Pretreatment with Pamidronate Decreases Bone Formation but Increases Callus Bone Volume in a Rat Closed Fracture Model.

Clinical concerns have been raised over prior exposure to bisphosphonates impairing fracture healing. To model this, groups of male Wistar rats were assigned to saline control or treatment groups receiving 0.15 mg/kg (low dose), 0.5 mg/kg (medium dose), and 5 mg/kg (high dose) Pamidronate (PAM) twice weekly for 4 weeks. At this point, closed fractures were made using an Einhorn apparatus, and bisphosphonate dosing was continued until the experimental endpoint. Specimens were analyzed at 2 and 6 weeks (N = 8 per group per time point). Twice weekly PAM dosing was found to have no effect on early soft callus remodeling at 2 weeks post fracture. At this time point, the highest dose PAM group gave significant increases in bone volume (+ 10%, p < 0.05), bone mineral content (+ 30%, p < 0.01), and bone mineral density (+ 10%, p < 0.01). This PAM dosing regimen showed more substantive effects on hard callus at 6 weeks post fracture, with PAM treatment groups showing + 46-79% increased bone volume. Dynamic bone labeling showed reduced calcein signal in the PAM-treated calluses (38-63%, p < 0.01) and reduced MAR (32-49%, p < 0.01), suggesting a compensatory reduction in bone anabolism. These data support the concept that bisphosphonates lead to profound decreases in bone turnover in fracture repair, however, this does not affect soft callus remodeling.

The Evaluation of Therapeutic Efficacy and Safety Profile of Simvastatin Prodrug Micelles in a Closed Fracture Mouse Model.

PURPOSE: To evaluate the therapeutic efficiency of a micellar prodrug formulation of simvastatin (SIM/SIM-mPEG) and explore its safety in a closed femoral fracture mouse model. METHODS: The amphiphilic macromolecular prodrug of simvastatin (SIM-mPEG) was synthesized and formulated together with free simvastatin into micelles. It was also labeled with a near infrared dye for in vivo imaging purpose. A closed femoral fracture mouse model was established using a three-points bending device. The mice with established closed femoral fractures were treated with SIM/SIM-mPEG micelles, using free simvastatin and saline as controls. The therapeutic efficacy of the micelles was evaluated using a high-resolution micro-CT. Serum biochemistry and histology analyses were performed to explore the potential toxicity of the micelle formulation. RESULTS: Near Infrared Fluorescence (NIRF) imaging confirmed the passive targeting of SIM/SIM-mPEG micelles to the bone lesion of the mice with closed femoral fractures. The micelle was found to promote fracture healing with an excellent safety profile. In addition, the accelerated healing of the femoral fracture also helped to prevent disuse-associated ipsilateral tibia bone loss. CONCLUSION: SIM/SIM-mPEG micelles were found to be an effective and safe treatment for closed femoral fracture repair in mice. The evidence obtained in this study suggests that it may have the potential to be translated into a novel therapy for clinical management of skeletal fractures and non-union.

[Importance of local antibiotics in the prophylaxis and treatment of fracture-associated infections]. / Stellenwert lokaler Antibiotika für die Prophylaxe und Therapie frakturassoziierter Infektionen.

BACKGROUND: Fracture-associated infections (FRI) are a severe complication that lead to higher morbidity and high costs for the healthcare system. An effective prophylaxis and treatment of FRI are therefore of great interest. OBJECTIVE: The aim of this review is to summarize the available evidence on the use of local antibiotics for the prophylaxis and treatment of FRI. MATERIAL AND METHODS: A thorough search and a narrative synthesis of the available literature were performed. Their depiction is supplemented by an illustrative presentation of a case report. RESULTS: A robust consensus definition of FRI has existed since 2018. The current use of local antibiotics for the prophylaxis and treatment of FRI in Germany is heterogeneous. There is no consensus on local antibiotic treatment of FRI. The available literature shows an advantage for the additive local antibiotic treatment of open fractures. In closed fractures there is a tendency towards an advantage especially in the presence of further risk factors (long duration of external fixation, higher degree of closed tissue damage, compartment syndrome). According to analogous data from the field of endoprosthetics, additive local antibiotic treatment could also be advantageous under closed soft tissue conditions. The evidence is insufficient to enable the recommendation for a specific antibiotic or a specific mode of application. Local and systemic adverse reactions are frequently discussed in the literature but their incidence is low. CONCLUSION: Overall, additive local antibiotic treatment is to be recommended for open fractures and in closed fractures in the presence of other risk factors. Local and systemic adverse reactions as well as the development of antibiotic resistance must be weighed up in individual cases.

Implementation of a short course of prophylactic antibiotic treatment for prevention of postoperative infections in clean orthopaedic surgeries.

BACKGROUND & OBJECTIVES: Perioperative antimicrobial prophylaxis constitutes the bulk of antimicrobial consumption in any hospital. This study was conducted at a level 1 Trauma Centre of a tertiary care hospital of India to assess the efficacy of a short (24 h) course of perioperative antibiotic prophylactic regimen in preventing surgical site infections (SSI) in open reduction and internal fixation (ORIF) of closed fractures of limbs and to assess if the same can be implemented as a general policy. METHODS: Patients of either sex, aged 18 yr or more, who were scheduled for ORIF and were willing and able to give informed consent, were included in the study. Patients were randomly allocated into two groups. Group 1 (n=100) received 3 doses of 1 g i.v. cefuroxime perioperatively spaced 12 h apart and group 2 (n=97) received the conventional existing regimen [5 days of i.v. antibiotics (cefuroxime 1 g twice daily along with amikacin 15 mg/kg in 2 divided doses), followed by oral cefuroxime, 500 mg twice daily till suture removal]. RESULTS: Of the 197 patients, four patients developed a surgical site infection (three with methicillin resistant Staphylococcus aureus and one Acinetobacter baumanii). Of these, two patients were in group 1 and the remaining two in group 2. These patients were treated with i.v. antibiotics based on the culture and antimicrobial sensitivity reports. The cost of the short course treatment was ` 150 per patient as compared to ` 1,900 per patient for conventional regimen. INTERPRETATION & CONCLUSIONS: There was no significant difference in rates of SSI among the two groups in our study. Cost evaluation revealed that shorter course was less expensive than conventional long course regimen. Implementation of a short course perioperative regimen will go a long way in reducing antimicrobial resistance, cost and adverse reactions to antimicrobials.

Experimental stimulation of bone healing with teriparatide: histomorphometric and microhardness analysis in a mouse model of closed fracture.

Fracture consolidation is a crucial goal to achieve as early as possible, but pharmacological stimulation has been neglected so far. Teriparatide has been considered for this purpose for its anabolic properties. We set up a murine model of closed tibial fracture on which different doses of teriparatide were tested. Closed fracture treatment avoids any bias introduced by surgical manipulations. Teriparatide's effect on callus formation was monitored during the first 4 weeks from fracture. Callus evolution was determined by histomorphometric and microhardness assessment. Daily administration of 40 µg/kg of teriparatide accelerated callus mineralization from day 9 onward without significant increase of sizes, and at day 15 the microhardness properties of treated callus were similar to those of bone tissue. Teriparatide considerably improved callus consolidation in the very early phases of bone healing.

BMP-7 in combination with estrogen enhances bone formation in a fracture callus explant culture.

In postmenopausal women, estrogen withdrawal results in decrease in bone density or osteoporosis. Osteoporosis leads to fracture and retards bone-healing response. Bone morphogenetic protein-7 (BMP-7), a member of the transforming-growth factor-beta superfamily, has been shown as a promising candidate that stimulates bone growth in its application to fracture healing. The purpose of this study was to determine whether BMP-7 could enhance bone formation in the absence of estrogen. Female rats underwent a controlled closed fracture at the midshaft of the right femur. The callus tissues were harvested from the fracture site eight days following the fracture, and were cultured in serum-free media. The explanted callus tissues were then treated with BMP-7, estrogen (E2) or both. We assessed bone formation by measuring alkaline phosphatase (AP) activity, expression of an osteogenic transcription factor, Runt-related transcription factor-2 (Runx2), production of nitric oxide (NO), and calcium mineralization. Supplementation of serum-free cultures with BMP-7 alone increased cell proliferation by twofold, caused a 6.5-fold increase in AP activity, and enhanced calcium mineralization after 48 h. Moreover, BMP-7 in combination with E2 caused a 8.2-fold increase in the AP activity. Runx2 protein expression was increased following stimulation with BMP-7 and E2. Interestingly, E2 induced the amount of NO production by twofold, whereas BMP-7 did not, either alone or with E2. Thus, BMP-7 could enhance early and late markers of bone fracture healing in callus explant cultures, except for NO. BMP-7 could be a promising growth factor in the treatment of fractures as a consequence of osteoporosis.

[Analysis of the effects of different medicines on hypercoagulability state variations of femoral shaft fracture and after its operation].

OBJECTIVE: To explore the role of Tong Mai Tang & Lornoxicam on the serum concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin (IL-6) , D-dipolymer( D-Di), Platelet count (PLC) in treatment of femoral shaft fracture among period surgery time. METHODS: We selected 120 cases of traumatic femoral shaft fracture patients according to the inclusion criteria and exclusion criteria, which were randomized dividend into four groups (I, II, III, IV respectively) of the same size based on the random number table method of 30 patients each. Therapeutic methods of four groups following as: Group I, Tpanax Notoginseng Pills PO; Group II, Tpanax Notoginseng Pills PO, Lornoxicam For Injection, 8 mg IM; Group III, Tpanax Notoginseng Pills PO, Tong Mai Decoctions 200 mL PO; Group IV, Tpanax Notoginseng Pills PO, Lornoxicam For Injection 8 mg IM, Tong Mai Decoctions 200 mL PO. The above medications were administered to the four groups after admission to hospital the next day. Peripheral blood samples were taken for immune determination of pro-inflammatory cytokines of TNF-alpha, IL-6, D-Di, PLC in blood serum on the 2nd and 6th day before operation and on the 8th and 13th day after operation in the morning. And all patients received liver and kidney function examination 2nd and 13th day after admission. Analysis of variance and least significant difference-test were done with the help of SPSS 17.0 statistic software. RESULTS: The difference among four groups in TNF-alpha and IL-6 were significant (P < 0.05). And there were also significant statistic difference between group II/III/IV and group I group (P < 0.05). But the difference between group II and group III was insignificant (P > 0.05). However, the group contrast result between group IV and group II/III had statistics difference (P < 0.05). The difference in D-Di PLC at 6th day and 8th day were significant (P < 0.05). The group comparisons in group I/II/IV were also significant. There were non-statistics significance in group II compared 6th day/8th day with 2nd day (P > 0.05). The comparison between the 13th day with the first three time sections had statistics significance. And there were statistics significance at the 13th day between group IV and group II (P < 0.05). CONCLUSION: The serum concentrations of TNF-alpha, IL-6, D-Di and PLC level were significantly increased in peroperative period, These results seem to indicate that the Tong Mai Decoctions & Lornoxicam may play an important role in inhibiting the release of TNF-alpha, IL-6, D-Di and PLC into the blood stream and decreasing the incunabula complication at early traumatic stage. The Tong Mai Decoctions & Lornoxicam was the worth promoting screened China and the West union medication combination.

Cordycepin promotes osteogenesis of bone marrow-derived mesenchymal stem cells and accelerates fracture healing via hypoxia in a rat model of closed femur fracture.

Fracture is the most frequently encountered traumatic large-organ injury observed in human patients. Cordycepin possesses beneficial effects in osteogenesis of mesenchymal stem cells (MSCs), but its effect on fracture healing is largely unknown. A rat model of closed femur fracture was established, and treated with therapy using bone marrow-derived MSCs (BMMSCs). The effect of cordycepin on the osteogenic process of BMMSCs in vitro was evaluated by Alizarin Red S (ARS) staining and expressions of osteogenic marker genes. Radiographic evaluations and four-point bending mechanical testing were performed on model rats after BMMSC treatment, to assess the effect of cordycepin on fracture healing. Cordycepin promoted osteogenesis of BMMSCs in vitro, and enhanced radiographic parameters and mechanical properties in rat closed femur fracture model using BMMSC therapy in vivo. A hypoxia inhibitor echinomycin could negate the above-mentioned therapeutic effects of cordycepin, indicating that the beneficial effects of cordycepin were mediated via hypoxic response pathway. This study demonstrates that cordycepin promotes osteogenesis of BMMSCs and accelerates fracture healing via hypoxia in a rat model of closed femur fracture, and proposes the clinical potential of cordycepin in bone fracture treatments.

Osteogenic protein-1 overcomes inhibition of fracture healing in the diabetic rat: a pilot study.

Type I diabetes mellitus inhibits fracture healing and leads to an increase in complications. As a pilot study, we used a closed fracture model in the diabetic rat to address the question of whether osteogenic protein-1 (OP-1) in a collagen carrier can overcome this inhibition by increasing the area of the newly mineralized callus and femoral torque to failure compared with diabetic animals with fractures treated without OP-1. Diabetes was created in 54 rats by injection of streptozotocin. After 2 weeks, a closed femur fracture was created using a drop-weight impaction device. Each fracture site was immediately opened and treated with or without 25 microg OP-1 in a collagen carrier. Animals were euthanized after 2 or 4 weeks. Fracture healing was assessed by callus area from high-resolution radiographs, callus strength from torsional failure testing, and undecalcified histologic analysis. The area of newly mineralized callus was greater in diabetic animals treated with 25 microg OP-1/carrier compared with diabetic animals with untreated fractures and with fractures treated with carrier alone. This increase in callus area did not translate into an equivalent increase in torque to failure. Osteogenic protein-1 showed some evidence of overcoming the inhibition of fracture healing in the diabetic rat.

Single- versus multiple-dose antibiotic prophylaxis in the surgical treatment of closed fractures: a meta-analysis.

OBJECTIVES: The use of prophylactic antibiotics in the surgical treatment of closed long bone fractures is well established. The duration and dosage of prophylaxis, however, vary significantly among surgeons. A systematic review and meta-analysis were performed to determine if multiple-dose perioperative antibiotic prophylaxis is more effective than a single preoperative dose in the prevention of surgical wound infections during the treatment of closed long bone fractures. DATA SOURCES: Articles were identified by searching the following medical databases: Medline, Medline In Process & Other Non-indexed Citations, Embase, CENTRAL, and the Cochrane Database of Systematic Reviews. Relevant conference proceedings and the reference section of selected manuscripts were also searched for additional studies. STUDY SELECTION: Studies were included if they were prospective randomized controlled trials of patients with closed fractures treated with surgical fixation or arthroplasty. The interventions must have directly compared a single preoperative prophylactic dose to a multiple-dose perioperative strategy. Studies were excluded if they involved open fractures. DATA EXTRACTION: The demographic information, prophylaxis strategy, wound infection rate, and risk ratio were extracted from each article. DATA SYNTHESIS: Seven trials and 3,808 patients were pooled using a random effects model. When compared to a regimen of multiple doses of prophylactic antibiotics, administration of a single preoperative dose has a risk ratio of 1.24 (95% CI 0.60-2.60). The pooled risk difference between the 2 strategies is 0.005 (95% CI -0.011-0.021). Neither result is significant. CONCLUSIONS: In the setting of closed long bone fractures, the pooled results failed to demonstrate superiority of multiple-dose prophylaxis over a single-dose strategy. The pooled estimates suggest that surgical wound infections are relatively rare events and that any potential difference in infection rates between prophylaxis strategies is likely quite small. However, because the confidence interval surrounding the pooled risk ratio spans 1.0 by such a large amount, we are unable to definitively recommend a preferred dosing regimen to prevent surgical wound infections. Although future research is required to ensure our prophylaxis decisions continue to be evidence based and cost-effective, it is unlikely that a single clinical trial will be able to provide the answer. The use of other quantitative methods, such as cost-effectiveness analysis, may be helpful in modeling an optimal prophylaxis strategy.

Effects of growth hormone in patients with tibial fracture: a randomised, double-blind, placebo-controlled clinical trial.

OBJECTIVE: Investigate whether intervention with GH after tibial fracture enhances fracture healing. DESIGN: Randomised, double-blind, placebo-controlled study in 406 patients (93 women, 313 men, age: 18-64 years) with tibial fracture. METHODS: Patients were stratified by tibial fracture (open or closed) and allocated to placebo or GH treatment (15, 30 or 60 mug/kg daily, until clinically assessed healing or until 16 weeks post-surgery). Primary outcome was time from surgery until fracture healing and assessment of healing was done centrally and observer blinded. Patients reported for evaluation every 4 weeks until 24 weeks, and at 9 and 12 months. RESULTS: GH did not accelerate time to healing in the combined group of open and closed fractures. When separately analysing the closed and open fractures, a significant difference in time to healing was observed between treatment groups, exclusively in the closed fractures (P<0.05; subgroup analysis revealed that the 60 microg/kg group was significantly different from placebo). The relative risk of fracture healing for 60 microg/kg versus placebo during the 12 month was: all fractures, 1.16; 95% CI: (0.86; 1.57) (ns); closed fractures, 1.44; 95% CI: (1.01; 2.05; P<0.05); open fractures, 0.75; 95% CI: (0.42; 1.31) (ns). The estimated median number of days before fracture healing in closed fractures was 95 with 60 microg/kg versus 129 with placebo (95% CI: (94; 129) and (94; 249)) corresponding to approximately 26% decrease in healing time. CONCLUSIONS: In the overall group of open and closed tibial fractures, no significant enhancement of fracture healing was observed with GH, whereas in closed tibial fractures, GH accelerated healing significantly.

Dose and time-dependent effects of cyclooxygenase-2 inhibition on fracture-healing.

BACKGROUND: Fracture-healing is impaired in mice lacking a functional cyclooxygenase-2 (COX-2) gene or in rats continuously treated with COX-2 inhibitors. These observations indicate that COX-2 is a critical regulator of fracture repair. Nonsteroidal anti-inflammatory drugs are commonly used to treat pain associated with musculoskeletal trauma and disease. Nonsteroidal anti-inflammatory drugs inhibit COX-2 function and in so doing can impair fracture-healing. The goal of the present study was to determine how variations in nonsteroidal anti-inflammatory drug therapy ultimately affect fracture-healing. METHODS: Closed femoral fractures were made in female Sprague-Dawley rats. The rats were treated with different doses of celecoxib (a COX-2-selective nonsteroidal anti-inflammatory drug) or were treated for different periods before or after fracture with celecoxib. Eight weeks after the fracture, healing was assessed with radiography and destructive torsional mechanical testing. The effect of celecoxib treatment on fracture callus prostaglandin E2 and F(2alpha) levels was determined as a measure of cyclooxygenase activity. RESULTS: Celecoxib doses as small as 2 mg/kg/day reduced fracture callus mechanical properties and caused a significant increase in the proportion of nonunions. Similarly, treatment with celecoxib at a dose of 4 mg/kg/day for just five days reduced fracture callus mechanical properties and significantly increased the proportion of nonunions. Conversely, celecoxib therapy prior to fracture or initiated fourteen days after fracture did not significantly increase the proportion of nonunions. Celecoxib treatment at a dose of 4 mg/kg/day reduced fracture callus prostaglandin E2 and F(2alpha) levels by >60%. CONCLUSIONS: COX-2-selective nonsteroidal anti-inflammatory drug therapy during the early stages of fracture repair significantly reduced fracture callus mechanical properties at later stages of healing and increased the proportion of nonunions in this animal model.

The effect of teicoplanin on fracture healing: an experimental study.

OBJECTIVES: This study aims to investigate the effect of teicoplanin on fracture healing stereologically and histopatologically. MATERIALS AND METHODS: Twenty male Wistar albino rats were separated into two as the study (teicoplanin) and control groups. After intramedullary fixation of the right tibia of all the rats with 0.5 mm Kirschner wire under general anesthesia, standard closed shaft fractures were created using fracture formation apparatus. Teicoplanin (10 mg/kg) and saline were administered intraperitoneally to the study and control groups, respectively. Control radiographs were taken at the end of the procedure and the rats were sacrificed after 28 days. New bone and connective tissue volumes were calculated on obtained tissue samples using unbiased stereological and histopathological techniques. RESULTS: It was observed that teicoplanin increased the formation of bone, vascularization, and connective tissue. There was a statistically significant difference between the two groups in respect of bone and vascular total volume (p<0.05). Although an increase was observed in connective tissue total volume, no statistically significant difference was detected between the two groups (p>0.05). CONCLUSION: In addition to its antibacterial effect, teicoplanin may increase new bone formation; thus, it may be used safely in the treatment of bone defects accompanied with infection.

A comparison between the effects of acetaminophen and celecoxib on bone fracture healing in rats.

OBJECTIVES: This study compared the acute treatment effects of systemic analgesics with (celecoxib) and without anti-inflammatory activity (acetaminophen) on bone fracture healing. STUDY DESIGN: Longitudinal time study of fracture healing in rats. METHODS: Closed, mid diaphyseal femur fractures were produced in female Sprague-Dawley rats. The rats were treated for 10 days after fracture with 60 or 300 mg/kg of acetaminophen, 3 or 6 mg/kg of celecoxib, or vehicle by once-daily oral dosing. Fracture healing was measured after 8 weeks by radiographic examination, mechanical testing, and histology. RESULTS: Radiographic scoring indicated that acute celecoxib treatment significantly impaired fracture healing; acetaminophen treatment had no negative effect. Mechanical testing supported the radiographic observations. No negative effects of celecoxib or acetaminophen treatment on the structural properties (peak torque and torsional rigidity) of the healing femurs were detected. In contrast, celecoxib treatment, but not acetaminophen treatment, significantly reduced the material properties (maximum shear stress and shear modulus) of the healing femurs (P < 0.001). Post-mechanical testing examination of the healing femurs found that 73% of the vehicle-treated or acetaminophen-treated femurs had healed as unions (30/41), 27% failed as incomplete unions (11/41), and none failed as nonunions (0%). In contrast, only 21% of the fractured femurs from the celecoxib treated rats had healed as unions (7/34), 53% failed as incomplete unions (18/34), and 26% failed as nonunions (9/34). The proportion of nonunions among the celecoxib-treated rats was significantly higher compared with the control and acetaminophen-treated rats (P < 0.001). Histologic examination indicated that similar to previous studies, celecoxib treatment, but not acetaminophen treatment, altered normal fracture callus morphology in which cartilage rather than new bone abuts the fracture site. CONCLUSIONS: No negative effect from acute acetaminophen treatment on fracture healing was detected. In contrast, acute treatment with celecoxib, a selective cyclooxygenase-2 inhibitor with anti-inflammatory activity, significantly impaired fracture healing.

Increased mechanical strength of healing rat tibial fractures treated with biosynthetic human growth hormone.

The effects of biosynthetic human growth hormone on the biomechanical properties of healing tibial fractures and intact bones in the rat were studied after 20 and 40 days of healing. Growth hormone, 2.0 mg per kg per day, was given subcutaneously in two daily doses. Control animals were injected with a corresponding volume of saline. After 20 days of fracture healing, there were no differences in mechanical properties between the healing fractures and intact bones. After 40 days, the ultimate load and maximum stiffness of the fractures of the b-hGH injected animals had increased to more than 400% of the corresponding values of the saline injected animals, and ultimate stress and energy absorption at ultimate load had increased to 270% compared with the saline injected animals. Ultimate load, stiffness, and energy absorption of the intact bones increased in the b-hGH injected animals, but no differences were found in ultimate stress values or normalized energy, indicating that the changes in the intact bones were quantitative phenomena.

Spatial and temporal gene expression in chondrogenesis during fracture healing and the effects of basic fibroblast growth factor.

Chondrogenesis is an essential component of endochondral fracture healing, though the molecular and cellular events by which it is regulated have not been fully elucidated. In this study, we used a rat model of closed fracture healing to determine the spatial and temporal expression of genes for cartilage-specific collagens. Furthermore, to determine the effects of basic fibroblast growth factor (bFGF) on chondrogenesis in fracture healing, we injected 100 microg recombinant human bFGF into the fracture site immediately after fracture. In normal calluses, pro-alpha1(II) collagen mRNA (COL2A1) was detected in proliferative chondrocytes beginning on day 4 after the fracture, and pro-alpha1(X) collagen mRNA (COL10A1) in hypertrophic chondrocytes beginning on day 7. In FGF-injected calluses, the cartilage enlarged in size significantly. On day 14, both COL2A1- and COL10A1-expressing cells were more widely distributed, and the amounts of COL2A1 and COL10A1 mRNAs were both approximately 2-fold increased when compared with uninjected fractures. Temporal patterns of expression for these genes were, however, identical to those found in normal calluses. The number of proliferating cell nuclear antigen-positive cells was increased in the non-cartilaginous area in the bFGF-injected calluses by day 4. The present molecular analyses demonstrate that a single injection of bFGF enhances the proliferation of chondroprogenitor cells in fracture callus, and thus contributes to the formation of a larger cartilage. However, maturation of chondrocytes and replacement of the cartilage by osseous tissue are not enhanced by exogenous bFGF, and this results in the prolonged cartilaginous callus phase. We conclude that, in the healing of closed fractures of long bones, exogenous bFGF has a capacity to enlarge the cartilaginous calluses, but not to induce more rapid healing.

Efficacy of antibiotics in low-velocity gunshot fractures.

We have investigated the efficacy of intravenous antibiotic therapy as a prophylactic measure to prevent infection following low-velocity gunshot fractures. Ninety-six consecutive patients were randomized prospectively to either an antibiotic group (Group I) or a nonantibiotic group (Group II) and were followed in a special gunshot wound clinic. Only patients with fractures that could be treated by closed techniques and did not require internal fixation were included. Sixty-seven patients (73 fractures) were followed radiographically. At follow-up, 36 fractures in Group 1 and 37 fractures in Group II comprised the study group. A total of two infections, one in each group, was documented. No significant infection prophylaxis was demonstrated by the use of intravenous antibiotics in these injuries.

Healing of fresh tibial fractures with OP-1. A preliminary report.

Osteogenic proteins (OP) are elements of a class of natural growth factors called Bone Morphogenetic Proteins (BMP). A specific member of this class is OP-1, a human recombinant protein that has osteogenic properties. The osteoinductive and osteoconductive properties of OP-1, with its specific collagen matrix, promote the generation of new functionally active, biologically and biomechanically mature bone. We carried out a clinical study to verify the potential of this protein in fresh tibial closed fractures, using OP-1 associated with osteosynthesis by means of a monolateral external fixator.

[Effect of radix Salviae miltiorrhizae on calcium, zinc, copper content in serum, callus and bony tissue in early stage of healing process in rat closed tibial fracture].

Changes of calcium, zinc, copper contents in serum, callus and bony tissue in the early stage of the healing process of rat closed tibial fracture, also the changes of them with radix Salviae miltiorrhizae (RSM) treatment were studied. It was found that calcium, zinc contents and Zn/Cu ratio increased significantly and the rise of serum copper content was inhibited by the administration of RSM after fracture. Zn/Cu ratio in fracture callus was correlated to the calcium content in fracture callus. These findings suggested that the effect of the promotion of RSM on fracture healing was related to the increased zinc content in serum, also related to the acceleration of mobilization of zinc in fractured bone, and to the acceleration of fracture callus formation and mineralization process by the increased zinc and Zn/Cu ratio in the callus of the fracture.

[Treatment of tibial shaft fractures in Denmark]. / Behandling af crusfrakturer i Danmark.

INTRODUCTION: Only a few randomised studies have been published on the treatment of tibial shaft fractures. We therefore expected a great diversity in the choice of treatment methods in Denmark. In order to analyse this, we carried out a questionnaire investigation. MATERIAL AND METHODS: In autumn 1997, a questionnaire was sent to all departments in Denmark where tibial fractures are treated. The fractures were classified according to stability, amount of energy, and the degree of soft tissue injury. RESULTS: Ninety-three per cent of the departments answered the questionnaire. We present here the results with respect to the use of antibiotics, thrombosis prophylaxis, invasive pressure measuring, and the choice of treatment: conservative or operative methods and techniques. DISCUSSION: As expected, we found a significant variation in the choice of treatment of tibial shaft fractures in Denmark. This is consistent with the recommendations in the literature, which vary somewhat and are mostly based on non-randomised studies.