Falk Mittag

Laminin-5 and type I collagen promote adhesion and osteogenic differentiation of animal serum-free expanded human mesenchymal stromal cells

Mesenchymal stromal cells (MSC) are differentiation competent cells and may generate, among others, mature osteoblasts or chondrocytes in vitro and in vivo. Laminin-5 and type I collagen are important components of the extracellular matrix. They are involved in a variety of cellular and extracellular activities including cell attachment and osteogenic differentiation of MSC. MSC were isolated and expanded using media conforming good medical practice (GMP)-regulations for medical products. Cells were characterized according to the defined minimal criteria for multipotent MSC. MTT- and BrdU-assays were performed to evaluate protein-dependent (laminin-5, laminin-1, type I collagen) metabolic activity and proliferation of MSC. MSC-attachment assays were performed using protein-coated culture plates. Osteogenic differentiation of MSC was measured by protein-dependant mineralization and expression of osteogenic marker genes (osteopontin, alkaline phophatase, Runx2) after three, seven and 28 days of differentiation. Marker genes were identified using quantitative reverse-transcription polymerase chain reaction. Expansion of MSC in GMP-conforming media yielded vital cells meeting all minimal criteria for MSC. Attachment assay revealed a favorable binding of MSC to laminin-5 and type I collagen at a protein concentration of 1–5 fmol/µL. Compared to plastic, osteogenic differentiation was significantly increased by laminin-5 after 28 days of culture (P<0.04). No significant differences in gene expression patterns were observed. We conclude that laminin-5 and type I collagen promote attachment, but laminin-1 and laminin-5 promote osteogenic differentiation of MSC. This may influence future clinical applications.

The development of whole blood titanium levels after instrumented spinal fusion – Is there a correlation between the number of fused segments and titanium levels?

BackgroundMost modern spinal implants contain titanium and remain in the patient’s body permanently. Local and systemic effects such as tissue necrosis, osteolysis and malignant cell transformation caused by implants have been described. Increasing tissue concentration and whole blood levels of ions are necessary before a disease caused by a contaminant develops. The aim of the present study was the measurement of whole blood titanium levels and the evaluation of a possible correlation between these changes and the number of fused segments.MethodsA prospective study was designed to determine changes in whole blood titanium levels after spinal fusion and to analyze the correlation to the number of pedicle screws, cross connectors and interbody devices implanted.Blood samples were taken preoperatively in group I (n = 15), on the first, second and 10th day postoperatively, as well as 3 and 12 months after surgery.Group II (n = 16) served as a control group of volunteers who did not have any metal implants in the body. Blood samples were taken once in this group.The number of screw-rod-connections and the length of the spinal fusion were determined using radiographic pictures. This study was checked and approved by the ethical committee of the University of Tuebingen.ResultsThe mean age in group I was 47 ± 22 years (range 16 - 85 years). There were three male (20%) and twelve female (80%) patients. The median number of fused segments was 5 (range 1 to 11 segments).No statistically significant increase in the titanium level was seen 12 months after surgery (mean difference: -7.2 μg/l, 95% CI: -26.9 to 12.5 μg/l, p = 0.446). By observing the individual titanium levels, 4 out of 15 patients demonstrated an increase in titanium levels 12 months after surgery.No statistically significant correlation between fused segments (r = -0.188, p = 0.503) length of instrumentation (r = -0.329, p = 0.231), number of interbody devices (r = -0.202, p = 0.291) and increase of titanium levels over the observation period was seen.ConclusionsInstrumented spinal fusion does not lead to a statistically significant increase in whole blood titanium levels. There seems to be no correlation between the number of pedicle screws, cross connectors and interbody devices implanted and the increase of serum titanium levels.

Aneurysm of the Femoral Artery Caused by Aseptic Loosening and Migration of a Burch-Schneider Cage

Reinforcement cages are widely used for the treatment of large acetabular defects. We report a rare case of an aseptic loosened Burch-Schneider cage causing an aneurysm of the femoral artery and life-threatening bleeding, large hematoma, and signs of hyperfibrinolysis. After performing several diagnostic procedures, the patient underwent extensive interdisciplinary revision surgery. Initial unspecific symptoms such as pain, swelling, and hematoma of the leg after acetabular reconstructions using reinforcement cages should alert clinicians to consider the possibility of vascular complications.

Radiographic signs for detection of femoroacetabular impingement and hip dysplasia should be carefully used in patients with osteoarthritis of the hip

BackgroundDuring the last years, terms like acetabular retroversion, excessive overcoverage, and abnormal head-neck-junction with the so called “pistol-grip-deformity” has been added to the classical description of hip dysplasia. These anatomical changes could lead to a femoroacetabular impingement (FAI). Both kinds of FAI has been indentified as a main reason for hip pain and progressive degenerative changes leading to early osteoarthritis of the hip. A lot of radiographic criteria on pelvic views have been established to detect classical dysplasia and FAI. The present study was initiated to assess the hypothesis that age and severity of osteoarthritis affect measurements of different radiographic parameters.MethodsThe pelvic radiographs of 1614 patients were measured for head-ratio, CE-angle, roof obliquity, extrusion-index, depth-to-width ratio, CCD-angle, sharp’s angle. To evaluate the severity of osteoarthritis of the hip the classification by Kellgren and Lawrence was used. Associations between age and radiographic parameters or severity of osteoarthritis were assessed by Spearman’s (ρ) or Kendall’s (r) rank correlation coefficient, respectively.Results366 (22.7%) patients presented no sign of osteoarthritis, 367 (22.7%) patients presented I° osteoarthritis, 460 (28.5%) patients presented II° osteoarthritis, 307 (19%) III° osteoarthritis and 114 (7.1%) IV° osteoarthritis of the hip. The mean head-ratio of all patients was 1.13 ± 0.26 (0.76 – 2.40), the mean CE-angle 40.05° ± 10.13° (0° - 70°), the mean roof obliquity was 35.27°± 4.96° (10° – 55°), the mean extrusion-index was 12.99 ± 9.21 (6.20 – 95.2), the mean depth-to-width ratio was 59.30 ± 8.90 (6.30 – 100), the mean CCD-angle was 127.68° ± 7.22° (123° – 162°) and the mean sharp’s angle was 9.75° ± 5.40° (1° - 34°) There was a weak association between age and the severity of osteoarthritis of the hips (left: r = 0.291; right: r = 0.275; both P < 0.001) with higher osteoarthritis levels observable for elderly patients).ConclusionSeverity of osteoarthritis has a negative impact on measurements of different radiographic parameters. Therefore - in our opinion - epidemiological studies on prearthrotic deformities should only be performed in healthy adults with no signs of osteoarthritic changes.

Cytotoxic effect and tissue penetration of phenol for adjuvant treatment of giant cell tumours

Local adjuvant treatment of giant cell tumours (GCTs) of the bone with phenol has led to a significant reduction in recurrence rates. In the current study, the optimal phenol concentration and duration of intralesional exposure were evaluated. Specimens of GCTs were exposed to various concentrations of phenol solution (6, 60 and 80%) for either 1 or 3 min. Following embedding in glutaraldehyde, the tumour cell layers were examined by transmission electron microscopy. Destroyed cell organelles indicated the penetration depth as a sign of denaturation. Incubation of GCT specimens with 6% phenol solution for 3 min resulted in the most tissue damage and the deepest tissue penetration of ∼200 μm. Incubation with 60 and 80% phenol solution reached a penetration depth of only ∼100 μm. Phenol instillation may be used for the treatment of small scattered cellular debris following intralesional curettage; however, it is not suitable for treatment of remaining solid tumour tissue of GCT. The use of high phenol concentrations has no benefit and increases the risk of local or systemic intoxication.

Predictive Value of Preoperative Digital Templating in THA Depends on the Surgical Experience of the Performing Physician

Digital preoperative templating is increasingly used to predict the correct component size in total hip arthroplasty (THA). Experienced surgeons could avoid the new technique and rely on a digital template done by a younger colleague. We compared the accuracy of preoperative templating between orthopedic residents (group A) and an experienced orthopedic surgeon (group B). In 106 cases, the software-predicted component sizes of both groups were compared with component sizes placed surgically. An accurate prediction of the acetabular component was achieved in 63% of cases in group A compared with 88% of cases in group B (P=.001). Concerning the femoral component, accurate prediction was achieved in 89% in group A and 97% in group B (P=.021). If performed by an experienced orthopedic surgeon, digital templating is an accurate method to predict the prosthetic component size in THA.

The influence of ibandronate treatment on bone density and biochemical bone markers in patients with osteogenesis imperfecta

Osteogenesis imperfecta (OI) is characterized by different signs including increased bone fragility, short stature, blue sclera, abnormal tooth growth and often secondary immobility. No curative therapy has been found for this rare disease up to now, and different pharmacological substances have been tried as treatment for severe forms of OI. Promising results were seen with intravenous bisphosphonates in the treatment of patients with OI. The aim of present study was to show the effect of intravenous ibandronate therapy on bone density and bone metabolism markers. We analyzed the data of 27 patients with the diagnosis of OI who were treated off-label with intravenous ibandronate. Ibandronate was administered by intravenous infusion every three months at a dosage of 0.3–2 mg. Bone turnover markers and bone density were measured before starting therapy and every three months during treatment. Bone density was measured by using an ultrasound imaging system providing an accurate image of the calcaneus and by evaluating broadband ultrasound attenuation (BUA). Twenty-seven patients were treated with intravenous ibandronate during the observation period. 18 were female. The mean age of all patients was 23.9 years ± 19.6 (range 4–63). Seventeen patients were categorized to have OI Type I, 5 patients to have OI Type III and 5 patients to have OI Type IV. There was a statistically significant decrease in total alkaline phosphatase (P<0.0001). We detected also a statistically significant decrease in the ratio urinary deoxypyridinoline/urinary creatinine (P=0.0048) and the ratio urinary pyridinoline/urinary creatinine (P<0.0001) respectively. There was also a statistically significant increase in serum magnesium (P=0.034) and BUA (P=0.0071). No statistically significant changes were seen for total serum calcium (P=0.16), the ratio of urine calcium/urine creatinine (P=0.29), alkaline phosphatase (isoform bone) (P=0.3), procollagen-I-peptide (P=0.5), osteocalcin (P=0.9), serum phosphatase (P=0.71), parathormone (P=0.11) and the ratio urine phosphatase/urine creatinine (P=0.58) Therapy with ibandronate in patients with OI leads to a normalisation of bone turnover markers and increasing bone density. Therefore serum alkaline phosphatase and bone density are possible parameters to monitor bisphosphonate treatment in patients with OI.

Fusion Following Failed Total Ankle Replacement

Although mid- to long-term results after total ankle replacement have improved because of available second- and third-generation devices, failure of total ankle replacement is still more common compared with total hip replacement and total knee replacement. The portfolio of available total ankle replacement revision component options is small. Furthermore, the bone stock of the tibiotalar region is scarce making it difficult and in some situations impossible to perform revision total ankle replacement. In these cases tibiotalar and tibiotalocalcaneal fusions are valuable options. This article describes which surgical procedures should be performed depending on the initial situation and gives detailed advice on surgical technique, postoperative care, and clinical results.

Giant Gouty Tophi of the Hand and Wrist

Gout is an inflammatory-rheumatic disease characterized by an elevated serum urate concentration and recurrent flares, including painful, hot, red, and swollen joints and surrounding tissue. Untreated gout often develops into a chronic disease with tophi and destruction of joint surfaces. Giant tophi are often resistant to medication and change in diet.This article presents a case of a 44-year-old man with giant gouty tophi at his hand and wrist. The last acute gout flare in his left wrist was approximately 3 years prior. For 2 years he had refused adequate nutrition, such as a low-purine diet, and had refused to take any preventive medication. Blood urate level was elevated to 8.7 mg/dL (normal range, 3.4-7.0 mg/dL). In time, the tophi led to a massive limitation of motion and use of especially the left wrist and thumb. Under the condition that the patient changed his diet and took the medication for his underlying disease, we surgically removed the almost skin-perforating tophi. Surgical debulking significantly improved joint function and cosmetic appearance.The best treatment for gouty tophi is prevention by ensuring adequate nutrition, treating the underlying causes, and taking effective medication. In the case of massive limitation of joint motion, skin breakdown with risk of infection, and compression of neurovascular structures, surgical debulking of the tophi should be considered.

A classification-system improves the intra- and interobserver reliability of radiographic diagnosis of “pistol-grip-deformity”

Early detection of pistol-grip-deformity may be beneficial in optimising the outcome and the cost effectiveness of surgery. It is important to identify reliable radiographic parameters in assessing femoro-acetabular impingement (FAI) to develop a treatment algorithm. Radiographs of 47 patients ranging from “pistol grip deformity” to a normal head-neck-junction were measured for alpha angle and head ratio, and then classified by two different observers. The Bland-Altman plot was used for inter- and intraobserver agreement of alpha angle and head ratio. Inter- and intraobserver agreement for classification of “pistol grip deformity” was determined using weighted Cohens kappa coefficient. Observer I achieved a kappa coefficient of 0.97. Observer II achieved a kappa coefficient of 0.92. An interobserver kappa coefficient between 0.87 and 0.92 was achieved by using a classification system. By testing for interobserver agreement, a bias of –0.004 with an upper limit of 0.461 and a lower limit of –0.47 was seen for the ratio and a bias of –3.7 with an upper limit of 17.2 and a lower limit of –24.6 for the alpha angle. Therefore, poor results were seen for intra- and interobserver reliability by using only a single plane for classification of “pistol grip deformity”. The strength of agreement could be improved by using a classification system (based on two planes).