concerning the harvest site was identified, HT seems to be favorable for patients who work in a kneeling position.

Potential prognostic factors predicting secondary amputation in third-degree open lower limb fractures.

BACKGROUND: With regard to the improved surgical possibilities and the rising tendency of attempted limb salvage, the topic of secondary amputation becomes increasingly important. The aim of this study was to identify potential prognostic factors predicting secondary amputation in third-degree open lower limb fractures. METHODS: All patients experienced third-degree open fractures of the lower limb without primary amputation (1994-2012). Prognostic factors were investigated to explain the final outcome of these patients (limb salvage vs. secondary amputation). RESULTS: From a total of 408 open diaphyseal tibia fractures, 93 consecutive fractures were identified (Gustilo-Anderson [G/A] type IIIA, n = 38; G/A type IIIB, n = 41; G/A type IIIC, n = 14) including seven patients with primary amputation. Definite limb salvage was achieved in 72 patients (88%), whereas in 10 patients (12%), secondary amputation was necessary. The median time to secondary amputation was 12 days (range, 2-1,573 days). The median Injury Severity Score (ISS) was 11 (range, 9-41), and the median Mangled Extremity Severity Score (MESS) was 4 (range, 2-9). The MESS was significantly higher in the amputation group compared with the limb salvage group (p = 0.0001). Furthermore, statistical testing revealed that the amount of complex fractures (p = 0.0132), the soft tissue damage (p = 0.0050), the vascular injury rate (p = 0.0110) and the fasciotomy rate (p = 0.0468) were significantly higher in the amputation group. In 60%, the limitations for limb salvage were infectious complications and/or, in 40%, was irreversible vessel occlusion after initial vessel reconstruction. CONCLUSION: The current study findings indicate that MESS is highly prognostic, but considering the significant advances in reconstructive techniques, decision making in patients with an MESS of 7 or greater should be reevaluated for the everyday clinical use. LEVEL OF EVIDENCE: Prognostic study, level III. Therapeutic study, level IV.

Seymour fractures: retrospective analysis and therapeutic considerations.

PURPOSE: To analyze the management of Seymour fractures (juxta-epiphyseal fractures of the terminal phalanx of the finger in conjunction with flexion deformity at the fracture site, laceration of the nail bed, and frequently ungual subluxation) and to determine clinical and radiographic results following operative or conservative treatment. METHODS: Clinical and radiological results of 24 skeletally immature patients (7 girls and 17 boys; mean age, 8.5 y) with Seymour fractures were evaluated. Assessment after a mean follow-up of 10 years (range, 1-18 y) included the range of motion, the modified Kapandji index, growth disturbance of the effected digit and nail, pain according to the visual analog scale, and patients' satisfaction. RESULTS: Nine patients received nonoperative treatment. Operative management included debridement, open reduction, and fixation in 9. Owing to instability, an additional K-wire passing across the distal interphalangeal joint was used in 5. In 1 patient, the nail was removed. All surgically treated patients received a splint and perioperative cephalosporin. Twenty-three patients out of 24 gained full motion (mean, 80°; range, 65°-90°). The average modified Kapandji index was 5.0 for extension and 4.8 for flexion. Long-term minor growth disturbance of the distal phalanx (seen on radiographs at high amplification only) and nail were noted in 5 patients, and solitary nail dystrophies were observed in 6 patients. Nine of the 11 nail growth irregularities were not a relevant cosmetic problem for the patients. Patients' satisfaction assessment revealed a good clinical outcome. There was neither flexion deformity nor infection in our collective. At the 1-year follow-up examination, the average visual analog score was 0.6 (range, 0-2). CONCLUSIONS: According to the literature, the Seymour fracture is an often-underestimated injury, and open cases are prone to infection. Evaluation of the outcome in our collective demonstrated good results with the treatment approaches described. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Crossed pinning in paediatric supracondylar humerus fractures: a retrospective cohort analysis.

PURPOSE: The aim of this study was to analyse the management of displaced paediatric supracondylar humerus fractures at our Level I Trauma Centre and to determine clinical and radiographic long-term results following operative treatment. METHODS: Clinical and radiological results of 78 paediatric patients (29 female, 49 male; mean age 5.1 years) with supracondylar humerus fractures, treated from 1992 to 2004, were evaluated. Gartland's classification yielded 32 type II, 44 type III and further two flexion injuries. In all patients the follow-up period exceeded 12 months. Assessment after an average of 8.1 years (1.1-19.5) included neurovascular examination, Flynn's criteria (elbow function and carrying angle), pain, complications (infections, growth disturbances or iatrogenic nerve injuries) and measurement of the humeroulnar angle. RESULTS: According to Flynn's criteria 73 patients (93.5 %) had a satisfactory outcome, while five (6.4 %) were graded as unsatisfactory (two due to cubitus varus and three because of limited elbow motion). The visual analogue scale (VAS) score averaged 0 (range 0-1) and the mean carrying angle measured 8.4° (-8 to 20°), compared to 10.8° on the contralateral side (2-20°). Injury-related complications yielded absent pulses in four (5.1 %), five (6.4 %) primary median, two (2.6 %) primary radial and one (1.3 %) primary ulnar nerve injury. Treatment-related complications included a secondary displacement and one iatrogenic radial nerve palsy. Based on primary nerve lesion as a dependent variable, statistical analysis showed that age had a significant influence revealing that older paediatric patients had a significantly higher risk (p = 0.02). Functional outcome as a dependent variable revealed an indirect proportion to the clinical carrying angle, achieving statistical significance (p < 0.01). CONCLUSIONS: Crossed pinning in paediatric supracondylar humerus fractures is an effective method. Evaluation of the outcome in our study group demonstrated good results with the treatment approach described.

Is the expression of Transforming Growth Factor-Beta1 after fracture of long bones solely influenced by the healing process?

PURPOSE: Circulating TGF-ß1 levels were found to be a predictor of delayed bone healing and non-union. We therefore aimed to investigate some factors that can influence the expression of TGF-ß1. The correlation between the expression of TGF-ß1 and the different socio-demographic parameters was analysed. METHODS: Fifty-one patients with long bone fractures were included in the study and divided into different groups according to their age, gender, cigarette smoking status, diabetes mellitus and regular alcohol intake. TGF-ß1 levels were analysed in patient's serum and different groups were retrospectively compared. RESULTS: Significantly lower TFG-ß1 serum concentrations were observed in non-smokers compared to smokers at week 8 after surgery. Significantly higher concentrations were found in male patients compared to females at week 24. Younger patients had significantly higher concentrations at week 24 after surgery compared to older patients. Concentrations were significantly higher in patients without diabetes compared to those with diabetes at six weeks after surgery. Patients with chronic alcohol abuse had significantly higher concentrations compared to those patients without chronic alcohol abuse. CONCLUSION: TGF-ß1 serum concentrations vary depending upon smoking status, age, gender, diabetes mellitus and chronic alcohol abuse at different times and therefore do not seem to be a reliable predictive marker as a single-point-in-time measurement for fracture healing.

Elevated transforming growth factor-beta 1 (TGF-ß1) levels in human fracture healing.

INTRODUCTION: Transforming growth factor-beta 1(TGF-ß1) is a regulatory protein, involved in bone fracture healing. Circulating TGF-ß1 levels have been reported to be a predictor of delayed bone healing and non-union, suggesting active relationship between tissue and circulating TGF-ß1 in fracture healing. The purpose of this study was to analyse TGF-ß1 local and serum concentrations in fracture healing to further contribute to the understanding of molecular regulation of fracture healing. PATIENTS AND METHODS: Serum samples of 113 patients with long bone fractures were collected over a period of 6 months following a standardised time schedule. TGF-ß1 serum concentrations were measured using ELISA. Patients were assigned to 2 groups: Group 1 contained 103 patients with physiological healing. Group 2 contained 10 patients with impaired healing. Patients in both groups were matched. One patient of the group 2 had to be excluded because of missing match partner. In addition, fracture haematoma from 11 patients of group 1 was obtained to analyse local TGF-ß1 concentrations. 33 volunteers donated serum which served as control. RESULTS: TGF-ß1 serum concentrations increased during the early healing period and were significantly higher in patients with physiological healing compared to controls (P=0.04). Thereafter, it decreased continuously between weeks 2 and 8 and fell again after week 8. TGF-ß1 serum concentrations in patients with physiological healing were significantly higher at week 24 compared to controls (P=0.05). In non-unions, serum concentrations differed significantly from those of controls at week 6 (P=0.01). No significant difference in between patients with physiological and impaired fracture healing was observed. Fracture haematoma contained significantly higher TGF-ß1 concentrations than peripheral serum of the patients (P=0.017). CONCLUSION: Elevated levels of TGF-ß1 in haematoma and in serum after bone fracture especially during the entire healing process indicate its importance for fracture healing.