Jukka Ristiniemi

Application of BMP-7 to tibial non-unions: A 3-year multicenter experience

SUMMARY The effective treatment of the often debilitating, longlasting and large-asset-consuming complication of fracture non-unions has been in the centre of scientific interest the last decades. The use of alternative bone substitutes to the gold standard of autologous graft includes the osteoinductive molecules named bone morphogenetic proteins (BMPs). A multicenter registry and database (bmpusergroup.co.uk) focused on the application of BMP-7/OP-1 was created in December 2005. We present the preliminary results, using the prospective case-series of aseptic tibial non-unions as an example. Sixty-eight patients fulfilled the inclusion criteria for this observational study, with a minimum follow-up of 12 months. The median duration of tibial non-union prior to BMP-7 application was 23 months (range 9-317 mo). Patients had undergone a median of 2 (range 0-11) revision procedures prior to the administration of BMP-7. In 41% the application of BMP-7 was combined with revision of the fixation at the non-union site. Non-union healing was verified in 61 (89.7%) in a median period of 6.5 months (range 3-15 mo). No adverse events or complications were associated with BMP-7 application. The safety and efficacy of BMP-7 was verified in our case series, and was comparable to the existing evidence. The establishment of multicenter networks and the systematic and long-term follow- up of these patients are expected to provide further information and significantly improve our understanding of this promising osteoinductive bone substitute.

Hook-plate fixation of unstable lateral clavicle fractures: A report on 63 patients

Background Hook-plate fixation of unstable lateral clavicle fractures has given promising results in previous reports, but numbers of patients have been small. We assessed the results of this technique in 63 patients. Patients and methods 63 patients with unstable lateral clavicle fractures were operated on at Oulu University Hospital during 1997–2004, using a clavicle hook-plate. Fracture union and complications were assessed retrospectively from case records and radiographs. The subjective part of the Constant score, Oxford shoulder questionnaire data and subjective shoulder value (SSV) were assessed after an average of 3.6 years in 58 patients. 31 patients were reviewed at the outpatient clinic, using complete Constant scores and radiographs of both acromioclavicular joints. Results 59 fractures united uneventfully. There was 1 case of delayed union and 3 nonunions, but only 1 of these required surgery. Additional complications involved 1 case of infection, 1 frozen shoulder and 3 cases of late fracture medial to the plate. The mean Oxford score was 15, the mean for the subjective part of the Constant score was 32, and the SSV was 86%. Interpretation Clavicle hook-plate fixation of unstable lateral clavicle fractures results in a good union rate and good shoulder function.

The Mechanism of Action of Induced Membranes in Bone Repair

BACKGROUND Inducement of foreign-body granulation tissue is a relatively novel therapeutic modality in bone repair. A two-stage bone reconstruction method, known as the Masquelet technique, combines inducement of a granulation tissue membrane and subsequent bone autografting as a biphasic technique allowing reconstruction of large bone defects. In light of their already well-characterized osteogenesis-improving capabilities in animals, we performed this translational study to investigate these membranes in patients. METHODS Fourteen patients with complicated fractures and bone defects were randomly selected for this study. Biopsy samples of foreign-body-induced membranes were collected at different time points during scheduled surgical procedures. The membranes were co-cultured with mesenchymal stromal cells, and differentiation into the osteoblastic lineage was assessed by measuring alkaline phosphatase activity, aminoterminal propeptide of type-I procollagen (PINP) production, and Ca2+ concentration. Histological characteristics were evaluated with image analysis. Quantitative reverse transcription polymerase chain reaction was used to measure vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and type-I collagen (Col-1) expression. RESULTS The induced membranes were characterized histologically by maturating vascularized fibrous tissue. The vascularization was greatest in one-month-old samples and decreased to <60% in three-month-old samples. One-month-old membrane samples had the highest expression of VEGF, IL-6, and Col-1, whereas two-month-old membranes expressed <40% of the levels of the one-month-old membranes. Specific alkaline phosphatase activity, PINP production, and Ca2+ concentration were increased in co-cultures when a membrane sample was present. In cultures of one-month-old membranes, PINP production was more than two times and Ca2+ deposition was four times higher than that in cultures of two-month-old membranes. CONCLUSIONS The induced membranes have osteogenesis-improving capabilities. These capabilities, however, appear to decrease over time. We speculate that the optimal time for performing second-stage surgery may be within a month after implantation of foreign material.

Intramedullary nailing of humeral shaft fractures. A retrospective study of 126 cases.

Antegrade intramedullary nailing with four different implants was used in 126 humeral shaft fractures. There were 74 acute fractures, 17 pathologic fractures, 16 fractures malaligned in a hanging cast or brace, 15 fractures with delayed union and 4 fractures that were nailed after failed open reduction and internal fixation. The nonunion rate was 21/95 after primary operation, and after reoperations 14/95. Distraction of the fracture was a significant cause of nonunion, but not type of fracture, localization, implant, and delay between injury and surgery. Shoulder joint function was significantly impaired in 25/67 patients. The patients regarded the result as good or satisfactory in 41/67 of the cases who were followed mean 3 (0.5-10) years. We conclude that antegrade intramedullary nailing of humeral shaft fractures leads to a substantial risk of non-union and impairment of shoulder function. It can be recommended as primary treatment only when nonoperative treatment is likely to fail.

Intraoperative assessment of the stability of the distal tibiofibular joint in supination-external rotation injuries of the ankle: sensitivity, specificity, and reliability of two clinical tests.

BACKGROUND This study was designed to assess the sensitivity, specificity, and interobserver reliability of the hook test and the stress test for the intraoperative diagnosis of instability of the distal tibiofibular joint following fixation of ankle fractures resulting from supination-external rotation forces. METHODS We conducted a prospective study of 140 patients with an unstable unilateral ankle fracture resulting from a supination-external rotation mechanism (Lauge-Hansen SE). After internal fixation of the malleolar fracture, a hook test and an external rotation stress test under fluoroscopy were performed independently by the lead surgeon and assisting surgeon, followed by a standardized 7.5-Nm external rotation stress test of each ankle under fluoroscopy. A positive stress test result was defined as a side-to-side difference of >2 mm in the tibiotalar or the tibiofibular clear space on mortise radiographs. The sensitivity and specificity of each test were calculated with use of the standardized 7.5-Nm external rotation stress test as a reference. RESULTS Twenty-four (17%) of the 140 patients had a positive standardized 7.5-Nm external rotation stress test after internal fixation of the malleolar fracture. The hook test had a sensitivity of 0.25 (95% confidence interval, 0.12 to 0.45) and a specificity of 0.98 (95% confidence interval, 0.94 to 1.0) for the detection of the same instabilities. The external rotation stress test had a sensitivity of 0.58 (95% confidence interval, 0.39 to 0.76) and a specificity of 0.96 (95% confidence interval, 0.90 to 0.98). Both tests had excellent interobserver reliability, with 99% agreement for the hook test and 98% for the stress test. CONCLUSIONS Interobserver agreement for the hook test and the clinical stress test was excellent, but the sensitivity of these tests was insufficient to adequately detect instability of the syndesmosis intraoperatively.

Syndesmotic Fixation in Supination-External Rotation Ankle Fractures A Prospective Randomized Study

Background: This study compared mid-term functional and radiologic results of syndesmotic transfixation with no fixation in supination external rotation (SER) ankle fractures with intraoperatively confirmed syndesmosis disruption. Our hypothesis was that early-stage good functional results would remain and unfixed syndesmosis disruption in SER IV ankle fractures would not lead to an increased incidence of osteoarthritis. Methods: A prospective study of 140 operatively treated patients with Lauge-Hansen SER IV (Weber B) ankle fractures was performed. After bony fixation, the 7.5-Nm standardized external rotation stress test for both ankles was performed under fluoroscopy. A positive stress examination was defined as a difference of more than 2 mm side-to-side in the tibiotalar or tibiofibular clear spaces on mortise radiographs. The patients were randomized to either syndesmotic screw fixation (13 patients) or no syndesmotic fixation (11 patients). After a minimum of 4 years of follow-up (mean, 58 months), ankle function and pain (Olerud-Molander, a 100-mm visual analogue scale [VAS] for ankle function and pain) and quality of life (RAND-36) of all 24 patients were assessed. Ankle joint congruity and osteoarthritis were assessed using mortise and lateral projection plain weight-bearing radiographs and magnetic resonance imaging (MRI; 3T) scans. Results: Improvement in Olerud-Molander score, VAS, and RAND-36 showed no significant difference between groups during the follow-up. In the syndesmotic transfixation group, improvements in all functional parameters and pain measurements were not significant, whereas in the group without syndesmotic fixation, the Olerud-Molander score improved from 84 to 93 (P = .007) and the pain (VAS) score improved from 11 to 4 (P = .038) from 1 year to last follow-up. X-ray or MRI imaging showed no difference between groups at the last follow-up visit. Conclusion: With the numbers available, no significant difference in functional outcome or radiologic findings could be detected between syndesmosis transfixation and no-fixation patients with SER IV ankle fracture after a minimum of 4 years of follow-up. Level of Evidence: Level II, prospective comparative study.

Staged method using antibiotic beads and subsequent autografting for large traumatic tibial bone loss: 22 of 23 fractures healed after 5-20 months.

Introduction The vascularity of surrounding soft tissues, which is related to muscle cover, is important for the healing of traumatic bone loss. Muscle cover on the distal tibia is limited compared to the diaphyseal and proximal tibia, and delayed healing of fractures in this area is common. We evaluated the healing of traumatic bone loss in the proximal, diaphyseal, and distal tibia. Patients and methods 23 open tibial fractures with substantial bone loss (mean 52 (34–104) mm) were treated using a staged method with antibiotic-impregnated beads and later autologous bone grafting at second-stage surgery on average 8 weeks after the injury. Results 22 fractures healed after mean 40 (20–79) weeks. The average healing time in the distal tibia (mean 30 weeks) was 7 weeks shorter (95% CI: 12–26 weeks) than in the proximal tibia (37 weeks), and 16 weeks shorter (95% CI: 3–29 weeks) than in the tibial shaft (47 weeks). The length of the bone and the type of soft tissue cover (free muscle or secondary suture) had no effect on healing time. Interpretation Our study suggests that the method we used is applicable in all parts of the tibia, although the healing of bone loss is slower in the diaphyseal tibia than in the proximal and distal tibia.

Bone morphogenetic proteins in open fractures: past, present, and future

The management of open fractures continues to be complicated by high rates of treatment failure and significant patient disability and dissatisfaction. The use of bone morphogenetic proteins (BMPs) in the treatment of open fractures has been assessed by a number of different clinical trials, both in the acute management of open fractures and in the delayed reconstruction of bone defects secondary to open fracture. This review describes the scientific basis for the use of BMPs in open fractures, reviews the current evidence for their use in open fractures, provides grades of recommendation for the different uses of BMPs in open fractures, and identifies important areas for additional research.

Acromial shape in asymptomatic subjects: A study of 305 shoulders in different age groups

Background: It has been reported that acromial morphology and age have an independent association with rotator cuff pathology. In a recent study, we found the acromial angle of patients with stage III impingement syndrome (tear in the rotator cuff, according to the Neer classification of shoulder impingement syndrome) to be significantly greater than the acromial angle of their age-matched healthy controls. Purpose: To find out if acromial shape also changes, i.e., becomes more curved with age, in shoulders without any rotator cuff problems or previous shoulder surgery. Material and Methods: Standard supraspinatus outlet view (SOV) was obtained from both shoulders of healthy persons with no shoulder-related problems or previous shoulder surgery (n = 305; 36 SOVs for subjects aged 21–30 years, 60 for 31–40 years, 67 for 41–50 years, 52 for 51–60 years, 48 for 61–70 years, and 42 for over 71 years of age). Acromial angle, tilt, and the type of the acromion were evaluated. Results: There were no statistically significant differences in the evaluated morphological parameters between the different age groups. Conclusion: Our results suggest that the shape of the acromion does not change with age in individuals who do not have any rotator cuff pathology. According to our results, the changes in acromial morphology seem to be similar in each age group.

External fixation of tibial pilon fractures and fracture healing.

Distal tibial fractures are rare and difficult to treat because the bones are subcutaneous. External fixation is commonly used, but the method often results in delayed union. The aim of the present study was to find out the factors that affect fracture union in tibial pilon fractures. For this purpose, prospective data collection of tibial pilon fractures was carried out in 1998-2004, resulting in 159 fractures, of which 83 were treated with external fixation. Additionally, 23 open tibial fractures with significant > 3 cm bone defect that were treated with a staged method in 2000-2004 were retrospectively evaluated. The specific questions to be answered were: What are the risk factors for delayed union associated with two-ring hybrid external fixation? Does human recombinant BMP-7 accelerate healing? What is the role of temporary ankle-spanning external fixation? What is the healing potential of distal tibial bone loss treated with a staged method using antibiotic beads and subsequent autogenous cancellous grafting compared to other locations of the tibia? The following risk factors for delayed healing after external fixation were identified: post-reduction fracture gap of >3 mm and fixation of the associated fibula fracture. Fracture displacement could be better controlled with initial temporary external fixation than with early definitive fixation, but it had no significant effect on healing time, functional outcome or complication rate. Osteoinduction with rhBMP-7 was found to accelerate fracture healing and to shorten the sick leave. A staged method using antibiotic beads and subsequent autogenous cancellous grafting proved to be effective in the treatment of tibial bone loss. Healing potential of the bone loss in distal tibia was at least equally good as in other locations of the tibia.