Does the use of polymethyl-methacrylate cement after intralesional curettage of giant cell tumors of appendicular bone guarantee reduced local recurrence rates? A retrospective analysis.

PURPOSE: Polymethyl-methacrylate cement (PMMA) is often used as bone defect reconstruction material after surgical removal of giant cell tumors. The purpose of this study was to investigate if the application of PMMA improves the local recurrence rates for giant cell tumors (GCT) of appendicular bone treated with intralesional curettage. METHODS: A retrospective analysis of all appendicular GTCs treated at two major Danish sarcoma centres between the 1st of January 1998 and December 31st 2013; minimum follow-up of 3.0 years (median: 8.9; 1.3-18.7 years). Kaplan-Meier survival model, log-rank and multivariate Cox regression were used to calculate and compare local recurrence rates. p-values <0.05 were considered statistically significant. RESULTS: 102 patients (M59/F43), median age 31Y (11-84) were included in this study. The overall 3-years local recurrence-rate was 19.9% (95%CI: 11.9-27.9%); 91% had occurred within 3 years. In patients treated with intralesional curettage (n = 64), the 3-years recurrence-rate was 30.6% (95%CI: 18.8-42.4%), compared to 2.6% (95%CI: 0.0-7.8%) in patients treated with wide resection or amputation (n = 38), p < .001. The 3-years recurrence-rate for patients treated with intralesional curettage and reconstruction using PMMA was 29.0% (95%CI: 12.6-45.4%) and without PMMA: 31.8% (95%CI: 15.2-48.4%), p = .83. CONCLUSION: We found that the use of PMMA for bone defect reconstruction after intralesional curettage of GTCs in the appendicular skeleton did not ensure a reduced risk of local recurrence.

Occlusive wound closure prevents prolonged wound discharge-A randomised controlled trial in patients undergoing tumour resection and endoprosthetic reconstruction of the proximal femur because of metastatic bone disease.

Prolonged wound discharge is a common postoperative complication of orthopaedic procedures and a risk factor for implant-related infection. Occlusive wound closure methods have previously been suggested to reduce or even prevent this complication. We performed a randomised controlled trial on 70 patients who underwent surgical treatment for metastatic bone disease involving the proximal femur at our centre between January 2017 and August 2018. At conclusion of the tumour resection and endoprosthetic reconstruction procedure, patients were randomised to either occlusive wound closure (n = 35), using the Dermabond Prineo-22 skin closure system, or routine wound closure with conventional skin staples (n = 35). Skin closure with occlusive wound closure resulted in a lesser degree (P < .0001) and shorter duration of postoperative wound discharge (HR 2.89 [95% CI 1.6-5.05], P < .0018). Compared with staples, surgical wounds were already dry after a mean of 3.5 days [95% CI 3.2-3.9] versus 6.1 days [95% CI 4.8-7.3] (P < .0001). Prolonged wound discharge for 7 days or more was observed in 23% of patients (n = 8) in the Staples-group but was entirely absent in the occlusive wound closure group (P < .003). This study provides strong evidence that occlusive wound closure reduces frequency, degree, and duration of wound discharge in a patient population at particularly high risk for this complication.

Total calcaneal reconstruction using a massive bone allograft and a distally pedicled osteocutaneous fibula flap: A novel technique to prevent amputation after calcaneal malignancy.

In patients with primary calcaneal malignancies, such as Ewing's sarcoma, radical treatment with amputation of the foot can result in serious functional impairment and chronic pain. Total calcanectomy followed by the reconstruction of the calcaneal defect offers an alternative treatment to amputation. Capanna et al. described a technique for successfully reconstructing long limb segmental bone defects using a free fibula flap placed within the intramedullary canal of an allograft. We present both a review of the literature on calcaneal reconstruction and describe how the principles of Capanna can be adapted to reconstruct the calcaneus. Total calcanectomy due to Ewing's sarcoma and the subsequent application of this novel reconstructive technique was performed in two young patients aged 5 and 16 years. The reconstruction was achieved by inserting a distally pedicled osteocutaneous fibula flap within the reamed canal of an allograft and placing the composite in the calcaneal defect. Reconstruction was successful with complete bone union between the allograft and the adjacent bone. There were no fractures or infections and both flaps survived. Functional outcome was assessed with a physiotherapist at a follow-up period of 2 years postoperatively, showing near-normal ambulance. This novel technique proved excellent as a limb salvage procedure, avoiding amputation, and offering a satisfactory oncological and functional outcome.

Establishment and effects of allograft and synthetic bone graft substitute treatment of a critical size metaphyseal bone defect model in the sheep femur.

Assessment of bone graft material efficacy is difficult in humans, since invasive methods like staged CT scans or biopsies are ethically unjustifiable. Therefore, we developed a novel large animal model for the verification of a potential transformation of synthetic bone graft substitutes into vital bone. The model combines multiple imaging methods with corresponding histology in standardized critical sized cancellous bone defect. Cylindrical bone voids (10 ml) were created in the medial femoral condyles of both hind legs (first surgery at right hind leg, second surgery 3 months later at left hind leg) in three merino-wool sheep and either (i) left empty, filled with (ii) cancellous allograft bone or (iii) a synthetic, gentamicin eluting bone graft substitute. All samples were analysed with radiographs, MRI, µCT, DEXA and histology after sacrifice at 6 months. Unfilled defects only showed ingrowth of fibrous tissue, whereas good integration of the cancellous graft was seen in the allograft group. The bone graft substitute showed centripetal biodegradation and new trabecular bone formation in the periphery of the void as early as 3 months. µCT gave excellent insight into the structural changes within the defects, particularly progressive allograft incorporation and the bone graft substitute biodegradation process. MRI completed the picture by clearly visualizing soft tissue ingrowth into unfilled bone voids and presence of fluid collections. Histology was essential for verification of trabecular bone and osteoid formation. Conventional radiographs and DEXA could not differentiate details of the ongoing transformation process. This model appears well suited for detailed in vivo and ex vivo evaluation of bone graft substitute behaviour within large bone defects.

Antibiotic Elution Characteristics and Pharmacokinetics of Gentamicin and Vancomycin from a Mineral Antibiotic Carrier: An in vivo Evaluation of 32 Clinical Cases.

Introduction: Locally implanted antibiotic-eluting carriers may be a valuable adjuvant to the management of prosthetic joint infections. Aim: to assess local and plasma antibiotic concentrations as well as cumulative antibiotic urine excretion associated with clinical use of a gentamicin - or vancomycin-loaded mineral composite antibiotic carrier. Methods: 32 patients (male/female=19/13, mean age=56; 21-82 years) were prospectively followed after implantation of gentamicin (n=11), vancomycin (n=15), or a combination (n=7), using an antibiotic carrier (CERAMENT™|G or CERAMENT™|V, mean amount 11 (3-20) mL) during resection arthroplasty of the hip/knee. We measured antibiotic concentrations in plasma (1h, 3h, 24h, 48h and 72h post-implantation), urine (24h, 48h and 72h post-implantation) and in drain (n=15). Results: We observed low antibiotic concentrations in plasma (Gentamicin: 0.33 mg/L (95%-CI: 0.25-0.44) and vancomycin: 1.33 mg/L (95%-CI: 1.02-1.66)) and high concentrations in drain (Gentamicin: mean 57.8 mg/L (95%-CI: 45.8-69.7) and vancomycin: mean 234.4 mg/L (95%-CI: 198.9-269.7)). Use of a drain was associated with a statistically significant reduction in vancomycin urine excretion (55.6% (95% CI: 36.45-74.92) to 28.71% (95% CI: 13.07-44.35), p=0.042). A similar trend was observed for gentamicin (34.17% (95% CI: 24.62-43.72) to 16.22% (95% CI: 0-33.86), p=0.078). Conclusions: CERAMENT™G/V was associated with safe plasma concentrations and high local concentrations above minimum inhibitory concentration. Installation of a surgical drain results in removal of a substantial amount of antibiotics and reduces antibiotic urine excretion.

Treatment of benign and borderline bone tumors with combined curettage and bone defect reconstruction.

PURPOSE:: The management of bone defects following simple curettage of bone tumors is controversial and in light of the numerous emerging substitutes for bone grafts, we wished to review and report our experience with the use of cancellous allograft bone in the treatment of benign and borderline bone tumors. METHODS:: We reviewed the medical records of 164 consecutive patients with benign or borderline bone tumors treated with simple curettage at our orthopedic oncology center between 2009 and 2013. Postoperative radiological changes were evaluated by a modified Neer's classification in defects that were subsequently reconstructed with allograft bone ( n = 133). RESULTS:: Simple curettage with subsequent defect filling using allograft bone was the surgical procedure performed in the majority of our patients (81%) and was associated with a low overall 2.5-year local recurrence (LR; 9.8%) and complication rate (7.5%). The radiological appearance of the grafted defects was deemed satisfactory in 85% of cases, with signs of either complete or partial healing present 6-12 months postoperatively. With respect to pathology, we found high rates of LR in giant cell tumors (GCTs) of bone, simple cysts (SCs) in children, and preexisting local recurrent disease. We did not observe any allograft-related complications. CONCLUSIONS:: Simple curettage and bone defect reconstruction with bone allograft is a sufficient treatment for most benign bone lesions and is associated with a low complication rate. For high-risk entities, such as GCTs of bone, SCs in children, and recurrent disease, additional adjuvant treatment could be considered to avoid LR.

Early Clinical and Radiological Experience with a Ceramic Bone Graft Substitute in the Treatment of Benign and Borderline Bone Lesions.

Substitutes for bone grafts experience increasing popularity, but the need for defect-filling following simple curettage of benign bone lesions is controversial. In this study, we wish to objectively report the radiological changes following bone defect-filling using a composite ceramic bone graft substitute, as well as the clinical results and complications. We evaluated 35 surgically treated benign bone lesions with subsequent defect-filling using two variants of a composite ceramic bone graft substitute (CERAMENT|BONE VOID FILLER or CERAMENT|G, BONESUPPORT AB, SWEDEN). After one year, a normal cortical thickness surrounding the defect was seen in approximately 80% of patients. Inside the defect-cavity, an almost complete product-resorption was seen after one year. The most common complication was a post-operative inflammatory soft-tissue reaction, seen in 7 patients (20%), which resolved without further treatment, although short-term antibiotic treatment was initiated at a local hospital in 6 patients, due to suspected wound infection. In summary, cortical thickness most commonly normalizes after bone tumor removal and filling of the bone defect using this particular composite ceramic bone graft substitute. The ceramic substitute undergoes resorption, which causes progressive changes in the radiological appearance inside the bone defect.

Comparison of two alternative wound closure methods for tumor arthroplasty of the hip: A frequency matched cohort study.

OBJECTIVE: To examine the effect of an alternative wound closure method after tumor arthroplasty of the hip compared to routine wound closure with skin staples. METHOD: Single center, frequency matched cohort study. We reviewed all patients who underwent tumor resection and endoprosthetic reconstruction of the proximal femur for pathologic fracture due to metastatic bone disease or malignant hematologic bone disease at our center between 2010 and 2014. All patients treated with occlusive wound closure (OWC), a combination of intradermal suture, Steri-Strips™, and an occlusive skin adhesive, during this period ( n = 35), were compared to an equally sized frequency matched group of patients having undergone routine wound closure with conventional skin staples. RESULTS: Patients with OWC were significantly faster to achieve dry wound status and consequently had significantly shorter administration of antibiotics and hospital stay. Compared to the patients with conventional wound closure with staples, their wounds were already dry after a mean 3.4 days (vs. 6.7 days [95%CI: 3-3.8 vs. 5.5-7.9], p < 0.0001), they received antibiotics for a mean 4.2 days (vs. 6.8 days [95%CI: 3.7-4.8 vs. 5.5-8.0], p < 0.0003) and their mean hospital stay was 6.3 days (vs. 8.0 days [95%CI: 5.5-7 vs. 6.8-9.3], p < 0.015). Prolonged wound discharge (PWD) for 7 days or more was observed in 34% of patients ( n = 12) in the conventional group, whereas this complication was completely absent ( n = 0) in the investigational group. For every three patients treated with OWC, one complication of PWD over 7 days is avoided (number needed to treat = 3). CONCLUSION: Compared to conventional staples, OWC appears to significantly reduce wound complications, use of antibiotics, and hospital stay in patients undergoing tumor arthroplasty procedures of the hip. As such, it may also contribute to a reduction of the substantially increased risk for prosthetic joint infection in this patient population.

Natural Course of Local Bone Mineralization After Treatment of Benign or Borderline Bone Tumors and Cysts With a Composite Ceramic Bone Graft Substitute.

After surgical bone tumor removal, filling of the bone defect is frequently performed using a bone graft or bone graft substitute. During follow-up, precise quantification of changes in bone mineral density, within the treated bone defect, is very difficult using conventional X-ray examinations. The objectives of this study were to characterize the pattern of resorption/biodegradation of a composite calcium sulfate/hydroxyapatite bone graft substitute and to quantify the bone defect healing with repeated dual-energy X-ray absorptiometry (DXA) measurements. Seventeen patients treated for 18 benign bone lesions, with subsequent defect filling using 2 variants of a composite ceramic bone graft substitute (CERAMENT™|BONE VOID FILLER or CERMAMENT™|G, BONESUPPORT AB, Lund, Sweden), were scanned postoperatively and after 2, 6, 12, 26, and 52 wk using DXA. After an initial increase in bone mineral density after implantation of the bone graft substitute, bone mineral density decreased in the bone defect region throughout the 52 wk: rapidly in the first 12 wk and slower in the remaining weeks. Despite this continuous decrease, bone mineral density remained, on average, 25% higher in the operated extremity, compared with the nonoperated extremity, after 52 wk. The observed pattern of reduction in bone mineral density is consistent with the anticipated resorption of calcium sulfate within the bone graft substitute during the first 12 wk after surgery. We believe the DXA technique provides a precise method for quantification of bone graft resorption, but for evaluation of new bone formation, 3-dimensional imaging is needed.

* Composite Biomaterial as a Carrier for Bone-Active Substances for Metaphyseal Tibial Bone Defect Reconstruction in Rats.

Restoring lost bone is a major challenge in orthopedic surgery. Currently available treatment strategies have shortcomings, such as risk of infection, nonunion, and excessive resorption. Our primary aim was to study if a commercially available gentamicin-containing composite calcium sulfate/hydroxyapatite biomaterial (GBM) could serve as a carrier for local delivery of bone morphogenic protein-2 (BMP-2) and zoledronic acid (ZA) in a tibia defect model in rats. Empty and allograft-filled defects were used as controls. A 3 × 4-mm metaphyseal bone defect was created in the proximal tibia, and the rats were grouped according to defect filling: (1) Empty, (2) Allograft, (3) GBM, (4) GBM + ZA, and (5) GBM + ZA + BMP-2. In vivo microcomputed tomography (micro-CT) images at 4 weeks showed significantly higher mineralized tissue volume (MV) in the intramedullary defect region and the neocortical/callus region in all GBM-treated groups. After euthanization at 8 weeks, ex vivo micro-CT showed that addition of ZA (GBM + ZA) and BMP-2 (GBM + ZA + BMP-2) mainly increased the neocortical and callus formation, with the highest MV in the combined ZA and BMP-2-treated group. Qualitative histological analysis, verifying the increased neocortical/callus thickness and finding of trabecular bone in all GBM-treated groups, supported that the differences in MV measured with micro-CT in fact represented bone tissue. In conclusion, GBM can serve as a carrier for ZA and BMP-2 leading to increased MV in the neocortex and callus of a metaphyseal bone defect in rats.

A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone.

In orthopedic surgery, large amount of diseased or injured bone routinely needs to be replaced. Autografts are mainly used but their availability is limited. Commercially available bone substitutes allow bone ingrowth but lack the capacity to induce bone formation. Thus, off-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay early resorption. In-vitro, the biphasic material released 90% of rhBMP-2 and 10% of ZA in the first week. No major changes were found in the surface structure using scanning electron microscopy (SEM) or in the mechanical properties after adding rhBMP-2 or ZA. In-vivo bone formation was studied in an abdominal muscle pouch model in rats (n = 6/group). The mineralized volume was significantly higher when the biphasic material was combined with both rhBMP-2 and ZA (21.4 ± 5.5 mm(3)) as compared to rhBMP-2 alone (10.9 ± 2.1 mm(3)) when analyzed using micro computed tomography (µ-CT) (p < 0.01). In the clinical setting, the biphasic material combined with both rhBMP-2 and ZA can potentially regenerate large volumes of bone.

Low infection rate after tumor hip arthroplasty for metastatic bone disease in a cohort treated with extended antibiotic prophylaxis.

Background. Compared to conventional hip arthroplasty, endoprosthetic reconstruction after tumor resection is associated with a substantially increased risk of periprosthetic joint infection (PJI), with reported rates of around 10% in a recent systematic review. The optimal duration of antibiotic prophylaxis for this patient population remains unknown. Material and Methods. To establish the infection rate associated with prolonged antibiotic prophylaxis in our department, we performed a retrospective review of all adult patients who underwent endoprosthetic reconstruction of the proximal femur after tumor resection for metastatic bone disease during a 4-year period from 2010 to 2013 (n = 105 patients). Results. Intravenous antibiotic prophylaxis was administrated for an extended duration of a mean of 7.4 days. The overall infection rate was 3.6% (4/111 implants), infection free survival was 96% at 2 years, and the risk of amputation associated with infection was 25% (1/4 patients). Discussion. Preemptive eradication of bacterial contamination may be of value in certain clinical situations, where the risk level and consequences of implant-associated infection are unacceptable. Our findings suggest that extended postoperative antibiotic prophylaxis may reduce the risk of PJI in patients undergoing tumor resection and endoprosthetic replacement for metastatic bone disease associated impending or de facto pathologic fractures of the proximal femur.

Persistent wound drainage after tumor resection and endoprosthetic reconstruction of the proximal femur.

PURPOSE: To examine the prevalence of prolonged wound drainage (PWD) after tumor resection and endoprosthetic reconstruction of the hip. METHODS: Retrospective review of 86 consecutive patients with metastatic bone disease, malignant hematologic bone disease or bone sarcoma, treated with tumor resection and subsequent endoprosthetic reconstruction of the proximal femur, between 2010 and 2012, in a single center. RESULTS: PWD for 7 days or more was observed in 41 cases (48%). The wounds only ceased oozing after a mean of 8.4 days, leading to prolonged administration of prophylactic antibiotics (mean 8.7 days) and length of hospital stay (mean 10.2 days). Total femur replacement, bone sarcoma and additional pelvic reconstruction were identified as significant independent risk factors for an even longer duration of PWD. CONCLUSION: Compared to conventional hip arthroplasty, PWD appears to be significantly more prevalent in patients undergoing tumor arthroplasty procedures of the hip. Given the potentially increased risk for periprosthetic joint infection (PJI), increased awareness, identification and implementation of adequate strategies for prevention and treatment of this avoidable complication are warranted.

Preliminary biomechanical proof of concept for a hybrid locking plate/variable pitch screw construct for anterior fixation of type II odontoid fractures.

STUDY DESIGN: A human cadaveric biomechanical proof-of-concept study. OBJECTIVE: To test whether adding a locking plate to the anterior surface of C2 attaching directly to the interfragmentary screw may reduce potential for anterior screw cutout and improve construct strength. SUMMARY OF BACKGROUND DATA: The most common mode of failure for screw fixation of dens fractures is via cutout at the anterior body of C2. METHODS: A human, cadaveric model of type II dens fractures was created and fixed using either a headless, fully threaded variable pitch screw (FTVPS) or a screw with an attachable locking plate construct (LPC). Following quasistatic loading to failure, stiffness and load to failure were compared using t tests. Mode of failure was determined from radiographical and gross inspection. RESULTS: Load to failure was greater for the LPC than for the FTVPS alone (498 N vs. 362 N, P = 0.04). The LPC consistently failed via compression of cancellous bone posterior to the lag screw, whereas the FTVPS constructs failed via cutout of the screw from the anterior C2 body. CONCLUSION: Locking plate supplementation of anterior screw fixation of type II odontoid fractures improves construct strength and changes the failure mechanism from anterior screw cutout to posterior displacement of the screw. An attachable locking plate/interfragmentary screw construct may improve clinical outcomes for these fractures.

Biomechanical comparison of a fully threaded, variable pitch screw and a partially threaded lag screw for internal fixation of Type II dens fractures.

STUDY DESIGN: Stiffness and load to failure were studied in a human cadaver model of Type II odontoid fractures stabilized with either a single partially threaded lag screw and washer or a headless fully threaded variable pitch screw. OBJECTIVE: To determine whether a headless fully threaded variable pitch screw provides biomechanically superior fixation of Type II odontoid fractures in comparison with a partially threaded, cannulated lag screw and washer. SUMMARY OF BACKGROUND DATA: Surgical treatment of Anderson and D'Alonzo Type II odontoid fractures is often performed using a partially threaded cannulated screw and washer. Reported clinical failure rates of this construct are as high as 20%. This technique requires perforation of the cortex of the tip of the dens, placing the brainstem and vertebrobasilar circulation at risk. A headless fully threaded variable pitch screw has not been described for this application. METHODS: A transverse osteotomy was created at the base of the dens in 16 human cadaver C2 specimens and stabilized using either a headless fully threaded variable pitch screw or a partially threaded cannulated lag screw and washer. Specimens were loaded to failure under a static, posteriorly directed force applied to the surface of the dens. Stiffness and load to failure were measured and the mode of failure for each specimen was determined. RESULTS: Stiffness and load to failure were greater for the headless, fully threaded variable pitch screw compared with the partially threaded lag screw and washer. The mode of failure for all specimens was via anterior screw cut-out at the C2 vertebral body. CONCLUSION: A headless, fully threaded variable pitch screw was biomechanically favorable in comparison with a partially threaded lag screw and washer in this cadaver model of Type II dens fractures. The mode of failure at the C2 vertebral body may have important implications for further improvements in construct strength.

Mechanical stiffness of segmental versus nonsegmental pedicle screw constructs: the effect of cross-links.

STUDY DESIGN: A biomechanical study in porcine spines of the construct stiffness effects of segmental pedicle screws. Stiffness effects of supplementation of nonsegmental screw constructs with cross-links was also evaluated. OBJECTIVE: To assess the biomechanical differences between constructs using segmental versus nonsegmental pedicle screw-based instrumentation as well as the effect of cross-links. SUMMARY OF BACKGROUND DATA: An in vitro biomechanical comparison of segmental versus nonsegmental pedicle screw constructs with and without cross-links using porcine lumbar vertebrae was performed. Mechanical trade-offs of reducing the number of pedicle screws in a given construct and substituting a cross-link for a pair of screws are not well understood. METHODS: Three, 4, and 5-vertebral segments from 18 porcine spines were instrumented with segmental and nonsegmental pedicle screw constructs, and with nonsegmental screws augmented with cross-links. Unconstrained biomechanical testing in flexion, extension, and axial rotation with 6 degree-of-freedom motion tracking was performed. Statistical comparisons of stiffness data were conducted using 2-tailed paired t tests. RESULTS: There was a statistically significant increase in stiffness between models with segmental pedicle screws compared to nonsegmental pedicle screws in 6 of the 9 mechanical tests. The remaining 3 tests approached but did not reach statistical significance (P = 0.087, 0.062, and 0.078). When cross-links were added to the nonsegmental models, differences in stiffness compared to segmental pedicle screws were largely eliminated, decreasing well below statistical significance in 8 of 9 tests. The highest difference in nonsegmental models with cross-links and segmental pedicle screw models was observed for the 5-vertebrae fusion models, for which axial rotation testing maintained statistically significant differences (P = 0.006), and flexion testing approached significance (P = 0.062). CONCLUSIONS: Segmental pedicle screw constructs increased mechanical stiffness compared to nonsegmental constructs in our fusion models. Placement of a single cross-link with nonsegmental screws eliminated statistical differences for 3 and 4-vertebral level constructs, and may be a satisfactory alternative in this clinical setting. Caution in applying these results inlonger constructs is recommended, given persistent increased stiffness found for the segmental 5-vertebral level models.