Objectives. The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known. Methods. In this study, TGF-β1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-β1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours. Results. A significant decrease in the survival rate of co-cultured chondrocytes was found. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay demonstrated that mechanical stress-induced apoptosis occurred significantly in co-cultured chondrocytes but administration of the TGF-β1 receptor inhibitor, SB-505124, can significantly reverse these effects. Abdominal administration of SB-505124 can attenuate markedly articular cartilage degradation in OA rats. Conclusion. Mechanical stress-induced overexpression of TGF-β1 from osteoclasts is responsible for chondrocyte apoptosis and cartilage degeneration in OA. Administration of a TGF-β1 inhibitor can inhibit articular cartilage degradation. Cite this article: R-K. Zhang, G-W. Li, C. Zeng, C-X. Lin, L-S. Huang, G-X. Huang, C. Zhao, S-Y. Feng, H. Fang. Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-β1). Bone Joint Res 2018;7:587–594. DOI: 10.1302/2046-3758.711.BJR-2018-0057.R1

Objectives

Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls.

We investigated the antibiotic concentration in fresh-frozen femoral head allografts harvested from two groups of living donors. Ten samples were collected from patients with osteoarthritis of the hip and ten from those with a fracture of the neck of the femur scheduled for primary arthroplasty. Cefazolin (1 g) was administered as a pre-operative prophylactic antibiotic. After storage at −80°C for two weeks the pattern of release of cefazolin from morsellised femoral heads was evaluated by an in vitro broth elution assay using high-performance liquid chromatography. The bioactivity of the bone was further determined with an agar disc diffusion and standardised tube dilution bioassay. The results indicated that the fresh-frozen femoral heads contained cefazolin. The morsellised bone released cefazolin for up to four days. The concentration of cefazolin was significantly higher in the heads from patients with osteoarthritis of the hip than in those with a fracture. Also, in bioassays the bone showed inhibitory effects against bacteria. We concluded that allografts of morsellised bone from the femoral head harvested from patients undergoing arthroplasty of the hip contained cefazolin, which had been administered pre-operatively and they exhibited inhibitory effects against bacteria in vitro

We carried out a cross-sectional study with analysis of the demographic, clinical and laboratory characteristics of patients with metal-on-metal hip resurfacing, ceramic-on-ceramic and metal-on-polyethylene hip replacements. Our aim was to evaluate the relationship between metal-on-metal replacements, the levels of cobalt and chromium ions in whole blood and the absolute numbers of circulating lymphocytes. We recruited 164 patients (101 men and 63 women) with hip replacements, 106 with metal-on-metal hips and 58 with non-metal-on-metal hips, aged < 65 years, with a pre-operative diagnosis of osteoarthritis and no pre-existing immunological disorders.

Laboratory-defined T-cell lymphopenia was present in13 patients (15%) (CD8⁺ lymphopenia) and 11 patients (13%) (CD3⁺ lymphopenia) with unilateral metal-on-metal hips. There were significant differences in the absolute CD8⁺ lymphocyte subset counts for the metal-on-metal groups compared with each control group (p-values ranging between 0.024 and 0.046). Statistical modelling with analysis of covariance using age, gender, type of hip replacement, smoking and circulating metal ion levels, showed that circulating levels of metal ions, especially cobalt, explained the variation in absolute lymphocyte counts for almost all lymphocyte subsets.

The aim of our study was to investigate whether placing of the femoral component of a hip resurfacing in valgus protected against spontaneous fracture of the femoral neck. We performed a hip resurfacing in 20 pairs of embalmed femora. The femoral component was implanted at the natural neck-shaft angle in the left femur and with a 10° valgus angle on the right. The bone mineral density of each femur was measured and CT was performed. Each femur was evaluated in a materials testing machine using increasing cyclical loads. In specimens with good bone quality, the 10° valgus placement of the femoral component had a protective effect against fractures of the femoral neck. An adverse effect was detected in osteoporotic specimens. When resurfacing the hip a valgus position of the femoral component should be achieved in order to prevent fracture of the femoral neck. Patient selection remains absolutely imperative. In borderline cases, measurement of bone mineral density may be indicated

In spite of extensive accounts describing the blood supply to the femoral head, the prediction of avascular necrosis is elusive. Current opinion emphasises the contributions of the superior retinacular artery but may not explain the clinical outcome in many situations, including intramedullary nailing of the femur and resurfacing of the hip. We considered that significant additional contribution to the vascularity of the femoral head may exist. A total of 14 fresh-frozen hips were dissected and the medial circumflex femoral artery was cannulated in the femoral triangle. On the test side, this vessel was ligated, with the femoral head receiving its blood supply from the inferior vincular artery alone. Gadolinium contrast-enhanced MRI was then performed simultaneously on both control and test specimens. Polyurethane was injected, and gross dissection of the specimens was performed to confirm the extraosseous anatomy and the injection of contrast. The inferior vincular artery was found in every specimen and had a significant contribution to the vascularity of the femoral head. The head was divided into four quadrants: medial (0), superior (1), lateral (2) and inferior (3). In our study specimens the inferior vincular artery contributed a mean of 56% (25% to 90%) of blood flow in quadrant 0, 34% (14% to 80%) of quadrant 1, 37% (18% to 48%) of quadrant 2 and 68% (20% to 98%) in quadrant 3. Extensive intra-osseous anastomoses existed between the superior retinacular arteries, the inferior vincular artery and the subfoveal plexus.

A total of 20 pairs of fresh-frozen cadaver femurs were assigned to four alignment groups consisting of relative varus (10° and 20°) and relative valgus (10° and 20°), 75 composite femurs of two neck geometries were also used. In both the cadaver and the composite femurs, placing the component in 20° of valgus resulted in a significant increase in load to failure. Placing the component in 10° of valgus had no appreciable effect on increasing the load to failure except in the composite femurs with varus native femoral necks. Specimens in 10° of varus were significantly weaker than the neutrally-aligned specimens.

The results suggest that retention of the intact proximal femoral strength occurs at an implant angulation of ≥ 142°. However, the benefit of extreme valgus alignment may be outweighed in clinical practice by the risk of superior femoral neck notching, which was avoided in this study.

A cadaver study using six pairs of lower limbs was conducted to investigate the accuracy of computer navigation and standard instrumentation for the placement of the Birmingham Hip Resurfacing femoral component. The aim was to place all the femoral components with a stem-shaft angle of 135°.

The mean stem-shaft angle obtained in the standard instrumentation group was 127.7° (120° to 132°), compared with 133.3° (131° to 139°) in the computer navigation group (p = 0.03). The scatter obtained with computer-assisted navigation was approximately half that found using the conventional jig.

Computer navigation was more accurate and more consistent in its placement of the femoral component than standard instrumentation. We suggest that image-free computer-assisted navigation may have an application in aligning the femoral component during hip resurfacing.

We studied the reliability of the Singh classification of trabecular bone structure in the proximal femur as a measure of osteoporosis, using kappa statistics. Radiographs of fractures of the femoral neck or trochanteric region in 80 consecutive patients were assessed by six observers. The interobserver variation was large; only three of 72 radiographs were given the same classification by all six observers and the kappa values ranged from 0.15 to 0.54. The intraobserver variation showed substantial strength of agreement; kappa values ranged from 0.63 to 0.88. In 77 patients dual-energy X-ray absorptiometry was used to measure bone mineral density. The results were compared with those of the Singh classification: we found no correlation