Synthetic bone substitutes provide an alternative to autograft but do not give equivalent clinical results. Their performance may be enhanced by adding osteogenic growth factors. In this study, TGFβ1 was absorbed on to a carrier of β tricalcium phosphate and Gelfoam® and used to fill a defect around a tibial implant in a rat model of revision arthoplasty. We added 0.0, 0.02 μg, 0.1 μg or 1.0 μg of TGFβ1 to the carrier and then implanted it around an hydroxyapatite-coated stainless-steel pin in the proximal tibia of rats. The tibiae were harvested at three, six or 26 weeks and the amount of bone formation and ceramic resorption were assessed. TGFβ1 had no effect on the amount of bone in the defect, the amount of fluorescent label incorporated or the rate of mineral apposition. The growth factor did not significantly affect the amount of β TCP remaining in the tissue at any of the time points

Polymethylmethacrylate remains one of the most enduring materials in orthopaedic surgery. It has a central role in the success of total joint replacement and is also used in newer techniques such as percutaneous vertebroplasty and kyphoplasty. This article describes the current uses and limitations of polymethylmethacrylate in orthopaedic surgery. It focuses on its mechanical and chemical properties and links these to its clinical performance. The behaviour of antibiotic-loaded bone cement are discussed, together with areas of research that are now shedding light upon the behaviour of this unique biomaterial

Cancer-induced bone diseases are often associated with increased bone resorption and pathological fractures. In recent years, osteoprotective agents such as bisphosphonates have been studied extensively and have been shown to inhibit cancer-related bone resorption in experimental and clinical studies. The third-generation bisphosphonate, ibandronate (BM 21.0955), is a potent compound for controlling tumour osteolysis and hypercalcaemia in rats bearing Walker 256 carcinosarcoma. We have studied the effect of ibandronate given as an interventional treatment on bone strength and bone loss after the onset of tumour growth in bone. Our results suggest that it is capable of preserving bone quality in rats bearing Walker 256 carcinosarcoma cells. Since other bisphosphonates have produced comparable results in man after their success in the Walker 256 animal models our findings suggest that ibandronate may be a powerful treatment for maintaining skeletal integrity in patients with metastatic bone disease

The histology and mechanics of leg lengthening by callus distraction were studied in 27 growing rabbits. Tibial diaphyses were subjected to subperiosteal osteotomy, held in a neutral position for 10 days and then slowly distracted at 0.25 mm/12 hours, using a dynamic external fixator. Radiographs showed that the gap became filled with callus having three distinct zones. Elongation appeared to occur in a central radiolucent zone; this was bounded by two sclerotic zones. Histologically, the radiolucent zone consisted of longitudinally arranged cartilage and fibrous tissue while the sclerotic zones were formed by fine cancellous bone. New bone occasionally contained islands of cartilage, suggesting it had been formed by endochondral ossification. After completion of distraction, the two sclerotic zones fused, shrank and were eventually absorbed, leaving tubular bone with a new cortex. When the periosteum had been removed at the operation, callus formation was markedly disturbed and there was failure of bone lengthening. Scraping of endosteum, in contrast, did not have a pronounced effect. These results suggest that the preservation of periosteum is essential if bone lengthening by callus distraction is to succeed, and that preservation of the periosteum is more important than careful corticotomy

We studied the effects of high-dose irradiation on the mechanical properties and morphology of cortical bone in rabbits for 52 weeks after a single dose of 50 Gy of electron-beam to the tibia. After four weeks, the bending strength of the irradiated bone was unchanged, but at 12 weeks, the strength had decreased significantly. At 24 weeks after irradiation mean strength was less than half of controls but by 52 weeks there was a tendency toward recovery. Similar, synchronous changes of damage and recovery were seen in cortical porosity, haematopoietic cells in the bone marrow and endosteal new bone formation

An increased long-term survival of patients with malignant tumours also increases the possibility of the development of skeletal metastases and pathological fractures. The management of bone metastases includes the removal of gross disease and the administration of local adjuvants. We have investigated the possibility of adding antiblastic drugs to acrylic cement. Cylinders of acrylic cement were manufactured containing three different antiblastic drugs, methotrexate, cisplatin and doxorubicin. We performed in vitro analysis on MCF-7 human breast cancer cells in order to evaluate the biological effect of the mixtures and surface analysis of the acrylic cement-cisplatin cylinders using energy-dispersive x-ray analysis (EDAX). All drugs were released in an active form from the cement. Each drug had a different effect on cell viability. Doxorubicin had the greatest effect on breast cancer cells. Surface analysis showed that antiblastic drugs were present in the form of granules. These results confirm the potential of antiblastic-loaded cement as a possible adjuvant in the local treatment of bone metastases. Further studies should be undertaken to determine whether the release of antiblastic drugs from cement is elution or if they are only released from the surface

1. The radiographs of paired living and dead rat tibiae, obtained in an experiment previously reported, have been examined by densitometry. 2. The dead bone became progressively less dense than the living bone as the duration of the implantation increased. 3. The change in density was related to the quantity, but not to the quality, of the bone tissue examined

The occurrence of a radiolucent line at the interface of bone and cement in total joint prostheses is a frequently observed, although little understood, phenomenon. Because of an operative technique utilised in instances of bone loss, we have, within a single implant mass used in each of a series of 18 total knee replacements, been able to observe two separate interfaces, one between bone and cement and the other between bone and cobalt chrome. The average period of observation was 32 months. All of the knees except one demonstrated a lucency at the bone-cement interface; only one of the knees had a similar lucency at the bone-CoCr interface. One of the knees was studied histologically. In the light of the universal observation of macrophages at bone-cement interfaces and the recent finding that osteoclasts are derived from macrophages, these observations are significant in relation to the aetiology of bone-cement lucencies

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

Our aim was to correlate the health status with objective and radiological outcomes in patients treated by open reduction and internal fixation for fractures of both bones of the forearm. We assessed 23 patients (24 fractures) subjectively, objectively and radiologically at a mean of 34 months (11 to 72). Subjective assessment used the disability of the arm, shoulder and hand (DASH) and musculoskeletal functional attachment (MFA) questionnaires. The range of movement of the forearm and wrist, grip and pinch strength were measured objectively and standardised radiographs were evaluated. In general, patients reported good overall function based on the DASH (mean 12; range 0 to 42) and MFA (mean 19; range 0 to 51) scores. However, pronation and grip and pinch strength were significantly decreased (p < 0.005). These deficiencies correlated with poorer subjective outcomes. Operative stabilisation of fractures of the radius and ulna led to a reliably acceptable functional outcome. However, despite these generally satisfactory results, the outcome scores worsened with reduction in the range of movement of the forearm and wrist

We prospectively evaluated the percutaneous injection of autogenous bone marrow for the treatment of active simple bone cysts in ten consecutive children with cysts in the proximal humerus, proximal femur or tibia. The treatment included percutaneous biopsy, aspiration of fluid and the injection of autogenous bone marrow aspirated from the iliac crest. All the patients became painfree after a mean of two weeks and resumed full activities within six weeks. All ten cysts consolidated radiologically and showed remarkable remodelling within four months. Review at 12 to 48 months showed satisfactory healing without complications. Percutaneous injection of autologous bone marrow appears to be an effective treatment for active simple bone cysts

Femoral impaction bone allografting has been developed as a means of restoring bone stock in revision total hip replacement. We report the results of 75 consecutive patients (75 hips) with a mean age of 68 years (35 to 87) who underwent impaction grafting using the Exeter collarless, polished, tapered femoral stem between 1992 and 1998. The mean follow-up period was 10.5 years (6.3 to 14.1). The median pre-operative bone defect score was 3 (interquartile range (IQR) 2 to 3) using the Endo-Klinik classification. The median subsidence at one year post-operatively was 2 mm (IQR 1 to 3). At the final review the median Harris hip score was 80.6 (IQR 67.6 to 88.9) and the median subsidence 2 mm (IQR 1 to 4). Incorporation of the allograft into trabecular bone and secondary remodelling were noted radiologically at the final follow-up in 87% (393 of 452 zones) and 40% (181 of 452 zones), respectively. Subsidence of the Exeter stem correlated with the pre-operative Endo-Klinik bone loss score (p = 0.037). The degree of subsidence at one year had a strong association with long-term subsidence (p < 0.001). There was a significant correlation between previous revision surgery and a poor Harris Hip score (p = 0.028), and those who had undergone previous revision surgery for infection had a higher risk of complications (p = 0.048). Survivorship at 10.5 years with any further femoral operation as the end-point was 92% (95% confidence interval 82 to 97)

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

Intramedullary rods manufactured from polyacetal were used to fix diaphyseal fractures in osteoporotic bone. They are pliable and can be introduced without further damage to such bone. Their low elastic modulus induces abundant callus. They can be locked with cortical bone screws without the need of jigs or radiographic control. Nine femoral and five tibial fractures were fixed in 10 patients, all with osteoporosis; 13 united primarily; one required bone grafting. No implant broke; however, no ambulant patient weighed more than 75 kg. The rods offer a promising treatment for diaphyseal fractures in osteoporotic bone

In a prospective study of 14 patients undergoing total hip replacement we have used dual-energy X-ray absorptiometry (DEXA) to investigate remodelling of the bone around two different designs of cementless femoral prosthesis. The bone mineral density (BMD) was measured at 12-weekly intervals for a year. Eight patients (group A) had a stiff, collarless implant and six (group B) a flexible isoelastic implant. Patients in group A showed a decrease in BMD from 14 weeks after operation. By 12 months, the mean loss in BMD was 27%, both medially and laterally to the proximal part of the implant. Those in group B showed an overall increase in BMD which reached a mean of 12.6% on the lateral side of the distal portion of the implant. Our results support the current concepts of the effects of stem stiffness and flexibility on periprosthetic remodelling

It is accepted that resurfacing hip replacement preserves the bone mineral density (BMD) of the femur better than total hip replacement (THR). However, no studies have investigated any possible difference on the acetabular side. Between April 2007 and March 2009, 39 patients were randomised into two groups to receive either a resurfacing or a THR and were followed for two years. One patient’s resurfacing subsequently failed, leaving 19 patients in each group. Resurfaced replacements maintained proximal femoral BMD and, compared with THR, had an increased bone mineral density in Gruen zones 2, 3, 6, and particularly zone 7, with a gain of 7.5% (95% confidence interval (CI) 2.6 to 12.5) compared with a loss of 14.6% (95% CI 7.6 to 21.6). Resurfacing replacements maintained the BMD of the medial femoral neck and increased that in the lateral zones between 12.8% (95% CI 4.3 to 21.4) and 25.9% (95% CI 7.1 to 44.6). On the acetabular side, BMD was similar in every zone at each point in time. The mean BMD of all acetabular regions in the resurfaced group was reduced to 96.2% (95% CI 93.7 to 98.6) and for the total hip replacement group to 97.6% (95% CI 93.7 to 101.5) (p = 0.4863). A mean total loss of 3.7% (95% CI 1.0 to 6.5) and 4.9% (95% CI 0.8 to 9.0) of BMD was found above the acetabular component in W1 and 10.2% (95% CI 0.9 to 19.4) and 9.1% (95% CI 3.8 to 14.4) medial to the implant in W2 for resurfaced replacements and THRs respectively. Resurfacing resulted in a mean loss of BMD of 6.7% (95% CI 0.7 to 12.7) in W3 but the BMD inferior to the acetabular component was maintained in both groups. These results suggest that the ability of a resurfacing hip replacement to preserve BMD only applies to the femoral side

We investigated the effects of low-intensity pulsed ultrasound on distraction osteogenesis in a rabbit model. Callotasis of the right tibia was performed in 70 male Japanese white rabbits using mini-external fixators. In the first part of the study in 64 animals using normal distraction (waiting period seven days; distraction rate 0.5 mm/12 hours; distraction period ten days), we evaluated the distraction site by radiography, measurement of the bone mineral density (BMD), mechanical testing, and histology. In the second part in six rabbits using fast distraction (waiting period 0 days; distraction rate 1.5 mm/12 hours; distraction period seven days) the site was evaluated radiologically. Half of the animals (35) had received ultrasound to their right leg (30mW/cm. 2. ) for 20 minutes daily after ceasing distraction (ultrasound group), while rigid fixation only was maintained in the other half (control group). With normal distraction, the hard callus area, as shown by radiography, the BMD, and the findings on mechanical testing, were significantly greater in those receiving ultrasound than in the control group. Histological analysis showed no tissue damage attributable to exposure to ultrasound. With fast distraction, immature bone regeneration was observed radiologically in the control group, while bone maturation was achieved in the ultrasound group. We conclude that ultrasound can accelerate bone maturation in distraction osteogenesis in rabbits, even in states of poor callotasis

The long-term effect of stainless steel and titanium alloy plates on structural remodelling and bone mass of osteotomised canine femora was studied and the effects of early and late removal of plates were compared in 27 adult Beagles. Radiological, histological, histomorphometric and tetracycline fluorescence studies led to three conclusions. First, the continuous (60 weeks) presence of plates, irrespective of their composition, delays remodelling and leads to a reduction of bone mass. This loss is significantly greater under stainless steel plates. Secondly, the removal of plates at eight weeks leads during the 52 ensuing weeks to a marked and widespread structural remodelling and to a return to normal bone mass, irrespective of the type of plate used. However, remodelling is more intense after titanium alloy plates have been used; it is not complete 60 weeks after osteotomy. Thirdly, removal of plates at 40 weeks activates remodelling during the ensuing 20 weeks to a lesser degree and to a more limited extent than early plate removal. The clinical significance of this study is that less rigid but stable internal fixation permits the radiological assessment of healing and thus the determination of the optimal moment for removal of the plates. It also reduces the degree of bone loss should the plate be left in situ for any reason

1. Twenty-five lower limbs, amputated above the knee for senile atherosclerosis with peripheral gangrene, have been investigated radiologically and histologically to determine the vascular patterns in ischaemic bone with particular reference to the tibia. These have been contrasted with the patterns found in non-atherosclerotic tubular bone. 2. The principal changes are the development of a diffuse vascularisation of compact and spongy bone; a widening of Haversian spaces which come to contain a variable number of sinusoidal blood vessels; and an increasing periosteal participation in cortical nutrition which is related to the severity and chronicity of the ischaemic process. 3. Views on the normal blood supply of long bones are discussed, and evidence is presented for regarding this as discrete and end-arterial in nature; in particular it is suggested that the normal cortex has a wholly medullary, centrifugal, arterial supply

Of fifteen patients treated by excision of the lunate bone and prosthetic replacement twelve had no pain at all or slight discomfort after exceptionally heavy work. All these were able to return to and continue at heavy manual jobs. Two patients continued to experience pain with vigorous use of the wrist but were none the less satisfied with their improvement. In one patient the operation failed and pain persisted unrelieved. We believe that the radiographs show that the prosthesis greatly minimises the distortion of the carpus after excision of the lunate bone and that the maintenance of a normal carpal architecture is important in the avoidance of osteoarthritis of the remaining joints. The results suggest that when the operation is technically successful degenerative changes do not occur despite prolonged and heavy use. The presence of osteoarthritis in the wrist before operation is not a contra-indication to prosthetic replacement because the degenerative process may remain stationary for several years after removal of the damaged lunate bone. The prosthesis has proved durable over many years and none of our patients having attained a good wrist has suffered a relapse. The operation entails a month off work for a heavy labourer and as little as a fortnight for those who do lighter jobs. These considerations prompt us to suggest its wider use in the treatment of Kienböck's disease