Association between apoptotis and CD4(+)/CD8(+) T-lymphocyte ratio in aseptic loosening after total hip replacement.

Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. While the osteolytic cascade initiated by cytokine release from macrophages has been studied extensively, the involvement of T-lymphocytes in this context is controversial and has been addressed by only a few authors. In a former study we detected that the quantity of T-lymphocytes may be influenced by apoptosis in patients with aseptic loosening. In this study we intended to find out more details about the apoptosis-induced shifting of the T-cell number. We focused our interest on the CD4(+) and CD8(+) T-cells and their relative ratio. Caspase-3 cleaved was evaluated immunohistochemically to detect apoptotic T-cells in capsules and interface membranes from patients with aseptic hip implant loosening and a varying degree of caspase-3 cleaved expression in CD4(+) and CD8(+) T-lymphocytes was detected. Moreover, a relationship between the intensity of the apoptotic reactions and the radiological extent of osteolysis was observed. The number of CD4(+) cells was decreased in the presence of strong apoptotic reactions, respectively extensive osteolysis, while CD8(+) cells were affected to a much lower degree. Thus, the CD4(+)/CD8(+) ratio changed from 1.0 in cases with only small areas of periprosthetic osteolysis and minimally intense apoptosis to 0.33 in cases with large areas of osteolysis. This may suggest a causal relationship between the apoptosis-induced shift in the CD4(+)/CD8(+) ratio and the osteolysis respectively aseptic loosening. It is possible that these findings may lead to a new understanding of particle-induced osteolysis.

Complication of a closed Colles-fracture: necrotising fasciitis with lethal outcome. A case report.

We report a case of a 77-year-old female patient who died 4 days after a closed colles-fracture of the right wrist because of secondary emerged necrotising fasciitis. At the time of visiting our emergency department, the patient reports about untypical pain and progressive swelling of the entire right arm 3 days following a fall onto the outstretched hand where she sustained a closed distal radius fracture. Within 6 h, the patient developed hypotension and fever leading to cardiac and respiratory failure. The emergent-induced diagnostic presented a severe septic situation in the laboratory examination of the blood samples, an apparent before unknown diabetes mellitus and an unknown bronchial carcinoma with part of post-stenosis pneumonia of the right lung. After initial CPR and stabilisation, the patient underwent an urgent and aggressive surgical debridement with fasciotomies of the muscle compartments of the entire right upper extremity. The microbiological investigation of the intraoperative taken specimens presented plentiful group-A-beta-haemolytic streptococcus. Despite a broad spectrum intravenous antibiotic therapy, intensive care support and a second look operation 12 h later with exarticulation of the right arm in the shoulder joint, the patient died of septic shock and multiorgan failure 34 h after admission.

The density of nociceptive SP- and CGRP-immunopositive nerve fibers in the dura mater lumbalis of rats is enhanced after laminectomy, even after application of autologous fat grafts.

A considerable number of patients complain about pain after lumbar surgery. The spinal dura mater has been debated as a possible source of this pain. However, there is no information if laminectomy influences the nociceptive sensory innervation of the dura. Therefore, we quantitatively evaluated the density of SP- and CGRP-immunopositive nerve fibers in the dura mater lumbalis in an animal model of laminectomy. Twelve adult Lewis rats underwent laminectomy, in six of them the exposed dura was covered by an autologous fat graft. Further six animals without surgical treatment served as controls. Six weeks after surgery, the animals were perfused and the lumbar dura was processed immunohistochemically for the detection of CGRP- and SP-containing nerve fibers. In controls, the peptidergic nerve fibers were found predominantly in the ventral but rarely in the dorsal dura mater lumbalis. After laminectomy, the density of SP- and CGRP-immunopositive neurons significantly increased in ventral as well as in dorsal parts of the dura. Axonal spines could be observed in some cases at the site of laminectomy. The application of autologous fat grafts failed to inhibit the significant increase in the density of peptidergic afferents. Thus, we have provided the first evidence that laminectomies induce an increase in the density of putative nociceptive SP- and CGRP-immunopositive neurons in the lumbar dura mater ascribable to an axonal sprouting of fine nerve fibers. This effect was not prevented by using autologous fat grafts. It is conceivable that the neuronal outgrowth of nociceptive afferents is a cause of low back pain observed after lumbar surgery.

Osseointegration of cementless implants with different bisphosphonate regimens.

Some evidence suggests a daily dose of bisphosphonates improves fixation of cementless metal implants by enhancing osseointegration. Because the necessity of daily administration may result in suboptimal adherence to therapy, single- dose administration is desirable. We examined whether a dose-equivalent single injection of the nitrogen-containing bisphosphonate ibandronate is as effective as a daily injection in improving the osseointegrated surface and enhancing periprosthetic bone mineralization (bone volume to tissue volume) of cementless metal implants. Uncoated titanium and hydroxyapatite-coated titanium implants were surgically inserted into the femoral medullary canal of 55 female Sprague Dawley rats. The animals were randomly assigned subcutaneous treatments with 25 microg/kg body weight ibandronate per day, a dose-equivalent single injection of 28 x 25 microg/kg body weight, or saline solution for control. Histomorphometric evaluation revealed an enhanced osseointegrated surface for hydroxyapatite-coated implants in both treatment groups, but only for daily injections for uncoated titanium implants. Bone volume to tissue volume was improved in both treatment groups. Our results suggest that an equivalent-dose single injection of ibandronate is as effective as a daily dose in improving osseointegration and stabilization of hydroxyapatite-coated titanium implants in this rat model.

Suppression of polyethylene particle-induced osteolysis by exogenous osteoprotegerin.

Alterations of the key regulators of osteoclastogenesis, receptor activator of NF-kappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) have been implicated in wear particle-induced osteolysis, the most common cause for implant failure in total joint replacements. This study investigated the effect of exogenous OPG on ultra-high-molecular-weight polyethylene (UHMWPE) particle-induced osteolysis. The murine calvarial osteolysis model was utilized in 28 C57BL/6J mice randomized to four groups. Group I underwent sham surgery only, group II received UHMWPE particles, and group III and IV particles and subcutaneous OPG starting from day 0 (group III) or day 5 (group IV) until sacrifice. After 2 weeks, calvaria were prepared for histology and histomorphometry. Bone resorption was measured within the midline suture using Giemsa staining and osteoclast numbers were determined using TRAP staining. UHMWPE particle implantation resulted in grossly pronounced osteoclastogenesis and bone resorption. Both immediate and delayed treatment with OPG counteracted these particle-induced effects significantly, suppressing osteoclast formation and bone resorption (p < 0.001 and p < 0.001, respectively). In conclusion, exogenous OPG markedly suppressed UHMWPE particle-induced osteolysis in a murine calvarial model. This important finding underscores the crucial significance of the OPG-RANKL-RANK signaling in wear particle-induced osteolysis. Exogenous OPG may prove an effective treatment modality for wear debris-mediated periprosthetic osteolysis after total joint arthroplasty.

Promotion of bone formation by simvastatin in polyethylene particle-induced osteolysis.

The effects of statins on bone formation in periprosthetic osteolysis have not been determined to date. We investigated the effect of the HMG-CoA reductase inhibitor simvastatin on osteoblastic bone formation under conditions of ultra-high molecular weight polyethylene (UHMWPE) particle-induced osteolysis. The murine calvarial osteolysis model was utilized in 21 C57BL/J6 mice randomized to three groups. Group I underwent sham surgery only, group II received UHMWPE particles, and group III, particles and simvastatin treatment. After 2 weeks, calvaria were processed for histomorphometry and stained with Giemsa dye. New bone formation was measured as osteoid tissue area within the midline suture. Bone thickness was quantified as indicator of net bone growth. Statistical analysis was performed using one-way ANOVA and a Student's t-test. New bone formation and bone thickness were significantly enhanced following simvastatin treatment. New bone formation was 0.008+/-0.008 mm2 in sham controls (group I), 0.015+/-0.012 mm2 after particle implantation without further intervention (group II), compared to 0.083+/-0.021 mm2 with particle implantation and simvastatin treatment (group III) (p=0.003). The bone thickness was 0.213+/-0.007 mm in group I, 0.183+/-0.005 mm in group II, and 0.238+/-0.009 mm in group III (p=0.00008). In conclusion, simvastatin treatment markedly promoted bone formation and net bone growth in UHMWPE particle-induced osteolysis in a murine calvarial model. These new findings indicate that simvastatin may have favorable osteoanabolic effects on wear debris-mediated osteolysis after total joint arthroplasty, involving local stimulation of osteoblastic bone formation.