High-dose methothrexate, a standard agent in the therapy protocols for osteosarcoma, has long been suspected to have a negative long-term effect on bone metabolism and bone mineral density, especially in children and young adults. Recent literature questioned this association as also the BMD of Ewing‘s sarcoma patients treated without methothrexate is known to be decreased. We therefore wanted to screen our patients treated for Ewing‘s sarcoma and osteosarcoma for osteopenia/osteoporosis-associated fractures. Between 1994 and 2008 107 patients below 50y of age were treated for bone malignancies including 51 Ewing’s sarcomas – 31 male and 20 female – with a mean age at diagnosis of 17y(±11SD) and 56 osteosarcomas – 36 male and 20 female – with a mean age of 23y(±12SD). We screened the patients‘ files for fractures after chemotherapy. We found five patients with not trauma-associated fractures – one Ewing‘s sarcoma(1/51;2%) and four osteosarcoma patients(4/56;7%). They presented one fracture of the proximal femur 107 months after tumour diagnosis, three fractures of the distal femur after 29, 51, and 72 months and two fractures of the proximal tibia after 29 and 32 months (one patient suffered from fractures affecting both – the distal femur and the proximal tibia). As presented in our case series fractures due to an osteoporotic process after chemotherapy for bone sarcomas are well known late effects. Although described in several studies therapeutic recommendations for pro-phylaxis are sparse. Furthermore the fact that fractures occurred in both types of sarcoma casts MTX as the main cause of chemotherapy-induced osteoporosis into doubt. Additionally we estimate a high number of unreported cases of premature osteoporosis because sarcoma patients are usually not tested for their BMD-levels. Therefore further studies using DEXA (dual-energy-x-ray-absorptiometry) to measure the patients BMDs after chemotherapy are needed.
Epitheloid haemangioendothelioma is a rare tumour of vascular origin. It is characterised by the appearance of epitheloid endothelial cells and occurs typically in soft-tissue, skin, and liver. Less frequently it is found in bone. The tumour is more often located in the long bones of the lower extremities, and the pelvis than in the upper extremities, vertebral column, and flat bones. The lesion nearly affects all age groups and there is a male predilection.
Epitheloid haemangioendothelioma of bone is a rare tumour and the diagnosis is quite difficult. Metastatic rate is about 20–30% and mortality about 10–20%. As presented in our cases bone involvement could either be attributed to primary haemangioendotheliomas of bone or to metastases of non-osseous forms. As in our cases it has been reported, that predicting prognosis is difcult, however nuclear atypia, mitotic activity, spindling of cells, and necrosis have been reported as negative prognostic factors.
Although fibrous dysplasia is a benign bone disease, in few cases patient are suffering from severe pain of the skeletal system. The aim of this study was to evaluate the current state regarding pain of patients with fibrous dysplasia treated at our hospital. We searched our digital database since 1990 for patients with fibrous dysplasia. Subsequent we verified the histological diagnosis by reviewing the final pathologic report. Additional we called the identified patients by phone to make an enquiry about their pain course and associated treatment. For rating pain intensity we used a numeric rating scale with a range within zero to ten. We identified 43 patients (21 male, 22 female) with an average age at initial diagnosis of 40 years (range 10 to 72years). The mean follow up was 6 years (range 1 to 23 years). Among these 43 patients we were able to contact 33 by phone. Initial diagnosis was made due to pain in 23 cases, nearly coequal by coincidental examination in 20 cases, for fracture in two cases and for local swelling and bone deformity each time in two cases. Thirty-six patients revealed monostotic and seven patients polyostotic involvement. The following locations were found: three times craniofacial, four times within the spine, eight times at the upper extremity, ten times in the pelvis and 31 times at the lower limb. Two patients were suffering additionally from Mazabraud Syndrome. Actual values at the numeric rating scale regarding pain ranged from 0 to 9 with a mean value of 1. Specific in the polyostotic group we found an average value of 3 and three of seven patients stated a value greater than 5 for persistent pain. Five patients with polyostotic involvement were treated with bisphosphonat for pain control with good response. It is remarkable that patients with polyostotic involvement have marked higher values for pain intensity at the numeric rating scale. So therefore we should have a closer look for potential reasons explaining that fact. In accordance with previous published studies we found that pain decreased by intermittent intravenous application of bisphosphonates.
The ability of hMSCs to differentiate into several mesenchymal cell lineages including the osteoblast lineage plays a key role in skeletogenesis and bone regeneration. Although the importance of physical factors in the development and maintenance of bone tissue has been recognized for many years and we previously demonstrated that mechanical strain constitutes an inherent stimulus for osteogenic differentiation of undifferentiated hMSCs, there is strong evidence to suggest that obesity is an independent factor in the risk of implant failure due to aseptic loosening or fracture after TJR. While mechanical complications and overload have been widely suggested, we hypothesized that the osteogenic mechanoresponse of hMSCs may be profoundly altered in obese patients. hMSCs were isolated from bone marrow of 10 donors (BMI ranging from 18.7 to 37.6 kg/m2). The individual response of unidfferentiated hMSCs to cyclic tensile strain (CTS) was determined in a two-armed study design (strained versus unstrained (CTR)) using a 4-point bending device, where strain was restricted to a maximum of 3,000 μstrain. Phenotypic effects were characterized by analyzing cell numbers, cell viability and ALP activity; mRNA levels of marker genes related to early osteogenic differentiation (RUNX2, ALPL, SPARC, SPP1), protein synthesis (COL1A1), and cell cycle (MKI67) were determined by real-time RT-PCR. Possible contributions to anthropomorphometric variables and individual triglycerides, cholesterin, glucose, leptin, adiponectin, resistin, and estradiol levels were evaluated by linear regression analysis. We found a significant up-regulation of the osteogenic marker genes due to CTS, including RUNX2 (1.9 fold), ALPL (2.4 fold), SPP1 (2.8 fold), and SPARC (4.1 fold), which was accompanied by an increase in cell-based ALP activity from 6.1 ± 1.2 μM/min/106 in CTR to 8.5 ± 1.7 μM/min/106 in CTS (plus 39.6 ± 9.8% SEM, P<
0.05). Cell density was significantly lower following CTS (minus 20.0 ± 4.7%, P<
0.05), which was also found for cell viability (XTT minus 17.8 ± 5.6%, P<
0.05). As a consequence, the phenotypic CTS response (ALP activity w/o normalization) ranged widely between donors (−30.8% to +60.1%) and was highly significant inverse correlated to donor’s BMI (r= −0.91, P<
0.0001). Additionally, leptin and estradiol levels determined within bone marrow plasma were significantly correlated with the phenotypic mechanoresponse (r=−0.71, P=0.028, and r=0.67; P=0.039; respectively). The findings demonstrate that the osteogenic mechanosensitivity of hMSCs is highly affected by physiological factors related to donor’s BMI. Such an upstream imprinting process within bone marrow may be an important area of further research, since obesity-linked problems constitute increasing concerns in orthopaedic surgery within the western world.
The induction of differentiation is a highly programmed lineage-specific process and several studies have provided great insight into the microenvironment affecting differentiation of multipotential hMSCs. In this regard, the importance of physical factors has been recognized for many years, but only little is known about its effects on undifferentiated hMSCs. The study aimed to determine the early osteogenic differentiation response to physiologically-based mechanical tensile strain with possible contributions to donor-specific physiological conditions. MSCs of ten donors were expanded under standard culture conditions, and the individual response to cyclic tensile strain (CTS) was determined in a two-armed study design (strained versus unstrained (CTR)). CTS was applied with a maximum of 3,000 μstrain. Genotypic characteristics (RUNX2, ALPL, SPARC, SPP1; COL1A1, MKI67, etc) as well as phenotypic effects (cell numbers, cell viability and ALP activity) were compared between CTR and CTS, and possible relations to donor-specific physiological characteristics including anthropomorphometric and biochemical variables were determined. We found a significant up-regulation of the osteogenic marker genes due to CTS, which was accompanied by an increase in cell-based ALP activity (plus 39.6 ± 9.8% SEM, P<
0.05). Cell density as well as XTT were significantly lower following CTS (minus 20.0 ± 4.7% and minus 17.8 ± 5.6%, respectively, P<
0.05). As a consequence, the ALP activity w/o normalization ranged widely from minus 30.8% to plus 60.1% between individual donors and was a function of donor’s BMI (r=−0.91, P<
0.0001), weight (r=−0.73, P=0.016), and age (r=−0.65, P=0.041). The findings demonstrate that
the application of CTS provides an inherent osteogenic differentiation stimulus for undifferentiated hMSCs in vitro, and the functional response of hMSCs to CTS was found to be highly related to donor’s BMI/fat mass, thus suggesting an upstream imprinting process of the hMSCs within bone marrow
Whereas thermography has already been used as an assessment of disease activity in some kinds of inflammatory arthritis, it is a new method for objektive pain evaluation in patients with joint prosthesis. To our knowledge, no study has tested the correlation between increase of temperature and anterior knee pain with total knee prosthesis yet. Thirteen patients were included in this study who suffered from anterior knee pain of the retinaculum patellae with total knee prosthesis. The patients were asked to walk 3 km before entering a room which was cooled down to 20 degrees Celsius. A black 1 cm times 4.5 cm square stripe was attached on the diameter of the patella and the patients rested for 20 minutes to cool down before thermographic fotos were taken from 90 degrees, 45 degrees, frontal medial and lateral. The evaluation of temperature difference of each side was performed by marking a 1cm times 2cm square field rectangular around the black stripe and comparing it with a reference point of the same size 3 cm distal of the field. The patients were compared with thirteen others, not suffering from anterior knee pain. Statistical analysis was performed using a t- test and a p value <
0.05 was considered to be significant. The temperature differences between the rectangular field and the reference point increased significantly on the medial (p= 0.00037) or lateral (p= 0.000002) pain side of the knee. The thirteen knees with knee pain had significantly higher temperature differences between medial and lateral temperature differences, than the knees without knee pain. We demonstrate a significant correlation between anterior knee pain and an increase of superficial skin temperature around the retinaculum patellae. To our knowledge, this is the first report of an objective assessment of pain of the retinaculum patellae with total knee prosthesis.
Aseptic loosening is the most frequent cause of implant failure in total hip arthroplasty (THA). Additionally, failure rate was still found by some authors to be increased in patients with osteonecrosis of the femoral head (ON-FH). It is well evidenced that low initial fixation and early migration precedes and predicts long-term failure rate of both, the acetabular and femoral component in THA. This independent, double-blind, randomized, controlled study was primarily designed to evaluate whether a single infusion of 4 mg of zoledronic acid is sufficient to prevent implant migration determined by the EBRA-digital method. Fifty patients were consecutively enrolled between July 2002 and March 2005 to receive either 4 mg zoledronic acid (ZOL) or saline solution (CTR) one day after THA (Zweymüller system, cementless). Plain radiographs were performed postoperatively and all parameters were evaluated at each follow-up meeting interval at 7 weeks, 6 months, 1 year, and yearly thereafter during a median follow-up period of 2.8 years (2 years minimum). In CTR, subsidence increased up to −1.2 mm ± 0.6 SD at 2 years in CTR (P<
0.001). Less, but a near curve-linear shaped migration pattern was found for the ace-tabular component, with an averaged medialization of 0.6 mm ± 1.0 SD and a cranialization of 0.6 mm ± 0.8 SD at 2 years (P<
0.05, Friedman ANOVA) at 2 years. In ZOL, a significant reduction in bone turnover markers was accompanied by a complete prevention of cup migration in both, the transverse and vertical direction (P<
0.05, ANOVA), while there was only a trend to a decreased subsidence in stems. The study provides useful data which are promising and support the suggestions that bisphosphonates may offer significant opportunities to reduce and prevent implant migration of THA, thus increasing long-term durability of THA especially in selected high-risk patients.
In several countries fine needle aspiration (FNA) biopsy of soft tissue tumours is regarded as a standard procedure. However, various problems using FNA compared to core needle biopsy have been reported. Less cell amount, blood and other non tumour tissue aspirated and cells torn out of their environment lead to problems in histological diagnose. The aim of this study was to measure the number of cells harvested by two new needle systems (THYROSAMPLER®) in comparison with the conventional fine needle system (C-FNA). The innovation of the new system is aeration after aspiration by a valve, so that undesired aspiration of blood, debris, and cells from outside the tumour during withdrawal of the needle is minimized. In a blinded setting, 45 punctures from fresh pig thyroid glands were made and analysed – 15 for each needle (C-FNA, single-needle with air valve T-ONE and multi needle system with air valve T-THREE). The aspirated cell material was evacuated into 10ml cell-culture liquid and calculated according to the manufacturer’s recommendations for the CASY cell counter (CASY® technology, Reutlingen). With each system, 15 punctures each were aspirated and the cells counted. With the T-ONE System the amount of vital cells was 688%, the amount of total cells 521% higher then using the C-FNA system. With the T-THREE System the amount of vital cells was 901%, the amount of total cells 798% higher then using the C-FNA system. The mean difference between C-FNA and T-ONE was significant regarding total number of cells (p=0.030) as well as number of vital cells (p=0.032). The needle systems with the air-valve led to a significantly higher cell amount in needle aspiration biopsy. According to the requirement of cytological diagnosis of soft tissue sarcomas more cell volume could be harvested, which is a well-defined benefit.
Silver is a long known local antimicrobial agent. The use of silver coated prostheses is a valuable option in some cases. Yet there are patients for whom the permanent implantation of large amounts of silver does not seem to be the perfect solution.
From 04/2004 to 01/2006 seventeen patients of slightly less impaired disposition were treated by a comparable two-stage procedure using silver-augmented cemented spacer prostheses or cement fills. Patients are closely observed regarding toxic side effects. Concentration of silver in blood and puncture samples are measured using an argon plasma mass spectrometer.
In the second group one patient of seventeen actually shows a persisting infection, but cannot be matched properly as he primarily suffered from a long-term infected knee arthrodesis. Silver concentrations ranged from a maximum of 1010 to 243 μg/kg (ppb) to a minimum of 84 to 304 μg/kg (ppb) with silver coating, and a maximum of 380 to 22,9 μg/kg (ppb) to a minimum of 76 to 5,02 μg/kg (ppb) with silver spacers. There are large individual differences in both groups. We found no signs of argyrosis or recently developed neurological deficits.
We conducted a prospective clinical study to determine the influence of personality traits on the subjective outcome of operative hallux valgus correction. The surgical technique used in all patients was the chevron osteotomy. Preoperatively, personality traits were evaluated by means of the Freiburg Personality Inventory (FPI-R). 42 patients (38 female, 4 male) could be enrolled in the analysis. The mean age of the patients at the time of operation was 48.3 years (20 to 70). Three months postoperatively 37 patients were satisfied, and 5 patients were not satisfied with the operative procedure. The comparison of the two groups (satisfied and dissatisfied patients) revealed statistically significant differences in the personality traits aggressiveness (p=0.003), extraversion (p=0.001) and health worries (p=0.04). The postoperative hallux valgus angles were 12.2° ± 7.8 and 13.4° ± 8.3 (p=0.74), and the first-second intermetatarsal angles were 7.4° ± 2.5 and 7.6° ± 4 (p=0.89) in the two groups. The results of the current study suggest that the patient’s subjective result after the operative hallux valgus correction is influenced by some individual personality profiles.
A prospective single-cohort study was designed to include 20 patients with enchondromas but was stopped because of poor early results. Four patients with an enchondroma, three in the proximal humerus and one in the distal femur, were treated by curettage and filling of the defect with Norian SRS cement. Clinical and radiological follow-up including CT and MRI was carried out for 18 months. All three patients with lesions in the proximal humerus had severe pain and limited movement of the shoulder. The radiological and CT appearances of the cement were unchanged at follow-up. There were characteristic appearances of synovitis and periosteitis on MRI in two patients. Since the cement induces a soft-tissue reaction the bony cavity should be sealed with the curetted and burred bone after curettage and introduction of Norian cement, especially in sites where a tourniquet cannot be applied.
We have investigated in a prospective, randomised placebo-controlled study the effect of high-dose aprotinin on blood loss in patients admitted for major surgery (revision arthroplasty of the hip or knee, or for resection of a soft-tissue sarcoma). The mean intraoperative blood loss was reduced from 1957 ml in the control group to 736 ml in the aprotinin group (p = 0.002). The mean requirement for intraoperative homologous blood transfusion in the aprotinin group was 1.4 units (95% CI 0.2 to 2.7) and 3.1 units (95% CI 1.7 to 4.6) in the control group (p = 0.033). The mean length of hospital stay was reduced from 27.8 days in the control group to 17.6 days in the aprotinin group which was not statistically significant. The intraoperative use of aprotinin in major orthopaedic operations significantly reduced blood loss and the required amount of packed cells. It may result in a decrease in the length of hospital stay and costs.
Primary malignant tumours should be resected with wide margins. This may be difficult to apply to lesions of the spine. We undertook total vertebrectomy on seven patients, four males and three females with a mean age at operation of 26.5 years (6.3 to 45.8). The mean follow-up was 52.3 months. Histological examination revealed a Ewing’s sarcoma in two patients and osteosarcoma, leiomyosarcoma, spindle-cell sarcoma, chondrosarcoma and malignant schwannoma in one each. In five patients, histological examination showed that a wide resection had been achieved. At follow-up there was no infection and a permanent neurological deficit was only seen in those patients in whom the surgical procedure had required resection of nerve roots. Despite the high demands placed on the surgeon and anaesthetist and the length of postoperative care we consider total vertebrectomy to be an appropriate procedure for the operative treatment of primary malignant lesions of the spine.
In 251 patients over a period of 15 years an uncemented Kotz modular femoral and tibial reconstruction mega prosthesis was implanted after resection of a malignant tumour of the lower limb. Twenty-one patients (8.4%) underwent revision for aseptic loosening, again using an uncemented prosthesis, and five of these required a further revision procedure. The median follow-up time from the first revision was 60 months (11 to 168) and after a second revision, 33 months (2 to 50). The probability of a patient avoiding aseptic loosening for ten years was 96% for a proximal femoral, 76% for a distal femoral and 85% for a proximal tibial implant. At the time of follow-up all radiographs were assessed according to the International Symposium of Limb Salvage criteria. The first radiological signs of aseptic loosening were always seen at the most proximal or distal part of the anchorage stem at a mean of 12 months (4 to 23) after the first implantation. Using the Musculoskeletal Tumor Society score for evaluation, the clinical results showed a mean of 88% of normal function.
We treated 106 patients with a peripheral osteoid osteoma by conventional surgical methods; 81 had curettage and 25 The rate of local recurrence after curettage was 12% and after We compared our findings with those reported in the literature after minimally invasive treatment and concluded that curettage can be regarded as the treatment of choice in patients in whom minimally invasive methods do not offer any advantage, for example, for subperiosteal tumours which are readily accessible, or when the diagnosis is unclear and further histological analysis is required.