This study was designed to test the hypothesis that the sensory innervation of bone might play an important role in sensing and responding to low-intensity pulsed ultrasound and explain its effect in promoting fracture healing. In 112 rats a standardised mid-shaft tibial fracture was created, supported with an intramedullary needle and divided into four groups of 28. These either had a sciatic neurectomy or a patellar tendon resection as control, and received the ultrasound or not as a sham treatment. Fracture union, callus mineralisation and remodelling were assessed using plain radiography, peripheral quantitative computed tomography and histomorphology. Daily ultrasound treatment significantly increased the rate of union and the volumetric bone mineral density in the fracture callus in the neurally intact rats (p = 0.025), but this stimulating effect was absent in the rats with sciatic neurectomy. Histomorphology demonstrated faster maturation of the callus in the group treated with ultrasound when compared with the control group. The results supported the hypothesis that intact innervation plays an important role in allowing low-intensity pulsed ultrasound to promote fracture healing

We have evaluated in vitro the accuracy of percutaneous and ultrasound registration as measured in terms of errors in rotation and version relative to the bony anterior pelvic plane in computer-assisted total hip replacement, and analysed the intra- and inter-observer reliability of manual or ultrasound registration. Four clinicians were asked to perform registration of the landmarks of the anterior pelvic plane on two cadavers. Registration was performed under four different conditions of acquisition. Errors in rotation were not significant. Version errors were significant with percutaneous methods (16.2°; p < 0.001 and 19.25° with surgical draping; p < 0.001), but not with the ultrasound acquisition (6.2°, p = 0.13). Intra-observer repeatability was achieved for all the methods. Inter-observer analysis showed acceptable agreement in the sagittal but not in the frontal plane. Ultrasound acquisition of the anterior pelvic plane was more reliable in vitro than the cutaneous digitisation currently used

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 haematoma occurring at the site of a fracture is known to play an important role in bone healing. We have recently shown the presence of progenitor cells in human fracture haematoma and demonstrated that they have the capacity for multilineage mesenchymal differentiation. There have been many studies which have shown that low-intensity pulsed ultrasound (LIPUS) stimulates the differentiation of a variety of cells, but none has investigated the effects of LIPUS on cells derived from human fracture tissue including human fracture haematoma-derived progenitor cells (HCs). In this in vitro study, we investigated the effects of LIPUS on the osteogenic activity of HCs. Alkaline phosphatase activity, osteocalcin secretion, the expression of osteoblast-related genes and the mineralisation of HCs were shown to be significantly higher when LIPUS had been applied but without a change in the proliferation of the HCs. These findings provide evidence in favour of the use of LIPUS in the treatment of fractures

Instruments used in surgery which rotate or vibrate at a high frequency can produce potentially contaminated aerosols. Such tools are in use in cemented hip revision arthroplasties. We aimed to measure the extent of the environmental and body contamination caused by an ultrasound device and a high-speed cutter. On a human cadaver we carried out a complete surgical procedure including draping and simulated blood flow contaminated with Staphylococcus aureus (ATCC 12600). After cemented total hip arthroplasty, we undertook repeated extractions of cement using either an ultrasound device or a high-speed cutter. Surveillance cultures detected any environmental and body contamination of the surgical team. Environmental contamination was present in an area of 6 x 8 m for both devices. The concentration of contamination was lower for the ultrasound device. Both the ultrasound and the high-speed cutter contaminated all members of the surgical team. The devices tested produced aerosols which covered the whole operating theatre and all personnel present during the procedure. In contaminated and infected patients, infectious agents may be present in these aerosols. We therefore recommend the introduction of effective measures to control infection and thorough disinfection of the operating theatre after such procedures

We have studied the relationship between movements of the foot and ankle and venous blood flow from the lower limb using colourflow Duplex ultrasound to determine the optimum type of exercise for promoting venous return. Studies of both active and passive movements were carried out on 40 limbs in 20 subjects (18 men; 2 women), with a median age of 27 years (20 to 54). We assessed ankle dorsiflexion and plantar flexion, subtalar inversion and eversion, and a combination of all movements. There was no difference in venous flow when comparing opposite limbs in a single subject (p > 0.5), but active exercises produced higher peak and mean velocities of blood flow than passive ones. The active combined movement produced the highest velocities with an increase of 38% in mean and of 58% in peak flow velocities, which were significantly greater than the peak and mean flow rates produced by passive movements. The active combined exercise would therefore be the most effective in eliminating stasis and could contribute to the prevention of deep-vein thrombosis

We performed a crossover study to evaluate the haemodynamic effect of active dorsal to plantar flexion and seven pneumatic compression devices in ten patients who had a total knee arthroplasty. Using the Acuson 128XP/10 duplex ultrasound unit with a 5MHz linear array probe, we assessed the augmentation of peak venous velocity and venous volume above and below the junction of the greater saphenous and common femoral veins in order to study both the deep and superficial venous systems. The pneumatic compression devices evaluated included two foot pumps (A-V Impulse System and PlexiPulse Foot), a foot-calf pump (PlexiPulse Foot-Calf), a calf pump (VenaFlow System) and three calf-thigh pumps (SCD System, Flowtron DVT and Jobst Athrombic Pump). The devices differed in a number of ways, including the length and location of the sleeve and bladder, the frequency and duration of activation, the rate of pressure rise, and the maximum pressure achieved. A randomisation table was used to determine the order of the test conditions for each patient. The enhancement of peak venous velocity occurred primarily in the deep venous system below the level of the saphenofemoral junction. The increases in peak venous velocity were as follows: active dorsal to plantar flexion 175%; foot pumps, A-V Impulse System 29% and PlexiPulse 65%; foot-calf pump, PlexiPulse, 221%; calf pump, VenaFlow, 302% and calf-thigh pumps, Flowtron DVT 87%, SCD System 116% and Jobst Athrombic Pump 263%. All the devices augmented venous volume, the greatest effect being seen with those incorporating calf compression. The increases in ml/min were found in the deep venous system as follows: foot pumps, A-V Impulse System 9.6 and PlexiPulse Foot 16.7; foot-calf pump, PlexiPulse, 38.1; calf pump, VenaFlow, 26.2; calf-thigh pumps, Flowtron DVT 61.5, SCD System 34.7 and Jobst Athrombic Pump 82.3. Active dorsal to plantar flexion generated 8.5 ml for a single calf contraction

We undertook a study of the anti-tumour effects of hyperthermia, delivered via magnetite cationic liposomes (MCLs), on local tumours and lung metastases in a mouse model of osteosarcoma. MCLs were injected into subcutaneous osteosarcomas (LM8) and subjected to an alternating magnetic field which induced a heating effect in MCLs. A control group of mice with tumours received MCLs but were not exposed to an AMF. A further group of mice with tumours were exposed to an AMF but had not been treated with MCLs. The distribution of MCLs and local and lung metastases was evaluated histologically. The weight and volume of local tumours and the number of lung metastases were determined. Expression of heat shock protein 70 was evaluated immunohistologically. Hyperthermia using MCLs effectively heated the targeted tumour to 45°C. The mean weight of the local tumour was significantly suppressed in the hyperthermia group (p = 0.013). The mice subjected to hyperthermia had significantly fewer lung metastases than the control mice (p = 0.005). Heat shock protein 70 was expressed in tumours treated with hyperthermia, but was not found in those tumours not exposed to hyperthermia.

The results demonstrate a significant effect of hyperthermia on local tumours and reduces their potential to metastasise to the lung.

We have designed a prospective study to evaluate the usefulness of prolonged incubation of cultures from sonicated orthopaedic implants. During the study period 124 implants from 113 patients were processed (22 osteosynthetic implants, 46 hip prostheses, 54 knee prostheses, and two shoulder prostheses). Of these, 70 patients had clinical infection; 32 had received antibiotics at least seven days before removal of the implant. A total of 54 patients had sonicated samples that produced positive cultures (including four patients without infection). All of them were positive in the first seven days of incubation. No differences were found regarding previous antibiotic treatment when analysing colony counts or days of incubation in the case of a positive result. In our experience, extending incubation of the samples to 14 days does not add more positive results for sonicated orthopaedic implants (hip and knee prosthesis and osteosynthesis implants) compared with a conventional seven-day incubation period.

Cite this article: Bone Joint J 2013;95-B:1001–6.

The aim of this randomised, controlled in vivo study in an ovine model was to investigate the effect of cylic pneumatic pressure on fracture healing. We performed a transverse osteotomy of the right radius in 37 sheep. They were randomised to a control group or a treatment group where they received cyclic loading of the osteotomy by the application of a pressure cuff around the muscles of the proximal forelimb. Sheep from both groups were killed at four or six weeks. Radiography, ultrasonography, biomechanical testing and histomorphometry were used to assess the differences between the groups. The area of periosteal callus, peak torsional strength, fracture stiffness, energy absorbed over the first 10° of torsion and histomorphometric analysis all showed that the osteotomies treated with the cyclic pneumatic pressure at four weeks were not significantly different from the control osteotomies at six weeks.

The effect of zoledronic acid on bone ingrowth was examined in an animal model in which porous tantalum implants were placed bilaterally within the ulnae of seven dogs. Zoledronic acid in saline was administered via a single post-operative intravenous injection at a dose of 0.1 mg/kg. The ulnae were harvested six weeks after surgery. Undecalcified transverse histological sections of the implant-bone interfaces were imaged with backscattered scanning electron microscopy and the percentage of available pore space that was filled with new bone was calculated. The mean extent of bone ingrowth was 6.6% for the control implants and 12.2% for the zoledronic acid-treated implants, an absolute difference of 5.6% (95% confidence interval, 1.2 to 10.1) and a relative difference of 85% which was statistically significant. Individual islands of new bone formation within the implant pores were similar in number in both groups but were 69% larger in the zoledronic acid-treated group. The bisphosphonate zoledronic acid should be further investigated for use in accelerating or enhancing the biological fixation of implants to bone.

Different calcaneal plates with locked screws were compared in an experimental model of a calcaneal fracture. Four plate models were tested, three with uniaxially-locked screws (Synthes, Newdeal, Darco), and one with polyaxially-locked screws (90° ± 15°) (Rimbus). Synthetic calcanei were osteotomised to create a fracture model and then fixed with the plates and screws. Seven specimens for each plate model were subjected to cyclic loading (preload 20 N, 1000 cycles at 800 N, 0.75 mm/s), and load to failure (0.75 mm/s).

During cyclic loading, the plate with polyaxially-locked screws (Rimbus) showed significantly lower displacement in the primary loading direction than the plates with uniaxially-locked screws (mean values of maximum displacement during cyclic loading: Rimbus, 3.13 mm (sd 0.68); Synthes, 3.46 mm (sd 1.25); Darco, 4.48 mm (sd 3.17); Newdeal, 5.02 mm (sd 3.79); one-way analysis of variance, p < 0.001).

The increased stability of a plate with polyaxially-locked screws demonstrated during cyclic loading compared with plates with uniaxially-locked screws may be beneficial for clinical use.

The ability to predict load-bearing capacity during the consolidation phase in distraction osteogenesis by non-invasive means would represent a significant advance in the management of patients undergoing such treatment. Measurements of stiffness have been suggested as a promising tool for this purpose. Although the multidimensional characteristics of bone loading in compression, bending and torsion are apparent, most previous experiments have analysed only the relationship between maximum load-bearing capacity and a single type of stiffness. We have studied how compressive, bending and torsional stiffness are related to the torsional load-bearing capacity of healing callus using a common set of samples of bone regenerate from 26 sheep treated by tibial distraction osteogenesis.

Our findings showed that measurements of torsional, bending and compressive stiffness were all suitable as predictors of the load-bearing capacity of healing callus. Measurements of torsional stiffness performed slightly better than those of compressive and bending stiffness.

Allograft bone is widely used in orthopaedic surgery, but peri-operative infection of the graft remains a common and disastrous complication. The efficacy of systemic prophylactic antibiotics is unproven, and since the graft is avascular it is likely that levels of antibiotic in the graft are low.

Using an electrical potential to accelerate diffusion of antibiotics into allograft bone, high levels were achieved in specimens of both sheep and human allograft. In human bone these ranged from 187.1 mg/kg in endosteal (sd 15.7) to 124.6 (sd 46.2) in periosteal bone for gentamicin and 31.9 (sd 8.9) in endosteal and 2.9 (sd 1.1) in periosteal bone for flucloxacillin. The antibiotics remained active against bacteria in vitro after iontophoresis and continued to elute from the allograft for up to two weeks.

Structural allograft can be supplemented directly with antibiotics using iontophoresis. The technique is simple and inexpensive and offers a potential means of reducing the rate of peri-operative infection in allograft surgery. Iontophoresis into allograft bone may also be applicable to other therapeutic compounds.