We tested in compression specimens of human proximal tibial trabecular bone from 31 normal donors aged from 16 to 83 years and determined the mechanical properties, density and mineral and collagen content. Young’s modulus and ultimate stress were highest between 40 and 50 years, whereas ultimate strain and failure energy showed maxima at younger ages. These age-related variations (except for failure energy) were non-linear. Tissue density and mineral concentration were constant throughout life, whereas apparent density (the amount of bone) varied with ultimate stress. Collagen density (the amount of collagen) varied with failure energy. Collagen concentration was maximal at younger ages but varied little with age. Our results suggest that the decrease in mechanical properties of trabecular bone such as Young’s modulus and ultimate stress is mainly a consequence of the loss of trabecular bone substance, rather than a decrease in the quality of the substance itself. Linear regression analysis showed that collagen density was consistently the single best predictor of failure energy, and collagen concentration was the only predictor of ultimate strain

Chondrocytes of the growth plate are generally assumed to undergo apoptosis, but the mechanisms which induce this cell death are not known. The Fas receptor is a mediator of the apoptotic signal in some systems. We studied its expression in situ in growth plates of rabbits aged from five to 20 weeks. In addition, we investigated the immunolocalisation in the growth plates of the bone proteins, osteonectin and osteocalcin, and the changes in their expression with age. The Fas-positive chondrocytes were found mostly in the hypertrophic zone, as were the osteonectin-positive and osteocalcin-positive cells. The percentage of Fas-positive cells increased with age whereas little change was found in the number of osteonectin-positive and osteocalcin-positive chondrocytes. Many of the Fas-positive chondrocytes were also TUNEL-positive. This strongly suggests that apoptosis in the growth plate is mediated through the Fas system. Double immunostaining for osteocalcin and Fas showed that not all hypertrophic chondrocytes were of the same cell type. Some chondrocytes stained for osteocalcin only, others for Fas only, while some were positive for both

We analysed the effects of commonly used medications on human osteoblastic cell activity in vitro, specifically proliferation and tissue mineralisation. A list of medications was retrieved from the records of patients aged > 65 years filed in the database of the largest health maintenance organisation in our country (> two million members). Proliferation and mineralisation assays were performed on the following drugs: rosuvastatin (statin), metformin (antidiabetic), metoprolol (β-blocker), citalopram (selective serotonin reuptake inhibitor [SSRI]), and omeprazole (proton pump inhibitor (PPI)). All tested drugs significantly stimulated DNA synthesis to varying degrees, with rosuvastatin 5 µg/ml being the most effective among them (mean 225% (. sd. 20)), compared with metformin 10 µg/ml (185% (. sd.  10)), metoprolol 0.25 µg/ml (190% (. sd. 20)), citalopram 0.05 µg/ml (150% (. sd. 10)) and omeprazole 0.001 µg/ml (145% (. sd. 5)). Metformin and metoprolol (to a small extent) and rosuvastatin (to a much higher extent) inhibited cell mineralisation (85% (. sd. 5)). Our results indicate the need to evaluate the medications prescribed to patients in terms of their potential action on osteoblasts. Appropriate evaluation and prophylactic treatment (when necessary) might lower the incidence and costs associated with potential medication-induced osteoporosis. Cite this article: Bone Joint J 2013;95-B:1575–80

The medial periosteal hinge plays a key role in fractures of the head of the humerus, offering mechanical support during and after reduction and maintaining perfusion of the head by the vessels in the posteromedial periosteum. We have investigated the biomechanical properties of the medial periosteum in fractures of the proximal humerus using a standard model in 20 fresh-frozen cadaver specimens comparable in age, gender and bone mineral density. After creating the fracture, we displaced the humeral head medial or lateral to the shaft with controlled force until complete disruption of the posteromedial periosteum was recorded. As the quality of periosteum might be affected by age and bone quality, the results were correlated with the age and the local bone mineral density of the specimens measured with quantitative CT. Periosteal rupture started at a mean displacement of 2.96 mm (. sd. 2.92) with a mean load of 100.9 N (. sd. 47.1). The mean maximum load of 111.4 N (. sd. 42.5) was reached at a mean displacement of 4.9 mm (. sd. 4.2). The periosteum was completely ruptured at a mean displacement of 34.4 mm (. sd. 11.1). There was no significant difference in the mean distance to complete rupture for medial (mean 35.8 mm (. sd. 13.8)) or lateral (mean 33.0 mm (. sd. 8.2)) displacement (p = 0.589). The mean bone mineral density was 0.111 g/cm. 3. (. sd. 0.035). A statistically significant but low correlation between bone mineral density and the maximum load uptake (r = 0.475, p = 0.034) was observed. This study showed that the posteromedial hinge is a mechanical structure capable of providing support for percutaneous reduction and stabilisation of a fracture by ligamentotaxis. Periosteal rupture started at a mean of about 3 mm and was completed by a mean displacement of just under 35 mm. The microvascular situation of the rupturing periosteum cannot be investigated with the current model

The purposes of this study were to define the range of laxity of the interosseous ligaments in cadaveric wrists and to determine whether this correlated with age, the morphology of the lunate, the scapholunate (SL) gap or the SL angle. We evaluated 83 fresh-frozen cadaveric wrists and recorded the SL gap and SL angle. Standard arthroscopy of the wrist was then performed and the grades of laxity of the scapholunate interosseous ligament (SLIL) and the lunotriquetral interosseous ligament (LTIL) and the morphology of the lunate were recorded. Arthroscopic evaluation of the SLIL revealed four (5%) grade I specimens, 28 (34%) grade II, 40 (48%) grade III and 11 (13%) grade IV. Evaluation of the LTIL showed 17 (20%) grade I specimens, 40 (48%) grade II, 28 (30%) grade III and one (1%) grade IV. On both bivariate and multivariate analysis, the grade of both the SLIL and LTIL increased with age, but decreased with female gender. The grades of SLIL or LTIL did not correlate with the morphology of the lunate, the SL gap or the SL angle. The physiological range of laxity at the SL and lunotriquetral joints is wider than originally described. The intercarpal ligaments demonstrate an age-related progression of laxity of the SL and lunotriquetral joints. There is no correlation between the grades of laxity of the SLIL or LTIL and the morphology of the lunate, the SL gap or the SL grade. Based on our results, we believe that the Geissler classification has a role in describing intercarpal laxity, but if used alone it cannot adequately diagnose pathological instability. We suggest a modified classification with a mechanism that may distinguish physiological laxity from pathological instability

Sex hormones play important roles in the regulation of the proliferation, maturation and death of chondrocytes in the epiphyseal growth plate. We have investigated the effects of male castration on the cell kinetics of chondrocytes as defined by the numbers of proliferating and dying cells. The growth plates of normal rabbits and animals castrated at eight weeks of age were obtained at 10, 15, 20 and 25 weeks of age. Our study suggested that castration led to an increase in apoptosis and a decrease in the proliferation of chondrocytes in the growth plate. In addition, the number of chondrocytes in the castrated rabbits was less than that of normal animals of the same age

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

We investigated several factors which affect the stability of cortical screws in osteoporotic bone using 18 femora from cadavers of women aged between 45 and 96 years (mean 76). We performed bone densitometry to measure the bone mineral density of the cortical and cancellous bone of the shaft and head of the femur, respectively. The thickness and overall bone mass of the cortical layer of the shaft of the femur were measured using a microCT scanner. The force required to pull-out a 3.5 mm titanium cortical bone screw was determined after standardised insertion into specimens of the cortex of the femoral shaft. A significant correlation was found between the pull-out strength and the overall bone mass of the cortical layer (r. 2. = 0.867, p < 0.01) and also between its thickness (r. 2. = 0.826, p < 0.01) and bone mineral density (r. 2. = 0.861, p < 0.01). There was no statistically significant correlation between the age of the donor and the pull-out force (p = 0.246), the cortical thickness (p = 0.199), the bone mineral density (p = 0.697) or the level of osteoporosis (p = 0.378). We conclude that the overall bone mass, the thickness and the bone mineral density of the cortical layer, are the main factors which affect the stability of a screw in human female osteoporotic cortical bone

Our aim was to determine the relationship between age and the mechanical and physical properties of trabecular bone, to describe the patterns in which the variations in these properties take place, and to investigate the influence of the physical properties on the mechanical characteristics of trabecular bone during growth. We used 30 lambs in three age groups and 20 sheep in two age groups. Cubes of subchondral bone were cut from the proximal tibia according to a standardised protocol. We performed non-destructive compression tests of the specimens in three orthogonal directions and compression tests to failure in the axial direction. The physical properties of the specimens were also determined. The data were correlated with age and compared in skeletally immature and mature animals. Multiple regression analyses were performed between the mechanical and the physical properties. Age correlated positively with elastic modulus, bone strength, energy absorption to failure, elastic energy, mechanical anisotropy ratio, tissue density, apparent density, apparent ash density, and bone mineral content, and inversely with ultimate strain, viscoelastic energy absorption, relative energy loss, the collagen content of bone and the percentage porosity. The values of all variables were significantly different in the skeletally mature and immature groups. The apparent density of trabecular bone tissue was found to be the major predictor of its compressive mechanical properties. Together with the content of bone muscle and bone collagen, the apparent density could explain 84% of the variation in the elastic modulus, whereas only a small portion of the variation in ultimate strain could be explained by the variation in apparent density

The aim of this study was to establish a classification system for the acromioclavicular joint using cadaveric dissection and radiological analyses of both reformatted computed tomographic scans and conventional radiographs centred on the joint. This classification should be useful for planning arthroscopic procedures or introducing a needle and in prospective studies of biomechanical stresses across the joint which may be associated with the development of joint pathology. We have demonstrated three main three-dimensional morphological groups namely flat, oblique and curved, on both cadaveric examination and radiological assessment. These groups were recognised in both the coronal and axial planes and were independent of age

We aimed to highlight the relationship between age and the architectural properties of trabecular bone, to outline the patterns in which the variations in these properties take place, and to investigate the influence of the architecture on the mechanical properties of trabecular bone in growing animals. We studied 30 lambs in three age groups and 20 sheep in two age groups. Cubes of subchondral bone were cut from the proximal tibia according to a standardised protocol. They were serially sectioned and their architectural properties were determined. Similar cubes were obtained from the identical anatomical position of the contralateral tibia and their compressive mechanical properties measured. The values obtained from the skeletally immature and mature individuals were compared. Multiple regression analyses were performed between the architectural and the mechanical properties. The bone volume fraction, the mean trabecular volume, the architectural and the mechanical anisotropy, the elastic modulus, the bone strength, the energy absorption to failure, and the elastic energy correlated positively with increasing age whereas the connectivity density, the bone surface density, the ultimate strain, the absorption of viscoelastic energy and the relative loss of energy correlated inversely. The values of all variables were significantly different in the skeletally mature and immature groups. We determined the patterns in which the variations took place. The bone volume fraction of the trabecular bone tissue was found to be the major predictor of its compressive mechanical properties. Together with the mean trabecular volume and the bone surface density, it explained 81% of the variations in the compressive elastic modulus of specimens obtained from the contralateral tibiae

Ultra-high-molecular-weight polyethylene (UHMWPE) components for total joint replacement generate wear particles which cause adverse biological tissue reactions leading to osteolysis and loosening. Sterilisation of UHMWPE components by gamma irradiation in air causes chain scissions which initiate a long-term oxidative process that degrades the chemical and mechanical properties of the polyethylene. Using a tri-pin-on-disc tribometer we studied the effect of ageing for ten years after gamma irradiation in air on the volumetric wear, particle size distribution and the number of particles produced by UHMWPE when sliding against a stainless-steel counterface. The aged and irradiated material produced six times more volumetric wear and 34 times more wear particles per unit load per unit sliding distance than non-sterilised UHMWPE. Our findings indicate that oxidative degradation of polyethylene after gamma irradiation in air with ageing produces more wear

We used a biodegradable mesh to convert an acetabular defect into a contained defect in six patients at total hip replacement. Their mean age was 61 years (46 to 69). The mean follow-up was 32 months (19 to 50). Before clinical use, the strength retention and hydrolytic in vitro degradation properties of the implants were studied in the laboratory over a two-year period. A successful clinical outcome was determined by the radiological findings and the Harris hip score. All the patients had a satisfactory outcome and no mechanical failures or other complications were observed. No protrusion of any of the impacted grafts was observed beyond the mesh. According to our preliminary laboratory and clinical results the biodegradable mesh is suitable for augmenting uncontained acetabular defects in which the primary stability of the implanted acetabular component is provided by the host bone. In the case of defects of the acetabular floor this new application provides a safe method of preventing graft material from protruding excessively into the pelvis and the mesh seems to tolerate bone-impaction grafting in selected patients with primary and revision total hip replacement

We assessed the prevalence of abnormal ankle reflexes in 1074 adult patients attending orthopaedic clinics and related it to age. Those with possible pathological causes of reflex loss were excluded. The absence of one or both reflexes was significantly related to increasing age; all patients under 30 years had both reflexes. Few had absent reflexes between 30 and 40 years, but over 40 years, the proportion with both reflexes absent increased rapidly from 5% (40 to 50 years) to 80% (90 to 100 years). Unilateral absence did not show the same pattern of increase being 3% to 5% at 40 to 60 years and 7% to 10% at over 60 years. Our results suggest that a significant number of ‘normal’ adults have unilateral absence of an ankle reflex, but this finding is rare enough to be a definite clinical sign, irrespective of age

We investigated the distribution of compressive ‘stress’ within cadaver intervertebral discs, using a pressure transducer mounted in a 1.3 mm diameter needle. The needle was pulled along the midsagittal diameter of a lumbar disc with the face of the transducer either vertical or horizontal while the disc was subjected to a constant compressive force. The resulting ‘stress profiles’ were analysed in order to characterise the distribution of vertical and horizontal compressive stress within each disc. A total of 87 discs from subjects aged between 16 and 87 years was examined. Our results showed that age-related degenerative changes reduced the diameter of the central hydrostatic region of each disc (the ‘functional nucleus’) by approximately 50%, and the pressure within this region fell by 30%. The width of the functional annulus increased by 80% and the height of compressive ‘stress peaks’ within it by 160%. The effects of age and degeneration were greater at L4/L5 than at L2/L3, and the posterior annulus was affected more than the anterior. Age and degeneration were themselves closely related, but the stage of degeneration had the greater effect on stress distributions. We suggest that structural changes within the annulus and endplate lead to a transfer of load from the nucleus to the posterior annulus. High ‘stress’ concentrations within the annulus may cause pain, and lead to further disruption

We evaluated the histological changes before and after fixation in ten knees of ten patients with osteochondritis dissecans who had undergone fixation of the unstable lesions. There were seven males and three females with a mean age of 15 years (11 to 22). The procedure was performed either using bio-absorbable pins only or in combination with an autologous osteochondral plug. A needle biopsy was done at the time of fixation and at the time of a second-look arthroscopy at a mean of 7.8 months (6 to 9) after surgery. The biopsy specimens at the second-look arthroscopy showed significant improvement in the histological grading score compared with the pre-fixation scores (p < 0.01). In the specimens at the second-look arthroscopy, the extracellular matrix was stained more densely than at the time of fixation, especially in the middle to deep layers of the articular cartilage. Our findings show that articular cartilage regenerates after fixation of an unstable lesion in osteochondritis dissecans

An injectable material consisting of calcium sulphate mixed with hydroxyapatite was investigated as a possible alternative to autograft in the restoration of bone defects. The material was studied both in vitro in simulated body fluid (SBF) and in vivo when implanted in rat muscles and into the proximal tibiae of rabbits. Variation in the strength and weight of the material during ageing in SBF was measured. Tissue response, material resorption and bone ingrowth were studied in the animal models. A good tissue response was observed in both the rat muscles and rabbit tibiae without inflammatory reactions or the presence of fibrous tissue. Ageing in SBF showed that during the first week carbonated hydroxyapatite precipitated on the surfaces of the material and this may enhance bone ingrowth

Medial open-wedge high tibial osteotomy has been gaining popularity in recent years, but adequate supporting material is required in the osteotomy gap for early weight-bearing and rapid union. The purpose of this study was to investigate whether the implantation of a polycaprolactone-tricalcium phosphate composite scaffold wedge would enhance healing of the osteotomy in a micro pig model. We carried out open-wedge high tibial osteotomies in 12 micro pigs aged from 12 to 16 months. A scaffold wedge was inserted into six of the osteotomies while the other six were left open. Bone healing was evaluated after three and six months using plain radiographs, CT scans, measurement of the bone mineral density and histological examination. Complete bone union was obtained at six months in both groups. There was no collapse at the osteotomy site, loss of correction or failure of fixation in either group. Staining with haematoxylin and eosin demonstrated that there was infiltration of new bone tissue into the macropores and along the periphery of the implanted scaffold in the scaffold group. The CT scans and measurement of the bone mineral density showed that at six months specimens in the scaffold group had a higher bone mineral density than in the control group, although the implantation of the polycaprolactone-tricalcium phosphate composite scaffold wedge did not enhance healing of the osteotomy

The operative treatment of fractures of the proximal humerus can be complicated by poor bone quality. Our aim was to evaluate a new method which allows prediction of the bone quality of the proximal humerus from radiographs. Anteroposterior radiographs were taken of 19 human cadaver humeri. The cortical thickness was measured at two levels of the proximal humeral diaphysis. The bone mineral density (BMD) was determined for the humeral head (HH), the surgical neck (SN), the greater tuberosity (GT) and lesser tuberosity (LT) using dual-energy x-ray absorptiometry. The mean cortical thickness was 4.4 ± 1.0 mm. Specimens aged 70 years or less had a significantly higher cortical thickness than those aged over 70 years. A significant positive correlation was found between cortical thickness and the BMD for each region of interest. The cortical thickness of the proximal diaphysis is a reliable predictor of the bone quality of the proximal humerus

Previous studies have shown that low-density, rod-like trabecular structures develop in regions of low stress, whereas high-density, plate-like trabecular structures are found in regions of high stress. This phenomenon suggests that there may be a close relationship between the type of trabecular structure and mechanical properties. In this study, 160 cancellous bone specimens were produced from 40 normal human tibiae aged from 16 to 85 years at post-mortem. The specimens underwent micro-CT and the microstructural properties were calculated using unbiased three-dimensional methods. The specimens were tested to determine the mechanical properties and the physical/compositional properties were evaluated. The type of structure together with anisotropy correlated well with Young’s modulus of human tibial cancellous bone. The plate-like structure reflected high mechanical stress and the rod-like structure low mechanical stress. There was a strong correlation between the type of trabecular structure and the bone-volume fraction. The most effective microstructural properties for predicting the mechanical properties of cancellous bone seem to differ with age