EULAR/EFORT recommendations for management of patients older than 50†years with a fragility fracture and prevention of subsequent fractures.

The European League Against Rheumatism (EULAR) and the European Federation of National Associations of Orthopaedics and Traumatology (EFORT) have recognised the importance of optimal acute care for the patients aged 50 years and over with a recent fragility fracture and the prevention of subsequent fractures in high-risk patients, which can be facilitated by close collaboration between orthopaedic surgeons and rheumatologists or other metabolic bone experts. Therefore, the aim was to establish for the first time collaborative recommendations for these patients. According to the EULAR standard operating procedures for the elaboration and implementation of evidence-based recommendations, 7 rheumatologists, a geriatrician and 10 orthopaedic surgeons met twice under the leadership of 2 convenors, a senior advisor, a clinical epidemiologist and 3 research fellows. After defining the content and procedures of the task force, 10 research questions were formulated, a comprehensive and systematic literature search was performed and the results were presented to the entire committee. 10 recommendations were formulated based on evidence from the literature and after discussion and consensus building in the group. The recommendations included appropriate medical and surgical perioperative care, which requires, especially in the elderly, a multidisciplinary approach including orthogeriatric care. A coordinator should setup a process for the systematic investigations for future fracture risk in all elderly patients with a recent fracture. High-risk patients should have appropriate non-pharmacological and pharmacological treatment to decrease the risk of subsequent fracture.

EULAR/EFORT recommendations for the diagnosis and initial management of patients with acute or recent onset swelling of the knee.

OBJECTIVES: The European League Against Rheumatism (EULAR) and the European Federation of National Associations of Orthopaedics and Traumatology (EFORT) have recognised the importance of variation in diagnostic and therapeutic performance across disciplines, have found consensus in starting task forces aiming at achieving diagnostic and therapeutic uniformity, and have identified medical conditions with which representatives of both organisations will frequently be confronted in common clinical practice. The aim of the present work was to establish recommendations for the diagnosis and initial management of patients presenting with acute or recent onset swelling of the knee. METHODS: The EULAR standard operating procedures for the elaboration and implementation of evidence-based recommendations were followed. RESULTS: In all, 11 rheumatologists from 11 countries and 12 orthopaedic surgeons from 7 countries met twice under the leadership of 2 conveners, a clinical epidemiologist and a research fellow. After carefully defining the content and procedures of the task force, research questions were developed, a comprehensive literature search was performed and the results were presented to the entire committee. Subsequently, a set of 10 recommendations was formulated based on evidence from the literature if available, and after discussion and consensus building. CONCLUSIONS: This is the first combined interdisciplinary project of rheumatologists and orthopaedic surgeons, successfully aiming at achieving consensus in the diagnosis and initial management of patients presenting with acute or recent onset swelling of the knee.

Osteoarthritis-patterns, cardio-metabolic risk factors and risk of all-cause mortality: 20 years follow-up in patients after hip or knee replacement.

Osteoarthritis (OA) is a common musculoskeletal disorder and occur in different patterns. However, its impact on long-term all-cause-mortality is inconclusive. STUDY AIMS: Investigate 20-year all-cause-mortality in patients with hip/knee arthroplasty (recruited 1995/1996, N = 809) from the Ulm Osteoarthritis Study-cohort, in comparison to general population. Furthermore, to enlighten the triangle between baseline life-style and cardio-metabolic risk factors, phenotypic OA-patterns (laterality, generalization, cause) and all-cause-mortality. Mortality was assessed during 20 years follow-up. Standardized mortality ratios (SMR), adjusted odds ratios and hazard ratios (aHR) were calculated. After five years cohort-mortality was reduced compared to the general population, however 20 years later assimilated (SMR = 1.11; 95%-CI 0.73-1.49). OA-patterns were associated with age, cholesterol, and overweight/obesity. In comparison to primary OA decreased mortality was observed for patients with secondary OA (aHR = 0.76; 95%-CI 0.61-0.95) adjusted for age, smoking, overweight/obesity, diabetes, hypertension, cardiac insufficiency, uric acid, and lower cholesterol. There was no increased mortality in patients after 20 years follow-up compared to general population. Significantly decreased mortality in secondary compared to primary OA suggests a subtype-specific involvement of systemic co-factors in determination of all-cause-mortality. Because cardio-metabolic risk factors were associated with increased risk of bilateral OA and lower long-term survival, those risk factors should be consequently targeted in OA-patients.

On the outcome of computer-assisted total knee replacement.

A number of studies have reported a significant improvement of the postoperative alignment, when computer-navigated total knee arthroplasty (TKA) was compared with conventional techniques. However, no studies are available on the functional and patient-relevant outcomes after computer-assisted knee replacement. In a prospective, randomized trial comparing 27 computer-assisted TKAs with 25 conventional implantations, the Knee Society Score was used to assess functional status, and the WOMAC questionnaire was used to record the disease-specific, patient-relevant outcome. At a twelve-month follow-up no significant difference was detected between the two patient groups in either the scores or the number of complications and range of postoperative knee flexion. The results are in agreement with those reported in other studies on the effect of conventional TKA. With the patient group of this size it can be concluded that computer-navigated TKA gives short-term resuits comparable with those achieved by conventional methods of implantation.

Differences in the views of orthopaedic surgeons and referring practitioners on the determinants of outcome after total hip replacement.

In order to assess current opinions on the long-term outcome after primary total hip replacement, we performed a multicentre, cross-sectional survey in 22 centres from 12 European countries. Different patient characteristics were categorised into 'decreases chances', 'does not affect chances', and 'increases chances' of a favourable long-term outcome, by 304 orthopaedic surgeons and 314 referring practitioners. The latter were less likely to associate age older than 80 years and obesity with a favourable outcome than orthopaedic surgeons (p < 0.001 and p = 0.006, respectively) and more likely to associate age younger than 50 years with a favourable outcome (p = 0.006). Comorbidity, rheumatoid arthritis, and poor bone quality were thought to be associated with a decreased chance of a favourable outcome. We found important differences in the opinions regarding long-term outcome after total hip replacement within and between referring practitioners and orthopaedic surgeons. These are likely to affect access to and the provision of total hip replacement.

Vascular endothelial growth factor stimulates chemotactic migration of primary human osteoblasts.

Recent studies have indicated a critical role for vascular endothelial growth factor (VEGF) during the process of endochondral ossification, in particular in coupling cartilage resorption with bone formation. Therefore, we studied the chemoattractive and proliferative properties of human VEGF-A on primary human osteoblasts (PHO) and compared these data with the effects of human basic fibroblast growth factor (bFGF) and human bone morphogenetic protein-2 (BMP-2). Furthermore, initial experiments were carried out to characterize VEGF-binding proteins on osteoblastic cells possibly involved in the response. For the first time, to our knowledge, we could demonstrate a chemoattractive effect of VEGF-A, but not VEGF-E, on primary human osteoblasts. The effect of VEGF-A was dose-dependent and did not reach a maximum within the concentration range tested (up to 10 ng/mL). The maximal effect observed was a chemotactic index (CI) of 2 at a concentration of 10 ng/mL. bFGF and BMP-2 exhibited maxima at 1.0 ng/mL with CI values of 2.5 and 2, respectively. In addition to its effect on cell migration, VEGF-A stimulated cell proliferation by up to 70%. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed the expression of VEGF receptors VEGFR-1 (Flt-1), VEGFR-2 (Kdr), and VEGFR-3 (Flt-4), as well as neuropilin-1 and -2. An in vitro kinase assay failed to demonstrate activation of VEGFR-2 upon stimulation with either VEGF-E or VEGF-A, consistent with the idea that the effect of VEGF-A on primary human osteoblasts is mediated via VEGFR-1. Taken together, our data establish that human osteoblasts respond to VEGF-A, suggesting a functional role for this growth factor in bone formation and remodeling.

Effects of excimer laser on healing of articular cartilage in rabbits.

This study examined healing of 1.0 mm diameter defects in rabbit knee articular cartilage for as long as 14 weeks after creation of the defects by either laser or drilling. The purpose of the research was to determine the effects of laser debridement of cartilage on the intrinsic biomechanical properties of the repair tissue. We therefore imitated chondral shaving and subchondral abrasion of cartilage by creating partial-thickness and full-thickness cartilage defects of standardized size with both excimer laser and drilling. Light and scanning electron microscopic examinations of the repair tissue showed that healing of osteochondral defects created by laser may be delayed compared with defects created by drilling, for at least 6 weeks postoperatively. Even though there initially was a considerable delay in healing in the laser group, neither laser nor drilling had any appreciable effects on the mechanical properties of the repair tissue, as demonstrated by biomechanical testing at 14 weeks. Specifically, the repair cartilage in the defects in the laser group had the following material properties (mean +/- SD): aggregate modulus, 0.40 +/- 0.24 MPa; Poisson's ratio, 0.37 +/- 0.08; permeability, 3.72 +/- 4.28 x 10(-15) m4/N.s; and thickness, 0.20 +/- 0.06 mm. The corresponding values for the defects in the drilling group were 0.39 +/- 0.23 MPa, 0.34 +/- 0.09, 3.82 +/- 3.44 x 10(-15) m4/N.s, and 0.22 +/- 0.09 mm. The repair tissue from both types of defects was pooled, and the values were compared with those for contralateral (control) tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Interactions between human osteoarthritic chondrocytes and synovial fibroblasts in co-culture.

OBJECTIVE: To imitate the in vivo joint situation and to allow cell interactions, a co-culture system of human osteoarthritic chondrocytes and synovial fibroblasts from a single joint was established and characterized with or without stimulation by IL-1 beta. METHODS: Culture settings included chondrocytes in alginate alone, synovial fibroblasts in monolayer alone and a co-culture of both. Proteoglycan (PG) synthesis was measured by 35S-incorporation, PG content by a dimethylmethylene blue assay, DNA content by a fluorometric assay, and prostaglandin-E2 and IL-1 beta release by ELISA. RESULTS: In co-culture PG synthesis by chondrocytes was significantly reduced in the presence of IL-1 beta (1 ng/ml) compared to controls. PG content of chondrocyte cultures was reduced for controls and IL-1 beta treated co-cultures. Synovial fibroblasts in co-culture did not show significant change of PG synthesis or content when compared to cells in mono-cell culture. PG release into the medium was relatively high in co-cultures. IL-1 beta significantly decreased the proliferation rate of chondrocytes in co-cultures and slightly increased prostaglandin-E2 release. CONCLUSIONS: Co-culturing of osteoarthritic chondrocytes and synovial fibroblasts from a single human joint allows interactions between both entities and may offer a useful tool to study the effects of mediators or new drugs under more in vivo like conditions compared to mono-cell cultures.

Reliability of radiological measurements in the assessment of hip dysplasia in adults.

Radiographic measurements are commonly used to quantify the treatment results of hip dysplasia and assess further need of operative treatment. We investigated the interobserver and intraobserver reliability of the commonest radiographic techniques in the assessment of hip dysplasia in skeletally mature adults. Three observers independently analysed 100 hip radiographs of patients with hip dysplasia aged between 16 and 32 years. We measured centre-edge angle of Wiberg, acetabular angle of Sharp, acetabular index of the weightbearing zone, acetabular index of depth to width, ACM-angle, MZ-distance, acetabular head index, lateral subluxation and neck-shaft angle. In addition, the radiographs were reviewed a second time 3 months apart by two of the observers to assess intraobserver reliability. We found a high correlation (intraclass correlation coefficient) for interobserver reliability (0.76-0.87) and intraobserver reliability (0.70-0.92) for all radiographic measurements except acetabular index of depth to width, ACM-angle and MZ-distance. Depending on the clinical question we therefore recommend the use of one of the reliable measurements to assess the radiograph of a dysplastic hip.

Ultrasonographic evaluation of Legg-Calve-Perthes disease based on sonoanatomic criteria and the application of new measuring techniques.

This study attempts an ultrasonographic classification of Legg-Calve-Perthes disease according to sonoanatomic and sonometric criteria. Four stages, similar to standard radiological staging, could reproducibly be found in 29 patients with unilateral disease. The stages could be significantly differentiated according to descriptive sonoanatomic criteria and partially newly introduced sonographic measurements, including epiphysis-metaphysis-index and acetabulum-epiphysis-distance. Sonographic evaluation of Perthes hips is a simple and standardised procedure, which can serve to stage and monitor the course of the disease and hence reduce the amount of X-ray exposure and treatment costs.

Measurement of femoral anteversion by magnetic resonance imaging--evaluation of a new technique in children and adolescents.

Anteversion of the femoral neck was measured by magnetic resonance imaging (MRI) in 19 children (37 hips) preoperatively before femoral rotation osteotomies. The results of this new technique were compared with values for anteversion obtained by computed-tomographic (CT) scanning and ultrasound. In order to determine the correlation between the three different methods and to assess their reliability, the measurements were performed independently by two observers at different times. There was a high correlation (Pearson's correlation coefficient) between MRI results and CT scan (r = 0.77) as well as MRI and sonography (r = 0.81), although the mean anteversion angles obtained by computerized tomography (34.0 degrees, range 5-82 degrees) and ultrasound (25.6 degrees, 10-40 degrees) were larger than the MRI values (23.2 degrees, 0-65 degrees), which can be explained by the different measurement techniques. Mean inter-rater as well as intra-rater reliability was high for MRI (r = 0.97 and r = 0.97) and CT (r = 0.99 and r = 0.96) but slightly less for sonography (r = 0.88 and r = 0.88). MRI is a novel method for evaluating femoral anteversion that does not require ionizing radiation, allows a precise anatomical measurement and reliable results. MRI is recommended for preoperative planning of pediatric femoral rotation osteotomy cases.

Biomechanical evaluation of a newly developed monocortical expansion screw for use in anterior internal fixation of the cervical spine. In vitro comparison with two established internal fixation systems.

STUDY DESIGN: The primary biomechanical stability of anterior internal fixation of the cervical spine obtained with a new monocortical expansion screw in vitro was evaluated. OBJECTIVES: To determine whether the anterior internal fixation of the spine obtained with the new monocortical expansion screw provides biomechanical stability comparable with that obtained with bicortical fixation. SUMMARY OF BACKGROUND DATA: The anterior plate instrumentation used with bicortical screw fixation in the cervical spine provides a primary stability superior to that associated with monocortical screw fixation. However, bicortical screws have the potential to perforate the posterior cortex. Therefore, monocortical instrumentation systems were developed, but without the biomechanical stability associated with bicortical systems. A new expansion screw for monocortical fixation was developed to improve biomechanical stability of monocortical systems. METHODS: Three different internal fixation systems were compared in this study: 1) H-plate with AO 3.5-mm bicortical screws, 2) cervical spine locking plate with monocortical screws, and 3) H-plate with the new monocortical expansion screws. Eight fresh human cadaver spine segments from C4 to C7 were tested in flexion-extension, axial rotation, and lateral bending using pure moments of +/- 2.5 Nm without axial preload. Five conditions were investigated consecutively: 1) intact spine; 2) uninstrumented spine with the segment C5-C6 destabilized; 3-5) instrumentation of the segment C5-C6 with the three implants mentioned above after removal of the disc and insertion of an interbody spacer. RESULTS: Between bicortical and monocortical expansion screw H-plate fixation, no significant differences were observed in all load cases concerning range of motion and neutral zone. The neutral zone and range of motion were significantly larger for the cervical spine locking plate than for bicortical and monocortical expansion screw fixation in all load cases, except neutral zone for axial rotation versus bicortical screw fixation. The instrumented cases only had a significantly lower range of motion and neutral zone than the intact cases in extension-flexion, whereas for lateral bending and axial rotation no significant differences could be observed. Because the experimental design precluded any cyclic testing, the data represent only the primary stability of the implants. CONCLUSIONS: In anterior instrumentation of the cervical spine using a H-plate, the new monocortical expansion screw provides the same biomechanical stability as the bicortical 3.5-mm AO screw and a significantly better biomechanical stability than the cervical spine locking plate. Therefore, the expansion screw may be an alternative to the bicortical fixation and does not involve the risk of penetration of the posterior vertebral body cortex.

In situ rigidity of a new sliding rod for management of the growing spine in Duchenne muscular dystrophy.

STUDY DESIGN: This biomechanical, in vitro laboratory study determined the static stiffness of a new telescoping rod and the axial motion of this implant during various loading conditions. OBJECTIVES: To compare the stability of the new telescoping rod with the classic Luque instrumentation, and to determine whether the sliding rod elongates or contracts during spine motion. SUMMARY OF BACKGROUND DATA: A new telescoping rod was developed to stabilize the spine in children with Duchenne muscular dystrophy and to provide capacity for spinal growth. METHODS: The stability of 11 instrumented calf spines was determined in flexion, extension, lateral bending, and torsion to determine the stiffnesses of the spines instrumented with these two implants. The telescoping motion in the left and right rod was measured in the new rod system. RESULTS: In flexion, the spines with the telescoping rods were stiffer than those with the Luque implant. However, no significant differences in the stiffness coefficients were found for extension, lateral bending, or torsion. The restoring force of the telescoping system was greater than that of the Luque system in all directions. All modes of loading produced an accommodating change of length in the construct. CONCLUSIONS: The dynamic telescoping system provides stiffness comparable with that of established systems while allowing elongation during growth of the young patient.

[The early radiological findings of idiopathic necrosis of the femoral head in adults (author's transl)]. / Röntgenologische Frühsymptome der idiopathischen Hüftkopfnekrose Erwachsener.

Idiopathic necrosis of the femoral head in adults occurs in about 2 to 3% of all cases of degenerative hip disease. Advanced necrosis with collapse of the head offers a difficult therapeutic problem in younger patients. Early radiological diagnosis is therefore important. The typical, early radiological findings were studied in a hundred patients with idiopathic necrosis of the femoral head. They consist of an area of sclerosis at the junction of the head and neck, with a periosteal response on the inferior margin of the neck. The relationship of these changes with mechanical stress and defective blood supply is discussed. Signs of more advanced necrosis are band-like sclerosis at the point of demarkation and sub-chondral decalcification of the femoral head. Recognition of the early radiological features improves the chances of successful treatment, particularly in the lower age group.

[The scintigraphic diagnosis of pseudo-arthroses following Harrington's spondylodesis (author's transl)]. / Szintigraphische Diagnostik von Pseudarthrosen nach Harrington-Spondylodese.

The development of pseudo-arthroses is the most common complication following operative treatment of severe scoliosis. Early recognition of this event is important to prevent recurrence of the curvature. The diagnosis is not possible by radiological examination of the rigid spine. Routine reexploration implies a second operation, which is unnecessary in the majority of patients with stable fusion. In an attempt to develop a non-invasive method for the diagnosis of pseudo-arthroses, bone scintigrams were carried out in 29 patients with idiopathic scoliosis twelve months after a Harrington's spondylodesis. In 24 patients (82.8%) a definite conclusion could be drawn, either of stable fusion (65.5%) or pseudo-arthrosis formation (17.3%). No pseudo-arthroses were missed by scintigraphy. These results indicate that bone scintigraphy plays an important role in the post-operative care after Harrington's spondylodesis.

BMP-4 of Xenopus laevis stimulates differentiation of human primary osteoblast-like cells.

Since bone morphogenetic proteins (BMPs) are highly homologous, we investigated the hypothesis that recombinant BMP-4 of the genome of Xenopus laevis (rxBMP-4) may influence the proliferation or differentiation of human primary osteoblast-like cells (HPOC), as occurs with recombinant human BMP (rhBMP-2). HPOC were incubated in the presence of either rxBMP-4, rhBMP-2 or basic fibroblast growth factor (rh-bFGF). The last two were used as positive controls and are known to induce differentiation or proliferation of HPOC, respectively. rxBMP-4 (50 ng/ml and 100 ng/ml) induced a differentiation of HPOC to almost the same extent as rhBMP-2, whereas the addition of rh-bFGF, applied in the same concentration, failed to have any influence on cell differentiation. rh-bFGF however, provoked an increase in cell proliferation of up to 150% when compared with non-stimulated HPOC, while rhBMP-2 and rxBMP-4 had no such effect. Our results indicate an equipotent effect of rhBMP-2 and rxBMP-4 obtained from Xenopus laevis on the differentiation and proliferation of human primary osteoblast-like cells.

First carpometacarpal and interphalangeal osteoarthritis of the hand in patients with advanced hip or knee OA. Are there differences in the aetiology?

Differences in the aetiology of osteoarthritis (OA) of the first carpometacarpal joints (CMC-1) and the interphalangeal joints (IP) have been reported. It was the purpose of this investigation to evaluate whether isolated OA of the first carpometacarpal joints and the interphalangeal joints differs in its aetiology, considering potential risk factors such as age, gender, body mass index, occupational history, OA in the hip or knee joints, hypertension and diabetes in patients with advanced hip or knee OA. Included in this investigation were 639 patients scheduled for either hip or knee replacement because of advanced OA. As well as a standardised interview and clinical examination, bilateral radiographs of both hands were obtained. According to the presence or absence of radiographic OA, participants were categorised as having CMC-1 OA (= 1 joint) or IP OA (= 2 joints), either isolated or in combination. Odds ratios (OR) and their 95% confidence intervals (CI) for potential determinants of OA were estimated using multivariable logistic regression. Of the total number of patients, 184 had CMC-1 OA and 424 IP OA. Patients with CMC-1 OA were more likely to be female (77.2%), and to have knee OA (62.5%) and hypertension (63.0%), than patients without CMC-1 OA. No differences between CMC-1 OA and IP OA were observed for the role of age, body mass index and diabetes. Age was associated with both CMC and IP OA. Female gender was independently associated with CMC-1 OA (OR=1.79; 95% CI: 1.16-2.74) but not with IP OA. Our data suggest a possible impact of age and female gender on the aetiology of CMC-1 OA and of age on IP-OA, at least in patients with advanced hip or knee OA.

Scoring prevalence and severity in gonarthritis: the suitability of the Kellgren & Lawrence scale.

In clinical and epidemiological studies the Kellgren & Lawrence (K&L) scale was mainly used in the past to determine the radiological prevalence and severity of gonarthritis. The dependency of this scoring system on the presence of osteophytes has been criticised, and owing to its varying reliability, its appropriateness in cross-sectional and longitudinal studies is questioned. It was the purpose of this study to test whether the dependency of the K&L scale on the presence of osteophytes is reflected in a higher correlation of the overall score with a separate scoring of 'osteophytes' than with other radiological features. Furthermore we compared the inter- and intrarater reliability with the reliability of individual radiological features. Knee radiographs of 40 patients were graded according to the K&L scale and for the presence and severity of five separate radiological features of osteoarthritis. We found a moderate correlation of the K&L scale with the radiological features of 'osteophytes', 'joint space narrowing' and 'flattening of condyles'. The intra- and inter-rater reliability of the K&L scale was higher than the reliability of the individual radiological features. The K&L scale seems not to be strongly dependent on the presence of osteophytes, i.e. there is not a higher correlation of the overall score with that feature than with other radiological features.

Anticoagulation: the present and future.

Thrombin is a central bioregulator of coagulation and is therefore a key target in the therapeutic prevention and treatment of thromboembolic disorders, including deep vein thrombosis and pulmonary embolism. The current mainstays of anticoagulation treatment are heparins, which are indirect thrombin inhibitors, and coumarins, such as warfarin, which modulate the synthesis of vitamin K-dependent proteins. Although efficacious and widely used, heparins and coumarins have limitations because their pharmacokinetics and anticoagulant effects are unpredictable, with the risk of bleeding and other complications resulting in the need for close monitoring with their use. Low-molecular-weight heparins (LMWHs) provide a more predictable anticoagulant response, but their use is limited by the need for subcutaneous administration. In addition, discontinuation of heparin treatment can result in a thrombotic rebound due to the inability of these compounds to inhibit clot-bound thrombin. Direct thrombin inhibitors (DTI) are able to target both free and clot-bound thrombin. The first to be used was hirudin, but DTIs with lower molecular weights, such as DuP 714, PPACK, and efegatran, have subsequently been developed, and these agents are better able to inhibit clot-bound thrombin and the thrombotic processes that take place at sites of arterial damage. Such compounds inhibit thrombin by covalently binding to it, but this can result in toxicity and nonspecific binding. The development of reversible noncovalent DTIs, such as inogatran and melagatran, has resulted in safer, more specific and predictable anticoagulant treatment. Oral DTIs, such as ximelagatran, are set to provide a further breakthrough in the prophylaxis and treatment of thrombosis.