Alternative and complementary therapies in osteoarthritis and cartilage repair.

Osteoarthritis (OA) is the most common joint condition and, with a burgeoning ageing population, is due to increase in prevalence. Beyond conventional medical and surgical interventions, there are an increasing number of 'alternative' therapies. These alternative therapies may have a limited evidence base and, for this reason, are often only afforded brief reference (or completely excluded) from current OA guidelines. Thus, the aim of this review was to synthesize the current evidence regarding autologous chondrocyte implantation (ACI), mesenchymal stem cell (MSC) therapy, platelet-rich plasma (PRP), vitamin D and other alternative therapies. The majority of studies were in knee OA or chondral defects. Matrix-assisted ACI has demonstrated exceedingly limited, symptomatic improvements in the treatment of cartilage defects of the knee and is not supported for the treatment of knee OA. There is some evidence to suggest symptomatic improvement with MSC injection in knee OA, with the suggestion of minimal structural improvement demonstrated on MRI and there are positive signals that PRP may also lead to symptomatic improvement, though variation in preparation makes inter-study comparison difficult. There is variability in findings with vitamin D supplementation in OA, and the only recommendation which can be made, at this time, is for replacement when vitamin D is deplete. Other alternative therapies reviewed have some evidence (though from small, poor-quality studies) to support improvement in symptoms and again there is often a wide variation in dosage and regimens. For all these therapeutic modalities, although controlled studies have been undertaken to evaluate effectiveness in OA, these have often been of small size, limited statistical power, uncertain blindness and using various methodologies. These deficiencies must leave the question as to whether they have been validated as effective therapies in OA (or chondral defects). The conclusions of this review are that all alternative interventions definitely require clinical trials with robust methodology, to assess their efficacy and safety in the treatment of OA beyond contextual and placebo effects.

GRAND-4: the German retrospective analysis of long-term persistence in women with osteoporosis treated with bisphosphonates or denosumab.

UNLABELLED: This retrospective database study assessed 2-year persistence with bisphosphonates or denosumab in a large German cohort of women with a first-time prescription for osteoporosis treatment. Compared with intravenous or oral bisphosphonates, 2-year persistence was 1.5-2 times higher and risk of discontinuation was significantly lower (P < 0.0001) with denosumab. INTRODUCTION: Persistence with osteoporosis therapies is critical for fracture risk reduction. Detailed data on long-term persistence (≥2 years) with bisphosphonates and denosumab are sparse. METHODS: From the German IMS® database, we included women aged 40 years or older with a first-time prescription for bisphosphonates or denosumab between July 2010 and August 2014; patients were followed up until December 2014. The main outcome was treatment discontinuation, with a 60-day permissible gap between filled prescriptions. Two-year persistence was estimated using Kaplan-Meier survival curves, with treatment discontinuation as the failure event. Denosumab was compared with intravenous (i.v.) and oral bisphosphonates separately. Cox proportional hazard ratios (HRs) for the 2-year risk of discontinuation were calculated, with adjustment for age, physician specialty, health insurance status, and previous medication use. RESULTS: Two-year persistence with denosumab was significantly higher than with i.v. or oral bisphosphonates (39.8 % [n = 21,154] vs 20.9 % [i.v. ibandronate; n = 20,472] and 24.8 % [i.v. zoledronic acid; n = 3966] and 16.7-17.5 % [oral bisphosphonates; n = 114,401]; all P < 0.001). Patients receiving i.v. ibandronate, i.v. zoledronic acid, or oral bisphosphonates had a significantly increased risk of treatment discontinuation than did those receiving denosumab (HR = 1.65, 1.28, and 1.96-2.02, respectively; all P < 0.0001). CONCLUSIONS: Two-year persistence with denosumab was 1.5-2 times higher than with i.v. or oral bisphosphonates, and risk of discontinuation was significantly lower with denosumab than with bisphosphonates. A more detailed understanding of factors affecting medication-taking behavior may improve persistence and thereby reduce rates of fracture.

Direct implantation of VX-2 carcinoma: a new rabbit bone model using a three-dimensional matrix as a carrier for the tumor cells.

BACKGROUND: Animal bone models are inevitable for musculoskeletal research. The induction of a local bone tumor is complex and time consuming. In this study a new model is presented using a direct implantation of tumor cells into the bone without a preliminary passaging of the cells. METHODS: A three-dimensional matrix consisting of alginate spheroids and carrying the VX-2 tumor suspension was used for implantation into the bone of 6 female New Zealand white rabbits. X-ray imaging, CT and MRI scans as well as a histological examination were carried out. RESULTS: All rabbits developed local bone tumor in the metaphysis of the femoral leg. Bone tumor was identifiable on average 6.2 weeks after implantation. Fluoroscopy, CT and MRI scans showed a cortical reaction but no destruction of the compact bone together with a mean tumor size of 14 mm. Histological examination revealed a tumor infiltration with an activation of osteoclasts and an osteoclastic resorption. CONCLUSION: The direct implantation of a VX-2 tumor suspension into the rabbit bone using alginate spheroids is an effective and reproducible way to successfully induce bone tumor. This new animal model allows further examination of surgical and minimal invasive therapy in musculoskeletal research.

The quality of applied bone cement depends on the chemical composition of the application system.

UNLABELLED: The exothermal reaction of polymethylmethacrylate leads to an extensive interaction between bone cement and the synthetic material of the application system. This chemical reaction changes the structure of the cement and might generate air inclusions. METHODS AND MATERIALS: Two application systems for bone cement made of polycarbonate (PC) and polypropylene (PP) were evaluated. The application systems were mounted in a testing unit. The testing device injects a defined amount of bone cement with a certain pressure. After the injection procedure a microscopic examination was carried out. RESULTS: There were no differences in the size and the design of the used syringes. Forty procedures were carried out. The time frame for application of the cement was 5 min in the PC group and 9 min in the PP group. There was a remarkable interaction between the plastics and the cement with the appearance of numerous air inclusions in the PC group. Barely any interaction was found in the PP group. CONCLUSION: Application systems made of PP enable a prolonged application time and a reduced number of air inclusions. Further research, especially on a molecular level as well as material tests on the quality of the applied bone cement, should be carried out.

Reduction of radiation dose during facet joint injection using the new image guidance system SabreSource: a prospective study in 60 patients.

Interventional procedures are associated with high radiation doses for both patients and surgeons. To reduce the risk from ionizing radiation, it is essential to minimize radiation dose. This prospective study was performed to evaluate the effectiveness in reducing radiation dose during facet joint injection in the lumbar spine and to evaluate the feasibility and possibilities of the new real time image guidance system SabreSource. A total of 60 patients, treated with a standardized injection therapy of the facet joints L4-L5 or L5-S1, were included in this study. A total of 30 patients were treated by fluoroscopy guidance alone, the following 30 patients were treated using the new SabreSource system. Thus a total of 120 injections to the facet joints were performed. Pain, according to the visual analogue scale (VAS), was documented before and 6 h after the intervention. Radiation dose, time of radiation and the number of exposures needed to place the needle were recorded. No significant differences concerning age (mean age 60.5 years, range 51-69), body mass index (mean BMI 26.2, range 22.2-29.9) and preoperative pain (VAS 7.9, range 6-10) were found between the two groups. There was no difference in pain reduction between the two groups (60 vs. 61.5%; P = 0.001) but the radiation dose was significantly smaller with the new SabreSource system (reduction of radiation dose 32.7%, P = 0.01; reduction of mean entrance surface dose 32.3%, P = 0.01). The SabreSource System significantly reduced the radiation dose received during the injection therapy of the lumbar facet joints. With minimal effort for the setup at the beginning of a session, the system is easy to handle and can be helpful for other injection therapies (e.g. nerve root block therapies).

Radiofrequency ablation of experimental bone metastases in nude rats.

PURPOSE: Animal models are indispensable to investigate bone metastasis and to test different preclinical therapy options. Radiofrequency ablation is an upcoming technique for palliating pain from bone metastases. The aim of this study was to generate osteolytic lesions and to enable a technique to achieve access to the bone to successfully carry out radiofrequency ablation. MATERIALS AND METHODS: Human breast cancer cell line MDA-MB-231 (10(5) tumor cells) was implanted into the femur of 10 nude rats using a drill hole after arthrotomy of the knee joint and opening of the femur through the notch. Weekly CT- and MRI-scans were performed to document number and size of bone metastases. Radiofrequency ablation (22G bipolar and impedance-controlled RF-applicator, 2-4 Watt, 3 min application time) was carried out. One week after RFA, the animals were sacrificed and macroscopic and histological examination followed. For statistical analysis, paired comparison procedures were used. RESULTS: Inoculation of the tumor cells was well tolerated. The mean time of the surgical procedure was 6 minutes. All animals developped local bone metastases. Mean time to metastasis was 8 weeks (range 7-10 weeks) after tumor cell implantation. No leakage of tumor cells and no soft part metastases occurred. Radiofrequency ablation was performed without complications. Imaging showed a complete ablation of the bone tumor in all rats. Histological findings confirmed a circular necrosis with an extensive destruction of tumor cells leaving a necrosis cavity. CONCLUSION: The experimental model presented here describes the first time the ability to carry out radiofrequency ablation in nude rats with intrafemoral induced osteolytic metastases of human breast cancer. RFA in human breast cancer cell line in nude rats is a feasible and useful possibility to evaluate and to test different RF-procedures. Additional treatment options like local chemotherapy or chemoembolization can be performed.

Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial.

BACKGROUND: Oral anticoagulants, such as dabigatran etexilate, an oral, direct thrombin inhibitor, that do not require monitoring or dose adjustment offer potential for prophylaxis against venous thromboembolism (VTE) after total knee replacement surgery. METHODS: In this randomized, double-blind study, 2076 patients undergoing total knee replacement received dabigatran etexilate, 150 mg or 220 mg once-daily, starting with a half-dose 1-4 hours after surgery, or subcutaneous enoxaparin 40 mg once-daily, starting the evening before surgery, for 6-10 days. Patients were followed-up for 3 months. The primary efficacy outcome was a composite of total VTE (venographic or symptomatic) and mortality during treatment, and the primary safety outcome was the incidence of bleeding events. RESULTS: The primary efficacy outcome occurred in 37.7% (193 of 512) of the enoxaparin group versus 36.4% (183 of 503) of the dabigatran etexilate 220 mg group (absolute difference, -1.3%; 95% CI, -7.3 to 4.6) and 40.5% (213 of 526) of the 150 mg group (2.8%; 95% CI, -3.1 to 8.7). Both doses were noninferior to enoxaparin based on the pre-specified noninferiority criterion. The incidence of major bleeding did not differ significantly between the three groups (1.3% versus 1.5% and 1.3% respectively). No significant differences in the incidences of liver enzyme elevation and acute coronary events were observed during treatment or follow-up. CONCLUSIONS: Dabigatran etexilate (220 mg or 150 mg) was at least as effective and with a similar safety profile as enoxaparin for prevention of VTE after total knee-replacement surgery.

The prevalence of vitamin D deficiency in patients with vertebral fragility fractures.

Hypovitaminosis D has been identified as a common risk factor for fragility fractures and poor fracture healing. Epidemiological data on vitamin D deficiency have been gathered in various populations, but the association between vertebral fragility fractures and hypovitaminosis D, especially in males, remains unclear. The purpose of this study was to evaluate serum levels of 25-hydroxyvitamin D (25-OH D) in patients presenting with vertebral fragility fractures and to determine whether patients with a vertebral fracture were at greater risk of hypovitaminosis D than a control population. Furthermore, we studied the seasonal variations in the serum vitamin D levels of tested patients in order to clarify the relationship between other known risk factors for osteoporosis and vitamin D levels. We measured the serum 25-OH D levels of 246 patients admitted with vertebral fractures (105 men, 141 female, mean age 69 years, sd 8.5), and in 392 orthopaedic patients with back pain and no fractures (219 men, 173 female, mean age 63 years, sd 11) to evaluate the prevalence of vitamin D insufficiency. Statistical analysis found a significant difference in vitamin D levels between patients with vertebral fragility fracture and the control group (p = 0.036). In addition, there was a significant main effect of the tested variables: obesity (p < 0.001), nicotine abuse (p = 0.002) and diabetes mellitus (p < 0.001). No statistical difference was found between vitamin D levels and gender (p = 0.34). Vitamin D insufficiency was shown to be a risk factor for vertebral fragility fractures in both men and women.

Ibandronate treatment decreases the effects of tumor-associated lesions on bone density and strength in the rat.

Bisphosphonate treatment is beneficial against symptoms of metastatic bone disease, although less is known about the effect of preventative treatment schedules. We investigated the effect of various treatment regimens of the bisphosphonate, ibandronate (IB), on the preservation of bone quality in a rat model of tumor-induced osteolysis. Osteolytic Walker 256 (W256) carcinosarcoma cells were implanted into the left femur of female Sprague-Dawley rats, resulting in a 10% reduction in bone mineral density (BMD), a 16% reduction in bone density (BD), and a 26% reduction in failure load compared with the right femur 28 days after implantation. IB was administered subcutaneously in five different treatment schedules: (1) IB PRE-POST received IB for 26 days, prior to implantation of W256 cells in the medullary canal of the femur, and for 28 additional days after surgery; (2) IB PRE-POST SHAM received the same IB administration, but with a sham operation; (3) IB PRE received IB injections before W256 cell insertion only; (4) IB PRE-0 received IB injections for 26 days and was then killed to serve as a time zero control; and (5) IB POST received sham injection with saline before W256 cell insertion, and then received IB injections for 28 days until killing. Controls (TUMOR ONLY) received sham injections with saline prior to W256 cell insertion, and then for 28 additional days until killing. We used dual-energy X-ray absorptiometry (DXA) to measure distal femur BMD and bone mineral content (BMC), peripheral quantitative computed tomography (pQCT) to measure distal femur BD, and torsion testing to obtain torsional failure load. Combined preventative and interventional IB treatment best preserved bone mass and strength, although all treatment schedules resulted in significant improvement compared with untreated controls (TUMOR ONLY). The possibility of reducing or even preventing skeletal morbidity in cancer patients with a high risk of developing metastatic spreading to bone is exciting, and warrants further exploration.

Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells.

Bone marrow contains a population of rare progenitor cells capable of differentiating into bone, cartilage, tendon, and other connective tissues. These cells, referred to as mesenchymal stem cells, can be purified and culture-expanded from animals and humans and have been shown to regenerate functional tissue when delivered to the site of musculoskeletal defects in experimental animals. To test the ability of purified human mesenchymal stem cells to heal a clinically significant bone defect, mesenchymal stem cells isolated from normal human bone marrow were culture-expanded, loaded onto a ceramic carrier, and implanted into critical-sized segmental defects in the femurs of adult athymic rats. For comparison, cell-free ceramics were implanted in the contralateral limb. The animals were euthanized at 4, 8, or 12 weeks, and healing bone defects were compared by high-resolution radiography, immunohistochemistry, quantitative histomorphometry, and biomechanical testing. In mesenchymal stem cell-loaded samples, radiographic and histologic evidence of new bone was apparent by 8 weeks and histomorphometry demonstrated increasing bone formation through 12 weeks. Biomechanical evaluation confirmed that femurs implanted with mesenchymal stem cell-loaded ceramics were significantly stronger than those that received cell-free ceramics. These studies demonstrate that human mesenchymal stem cells can regenerate bone in a clinically significant osseous defect and may therefore provide an alternative to autogenous bone grafts.

Conservative treatment measures in hemophilic arthropathy.

Intraarticular bleeding and muscle bleeding occur spontaneously or as a result of trauma in hemophilia A or B. The most common sites for hemarthrosis are the knees joints, elbows and ankles joints. Resorption of intraarticular blood induces reactive hemophilic synovitis. Hyperplasia of the synovium can be followed by recurrent bleedings. These early reactions can change to a chronic synovitis and cause cartilage damage, finally resulting in a complete destruction of the joint. Since 1981 158 adults and 61 children with a hemophilia A or B were treated at the Center for hemophilic disorders Frankfurt in an interdisciplinary approach. Consequent prophylactic treatment with factor substitution can prevent the incidence of severe hemarthrosis. Minor joint bleedings are treated by adequate factor substitution, temporarily non-weight bearing of the extremity, application of ice-packs and physical therapy. More severe joint hemorrhages should be aspirated in order to reduce the acute synovitis. This is followed by a consequent physical therapy (joint and soft tissue techniques) and anti-inflammatory drugs. The goal is a sufficient muscular balance of the joint, the improvement of the coordination, and the proprioception. The chronic synovitis is less painful and poorly responses to conservative interventions. Local ice application, sytemic and local anti-inflammatory treatment support the physical therapy. Soft heel shock absorber, elastic and semi-rigid bandages prevent recurrent bleeding episodes by shock absorption and decrease of synovial impingement. Synovectomy is indicated in cases of chronic persistent synovitis. Radiosynoviorthesis (RSO), which is an alternative in certain cases, has been performed with great success in 12 cases in our hospital. In advanced arthropathy joint mobilization should be the emphasis of the physical therapy. Bandages, crutches and ortopaedic shoe devices improve the walking capacity.

Prevalence, pathophysiology, diagnosis, and treatment of Willebrand syndrome in orthopedic-trauma patients.

The von Willebrand's Disease affects about 1-3 % of the population and it is undiagnosed in most people. Originally described by the Finish physician Erik von Willebrand in 1926 this disorder is associated with mucous membran bleeding including epistaxis, hypermenorhoea and excessive bleeding from surgery and dental procedures. In von Willebrands disease the patients have a quantitative or qualitative abnormality in the von Willebrand Factor (vWF) which has two major functions: it serves by bridging between platelets and injury site in the blood vessel wall, and it circulates as a complex with factor VIII, protecting it from rapid degradation. More than 20 different types and subtypes of vWD have been described but almost all patients can be classified as having 1 of the 2 most common types of vWD. About 70 % of patients have type 1 and about 10-20 % present themself with type 2A and 2B vWD type 3 in about 10 %. By taking a clinical history of bleeding it is important to think about vWD and to make the appropriate diagnosis. If the vWD is suspected diagnostic tests should include an activated partial thromboplastin time, bleeding time, factor VIII:C, Ristocetin cofactor, and vWF antigen. Additional testing of ristocetin induced plattlet adhesion (RIPA), the multimeric structure and collagen binding test and gen-analysis allow diagnosing the different types of v. Willebrand Disease. The treatment of choice in mild forms is the synthetic agent desmopressin. In patients with severe type 1, type 2B, 2N and type 3 or in people who do not response to desmopressin, the appropriate treatment is a factor VIII concentrate that is rich of vWF. Until now no recommendations in the orthopaedic literature have been found regarding diagnosis and treatment of vWS patients. Based on the experience with 43 orthopaedic patients presenting vWD over the last 15 years a contemporary guideline for the successful perioperative management of vWD in orthopaedic surgery is presented. In a close collaboration between the orthopaedic surgeon and the specialized haemostaseologist every invasive procedure in patients with vWD can be undertaken without the risk of excessive bleeding.

Phenotypical characterization of c-kit receptor deficient mouse femora using non-destructive high-resolution imaging techniques and biomechanical testing.

OBJECTIVE: Pathological processes in bone can lead to fatal health consequences. Therefore, it is important to study factors that possibly influence the activity of bone cells. The mast cell is a normal component of bone, storing and producing many potent bioactive substances. One of the most important factors to influence mast cell number, function, and phenotype is the c-kit ligand. A defect of the c-kit receptor leads to mast cell deficiency. In literature oversight, evidence for the importance of mast cells in skeletal homeostasis is compiled. METHODS: To investigate the influence of c-kit receptor deficiency on bone mass, geometry, microstructure, and strength, 30 femora of profoundly c-kit receptor deficient mouse mutants and 30 control group animals aged 8-20 weeks were phenotypically characterized using peripheral quantitative computed tomography (pQCT), micro-computed tomography (microCT) and 3-point-bending. RESULTS: The femora of the c-kit receptor and therefore mast cell deficient animals were significantly altered in bone mass and geometry but not in bone density and microstructure. The mutants had a lighter femur with a thinner shape. The lower load bearing capacity of the femora of mast cell deficient mouse mutants is more likely explained by the smaller amount of bone material than due to a change in intrinsic material properties. TECHNICAL CONSIDERATIONS: With the little dimensions of mouse bones, it is of prime importance to have precise methods to phenotypically characterize the bone. The pQCT allows the separate assessment and analysis of trabecular and cortical bone density, as well as a statement about bone geometry. Beyond it, the microCT-technique delivers a 3-D analysis of bone microstructure, which so far was only achieved with 2-D histomorphometry. microCT is an efficient alternative to destructive histological preparations allowing further biomechanical testing of the same specimens to also deliver measures for bone strength.

[Minimally invasive cement augmentation of osteoporotic vertebral compression fractures with the new radiofrequency kyphoplasty]. / Minimal-invasive Zementaugmentation von osteoporotischen Wirbelkörperfrakturen mit der neuen Radiofrequenz-Kyphoplastie.

OBJECTIVE: Minimally invasive cement augmentation of painful osteoporotic vertebral compression fractures in elderly patients. INDICATIONS: Painful osteoporotic vertebral compression fractures in elderly patients (> 65 years of age) after conservative therapy failure. Painful aggressive primary tumors of the spine or osteolytic metastases to the spine with high risk of vertebral fracture in the palliative care setting. CONTRAINDICATIONS: General contraindications for surgical interventions. Local soft-tissue infection. Osteomyelitis, discitis or systemic infection. Coagulopathy refractory to treatment or bleeding diathesis. Asymptomatic vertebral compression fractures. Burst of the posterior vertebral column with high degree of spinal canal stenosis. Primary or metastatic spinal tumors with epidural growth. SURGICAL TECHNIQUE: Prone position on a radiolucent operating table. Fluoroscopic localization of the fractured vertebra using two conventional C-arm devices (anteroposterior and lateral views). Fluoroscopic localization of the fractured vertebra using two conventional C-arm devices (anteroposterior and lateral views). An introducer is inserted through a small skin incision into the pedicle under fluoroscopic guidance. To create a site- and size-specific three-dimensional cavity in the center of the fractured vertebra, the navigational VertecoR™ MidLine Osteotome was inserted through the correctly sited introducer and guided fluoroscopically. As the MidLine Osteotome allows angulation of the tip up to 90° by rotating the handle, a cavity over the midline of the vertebral body can mainly be created through one pedicle. The radiofrequency activated cohesive ultrahigh viscosity PMMA cement (ER(2) bone cement) is injected stepwise on demand by remote control under continuous pressure from the hydraulic assembly into the vertebral body. POSTOPERATIVE MANAGEMENT: Bed rest for 6 h postoperatively in supine position. Early mobilization without a corset on the day of surgery. Specific back and abdominal exercises that strengthen the back and abdominal muscles. Pain dependent increase of weight bearing. Continue osteoporosis therapy and start specific drug therapy according to the local guidlines if necessary. RESULTS: In all, 44 patients (29 women, 15 men) with a mean age of 73.5 years with a total of 62 painful osteoporotic vertebral fractures were treated with RF kyphoplasty from May 2009 until July 2010, and followed over a period of 12 months. The mean operating time per patient was 36.2 min, the operating time per vertebra was 25.7 min. All the patients studied experienced an early and persistent significant pain relief even 12 months after therapy (8 ± 1.4 vs. 2.7 ± 1.9) according to the visual analogue pain scale. According to the Oswestry Disability Index (ODI) as a disease-specific disability measure all the patients improved significantly (p < 0.001) in the level of disability after operative treatment (56.2 ± 18.8 vs. 34.5 ± 16.6). Cement leakage was detected in 17 out of 62 (27.4 %) augmented vertebrae, whereas all the patients with cement leakage remained asymptomatic. One patient had subsequent vertebral fractures after a period of 6 months.

Radiofrequency ablation in experimental bone metastases using a controlled and navigated ablation device.

BACKGROUND: Radiofrequency ablation is a minimal invasive therapy in the treatment of bone metastases. In this study we present a new ablation system enabling an ablation in multiple directions and with an adaptable size and shape. MATERIAL AND METHODS: VX-2 tumor was used for the induction of experimental bone metastases in the femur of six New Zealand white rabbits. X-ray imaging as well as CT and MRI scans before and after treatment was carried out. After detecting bone tumor, radiofrequency ablation was performed. The ablation instrument contained a 10 g bipolar, articulated extendable electrode and a proprietary generator with an impedance controlled algorithm. All bones and the soft tissue were examined histologically. RESULTS: All animals developed local bone tumor. Mean duration until first osteolytic lesions on CT-scans was 48±14 days. The mean lesion area was 26 mm(2). No systemic tumor spread was seen. 6 radiofrequency procedures were carried out with a mean application time of 6 min±2:30 and an average temperature in the region of effect of 55 °C±4. MRI imaging demonstrated an ablation zone of 23±6 mm around the electrode. Histopathology showed an extensive heat necrosis with no remaining tumor cells in the ablation area. CONCLUSION: Radiofrequency ablation is a quickly developing treatment option on the field of minimal invasive bone tumor therapy. The electrode enables an ablation adapted to size and shape of the metastases. Further clinical studies are necessary to test and enhance this radiofrequency system.

Dabigatran versus enoxaparin for prevention of venous thromboembolism after hip or knee arthroplasty: a pooled analysis of three trials.

BACKGROUND: Three randomized, double-blind trials compared dabigatran, an oral direct thrombin inhibitor, with enoxaparin for the primary prevention of venous thromboembolism (VTE) in patients undergoing elective total hip and knee arthroplasty. OBJECTIVES AND METHODS: We conducted a pre-specified pooled analysis of these trials. 8,210 patients were randomized, of whom 8,135 were treated (evaluable for safety) with dabigatran 220 mg or 150 mg once-daily, or subcutaneous enoxaparin (40 mg once-daily or 30 mg twice-daily). Efficacy analyses were based on the modified intention-to-treat population of 6,200 patients with an evaluable outcome. The common risk difference (RD) of treatment effect between each dabigatran dose and enoxaparin was estimated using fixed-effects models, and statistical heterogeneity was estimated using the I2 statistic. RESULTS: The composite outcome of major VTE (proximal deep vein thrombosis and/or pulmonary embolism) and VTE-related mortality occurred in 3.3% of the enoxaparin group versus 3.0% of the dabigatran 220 mg group (RD vs. enoxaparin -0.2%, 95% CI -1.3% to 0.9%, I2=37%) and 3.8% of the 150 mg group (RD vs. enoxaparin 0.5%, -0.6% to 1.6%, I2=0%). Major bleeding occurred in 1.4% of the enoxaparin group versus 1.4% of the dabigatran 220 mg group (RD vs. enoxaparin -0.2%, -0.8% to 0.5%, I2=40%) and 1.1% of the 150 mg group (RD vs. enoxaparin -0.4%, -1.0% to 0.2%, I2=0%). CONCLUSIONS: Oral dabigatran was as effective as subcutaneous enoxaparin in reducing the risk of major VTE and VTE-related mortality after hip or knee arthroplasty and has a similar bleeding profile.

[Therapy of Paget's disease]. / Die Behandlung des Morbus Paget.

Paget's disease of bone, an often undiagnosed metabolic bone disease, can lead to dramatic skeletal changes with enlargement and bowing of the affected bones. The etiology of this localized bone disease has not yet been determined. Genetic factors and viral infections may be involved. Recently, the treatment options for Paget's disease have been greatly improved due to the development of potent bisphosphonates. These agents inhibit osteoclastic bone resorption and allow the suppression of the excessive bone turnover in Paget's disease. This leads to a stabilization of affected bones and to symptomatic improvements. Treatment should be initiated early after diagnosis to limit the extent of damage. The article gives an overview of recent perspectives on epidemiology, diagnosis, and treatment of the disease according to the new German guidelines for the diagnosis and therapy of Paget's disease.

[Diagnosis and treatment of postmenopausal osteoporosis and osteoporosis in men. German Guidelines Update 2006]. / Diagnostik und Therapie der postmenopausalen Osteoporose und der Osteoporose des Mannes. Update der Leitlinien 2006.

The treatment of osteoporosis and prevention of osteoporotic fractures consists of both non-drug and drug therapy. Components of non-drug therapy include the improvement of muscle strength and coordination, treatment of modifiable causes of falls, a diet rich in calcium and sufficient in calories, an adequate supply of Vitamin D and an individual assessment of drugs known to increase falls or osteoporosis. The updated DVO diagnostic and treatment guidelines for osteoporosis recommends a 30% 10-year probability for vertebral and hip fractures as an intervention threshold for drug treatment. Using epidemiological fracture data from central Europe, the guidelines provides an assessment of absolute 10-year fracture risk based on a combination of age, gender, prevalent fragility fractures, spine and total hip dual-energy x-ray absorptiometry (DXA) measurements and several other clinical risk factors.

[Bisphosphonates in oncology]. / Einsatz der Bisphosphonate in der Onkologie.

Since bone metastases occur as a result of hematogenous spreading of tumor cells, therapy with curative intent is no longer feasible and palliative options for treating and preventing skeletal events are essential. Today, bisphosphonates are established in the systemic treatment of bone metastases. This report provides an overview of molecular mechanisms of action and clinical data of bisphosphonates in patients with skeletal metastases of breast and prostate cancer as the most common solid tumors which spread to the bone.

[The use of bisphosphonates in arthroplasty]. / Anwendungsmöglichkeiten der Bisphosphonate in der Endoprothetik.

The use of bisphosphonates in joint arthroplasty is the latest field of application for these agents. The mechanism of action of bisphosphonates suggests that they may optimize long-term survival of the implant. Most important is their potency in suppressing periprosthetic osteolysis due to the inflammatory foreign body reaction of wear debris, to decrease periprosthetic osteopenia caused by stress-shielding and to improve the osseointegration of cementless metal implants. The present review provides the latest information on definite and presumed mechanisms of action of bisphosphonates and their clinical importance.