Hip abductor tendon pathology visualized by 1.5 versus 3. 0 Tesla MRIs.

INTRODUCTION: Hip abductor tendinopathies are becoming increasingly recognized as clinically relevant disorders. However, knowledge about prevalence of abductor tendinopathies and associated disorders of adjacent hip articular and periarticular structures is limited. In this context, the relative diagnostic value of 1.5-T vs. 3.0-T MRI magnets has not been studied yet. MATERIALS AND METHODS: Pelvic MRI scans of 1000 hips from 500 consecutive unselected patients (341 in 3.0-T/159 in 1.5-T magnets, with standardized scanning protocols over the entire study period) were analysed for the detection of abductor tendinosis, calcifying tendinitis, partial or full-thickness tears of the M. gluteus medius (GMed) and/or -minimus (GMin) and trochanteric bursitis (TB). The occurrence of these lesions was correlated to the presence of muscle atrophy (MA) of GMed/GMin, hip joint effusion (JE) and osteoarthritis (OA). RESULTS: Peritrochanteric lesions were observed with a prevalence of 31.4% of all patients (22.3% of all hips). TB occurred almost exclusively in the presence of GMed/GMin tendinopathies. Compared to overall prevalence, patients with MA displayed lesions of GMed/GMin or TB in 70%, patients, with OA in 30% and with JE in 23%. These lesions occurred significantly more often ipsilateral to MA and OA than contralateral (MA: 76.8% vs. 23.2%, p < 0.001; OA: 64.4% vs. 35.6%, p = 0.03; JE: 62.7% vs. 37.3%, p = 0.08). Significantly more tendon lesions, in particular specific radiological diagnoses like partial/full-thickness tears, were detected by 3.0-T MRI than by 1.5 T (p = 0.019). CONCLUSIONS: Peritrochanteric lesions are a prevalent pathology that should specifically be looked for, preferably by 3.0-T MRI, independent of concomitant hip joint pathology.

Symptomatic Os VesalianumA Case Report and Review of the Literature.

Os vesalianum is a rare accessory bone located proximal to the base of the fifth metatarsal in the peroneus brevis tendon. It is a radiographic diagnosis and mostly an asymptomatic incidental finding with a reported prevalence of 0.1% to 0.9%. Only 11 symptomatic cases have been described in the literature. Surgical therapy has been reported with good outcome in adults, whereas recurrence may follow excision during skeletal growth. We report a case of a 19-year-old girl with chronic weightbearing pain proximal to the base of the fifth metatarsal of her left foot. She first experienced exacerbated pain on increased loading when she started professional training as a shop assistant. Because several months of nonsurgical therapy failed, the decision was made to surgically excise the accessory bone from the peroneus brevis tendon via a longitudinal incision and a simple tendon-to-tendon reconstruction. Postoperative treatment consisted of using a walker to avoid weightbearing for 6 weeks, followed by a gradual return to full weightbearing as tolerated. At final follow-up, the patient was fully asymptomatic and was able to return to work. Citing this case, this article discusses differential diagnoses and treatment options for os vesalianum.

Deficiency of Thrombospondin-4 in Mice Does Not Affect Skeletal Growth or Bone Mass Acquisition, but Causes a Transient Reduction of Articular Cartilage Thickness.

Although articular cartilage degeneration represents a major public health problem, the underlying molecular mechanisms are still poorly characterized. We have previously utilized genome-wide expression analysis to identify specific markers of porcine articular cartilage, one of them being Thrombospondin-4 (Thbs4). In the present study we analyzed Thbs4 expression in mice, thereby confirming its predominant expression in articular cartilage, but also identifying expression in other tissues, including bone. To study the role of Thbs4 in skeletal development and integrity we took advantage of a Thbs4-deficient mouse model that was analyzed by undecalcified bone histology. We found that Thbs4-deficient mice do not display phenotypic differences towards wildtype littermates in terms of skeletal growth or bone mass acquisition. Since Thbs4 has previously been found over-expressed in bones of Phex-deficient Hyp mice, we additionally generated Thbs4-deficient Hyp mice, but failed to detect phenotypic differences towards Hyp littermates. With respect to articular cartilage we found that Thbs4-deficient mice display transient thinning of articular cartilage, suggesting a protective role of Thbs4 for joint integrity. Gene expression analysis using porcine primary cells revealed that Thbs4 is not expressed by synovial fibroblasts and that it represents the only member of the Thbs gene family with specific expression in articular, but not in growth plate chondrocytes. In an attempt to identify specific molecular effects of Thbs4 we treated porcine articular chondrocytes with human THBS4 in the absence or presence of conditioned medium from porcine synovial fibroblasts. Here we did not observe a significant influence of THBS4 on proliferation, metabolic activity, apoptosis or gene expression, suggesting that it does not act as a signaling molecule. Taken together, our data demonstrate that Thbs4 is highly expressed in articular chondrocytes, where its presence in the extracellular matrix is required for articular cartilage integrity.

Ceramic femoral component fracture in total knee arthroplasty: an analysis using fractography, fourier-transform infrared microscopy, contact radiography and histology.

Ceramic components in total knee arthroplasty (TKA) are evolving. We analyze the first case of BIOLOX delta ceramic femoral component fracture. A longitudinal midline fracture in the patellar groove was present, with an intact cement mantle and no bony defects. Fractographic analysis with laser scanning microscopy and white light interferometry showed no evidence of arrest lines, hackles, wake hackles, material flaws, fatigue or crack propagation. Analysis of periprosthetic tissues with Fourier-transform infrared (FT-IR) microscopy, contact radiography, histology, and subsequent digestion and high-speed centrifugation did not show ceramic debris. A macrophage-dominated response was present around polyethylene debris. We conclude that ceramic femoral component failure in this case was related to a traumatic event. Further research is needed to determine the suitability of ceramic components in TKA.

Structural brain changes in chronic pain reflect probably neither damage nor atrophy.

Chronic pain appears to be associated with brain gray matter reduction in areas ascribable to the transmission of pain. The morphological processes underlying these structural changes, probably following functional reorganisation and central plasticity in the brain, remain unclear. The pain in hip osteoarthritis is one of the few chronic pain syndromes which are principally curable. We investigated 20 patients with chronic pain due to unilateral coxarthrosis (mean age 63.25±9.46 (SD) years, 10 female) before hip joint endoprosthetic surgery (pain state) and monitored brain structural changes up to 1 year after surgery: 6-8 weeks, 12-18 weeks and 10-14 month when completely pain free. Patients with chronic pain due to unilateral coxarthrosis had significantly less gray matter compared to controls in the anterior cingulate cortex (ACC), insular cortex and operculum, dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex. These regions function as multi-integrative structures during the experience and the anticipation of pain. When the patients were pain free after recovery from endoprosthetic surgery, a gray matter increase in nearly the same areas was found. We also found a progressive increase of brain gray matter in the premotor cortex and the supplementary motor area (SMA). We conclude that gray matter abnormalities in chronic pain are not the cause, but secondary to the disease and are at least in part due to changes in motor function and bodily integration.

Human apolipoprotein E isoforms differentially affect bone mass and turnover in vivo.

The primary role of apolipoprotein E (apoE) is to mediate the cellular uptake of lipoproteins. However, a new role for apoE as a regulator of bone metabolism in mice has recently been established. In contrast to mice, the human APOE gene is characterized by three common isoforms APOE ε2, ε3, and ε4 that result in different metabolic properties of the apoE isoforms, but it remains controversial whether the APOE polymorphism influences bone traits in humans. To clarify this, we investigated bone phenotypes of apoE knock-in (k.i.) mice, which express one human isoform each (apoE2 k.i., apoE3 k.i., apoE4 k.i.) in place of the mouse apoE. Analysis of 12-week-old female k.i. mice revealed increased levels of biochemical bone formation and resorption markers in apoE2 k.i. animals as compared to apoE3 k.i. and apoE4 k.i., with a reduced osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) ratio in apoE2 k.i., indicating increased turnover with prevailing resorption in apoE2 k.i. Accordingly, histomorphometric and micro-computed tomography (µCT) analyses demonstrated significantly lower trabecular bone mass in apoE2 than in apoE3 and apoE4 k.i. animals, which was reflected by a significant reduction of lumbar vertebrae maximum force resistance. Unlike trabecular bone, femoral cortical thickness, and stability was not differentially affected by the apoE isoforms. To extend these observations to the human situation, plasma from middle-aged healthy men homozygous for ε2/ε2, ε3/ε3, and ε4/ε4 (n = 21, n = 80, n = 55, respectively) was analyzed with regard to bone turnover markers. In analogy to apoE2 k.i. mice, a lower OPG/RANKL ratio was observed in the serum of ε2/ε2 carriers as compared to ε3/ε3 and ε4/ε4 individuals (p = 0.02 for ε2/ε2 versus ε4/ε4). In conclusion, the current data strongly underline the general importance of apoE as a regulator of bone metabolism and identifies the APOE ε2 allele as a potential genetic risk factor for low trabecular bone mass and vertebral fractures in humans.

Modulation of bovine chondrocyte metabolism by free periosteal grafts in vitro.

PURPOSE: Autologous chondrocyte transplantation (ACT) is an established method in cartilage repair. Although long-term results show durable repair of isolated cartilage defects, some problems still remain. Since hypertrophy of the transplanted periosteum is a common problem, alternatives for periosteum are in demand. Periosteal grafts have been reported to stimulate neochondrogenesis via paracrine effects. The objective of this study was to evaluate the modulation of chondrocyte metabolism by periosteal grafts in vitro. METHODS: Periosteal explants and articular chondrocytes obtained from slaughtered adult cattle were co-cultured in a newly established perfusion system. The experimental groups were: 1. monocultured chondrocytes; 2. chondrocytes cultured with synovial supernatants; 3. chondrocytes cultured with periosteal supernatants; 4. chondrocytes co-cultured with periosteal explants. RESULTS: Chondrocyte proliferation, evaluated by measuring total DNA content, was prolongated by periosteal and synovial explants. Immunocytochemical staining of collagen type II was stronger in monoculture than in co-culture. Protein biosynthetic activity estimated by [³H]-proline incorporation, as well as extracellular matrix deposition for collagen type II, were reduced by periosteal and synovial explants. Additionally, co-culturing led to a decrease in aggrecan synthesis and release. The inhibiting effects were significantly stronger when cellular chondrocyte-periosteal cross-talk was made possible via paracrine effects. CONCLUSIONS: The results of our study suggest a catabolic effect of periosteal explants on isolated chondrocytes in vitro. Further investigations are necessary whether periosteum in ACT is dispensable.

Short-term activation of liver X receptors inhibits osteoblasts but long-term activation does not have an impact on murine bone in vivo.

Liver X receptors (LXRs) are nuclear receptors that play a crucial role in the transcriptional control of lipid metabolism. Pharmacological LXR activation is an attractive concept for the treatment of atherosclerosis. Genetic LXR deficiency in mice has been shown to have an effect on bone turnover and structure and LXR activation is known to influence the osteogenic differentiation of bone marrow stromal cells. Therefore, therapeutic pharmacological LXR activation may have relevant effects on bone. Here, using two synthetic LXR ligands, T0901317 and GW3965, we investigated the effect of LXR activation on murine osteoblasts and the influence of long-term LXR activation on bone in vivo in mice. Short term (48 h) in vitro treatment of primary murine osteoblasts with T0901317 resulted in a dose-dependent decrease of osteocalcin and alkaline phosphatase mRNA and protein. In vivo, a 6-day treatment of C57BL/6J mice with T0901317 led to a 40% reduction of serum osteocalcin concentrations. Long-term (12-week) oral administration of T0901317 or GW3965 influenced the expression of established LXR target genes in liver and intestine, but did not alter trabecular and cortical bone structure or bone turnover as determined by total skeleton radiography, histomorphometric analysis of lumbar vertebral trabecular bone, micro CT analysis of femur cortical bone and biochemical determination of bone formation and resorption markers. We conclude that short-term pharmacological LXR activation has the potential to profoundly influence osteoblast function, but that long-term LXR activation in vivo has no adverse effects on the murine skeleton.

Long-term results of the thrust plate prosthesis in patients with rheumatoid arthritis: a minimum 10-year follow-up.

BACKGROUND: The thrust plate prosthesis (TPP) is a hip prosthesis with metaphyseal fixation to the femur. Because the bone quality is reduced in patients with rheumatoid arthritis, this kind of fixation may have a higher failure rate than conventional stemmed endoprostheses in these patients. The aim of this investigation was to analyze the long-term results obtained with the TPP in patients with rheumatoid arthritis. METHODS: The survival of 51 implants in 46 patients with rheumatoid arthritis was analyzed. Clinical (Harris hip score) and radiological examinations were carried out on 47 of the 51 TPPs, with a post implantation follow-up period of at least 10 years. The Kaplan-Meier method was used to estimate the survival rates of the TPPs, with surgical revision due to the femoral implant as the endpoint of the investigation. RESULTS: The Harris hip score increased from 42.4 ± 6.5 points preoperatively to 86.6 ± 10.1 points at follow-up. The failure rate was 23% (6 aseptic and 5 septic loosening). The total rate of revision amounted to 36.2% (17/47 TPPs): six aseptic loosening of TPPs, five septic loosening of TPPs, four aseptic loosening of the acetabular component, one removal of the fishplate of a TPP, and one femoral fracture. Additionally one TPP showed radiolucent lines indicating prosthetic loosening. Revision surgeries to stemmed endoprostheses of the hip were without severe problems in any patients. CONCLUSIONS: The failure rate of the TPP was distinctly higher than that for conventional stemmed endoprostheses regarding aseptic and septic revisions. In cases with loosening of the TPP the preservation of the diaphyseal bone of the femur is poor and the TPP mostly needs a revision to a cemented stem. Thus, the estimated advantage of the TPP versus cementless stemmed prostheses for patients with rheumatoid arthritis is not evident. In conclusion, there is no evidence form this study to support the use of the TPP in this group of patients.

Apolipoprotein E-dependent inverse regulation of vertebral bone and adipose tissue mass in C57Bl/6 mice: modulation by diet-induced obesity.

The long prevailing view that obesity is generally associated with beneficial effects on the skeleton has recently been challenged. Apolipoprotein E (apoE) is known to influence both adipose tissue and bone. The goal of the current study was to examine the impact of apoE on the development of fat mass and bone mass in mice under conditions of diet-induced obesity (DIO). Four week-old male C57BL/6 (WT) and apoE-deficient (apoE(-/-)) mice received a control or a diabetogenic high-fat diet (HFD) for 16 weeks. The control-fed apoE(-/-) animals displayed less total fat mass and higher lumbar trabecular bone volume (BV/TV) than WT controls. When stressed with HFD to induce obesity, apoE(-/-) mice had a lower body weight, lower serum glucose, insulin and leptin levels and accumulated less white adipose tissue mass at all sites including bone marrow. While WT animals showed no significant change in BV/TV and bone formation rate (BFR), apoE deficiency led to a decrease of BV/TV and BFR when stressed with HFD. Bone resorption parameters were not affected by HFD in either genotype. Taken together, under normal dietary conditions, apoE-deficient mice acquire less fat mass and more bone mass than WT littermates. When stressed with HFD to develop DIO, the difference of total body fat mass becomes larger and the difference of bone mass smaller between the genotypes. We conclude that apoE is involved in an inverse regulation of bone mass and fat mass in growing mice and that this effect is modulated by diet-induced obesity.

Treatment of osteochondritis dissecans of the femoral condyle with autologous bone grafts and matrix-supported autologous chondrocytes.

The objective of this study was to determine the clinical outcome of combined bone grafting and matrix-supported autologous chondrocyte transplantation in patients with osteochondritis dissecans of the knee. Between January 2003 and March 2005, 21 patients (mean age 29.33 years) with symptomatic osteochondritis dissecans (OCD) of the medial or lateral condyle (grade III or IV) of the knee underwent reconstruction of the joint surface by autologous bone grafts and matrix-supported autologous chondrocyte transplantation. Patients were followed up at three, six, 12 and 36 months to determine outcomes by clinical evaluation based on Lysholm score, IKDC and ICRS score. Clinical results showed a significant improvement of Lysholm-score and IKDC score. With respect to clinical assessment, 18 of 21 patients showed good or excellent results 36 months postoperatively. Our study suggests that treatment of OCD with autologous bone grafts and matrix-supported autologous chondrocytes is a possible alternative to osteochondral cylinder transfer or conventional ACT.

Brain gray matter decrease in chronic pain is the consequence and not the cause of pain.

Recently, local morphologic alterations of the brain in areas ascribable to the transmission of pain were reported in patients suffering from chronic pain. Although some authors discussed these findings as damage or loss of brain gray matter, one of the key questions is whether these structural alterations in the cerebral pain-transmitting network precede or succeed the chronicity of pain. We investigated 32 patients with chronic pain due to primary hip osteoarthritis and found a characteristic gray matter decrease in patients compared with controls in the anterior cingulate cortex (ACC), right insular cortex and operculum, dorsolateral prefrontal cortex (DLPFC), amygdala, and brainstem. We then investigated a subgroup of these patients (n = 10) 6 weeks and 4 months after total hip replacement surgery, monitoring whole brain structure. After surgery, all 10 patients were completely pain free and we observed a gray matter increase in the DLPFC, ACC, amygdala, and brainstem. As gray matter decrease is at least partly reversible when pain is successfully treated, we suggest that the gray matter abnormalities found in chronic pain do not reflect brain damage but rather are a reversible consequence of chronic nociceptive transmission, which normalizes when the pain is adequately treated.

Expression of LRP1 by human osteoblasts: a mechanism for the delivery of lipoproteins and vitamin K1 to bone.

UNLABELLED: Accumulating clinical and experimental data show the importance of dietary lipids and lipophilic vitamins, such as vitamin K1, for bone formation. The molecular mechanism of how they enter the osteoblast is unknown. Here we describe the expression of the multifunctional LRP1 by human osteoblasts in vitro and in vivo. We provide evidence that LRP1 plays an important role in the uptake of postprandial lipoproteins and vitamin K1 by human osteoblasts. INTRODUCTION: Chylomicrons (CM) and their remnants (CR) represent the postprandial plasma carriers of dietary lipids. Dietary vitamin K1 is known to be transported in the circulation as part of CM/CR and is required by osteoblasts as an essential co-factor for the gamma-carboxylation of bone matrix proteins. The molecular mechanisms underlying the delivery of lipophilic substances to bone are not understood. In this study, the expression and function of CM/CR receptors was examined in human osteoblasts. MATERIALS AND METHODS: Four human osteoblast-like cell lines were analyzed: two osteosarcoma lines (MG63, SaOS-2) and two telomerase-immortalized human bone marrow stromal cell lines (hMSC-TERT [4] and [20]) after 1,25(OH)2 vitamin D3 induction of osteoblastic differentiation (hMSC-TERT-OB). Receptor expression was examined by Western blotting and immunohistochemistry of normal human bone sections. Endocytotic receptor function was analyzed by cellular uptake assays using fluorescent and radiolabeled human CR. Vitamin K1-enriched CR (CR-K1) were generated in vivo after oral vitamin administration and vitamin K1 uptake by osteoblasts was measured by HPLC. The effect of CR-K1 uptake on osteocalcin carboxylation was measured by ELISA. RESULTS: Osteoblasts exhibit high levels of protein expression of the CR receptors LRP1 and LDLR. VLDLR is expressed to a lower degree. Immunohistochemistry of normal human bone sections showed strong LRP1 expression by osteoblasts and marrow stromal cells. Uptake of fluorescent CR by osteoblasts resulted in the typical pattern of receptor-mediated endocytosis. CR uptake was stimulated by the exogenous addition of the lipoprotein receptor ligands apolipoprotein E and lipoprotein lipase. Uptake was reduced by the known LRP1 inhibitors RAP, lactoferrin, and suramin, but not by LDL, which exclusively binds to the LDLR. Vitamin K1 uptake by hMSC-TERT-OB after incubation with CR-K1 was also shown to be sensitive to LPL stimulation and the LRP1 specific inhibitor lactoferrin. CR-K1 uptake into osteoblasts stimulated the gamma-carboxylation of osteocalcin. CONCLUSION: Human osteoblasts express receptors of the LDLR family with a capacity for vitamin K1 uptake through CR endocytosis, a novel mechanism for the delivery of dietary lipids and lipophilic vitamins to human bone. The current data suggest that, among the expressed receptors, LRP1 plays a predominant role.