Although much has been published on the causes of slipped upper femoral epiphysis and the results of treatment, little attention has been given to the mechanism of the slip. This study presents the results of the analysis of 13 adolescent femora, and the attempts to reproduce the radiological appearances of a typical slip. The mean age of the skeletons was 13 years (11 to 15). It was found that the internal bony architecture in the zone of the growth plate was such that a slip of the epiphysis on the metaphysis (in the normal meaning of the word slip) could not take place, largely relating to the presence of a tubercle of bone projecting down from the epiphysis. The only way that the appearance of a typical slipped upper femoral epiphysis could be reproduced was by rotating the epiphysis posteromedially on the metaphysis. The presence and size of this peg-like tubercle was shown radiologically by CT scanning in one pair of intact adolescent femurs

Objectives. The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models. Materials and Methods. A literature search was performed on the Pubmed, Embase, and Web of Science databases, and relevant articles were selected. A total of 19 studies were included. Information on the animal, induction of osteoporosis, fracture technique, site and fixation, healing results, and utility of the model were extracted. Results. Fracture techniques included drill hole defects (3 of 19), bone defects (3 of 19), partial osteotomy (1 of 19), and complete osteotomies (12 of 19). Drill hole models and incomplete osteotomy models are easy to perform and allow the study of therapeutic agents but do not represent the usual clinical setting. Additionally, biomaterials can be filled into drill hole defects for analysis. Complete osteotomy models are most commonly used and are best suited for the investigation of therapeutic drugs or noninvasive interventions. The metaphyseal defect models allow the study of biomaterials, which are associated with complex and comminuted osteoporotic fractures. Conclusion. For a clinically relevant model, we propose that an animal model should satisfy the following criteria to study osteoporotic fracture healing: 1) induction of osteoporosis, 2) complete osteotomy or defect at the metaphysis unilaterally, and 3) internal fixation. Cite this article: R. M. Y. Wong, M. H. V. Choy, M. C. M. Li, K-S. Leung, S. K-H. Chow, W-H. Cheung, J. C. Y. Cheng. A systematic review of current osteoporotic metaphyseal fracture animal models. Bone Joint Res 2018;7:6–11. DOI: 10.1302/2046-3758.71.BJR-2016-0334.R2

Aims

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

We measured the insertion and extraction torque forces in a randomised study of 76 external fixation screws in 19 patients treated by hemicallotasis for osteoarthritis of the medial side of the knee. The patients were randomised to have either standard tapered screws (Orthofix 6/5 mm) or the same screws with hydroxyapatite (HA) coating. One patient had two standard and two HA-coated screws. All patients had an anterior external fixator (Orthofix T-garche), with two screws in the proximal tibial metaphysis parallel to and about 2 cm below the joint surface and two in the tibial diaphysis. The mean torque forces for insertion of the standard screws were 260 Ncm for the proximal to medial screw, 208 for the proximal to lateral screw and 498 and 546 Ncm for the diaphyseal pins. The corresponding forces for the HA-coated pins were not significantly different. The torque forces for the extraction of the standard pins were 2 Ncm for the proximal pins, 277 and 249 Ncm for the distal pins and 482, 478, 585 and 620 Ncm, respectively (p < 0.005) for the HA-coated pins. All 18 of the metaphyseal standard screws were loose at extraction (extraction force < 20 Ncm), but only one of the HA screws in the metaphysis was loose. In the diaphysis the standard screws lost about 40% of their fixation in contrast to the HA-coated screws which retained full fixation strength

Strains applied to bone can stimulate its development and adaptation. High strains and rates of strain are thought to be osteogenic, but the specific dose response relationship is not known. In vivo human strain measurements have been performed in the tibia to try to identify optimal bone strengthening exercises for this bone, but no measurements have been performed in the distal radial metaphysis, the most frequent site of osteoporotic fractures. Using a strain gauged bone staple, in vivo dorsal metaphyseal radial strains and rates of strain were measured in ten female patients during activities of daily living, standard exercises and falls on extended hands. Push-ups and falling resulted in the largest compression strains (median 1345 to 3146 με, equivalent to a 0.1345% to 0.3146% length change) and falling exercises in the largest strain rates (18 582 to 45 954 με/s). On the basis of their high strain and/or strain rates these or variations of these exercises may be appropriate for distal radial metaphyseal bone strengthening

We observed the healing process under rigid external fixation after Salter-Harris type-1 or type-2 physeal separation at the proximal tibia in immature rabbits. Metaphyseal vessels grew across the gap with little delay; the site of separation then came to lie in the metaphysis and was bridged by endochondral ossification. Union was achieved within two days in all rabbits. Progression of endochondral ossification repaired the separated physis, thus showing ‘primary healing of physeal separation’. This depends on accurate reduction and stable fixation to allow the survival of vessels across the gap

We have compared the changes in the pattern of the principal strains in the proximal femur after insertion of eight uncemented anatomical stems and eight customised stems in human cadaver femora. During testing we aimed to reproduce the physiological loads on the proximal femur and to simulate single-leg stance and stair-climbing. The strains in the intact femora were measured and there were no significant differences in principal tensile and compressive strains in the left and right femora of each pair. The two types of femoral stem were then inserted randomly into the left or right femora and the cortical strains were again measured. Both induced significant stress shielding in the proximal part of the metaphysis, but the deviation from the physiological strains was most pronounced after insertion of the anatomical stems. The principal compressive strain at the calcar was reduced by 90% for the anatomical stems and 67% for the customised stems. Medially, at the level of the lesser trochanter, the corresponding figures were 59% and 21%. The anatomical stems induced more stress concentration on the anterior aspect of the femur than did the customised stems. They also increased the hoop strains in the proximomedial femur. Our study shows a consistently more physiological pattern of strain in the proximal femur after insertion of customised stems compared with standard, anatomical stems

Intermittent treatment with parathyroid hormone (PTH) has an anabolic effect on both intact cancellous and cortical bone. Very little is known about the effect of the administration of PTH on the healing of fractures or the incorporation of orthopaedic implants. We have investigated the spontaneous ingrowth of callus and the formation of bone in a titanium chamber implanted at the medioproximal aspect of the tibial metaphysis of the rat. Four groups of ten male rats weighing approximately 350 g were injected with human PTH (1-34) in a dosage of 0, 15, 60 or 240 μg/kg/day, respectively, for 42 days from the day of implantation of the chamber. During the observation period the chamber became only partly filled with callus and bone and no difference in ingrowth distance into the chamber was found between the groups. The cancellous density was increased by 90%, 132% and 173% in the groups given PTH in a dosage of 15, 60 or 240 μg/kg/day, respectively. There was a linear correlation between bone density and the log PTH doses (r. 2. = 0.6). Our findings suggest that treatment with PTH may have a potential for enhancement of the incorporation of orthopaedic implants as well as a beneficial effect on the healing of fractures when it is given in low dosages

Six pairs of human cadaver femora were divided equally into two groups one of which received a non-cemented reference implant and the other a very short non-dependent experimental implant. Thirteen strain-gauge rosettes were attached to the external surface of each specimen and, during application of combined axial and torsional loads to the femoral head, the strains in both groups were measured. After the insertion of a non-cemented femoral component, the normal pattern of a progressive proximal-to-distal increase in strains was similar to that in the intact femur and the strain was maximum near the tip of the prosthesis. On the medial and lateral aspects of the proximal femur, the strains were greatly reduced after implantation of both types of implant. The pattern and magnitude of the strains, however, were closer to those in the intact femur after insertion of the experimental stem than in the reference stem. On the anterior and posterior aspects of the femur, implantation of both types of stem led to increased principal strains E1, E2 and E3. This was most pronounced for the experimental stem. Our findings suggest that the experimental stem, which has a more anatomical proximal fit without having a distal stem and cortex contact, can provide immediate postoperative stability. Pure proximal loading by the experimental stem in the metaphysis, reduction of excessive bending stiffness of the stem by tapering and the absence of contact between the stem and the distal cortex may reduce stress shielding, bone resorption and thigh pain

Objectives

Healing in cancellous metaphyseal bone might be different from midshaft fracture healing due to different access to mesenchymal stem cells, and because metaphyseal bone often heals without a cartilaginous phase. Inflammation plays an important role in the healing of a shaft fracture, but if metaphyseal injury is different, it is important to clarify if the role of inflammation is also different. The biology of fracture healing is also influenced by the degree of mechanical stability. It is unclear if inflammation interacts with stability-related factors.

Objectives

Electromagnetic fields (EMF) are widely used in musculoskeletal disorders. There are indications that EMF might also be effective in the treatment of osteoporosis. To justify clinical follow-up experiments, we examined the effects of EMF on bone micro-architectural changes in osteoporotic and healthy rats. Moreover, we tested the effects of EMF on fracture healing.

Objectives

The aim of this experimental study on New Zealand’s white rabbits was to investigate the transplantation of autogenous growth plate cells in order to treat the injured growth plate. They were assessed in terms of measurements of radiological tibial varus and histological characteristics.

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.

Platelet-leucocyte gel (PLG), a new biotechnological blood product, has hitherto been used primarily to treat chronic ulcers and to promote soft-tissue and bone regeneration in a wide range of medical fields. In this study, the antimicrobial efficacy of PLG against Staphylococcus aureus (ATCC 25923) was investigated in a rabbit model of osteomyelitis. Autologous PLG was injected into the tibial canal after inoculation with Staph. aureus. The prophylactic efficacy of PLG was evaluated by microbiological, radiological and histological examination. Animal groups included a treatment group that received systemic cefazolin and a control group that received no treatment.

Treatment with PLG or cefazolin significantly reduced radiological and histological severity scores compared to the control group. This result was confirmed by a significant reduction in the infection rate and the number of viable bacteria. Although not comparable to cefazolin, PLG exhibited antimicrobial efficacy in vivo and therefore represents a novel strategy to prevent bone infection in humans.

Soaking bone grafts in a bisphosphonate solution before implantation can prevent their resorption and increase the local bone density in rats and humans. However, recent studies suggest that pre-treatment of allografts with bisphosphonate can prevent bone ingrowth into impaction grafts. We tested the hypothesis that excessive amounts of bisphosphonate would also cause a negative response in less dense grafts. We used a model where non-impacted metaphyseal bone grafts were randomised into three groups with either no bisphosphonate, alendronate followed by rinsing, and alendronate without subsequent rinsing, and inserted into bone chambers in rats. The specimens were evaluated histologically at one week, and by histomorphometry and radiology at four weeks. At four weeks, both bisphosphonate groups showed an increase in the total bone content, increased newly formed bone, and higher radiodensity than the controls. In spite of being implanted in a chamber with a limited opportunity to diffuse, even an excessive amount of bisphosphonate improved the outcome. We suggest that the negative results seen by others could be due to the combination of densely compacted bone and a bisphosphonate.

We suggest that bisphosphonates are likely to have a negative influence where resorption is a prerequisite to create space for new bone ingrowth.

The re-establishment of vascularity is an early event in fracture healing; upregulation of angiogenesis may therefore promote the formation of bone. We have investigated the capacity of vascular endothelial growth factor (VEGF) to stimulate the formation of bone in an experimental atrophic nonunion model.

Three groups of eight rabbits underwent a standard nonunion operation. This was followed by interfragmentary deposition of 100 μg VEGF, carrier alone or autograft.

After seven weeks, torsional failure tests and callus size confirmed that VEGF-treated osteotomies had united whereas the carrier-treated osteotomies failed to unite. The biomechanical properties of the groups treated with VEGF and autograft were identical. There was no difference in bone blood flow.

We considered that VEGF stimulated the formation of competent bone in an environment deprived of its normal vascularisation and osteoprogenitor cell supply. It could be used to enhance the healing of fractures predisposed to nonunion.

A cavovarus foot deformity was simulated in cadaver specimens by inserting metallic wedges of 15° and 30° dorsally into the first tarsometatarsal joint. Sensors in the ankle joint recorded static tibiotalar pressure distribution at physiological load.

The peak pressure increased significantly from neutral alignment to the 30° cavus deformity, and the centre of force migrated medially. The anterior migration of the centre of force was significant for both the 15° (repeated measures analysis of variance (ANOVA), p = 0.021) and the 30° (repeated measures ANOVA, p = 0.007) cavus deformity. Differences in ligament laxity did not influence the peak pressure.

These findings support the hypothesis that the cavovarus foot deformity causes an increase in anteromedial ankle joint pressure leading to anteromedial arthrosis in the long term, even in the absence of lateral hindfoot instability.

We investigated the effect of pre-heating a femoral component on the porosity and strength of bone cement, with or without vacuum mixing used for total hip replacement.

Cement mantles were moulded in a manner simulating clinical practice for cemented hip replacement. During polymerisation, the temperature was monitored. Specimens of cement extracted from the mantles underwent bending or fatigue tests, and were examined for porosity.

Pre-heating the stem alone significantly increased the mean temperature values measured within the mantle (+14.2°C) (p < 0.001) and reduced the mean curing time (−1.5 min) (p < 0.001). The addition of vacuum mixing modulated the mean rise in the temperature of polymerisation to 11°C and reduced the mean duration of the process by one minute and 50 seconds (p = 0.01 and p < 0.001, respectively). In all cases, the maximum temperature values measured in the mould simulating the femur were < 50°C. The mixing technique and pre-heating the stem slightly increased the static mechanical strength of bone cement. However, the fatigue life of the cement was improved by both vacuum mixing and pre-heating the stem, but was most marked (+ 280°C) when these methods were combined.

Pre-heating the stem appears to be an effective way of improving the quality of the cement mantle, which might enhance the long-term performance of bone cement, especially when combined with vacuum mixing.

We have examined the deterioration of implant fixation after withdrawal of parathyroid hormone (PTH) in rats. First, the pull-out force for stainless-steel screws in the proximal tibia was measured at different times after withdrawal. The stimulatory effect of PTH on fixation was lost after 16 days. We then studied whether bisphosphonates could block this withdrawal effect. Mechanical and histomorphometric measurements were conducted for five weeks after implantation. Subcutaneous injections were given daily. Specimens treated with either PTH or saline during the first two weeks showed no difference in the mechanical or histological results (pull-out force 76 N vs 81 N; bone volume density 19% vs 20%). Treatment with PTH for two weeks followed by pamidronate almost doubled the pull-out force (152 N; p < 0.001) and the bone volume density (37%; ANOVA, p < 0.001). Pamidronate alone did not have this effect (89 N and 25%, respectively). Thus, the deterioration can be blocked by bisphosphonates. The clinical implications are discussed.

The aim of this study was to determine the effectiveness of antibiotic-impregnated implants in the prevention of bone infection. We used a model of contaminated fracture in goats to evaluate four treatment groups: no treatment, hand-made tobramycin-impregnated polymethylmethacrylate beads, commercially-available tobramycin-impregnated calcium sulphate pellets and commercially-available tobramycin-impregnated polymethylmethacrylate beads. Three weeks after intraosseous inoculation with streptomycin-resistant Staphylococcus aureus tissue cultures showed no evidence of infection in any of the antibiotic-treated groups. All of the cultures were positive in the untreated group. These results show that effective local antibiotic delivery can be obtained with both commercially-available products and with hand-made polymethylmethacrylate beads. The calcium sulphate pellets have the advantage of being bioabsorbable, thereby obviating the need for a second procedure to remove them.