Aims: Clinical use of BMP-7: actual situation The tibial pseudoarthrosis. The Friedlander paper can be considered the only golden standard about the clinical application. It is a prospective, randomized clinical trial comparing BMP-7 with fresh bone autograft. The results of the BMP-7 are similar under to use of fresh bone autograft. Some cases of very serious pseudoar-throsis treated with BMP-7 have demonstrated an high percentual of clinical recovery. In UOA of traumatology and in I Orthopaedic Clinic of Turin University the pseudoarthrosis are treated with the Ilizarov’s technique, not with the autologous transplantation, so Friedlander’s results are not discriminant for the our work.

Methods: In our department the guide lines for BMP-7 application are:

Delayed union of the docking point in pseudoarthrosis of long bones treated with the Ilizarov technique (resection and distractional osteogenesis) and traditional techniques (decortication and fresh bone autograft) not suitable for application. The treatment of a pseudoartrhosis is based on our classification in type: I, II, III, IV (septic).

Results: From 30/09/2002 till 28/02/2007 55 patients have been treated with BMP-7. In 5 cases it has been associated with autologus bone graft. The material is: 24 cases of traditional techniques failure, 17 cases in wich traditional techniques were unfeasible to be treated and 9 docking point nonunions, in 5 particular cases. Mean age is 38 years. Before last intervention, mean number of porevious operation is 6,5 with mean time before BMP procedures is 3 years. 43 patients healed, 9 are under treatment and 3 are failure. The mean time of healing was 4 months.

Conclusions: The series is strictly observational but results are effective in front of the complexity of cases. Late complications suggest that BMP-7 induces bone formation but mechanical function could need time to be achived.According to literature the BMP-7 should be usefull also in more simple cases but more prospective clinical double blind randomised series and cost decreasing are necessary to extend the indications for BMP-7 application.

The management of post-traumatic bone infections relies on antibiotic therapy and surgical debridement. Antibiotic concentration in infected bone is a major determinant of response to medical treatment.

The aim is to assess glycopeptides, fluoroquinolones and carbapenems diffusion in infected human bone, since they are widely used for treating bone infections.

Twenty-four patients with septic pseudoarthrosis undergoing surgical debridement and treated with glycopeptides/fluoroquinolones/carbapenems iv for > 1 week were studied. Plasma and bone specimens were collected intraoperatively at a mean of 4.8h after antibiotic administration. Antibiotic concentrations were measured by the HPLC-UV method.

Five patients received vancomycin: mean bone concentrations were 2.4mg/L in cortical and 7.1mg/L in cancellous bone, with a bone/plasma extraction of 12% and 36%, respectively.

Nine patients were treated with teicoplanin: bone concentrations were 2.5mg/L for cortical and 8.3mg/L for cancellous bone (14% and 46% of plasma levels).

Five patients received a fluoroquinolone. Ciprofloxacin concentrations were 1.8mg/L in cortical bone and 30.2mg/L in cancellous and newly formed bone (respective bone/plasma ratios 1.06 and 8.4). Levofloxacin concentrations were 0.3 and 2.69mg/L in cortical and cancellous bone, with diffusion rates of 12% and 108%, respectively.

Five patients received a carbapenem. Imipenem diffusion rates were respectively 7.5% and 58.3% for cortical and cancellous bone (bone concentrations 0.09 mg/L and 0.7 mg/L). Meropenem levels were 1.2 mg/L and 5.2 mg/L in cortical and cancellous bone, with respective diffusion rates of 3.6% and 15%.

Both glycopeptides provided concentrations exceeding the MIC of infecting agents, with satisfactory bone diffusion. Fluoroquinolones, especially ciprofloxacin, displayed excellent diffusion. Ciprofloxacin concentrations in cancellous and new bone were far higher than in plasma, suggesting accumulation into highly vascularized tissue. Imipenem had better diffusion than meropenem, but bone levels were under the MIC of susceptible agents. Glicopeptides and fluoroquinolones appear excellent options for bone infections, while carbapenems should be a second choice treatment.

Antibiotic concentration in infected bone is a major determinant of clinical response. As glycopeptides and fluoroquinolones are widely used for the treatment of bone infections, aim of our study was to assess their diffusion in infected human bone. Patients with a posttraumatic septic pseudoarthrosis undergoing debridement of infected tissue, who received a glycopeptide or a fluoroquinolone for > 1 week, were studied. Plasma and bone specimens were collected intraoperatively for phamacokinetic and microbiologic assays at a mean of 4.1h after antibiotic administration. Bone samples were crushed and concentrations were measured by HPLC-UV method. Overall plasma exposure was also determined with daily sampling. 16 patients were studied. 6 patients received iv vancomycin 1 g bid over a 1-hr infusion Bone cultures grew E. faecalis, MRSA and MRSE (MIC < 2 mg/L). Mean plasma concentration of vancomycin at time of osteotomy was 19.8 mg/L. Mean bone concentrations were 2.4 mg/L in cortical and 7.1 mg/L in cancellous bone, with a mean bone extraction of 12 % and 36 %, respectively. 4 patients were treated with iv teicoplanin 10/mg/Kg for MRSA infection (MIC < 2 mg/L). Mean bone concentrations were 8.9 mg/L and 37 mg/l respectively for cortical and cancellous bone, respectively corresponding to 6% and 25% of plasma levels. Six patients were treated with a fluoroquinolone. 3 patients received iv ciprofloxacin 400mg bid and E. coli grew from bone samples(MIC = 0.5 mg/L). Mean Plasma concentration of ciprofloxacin at the time of osteotomy was 3.6 mcg/mL. Mean bone concentrations were 1.7 mg/L in cortical bone and 30.2 mg/L in cancellous and newly formed bone, with respective bone/ plasma ratios of 0.5 and 8.4. 3 patients were administered iv levofloxacin 500mg qd and Enterobacter spp. were isolated (MIC = 1 mg/L). Mean plasma concentration at the time of surgery was 2.5 mcg/mL. Mean bone concentrations were 0.3 and 2.69 mcg/mL in cortical and cancellous bone, respectively. To our knowledge this is the first study that compares different antibiotic’s concentration in infected bone with the same dosing procedure. Both vancomycin and teicoplanin provided mean bone concentrations exceeding the susceptibility breakpoint of the infecting agents. Higher and constant glycopeptides plasma levels may be required for preventing recurrencies in bone infections. Only ciprofloxacin provided cortical bone concentrations higher than the susceptibility breakpoint of the infecting agent, and similar to those reported in non-infected bone. Ciprofloxacin concentration in cancellous bone and in bony callus were far higher than those detected in plasma, which may be related to an augmented vascularization and/or selective accumulation of fluoroquinolones into regenerating bone, as observed in children’s cartilage growth plate. Ciprofloxacin may be therefore preferred to levofloxacin.

In amputation or amputation-like injuries of lower limbs, only in a few cases reconstructive treatment with microsurgery is encouraged, according to evaluation of lesion by Mangled Extremity Severity Score (MESS). Replantation cases may require substantial bone shortening, as consequence to seriousness of the trauma or a deliberate choice to enable primary vessel and nerve repair. Callus distraction technique by external fixation, circular or axial, is a common method for recover lengthening in these cases of replanted or revascularized extremities.

We report six cases of lower limb replantation or revascularisation, with primary bone shortening from 3 to 7 cm and secondary lengthening by callus distraction.

It was always obtained equalization of lower extremities, with successful rehabilitation of the patients and low onset of complications during treatment.

1. Use of OP1: present situation

1.1 Tibial pseudoarthrosis. The work by Friedlander can be considered golden standard about the clinical application. It is a prospective, randomized clinical trial comparing OP-1 with fresh bone autograft. Results of the two techniques are similar under the clinical and radiographical point of view(1). Some cases of very serious pseudoarthrosis treated with OP1 have demonstrated an high percentual of clinical recovery(2). In the I Orthopaedic Clinic of Turin University pseudoarthrosis are treated with Ilizarov technique, not with the autologous transplantation, so Friedlander’s results are not discriminant for the our work.

1.2 Australian study of 163 patients with amputation risk was done an attempt with OP1 application, before of his commercialisation. In these cases the drug demonstrated to be very efficacious(3).

1.3 Concerning the fresh fractures, experience is limited to prospective, randomised, multicenter clinical trial. The conclusions are a reduction of consolidation delay and the number of reoperation in the OP1 treated group versus the not treated one(4).

2. In the I Orthopaedic Clinic of Turin University (UOSD Muscle-Skeletal Traumatology and External Fixation) guide lines for OP1 application are:

2.1 Delayed union of the docking point in pseudoar-throsis of long bones treated with the Ilizarov technique. OP1 is also used if traditional techniques are not suitable for application

2.2 Traditional techniques failure

2.3 First treatment in very difficult cases of limb reconstruction and bone nonunion

3. From 30/09/2002 till 27/09/2004, 19 patients have been treated with OP1. Middle age is 38 years (range 22–65). Before last intervention, middle number of operation is 6,5 (range 3–26) with middle time treatment of 4 years (range 1–31). 12 healed, 5 are under treatment and 2 are failure (osteomyelitis relapse). 10 tibias, 7 femurs, 1 humerus and 1 forearm were treated. The middle time of healing was 4 months (range 2–6).

Healing has been evaluated by clinical and radiographical point of view (handly evaluation of stability, function recuperation and image of bone consolidation). Radiographic images of bone consolidation are not strictly correlated with clinical stability and function recovery.

4. Conclusion:

4.1 The series is strictly observational. However results are satisfying, given the complexity of treated cases. More prospective randomised double blind clinical studies, and drug cost decrease are necessary to extend the indications for OP1 application.

The choice of treatment for open fractures is conditioned by the care of bone and soft tissue. Grade I open fractures can be treated as closed fractures, according to the centre’s protocol. In Grade II open fractures skin wounds must be left open, and the suture should be delayed for at least a week. Most authors perform fixation by means of intramedullary nails.

In our opinion, external fixation is the best choice in these cases. The skin cannot be closed in Grade III open fractures, and the basic point of treatment is adequate surgical debridement. The fixation must be done by external fixation. To achieve the treatment in an emergency situation, the device to be used must be quick and simple like a monolateral device that can be changed into a more complex one, such as an Ilizarov.

The Ilizarov technique uses distractional osteogenesis that can fill bone and soft tissue loss without further bone or soft tissue grafting.

Following these general guidelines, each district has its own particular approach to treating open fractures. Internal fixation by DCP plates is always indicated for forearm fractures. For a humerus fracture, simple direct shortening and external fixation can fill bone loss. Patients with fractures of the femur usually have multiple injuries. The problem is to provide a quick fixation in order to allow for easier intensive care. External fixation is the most indicated technique.

The choice of treatment for open fractures is conditioned by the care of bone and soft tissue. Grade I open fractures can be treated as closed fractures, according to the centre’s protocol. In Grade II open fractures skin wounds must be left open, and the suture should be delayed for at least a week. Most authors perform fixation by means of intramedullary nails.

In our opinion, external fixation is the best choice in these cases. The skin cannot be closed in Grade III open fractures, and the basic point of treatment is adequate surgical debridement. The fixation must be done by external fixation. To achieve the treatment in an emergency situation, the device to be used must be quick and simple like a monolateral device that can be changed into a more complex one, such as an Ilizarov.

The Ilizarov technique uses distractional osteogenesis that can fill bone and soft tissue loss without further bone or soft tissue grafting.

Following these general guidelines, each district has its own particular approach to treating open fractures. Internal fixation by DCP plates is always indicated for forearm fractures. For a humerus fracture, simple direct shortening and external fixation can fill bone loss. Patients with fractures of the femur usually have multiple injuries. The problem is to provide a quick fixation in order to allow for easier intensive care. External fixation is the most indicated technique.