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N Rushton

Publications and source records attributed to N Rushton.

At least 55 records · Page 3Linked to original sources

Spatial clustering of remodeling osteons in the femoral neck cortex: a cause of weakness in hip fracture?

Intracapsular femoral neck fractures are associated with decreased cortical width and increased proportions of Haversian canals with diameters greater than the normal mean plus 3 SD (i.e., >385 microm). Such canals might be formed if closely associated resorbing osteons merge; a cortical event analogous with the loss of cancellous connectivity. To test this, we investigated the pattern of osteon distribution in the aging femoral neck to determine if remodeling osteons were distributed in anatomical clusters. Femoral neck biopsies from female patients with intracapsular hip fractures (n = 13) were compared with age/gender-matched cadaveric controls (n = 13). Solochrome-stained sections were analyzed for Haversian canal location, canal diameter, and the presence of an osteoid surface. Clustering was investigated using statistical software with a cluster defined as two or more osteoid-bearing osteon centers within 0.75 mm of each other. Clusters occurred more frequently than would be expected by chance (p < 0.001). Fracture cases had more clusters per unit area (3.14 +/- 0.31 clusters/25 mm2 of cortical bone) than controls (1.89 +/- 0.22) (p = 0.002). In fracture cases, the antero-inferior, antero-superior, and infero-anterior regions had more clusters per 25 mm2 than comparable control regions (ant/inf: 4.12 +/- 0.79, 1.70 +/- 0.60,p = 0.025; ant/sup: 5.31 +/- 1.1, 1.80 +/- 0.59,p = 0.013; inf/ant: 3.15 +/- 0.49, 1.27 +/-0.29, p = 0.004). The mean number of clusters per 25 mm2 per region correlated with the mean porosity per region (adjusted r2 = 0.60;p = 0.014), and the total number of giant canals per region correlated with the total number of clusters per region (adjusted r2 = 0.58; p = 0.011). In conclusion, remodeling osteons are clustered or grouped anatomically, and fracture cases have more clusters than controls. Our data suggest that merging of adjacent, clustered osteons during resorption could lead to the rapid development of canals with excessive diameters and focal weakness. Clustering is greatest in those regions that we have previously shown to have the largest relative reductions in bone strength compared with controls and known to be maximally loaded during a sideways fall. This implicates the remodeling process underlying clustering of remodeling osteons in the aetiology of hip fracture.

Aged↗

The effects of the concentration of high-density polyethylene particles on the bone-implant interface.

We used a rat model in vivo to study the effects of the concentration of polyethylene particles on the bone-implant interface around stable implants in the proximal tibia. Intra-articular injections of 10(4), 10(6) or 10(8) high-density polyethylene (HDPE) particles per joint were given 8, 10 and 12 weeks after surgery. The animals were killed after 14 and 26 weeks and the response at the interface determined. Fibrous tissue was seen at the bone-implant interface when the head of the implant was flush with the top of the tibia but not when it was sunk below the tibial plateau. In the latter case the implant was completely surrounded by a shell of bone. The area of fibrous tissue and that of the gap between the implant and bone was related to the concentration of particles in the 14-week group (p < 0.05). Foreign-body granulomas containing HDPE particles were seen at the bone-implant interface in animals given 10(8) particles. The pathology resembles that seen around prostheses with aseptic loosening and we suggest that this is a useful model by which to study this process.

Animals↗

Intracapsular hip fracture: increased cortical remodeling in the thinned and porous anterior region of the femoral neck.

It has been shown previously that the antero-inferior cortex is subjected to maximal tensile stress during a fall onto the greater trochanter. We have recently shown that in cases of femoral neck fracture, cortical thinning and porosity is greatest in the anterior and antero-inferior region of the femoral neck. To investigate whether this is due to increased remodeling, we have quantified surface-based parameters associated with Haversian remodeling in femoral neck biopsies from women with intracapsular hip fracture and post-mortem controls. Cryostat sections of chilled biopsies were reacted for either tartrate-resistant acid phosphatase (TRAP) or alkaline phosphatase (ALP) activity. Proportions of active canals were determined in each quadrant (inferior, anterior, superior, posterior) of the femoral neck. The biopsies were then embedded in methacrylate to permit histomorphometry using Goldner's and Solochrome sections. In the cases there was no significant increase in the proportion of canals undergoing remodeling in the cortex as a whole (p = 0.846), but the regional distribution of remodeling was markedly different from that in the controls. In the anterior cortex, the proportion of canals undergoing remodeling was increased by 56% (p = 0.0087); in contrast there was a relative decrease of 35% in the superior region (p = 0.0047). In the anterior cortex of cases there were 76% and 42% increases in the proportions of eroded (p = 0.019) and osteoid-bearing (p = 0.041) canals, respectively. In the superior region, the decrease in the proportion of remodeling sites was due to a marked decrease in canals with an osteoid surface (51%; p = 0.0031). Covariance analysis with cortical porosity as the dependent variable showed that porosity was significantly dependent on the regional distribution of eroded (p = 0.033) but not on the distribution of forming (p = 0.153) canals (R(2)adj = 0.51). Cellular levels of TRAP and ALP were significantly elevated in the anterior region of cases compared with the controls (TRAP 55%, p = 0.006; ALP 36%, p = 0.003). For the posterior and inferior regions there were no marked differences in cellular TRAP and ALP levels compared with control values. These data show that the increased cortical thinning and increased porosity we have previously observed in the anterior cortex in cases of hip fracture are associated with increased indices of Haversian remodeling. These findings are consistent with the hypothesis that, in cases of hip fracture, remodeling imbalance in the anterior cortex is a continuing process up to the time of fracture and is due to increased osteoclastic cellular activity associated with an osteoblastic response that is inadequate to prevent bone loss.

Acid Phosphatase↗

Osteoporosis.

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Aged↗

Response of macrophages to poly(L-lactide) particulates which have undergone various degrees of artificial degradation.

This investigation looked at the effects of artificially degraded poly(L-lactide) particles on macrophages in vitro. The effects of very-low-molecular-weight unprocessed poly(L-lactide) and poly(glycolide) particles were also examined. There were no obvious trends in the data, suggesting that as the artificially degraded particles became more degraded, they became more or less toxic. Comparisons of the effects of low-molecular-weight poly(L-lactide) and poly(glycolide) particles did not reveal any differences between the effects of poly(L-lactide) particles and poly(glycolide) particles on cells in vitro. It is possible that the reason for this is that the cell line used here is less sensitive to particles than cultures of primary cells. Given this information and the fact that poly(glycolide) particles have been associated with osteolytic and inflammatory problems, this would suggest that further research into poly(L-lactide) implant degradation would be worthwhile.

Animals↗

Pro-inflammatory cytokines and the pathogenesis of Gaucher's disease: increased release of interleukin-6 and interleukin-10.

Gaucher's disease is characterized by hepatosplenomegaly, bone-marrow infiltration, osteonecrosis and bone thinning, associated with the presence of pathological macrophages that contain undegraded glycosphingolipids. To investigate the possible role of cytokines in the systemic and local manifestations of established Gaucher's disease, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF alpha) and interleukin-10 (IL-10) were measured in freshly-separated serum. Samples from eight male and 14 female patients with type 1 Gaucher's disease were compared with sera from 22 healthy age- and sex-matched controls. Concentrations of IL-6 and IL-10 were significantly elevated in sera from patients with Gaucher's disease (11.9 +/- 1.8 (SEM) pg/ml and 5.4 +/- 0.5 (SEM) pg/ml, respectively) compared with those of controls (4.1 +/- 0.9 (SEM) and 0.8 +/- 0.3 (SEM) pg/ml, p < 0.0001). No significant differences in concentrations of TNF alpha or IL-1 beta were identified. IL-6 has been implicated in the development of localized osteolysis in multiple myeloma and in the development of post-menopausal osteoporosis. High concentrations of IL-6 in the serum of patients with Gaucher's disease may thus reflect the development of the bone lesions commonly associated with this disorder. Since IL-6 and IL-10 are important regulators of lymphocyte growth and differentiation, and IL-6 concentrations were significantly raised in patients with oligo- or polyclonal increases in serum immunoglobulins, enhanced release of these cytokines from pathological macrophages provides a pathological link between Gaucher's disease and associated lympho-proliferative disorders.

Adult↗

The effects of particulate cobalt, chromium and cobalt-chromium alloy on human osteoblast-like cells in vitro.

Particulate wear debris can induce the release of bone-resorbing cytokines from cultured macrophages and fibroblasts in vitro, and these mediators are believed to be the cause of the periprosthetic bone resorption which leads to aseptic loosening in vivo. Much less is known about the effects of particulate debris on the growth and metabolism of osteoblastic cells. We exposed two human osteoblast-like cell lines (SaOS-2 and MG-63) to particulate cobalt, chromium and cobalt-chromium alloy at concentrations of 0, 0.01, 0.1 and 1.0 mg/ml. Cobalt was toxic to both cell lines and inhibited the production of type-I collagen, osteocalcin and alkaline phosphatase. Chromium and cobalt-chromium were well tolerated by both cell lines, producing no cytotoxicity and no inhibition of type-I collagen synthesis. At the highest concentration tested (1.0 mg/ml), however, chromium inhibited alkaline phosphatase activity, and both chromium and cobalt-chromium alloy inhibited osteocalcin expression. Our results clearly show that particulate metal debris can modulate the growth and metabolism of osteoblastic cells in vitro. Reduced osteoblastic activity at the bone-implant interface may be an important mechanism by which particulate wear debris influences the pathogenesis of aseptic loosening in vivo.

Alkaline Phosphatase↗

Periprosthetic bone loss and regional bone turnover in uncemented total hip arthroplasty: a prospective study using high resolution single photon emission tomography and dual-energy X-ray absorptiometry.

Single photon emission computed tomography (SPECT) at 6 and 12 months and dual-energy X-ray absorptiometry (DXA) at 0, 6, and 12 months were performed prospectively in 15 patients who had undergone uncemented total hip arthroplasty (THA) without any complications. Periprosthetic bone mineral density (BMD) decreased significantly in all regions of interests (ROIs) during 1 year of follow-up. The greatest annual decrease was found in the lesser trochanter region (22.1%). From 6-12 months, SPECT activity in the operated side decreased significantly (10-24%) in all ROIs, with the exception of the medial cortex ROI. In contrast, increases (8-36%) were found in the contralateral side. At 12 months, the operated versus control difference was still 10% in the lesser trochanter ROI, but as much as about 70% in the greater trochanter and tip ROIs. The decrease in BMD was significantly related to an increase in SPECT activity in the lesser trochanter region (r = -0.589, p < 0.05). In conclusion, increased periprosthetic SPECT activity seems to be associated with increased bone loss. We suggest that increased SPECT activity and subsequent bone loss reflect altered stress distribution and bone remodeling in the femur after prosthesis implantation.

Absorptiometry, Photon↗

Evaluation of periprosthetic bone using dual-energy x-ray absorptiometry: precision of the method and effect of operation on bone mineral density.

To assess the perioperative bone loss of femur during total hip arthroplasty (THA), periprosthetic bone mineral density (BMD) of the seven regions of interests (Gruen zones) was determined with dual-energy x-ray absorptiometry (DXA) preoperatively in both proximal femurs and postoperatively in the involved side in 53 patients with degenerative hip osteoarthrosis. The mean (standard deviation, SD) precision error (coefficient of variation percent, CV%) in various regions of interest (ROIs) based on two consecutive measurements (n = 16) were 2.3 (0.8)%, 2.5 (1.5)%, and 2.8 (1.6)% for uncemented stems, cemented stems, and control sides, respectively. Furthermore, the mean variability caused by the rotation of femur was 3.5 (1.4)%. The most significant perioperative bone loss (13.5-19.2%) was found in the calcar area (zone 7) after noncemented THA. Zone 4, representing the bone below the prosthesis, also showed BMD decreases. These decreases suggest perioperative bone loss owing to rasping and reaming the calcar and bone canal. However, after cemented THA, highly significant BMD increases were found in all the lateral zones. The calcar area was the only site where significant perioperative bone loss was detected (12.8%). In conclusion, DXA is a precise method for quantifying bone mass and density changes in the follow-up of THA. However, when interpreting the results, the preoperative BMD, differences between the femurs and the effect of operation on bone mass should be taken into account. We suggest that the best reference for BMD follow-up is the periprosthetic BMD of the involved side measured soon after the THA.

Absorptiometry, Photon↗

The effects of particulate polyethylene at a weight-bearing bone-implant interface. A study in rats.

In ten male rats we inserted ceramic 'drawing-pin' implants in weight-bearing positions within the right proximal tibia. Two animals were killed 6 weeks after surgery and two more 14 weeks after surgery. The remaining six received intra-articular injections of either high-density polyethylene (4 rats) or saline (2 rats) at 8, 10 and 12 weeks after surgery. These animals were killed two weeks after the last injection. Histological examination of the bone-implant interface in the control animals showed appositional bone growth around the implant at both 6 and 14 weeks. Polyethylene, but not saline, caused a chronic inflammatory response with numerous foreign-body giant cells in periprosthetic tissues. Our model of a stable, weight-bearing bone-implant interface provides a simple and reliable system in which to study in vivo the effects of particulate materials used in orthopaedic surgery.

Animals↗

Differences in mortality after fracture of hip: the east Anglian audit.

OBJECTIVE: To investigate differences between hospitals in clinical management of patients admitted with fractured hip and to relate these to mortality at 90 days. DESIGN: A prospective audit of process and outcome of care based on interviews with patients, abstraction from records with standard proforma, and follow up at three months. Data were analysed with chi 2 test and forward stepwise regression modelling of mortality. SETTING: All eight hospitals in East Anglia with trauma orthopaedic departments. PATIENTS: 580 consecutive patients admitted for fracture of neck of femur. MAIN OUTCOME MEASURE: Mortality at 90 days. RESULTS: Patients admitted to each hospital were similar with respect to age, sex, pre-existing illnesses, and activities of daily living before fracture. In all, 560 (97%) were treated surgically, by a range of grades of surgeon. Two hundred and sixty one patients (45%; range between hospitals 10-91%) received pharmaceutical thromboembolic prophylaxis, 502 (93%; 81-99%) perioperative antibiotic prophylaxis. The incidence of fatal pulmonary emboli differed between patients who received and those who did not receive prophylaxis against deep vein thrombosis (P = 0.001). Mortality at 90 days was 18%, differing significantly between hospitals (5-24%). One hospital had significantly better survival than the others (odds ratio 0.14; 95% confidence interval 0.04-0.48; P = 0.0016). CONCLUSIONS: No single factor or aspect of practice accounted for this protective effect. Lower mortality may be associated with the cumulative effects of several aspects of the organisation of treatment and the management of fracture of the hip, including thromboembolic pharmaceutical prophylaxis, antibiotic prophylaxis, and early mobilisation.

Aged↗

Early mobilization in the treatment of Colles' fracture: a 3 year prospective study.

Ninety consecutive women with unilateral Colles' fractures were randomized into two different treatment groups. The control group was treated for 5 weeks in conventional short-arm, below the elbow plaster of Paris casts. The other group (N = 45) was treated similarly in plaster casts for 3 weeks and then had flexible casting applied for the remaining 2 weeks which allowed for early joint mobilization. Functional recovery was assessed by measuring grip strength and joint mobility at intervals over the 3 years. Radiographic and overall assessments were also made during 3 year course of study. Virtually all patients reported greater comfort after switching to the flexible casting. Mean grip scores and joint mobilities were higher at all time points with early mobilization, reaching levels of statistical significance at 6 months for grip score and at 3 months for joint mobility. By 3 years most differences between treatment groups had resolved. We found no evidence that early mobilization was detrimental to recovery. We conclude that early mobilization is a satisfactory treatment option for Colles' fracture, and may, in fact, hasten functional recovery.

Adult↗

Role of inflammatory mediators and adhesion molecules in the pathogenesis of aseptic loosening in total hip arthroplasties.

Concentrations of prostaglandin E2, interleukin-6, and interleukin-8 were determined in the hip joint synovial fluid of 20 patients undergoing primary (n = 12) and revision (n = 8) total hip arthroplasties. Levels of soluble adhesion molecules were also investigated in these patients. There was a significant and marked increase in levels of prostaglandin E2 (P < .001), interleukin-6 (P < .011), interleukin-8 (P < .0002), soluble intercellular adhesion molecule 1 (P < .07), soluble vascular adhesion molecule 1 (P < .0006), and soluble endothelial leukocyte adhesion molecule 1 (P < .0003) in joint fluid of patients undergoing revision. On the basis of these observations, it is suggested that synovial fluid and its inflammatory contents could play a significant role in the pathogenesis of aseptic loosening in total hip arthroplasties.

Aged↗

Effect of exercise training programme on bone mineral density in novice college rowers.

Exercise has important effects on skeletal mineralization. Changes in bone mineral density (BMD) and bone mineral content (BMC) as measured by dual energy X-ray absorptiometry were investigated in a group of 17 male novice college oarsmen over a 7-month period and were compared with eight age-matched controls. The rowing training programme consisted of approximately 8 h rowing, 1 h weight training, and 1 h running per week. After 7 months training the mean BMD of the lumbar spine (L1-L4) had increased significantly by 2.9% (P < 0.001) and the mean BMC had increased by 4.2% (P < 0.001). There was no significant change in the control group. Neither group showed a significant change in BMD or BMC in the femoral neck, greater trochanter or Ward's triangle. This study provides further evidence that exercise plays an important role in bone mineral formation.

Absorptiometry, Photon↗

Bone remodelling in the proximal femur after Charnley total hip arthroplasty.

We measured bone mineral density (BMD) in the proximal femur by dual-energy X-ray absorptiometry (DEXA) in 20 patients after cemented total hip arthroplasty over a period of one year. We found a statistically significant reduction in periprosthetic BMD after six months on the medial side and on the lateral side adjacent to the mid and distal thirds of the prosthesis. At one year after operation there was a mean 6.7% reduction in BMD in the region of the calcar and a mean 5.3% increase in BMD in the femoral shaft distal to the tip of the implant. These changes reflect a pattern of reduced stress in the proximal femur and increased stress around the tip of the prosthesis. They support current concepts of bone remodelling in the proximal femur in response to prosthetic implantation.

Absorptiometry, Photon↗