Biomechanical Variability and Usability of a Novel Customizable Fracture Fixation Technique.

A novel in situ customizable osteosynthesis technique, Bonevolent™ AdhFix, demonstrates promising biomechanical properties under the expertise of a single trained operator. This study assesses inter- and intra-surgeon biomechanical variability and usability of the AdhFix osteosynthesis platform. Six surgeons conducted ten osteosyntheses on a synthetic bone fracture model after reviewing an instruction manual and completing one supervised osteosynthesis. Samples underwent 4-point bending tests at a quasi-static loading rate, and the maximum bending moment (BM), bending stiffness (BS), and AdhFix cross-sectional area (CSA: mm²) were evaluated. All constructs exhibited a consistent appearance and were suitable for biomechanical testing. The mean BM was 2.64 ± 0.57 Nm, and the mean BS was 4.35 ± 0.44 Nm/mm. Statistically significant differences were observed among the six surgeons in BM (p < 0.001) and BS (p = 0.004). Throughout ten trials, only one surgeon demonstrated a significant improvement in BM (p < 0.025), and another showed a significant improvement in BS (p < 0.01). A larger CSA corresponded to a statistically significantly higher value for BM (p < 0.001) but not for BS (p = 0.594). In conclusion, this study found consistent biomechanical stability both across and within the surgeons included, suggesting that the AdhFix osteosynthesis platform can be learned and applied with minimal training and, therefore, might be a clinically viable fracture fixation technique. The variability in BM and BS observed is not expected to have a clinical impact, but future clinical studies are warranted.

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.

Biomechanical performance of a novel light-curable bone fixation technique.

Traumatic bone fractures are often debilitating injuries that may require surgical fixation to ensure sufficient healing. Currently, the most frequently used osteosynthesis materials are metal-based; however, in certain cases, such as complex comminuted osteoporotic fractures, they may not provide the best solution due to their rigid and non-customizable nature. In phalanx fractures in particular, metal plates have been shown to induce joint stiffness and soft tissue adhesions. A new osteosynthesis method using a light curable polymer composite has been developed. This method has demonstrated itself to be a versatile solution that can be shaped by surgeons in situ and has been shown to induce no soft tissue adhesions. In this study, the biomechanical performance of AdhFix was compared to conventional metal plates. The osteosyntheses were tested in seven different groups with varying loading modality (bending and torsion), osteotomy gap size, and fixation type and size in a sheep phalanx model. AdhFix demonstrated statistically higher stiffnesses in torsion (64.64 ± 9.27 and 114.08 ± 20.98 Nmm/° vs. 33.88 ± 3.10 Nmm/°) and in reduced fractures in bending (13.70 ± 2.75 Nm/mm vs. 8.69 ± 1.16 Nmm/°), while the metal plates were stiffer in unreduced fractures (7.44 ± 1.75 Nm/mm vs. 2.70 ± 0.72 Nmm/°). The metal plates withstood equivalent or significantly higher torques in torsion (534.28 ± 25.74 Nmm vs. 614.10 ± 118.44 and 414.82 ± 70.98 Nmm) and significantly higher bending moments (19.51 ± 2.24 and 22.72 ± 2.68 Nm vs. 5.38 ± 0.73 and 1.22 ± 0.30 Nm). This study illustrated that the AdhFix platform is a viable, customizable solution that is comparable to the mechanical properties of traditional metal plates within the range of physiological loading values reported in literature.

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.

Pretreatment Plasma IL-6 and YKL-40 and Overall Survival after Surgery for Metastatic Bone Disease of the Extremities.

BACKGROUND: Plasma IL-6 and YKL-40 are prognostic biomarkers for OS in patients with different types of solid tumors, but they have not been studied in patients before surgery of metastatic bone disease (MBD) of the extremities. The aim was to evaluate the prognostic value of plasma IL-6 and YKL-40 in patients undergoing surgery for MBD of the extremities. PATIENTS AND METHODS: A prospective study included all patients undergoing surgery for MBD in the extremities at a tertiary referral center during the period 2014-2018. Preoperative blood samples from index surgery were included. IL-6 and YKL-40 concentrations in plasma were determined by commercial ELISA. A total of 232 patients (median age 66 years, IQR 58-74; female 51%) were included. RESULTS: Cox regression analysis was performed to identify independent prognostic factors for OS. IL-6 correlated with YKL-40 (rho = 0.46, p < 0.01). In univariate analysis (log2 continuous variable) IL-6 (HR = 1.26, 95% CI 1.16-1.37), CRP (HR = 1.20, 95% CI 1.12-1.29) and YKL-40 (HR = 1.25, 95% CI 1.15-1.37) were associated with short OS. In multivariable analysis, adjusted for known risk factors for survival, only log2(IL-6) was independently associated with OS (HR = 1.24, 95% CI 1.08-1.43), whereas CRP and YKL-40 were not. CONCLUSION: High preoperative plasma IL-6 is an independent biomarker of short OS in patients undergoing surgery for MBD.

Quantitative measurements of adaptive bone remodeling around the cemented Zimmer® segmental stem after tumor resection arthroplasty using dual-energy x-ray absorptiometry.

BACKGROUND: Limb salvage surgery (LSS) is the preferred method for treatment of patients with sarcomas and to a greater extent also to patients with metastatic bone disease. The aim of the present study was to evaluate the adaptive remodeling of the periprosthetic cortical bone after insertion of a tumor prosthesis with cemented stem. METHODS: A prospective study of 21 patients (F/M = 12/9), mean age 55 years (range 15-81) with metastatic bone disease (n = 9), sarcomas (n = 8) or aggressive benign tumors (n = 4) who underwent bone resection due to a tumor, and reconstruction with a tumor-prosthesis (Zimmer® Segmental 130 mm straight fluted cemented stem with trabecular metal (TM) collars) in the proximal femur (n = 10), distal femur (n = 9) or proximal tibia (n = 2). Measurements of bone mineral density (BMD) (g/cm2) were done postoperatively and after 3, 6, and 12 months using dual-energy X-ray absorptiometry. BMD was measured in 4 regions of interest around the cemented stem and in one region of interest 1 cm proximal from the ankle joint of the affected limb and measurement of the contralateral ankle was used as reference. Repeated measures ANOVA and students paired t-test was used to evaluate BMD changes over time. RESULTS: At 1-year follow-up, BMD decreased compared to baseline in all four regions of interest with a statistically significant bone loss of 8-15%. The bone loss was most pronounced (14-15%) in the 2 regions of interest closest to the trabecular metal (TM) collar and lowest (8%) adjacent to the tip of the stem. CONCLUSION: After 1 year the decrease in bone mineral density of the ankle on the affected limb was 9% and the contralateral ankle was close to baseline, thus suggesting that the periprosthetic bone mineral density changes during follow-up, mainly are caused by stress shielding and immobilization. TRIAL REGISTRATION: The study was approved by the Scientific Ethical Committee of the Capital Region of Denmark (J. No. H-2-2014-105) and the Danish Data Protection Agency (J. No.: 2012-58-00004 ).

Use of endoprostheses for proximal femur metastases results in a rapid rehabilitation and low risk of implant failure. A prospective population-based study.

BACKGROUND AND OBJECTIVES: Endoprosthesis is considered a durable implant for treating metastatic bone disease of the proximal femur (MBDf). OBJECTIVES:   â€¢ What is the revision risk after surgery for MBDf using endoprosthesis versus internal fixation?• When do patients with MBDf treated with endoprosthesis restore quality of life (QoL) and how long time does it take to rehabilitate functional outcome? METHODS: A prospective, population-based, multicentre study of 110 patients. Patients were followed for a minimum of two years after surgery. No patients were lost to implant failure nor survival follow-up. RESULTS: Forty-four patients were treated with internal fixation and 66 patients received endoprostheses. Two-year implant failure risk for internal fixation was 7% (95CI: 0-14%) versus 2% (95CI: 0-5%) for endoprostheses (p = 0.058).Eq-5D improved to the same level as one month prior to surgery six-weeks after surgery, and the score improved further six months after surgery (median score from 0.603 to 0.694, p = 0.007). MSTS score increased from 12 points after surgery to 23 points six-months after surgery (p<0.001). CONCLUSIONS: Endoprosthesis for treatment of MBDf results in low implant failure rate. Patients are satisfied with the functional outcome. QoL is restored six-weeks after surgery. Authors advocate for caution using internal fixation for MBDf due to findings of a possible high early postoperative revision risk.

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.

Incidence of surgical interventions for metastatic bone disease in the extremities: a population-based cohort study.

BACKGROUND: The incidence of surgery due to metastatic bone disease in the extremities (MBDex) and postoperative survival remain uninvestigated in the population. The aim of the current study was: to identify (1) incidence, demographics and survival of a population-based cohort of patients having surgery for MBDex (2) rate of referrals and referral pattern to a musculoskeletal tumour centre (MTC). MATERIAL AND METHOD: A prospective study of a consecutive population-based cohort of patients having surgery for MBDex from 2014 to 2016. Patient demographics, indication for surgery, oncological status, and postoperative survival was obtained from patient interviews, surveillance scans and patient records. RESULTS: We identified 164 patients treated for 175 bone lesions resulting in an incidence of MBDex surgery of 48.6 lesions/million inhabitants/year and a 10% risk of undergoing surgery for MBDex for every year liven with metastatic bone disease. The most common primary cancers were breast, lung, renal, prostate and myeloma. Twenty-nine lesions represented debut of cancer and 22 lesions debut of relapse of a previous cancer. Overall one-year survival was 41% (95% C.I.: 33%-48%). Fifty-nine percent of patients were referred for treatment at MTC. Patients referred had better prognostic baseline characteristic than patients treated at secondary surgical centres (SSC) (lower ASA score (p < .001), no visceral metastasis (p < .001), lower age (p < .001) and less aggressive primary cancer (p < .001)). The one-year probability of overall survival was higher for MTC patients compared to SSC patients (p < .001). CONCLUSIONS: Present study describes a prospective population-based cohort of patients having surgery for MBDex identifying incidence and postoperative survival. Referral of patient is biased by selection where 'long-term survivors' are referred for treatment at MTC. We can, however, not exclude that treatment centre influences chance of survival after surgery for MBDex although our study was not designed to identify any potential influence.

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.

Oxygen conserving mitochondrial adaptations in the skeletal muscles of breath hold divers.

BACKGROUND: The performance of elite breath hold divers (BHD) includes static breath hold for more than 11 minutes, swimming as far as 300 m, or going below 250 m in depth, all on a single breath of air. Diving mammals are adapted to sustain oxidative metabolism in hypoxic conditions through several metabolic adaptations, including improved capacity for oxygen transport and mitochondrial oxidative phosphorylation in skeletal muscle. It was hypothesized that similar adaptations characterized human BHD. Hence, the purpose of this study was to examine the capacity for oxidative metabolism in skeletal muscle of BHD compared to matched controls. METHODS: Biopsies were obtained from the lateral vastus of the femoral muscle from 8 Danish BHD and 8 non-diving controls (Judo athletes) matched for morphometry and whole body VO2max. High resolution respirometry was used to determine mitochondrial respiratory capacity and leak respiration with simultaneous measurement of mitochondrial H2O2 emission. Maximal citrate synthase (CS) and 3-hydroxyacyl CoA dehydrogenase (HAD) activity were measured in muscle tissue homogenates. Western Blotting was used to determine protein contents of respiratory complex I-V subunits and myoglobin in muscle tissue lysates. RESULTS: Muscle biopsies of BHD revealed lower mitochondrial leak respiration and electron transfer system (ETS) capacity and higher H2O2 emission during leak respiration than controls, with no differences in enzyme activities (CS and HAD) or protein content of mitochondrial complex subunits myoglobin, myosin heavy chain isoforms, markers of glucose metabolism and antioxidant enzymes. CONCLUSION: We demonstrated for the first time in humans, that the skeletal muscles of BHD are characterized by lower mitochondrial oxygen consumption both during low leak and high (ETS) respiration than matched controls. This supports previous observations of diving mammals demonstrating a lower aerobic mitochondrial capacity of the skeletal muscles as an oxygen conserving adaptation during prolonged dives.

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.

Antibiotic Containing Bone Substitute in Major Hip Surgery: A Long Term Gentamicin Elution Study.

Objectives: The objective is to present the antibiotic elution from a locally implanted gentamicin containing hydroxyapatite and calcium sulphate bone substitute with an extended follow up of 30 days. We also compare the pharmacokinetics of the ceramic bone substitute with a published study on gentamicin containing poly (methyl methacrylate) (PMMA) bone cement used in primary total hip arthroplasty. Methods: Gentamicin release was measured in the urine for a month and the serum for 4 days in 10 patients operated for trochanteric hip fractures and 10 patients in uncemented hip revisions. 17 patients were followed up at one year and 3 patients at 6 months. Results and Discussion: The gentamicin concentrations measured in serum were low and approximately 100 times less than in urine during the first days, indicating high local concentrations at the implant site. The elution from the biphasic bone substitute showed a stronger burst and higher gentamicin concentrations for the first week compared to that reported for PMMA used in hip arthroplasty. Also, for the bone substitute a complete gentamicin elution was obtained after 30 days, while for the PMMA cement sub-inhibitory MIC levels of gentamicin were still present in urine 60 days past surgery. No infections were detected. Conclusions: A new biphasic bone substitute containing antibiotics could potentially be used to prevent infection in patients treated for trochanteric hip fractures or uncemented hip revisions. The gentamicin elution from the bone substitute is efficient with high initial local gentamicin concentrations and complete release at 30 days.

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.

Implant and limb survival after resection of primary bone tumors of the lower extremities and reconstruction with mega-prostheses fifty patients followed for a mean of forteen years.

PURPOSE: Previous studies reported variable outcome and failure rates after mega-prosthetic reconstructions in the lower extremities. The purpose of this study was to make a long-term single-center evaluation of patients treated with limb-sparing surgery and reconstruction with mega-prostheses in the lower extremities. METHODS: We identified 50 patients (osteosarcoma (n = 30), chondrosarcoma (n = 9), osteoclastoma (n = 6), Ewing sarcoma (n = 4), angiosarcoma (n = 1)), who underwent limb-sparing reconstruction of the lower extremities (proximal femur (n = 9), distal femur (n = 29), proximal tibia (n = 9), and the entire femur (n = 3)) between 1985 and 2005. Surviving patients not lost to follow-up were evaluated using the MSTS score. Causes of failure were classified according to the Henderson classification. Kaplan-Meier survival analysis was used for evaluation of patient, prosthesis, and limb survival. RESULTS: Twenty-eight patients were alive at follow-up. Fifty-four percent had revision surgery (n = 27). The ten year patient survival was 60% (95%CI 46-74%); the ten year implant survival was 24% (95%CI 9-41%), and the ten year limb survival rate was 83% (95%CI 65-96%). Type 1 failure occurred in 9%, type 2 in 16%, type 3 in 28%, type 4 in 18%, and type 5 in 3%. Mean MSTS score was 21 (range, 6-30), representing a median score of 71%. CONCLUSIONS: Our long-term results with mega-prostheses justify the use of limb-salvage surgery and prosthetic reconstruction. Our results are fully comparable with other findings, with regard to limb and prosthesis survival, but also with regard to functional outcome.

Patient survival following joint replacement due to metastatic bone disease - comparison of overall patient and prostheses survival between cohorts treated in two different time-periods.

BACKGROUND: Improvements in medical treatment for cancer have increased survival of cancer patients. We hypothesize that improvement in cancer treatment is reflected in increased survival after surgical intervention for metastatic bone disease (MBD) and that subsequent revision surgery does not pose a risk for survival. METHODS: We identified a retrospective consecutive cohort who received bone resection and reconstruction (BRR) with implants (including total joint replacements (with or without wide resection) or bone reconstruction with an intercalary spacer or revisions procedures for failed implants with BBR technique) due to MBD from 2003 to 2008 (early cohort) and 2009 to 2013 (late cohort) at a tertiary referral center. We registered epidemiological data, type of implant (primary or a revision implant), patient survival (Kaplan-Meier), implant survival (competing risk analysis) and complications to surgery. RESULTS: Three hundred and eleven procedures were performed in 291 patients (289 primary BRR (270 patients, early cohort n = 130 late cohort n = 140) and 22 revision BRR (21 patients)). Overall survival was 44% (95% confidence intervals (95% CI): 39-50) and 32% (95% CI: 27-38) after 1 and 2 years. No difference in survival between the early and late cohort was found (p = .458), or between primary and revision BRR (p = .465). Time from diagnosis of cancer to surgery was shorter in the early cohort (p < .001). The cumulative incidence of failure of implant was 2% (95% CI: 0-3%) at 1 year and 3% (95% CI: 1-6%) at 2 years. One year cumulative implant failure for revision implants was 5% (95% CI: 0-13%) at 1 and 2 years. The risk of failure was not statistical significant between primary and revision implant (p = .293) in competing risk analysis. DISCUSSION: We were not able to identify an increased survival after surgery for MBD over time, however, we found an increased interval from diagnosis to surgery for MBD. This study suggests that revision surgery for MBD does not pose a risk for survival.

Survival and prognostic factors at time of diagnosis in high-grade appendicular osteosarcoma: a 21 year single institution evaluation from east Denmark.

BACKGROUND: Survival of patients with high-grade osteosarcoma (HOS), the most common primary bone cancer, has not improved significantly the last 30 years and the disease remains a major challenge. The purpose of this study is to evaluate survival in relation to prognostic factors at time of diagnosis among patients diagnosed with primary appendicular HOS in East Denmark between 1990 and 2010. MATERIAL AND METHODS: 101 patients (median age = 20 years, female/male ratio = 56/45) diagnosed with primary appendicular high-grade osteosarcoma between 1990 and 2010 were included in this study. Initially, 156 patients diagnosed with osteosarcoma between 1990 and 2010 were identified through the population based Regional Database of Pathology, which covers a population of approximately 2.7 million (east Denmark). 55 patients were excluded due to (A) tumor was low grade (n = 22), (B) located in axial skeleton (n = 18), (C) incorrect diagnosis (n = 11) or (D) biopsy represented a tumor relapse from a former primary osteosarcoma (n = 4). Overall survival was evaluated using the Kaplan-Meier survival analysis and log-rank test. Prognostic factors were analyzed using uni- and multivariate cox-regression method with variables scored equally in the model. p Values <.05 were considered statistically significant. RESULTS: The probability of 5- and 10-year survival was 51% (95% CI: 41-61) and 46% (95% CI: 36-56), respectively. Metastatic stage at diagnosis and tumor size ≥10 cm measured radiologically at the largest diameter were independent prognostic factors for decreased survival with significant increased hazard-risks of 3.5 (95% CI: 1.9-6.5) and 1.97 (95% CI: 1.1-3.6), respectively. DISCUSSION: In this single institution evaluation of primary appendicular HOS we found 5-and 10-year survival rates consistent with international standards for this patient group. Distant metastases and tumor size ≥10 cm at the time of diagnosis were independent prognostic factors for decreased survival in our cohort. These results underline the importance of awareness and early referral from the primary sector.

* 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.