Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and deterioration of bone microarchitecture, which results in increased bone fragility and fracture risk. Casein kinase 2-interacting protein-1 (CKIP-1) is a protein that plays an important role in regulation of bone formation. The effect of CKIP-1 on bone formation is mainly mediated through negative regulation of the bone morphogenetic protein pathway. In addition, CKIP-1 has an important role in the progression of osteoporosis. This review provides a summary of the recent studies on the role of CKIP-1 in osteoporosis development and treatment. Cite this article: X. Peng, X. Wu, J. Zhang, G. Zhang, G. Li, X. Pan. The role of CKIP-1 in osteoporosis development and treatment. Bone Joint Res 2018;7:173–178. DOI: 10.1302/2046-3758.72.BJR-2017-0172.R1

Objectives. Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis. Methods. We conducted a systematic search in several databases, including PubMed and Embase. A random-effects model was employed and results were assessed by the odds ratio (OR) and corresponding 95% confidence intervals (CI). Furthermore, with respect to each outcome, each intervention was ranked according to the surface under the cumulative ranking curve (SUCRA) value. Results. With respect to preventing new vertebral fractures (NVF), all ten drugs outperformed placebo, and etidronate proved to be the most effective treatment (OR 0.24, 95% CI 0.14 to 0.39). In addition, zoledronic acid and parathyroid hormone ranked higher compared with the other drugs. With respect to preventing clinical vertebral fractures (CVF), zoledronic acid proved to be the most effective drug (OR = 0.25, 95% CI 0.08 to 0.92), with denosumab as a desirable second option (OR = 0.48, 95% CI 0.22 to 0.96), when both were compared with placebo. As for adverse events (AE) and severe adverse events (SAE), no significant difference was observed. According to SUCRA, etidronate ranked first in preventing CVF; parathyroid hormone and zoledronic acid ranked highly in preventing NVF and CVF. Raloxifene was safe with a high rank in preventing AEs and SAEs though performed unsatisfactorily in efficacy. Conclusions. This study suggests that, taking efficacy and safety into account, parathyroid hormone and zoledronic acid had the highest probability of satisfactory performance in preventing osteoporotic fractures. Cite this article: G. Wang, L. Sui, P. Gai, G. Li, X. Qi, X. Jiang. The efficacy and safety of vertebral fracture prevention therapies in post-menopausal osteoporosis treatment: Which therapies work best? a network meta-analysis. Bone Joint Res 2017;6:452–463. DOI: 10.1302/2046-3758.67.BJR-2016-0292.R1

Objectives. Thermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature. Methods. In this study, a total of 38 frequently used antibiotic agents were maintained at 37°C in saline solution, and degradation and antibacterial activity assessed over six weeks. The impact of an initial supplementary heat exposure mimicking exothermically curing bone cement was also tested as this material is commonly used as a local delivery vehicle. Antibiotic degradation was assessed by liquid chromatography coupled to mass spectrometry, or by immunoassays, as appropriate. Antibacterial activity over time was determined by the Kirby-Bauer disk diffusion assay. Results. The heat exposure mimicking curing bone cement had minimal effect on stability for most antibiotics, except for gentamicin which experienced approximately 25% degradation as measured by immunoassay. Beta-lactam antibiotics were found to degrade quite rapidly at 37°C regardless of whether there was an initial heat exposure. Excellent long-term stability was observed for aminoglycosides, glycopeptides, tetracyclines and quinolones under both conditions. Conclusions. This study provides a valuable dataset for orthopaedic surgeons considering local application of antibiotics, and for material scientists looking to develop next-generation controlled or extended-release antibiotic carriers. Cite this article: E. Samara, T. F. Moriarty, L. A. Decosterd, R. G. Richards, E. Gautier, P. Wahl. Antibiotic stability over six weeks in aqueous solution at body temperature with and without heat treatment that mimics the curing of bone cement. Bone Joint J 2017;6:296–306. DOI: 10.1302/2046-3758.65.BJR-2017-0276.R1

In this study a combination of autologous chondrocyte implantation (ACI) and the osteochondral autograft transfer system (OATS) was used and evaluated as a treatment option for the repair of large areas of degenerative articular cartilage. We present the results at three years post-operatively. Osteochondral cores were used to restore the contour of articular cartilage in 13 patients with large lesions of the lateral femoral condyle (n = 5), medial femoral condyle (n = 7) and patella (n = 1). Autologous cultured chondrocytes were injected underneath a periosteal patch covering the cores. After one year, the patients had a significant improvement in their symptoms and after three years this level of improvement was maintained in ten of the 13 patients. Arthroscopic examination revealed that the osteochondral cores became well integrated with the surrounding cartilage. We conclude that the hybrid ACI/OATS technique provides a promising surgical approach for the treatment of patients with large degenerative osteochondral defects

Treatment with corticosteroids is a risk factor for non-traumatic avascular necrosis of the femoral head, but the pathological mechanism is poorly understood. Short-term treatment with high doses of methylprednisolone is used in severe neurotrauma and after kidney and heart transplantation. We investigated the effect of such treatment on the pattern of perfusion of the femoral head and of bone in general in the pig. We allocated 15 immature pigs to treatment with high-dose methylprednisolone (20 mg/kg per day intramuscularly for three days, followed by 10 mg/kg intramuscularly for a further 11 days) and 15 to a control group. Perfusion of the systematically subdivided femoral head, proximal femur, acetabulum, humerus, and soft tissues was determined by the microsphere technique. Blood flow in bone was severely reduced in the steroid-treated group. The reduction of flow affected all the segments and the entire epiphysis of the femoral head. No changes in flow were found in non-osseous tissue. Short-term treatment with high-dose methylprednisolone causes reduction of osseous blood flow which may be the pathogenetic factor in the early stage of steroid-induced osteonecrosis

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 intermittent administration of parathyroid hormone (PTH) increases the formation of bone by stimulating osteoblastic activity. Our study evaluates the possibility that intermittent treatment with PTH (1-34) may also enhance the implant-bone fixation of stainless-steel screws. Twenty-eight rats received one screw in either one (n = 8) or in both (n = 20) proximal tibiae. We administered either PTH (1-34) in a dosage of 60 μg/kg/day (n = 14) or vehicle (n = 14) over a period of four weeks. At the end of this time, the degree of fixation was assessed by measuring the removal torque on one screw in each rat (n = 28) and the pull-out strength on the contralateral screw (n = 20). PTH increased the mean removal torque from 1.1 to 3.5 Ncm (p = 0.001) and the mean pull-out strength from 66 to 145 N (p = 0.002). No significant differences in body-weight or ash weight of the femora were seen. Histological examination showed that both groups had areas of soft tissue at the implant-bone interface, but these appeared less in the PTH group. These results indicate that intermittent treatment with PTH may enhance the early fixation of orthopaedic implants

The treatment of fractures of the proximal tibia is complex and makes great demands on the implants used. Our study aimed to identify what levels of primary stability could be achieved with various forms of osteosynthesis in the treatment of diaphyseal fractures of the proximal tibia. Pairs of human tibiae were investigated. An unstable fracture was simulated by creating a defect at the metaphyseal-diaphyseal junction. Six implants were tested in a uniaxial testing device (Instron) using the quasi-static and displacement-controlled modes and the force-displacement curve was recorded. The movements of each fragment and of the implant were recorded video-optically (MacReflex, Qualysis). Axial deviations were evaluated at 300 N. The results show that the nailing systems tolerated the highest forces. The lowest axial deviations in varus and valgus were also found for the nailing systems; the highest axial deviations were recorded for the buttress plate and the less invasive stabilising system (LISS). In terms of rotational displacement the LISS was better than the buttress plate. In summary, it was found that higher loads were better tolerated by centrally placed load carriers than by eccentrically placed ones. In the case of the latter, it appears advantageous to use additive procedures for medial buttressing in the early phase

We have developed a new drug-delivery system using reconstituted bone xenograft to treat chronic osteomyelitis. This material, which has the capabilities of osteoinduction and osteoconduction, was supplemented with up to 2000 times the minimum inhibitory concentration of gentamicin against Staphylococcus aureus to prepare a gentamicin-reconstituted bone xenograft-composite (G-RBX-C). In a rabbit model, we evaluated the release of gentamicin from this composite in vivo, its capability for induction of ectopic bone and the repair of segmental defects of the radius. There was a high level of concentration of antibiotics, which was sustained for at least ten days. In the study of induction of ectopic bone, there was abundant woven bone in the G-RBX-C group two weeks after operation. At 16 weeks after implantation of G-RBX-C the radial defects had been repaired, with the formation of lamellar bone and recanalisation of the marrow cavity. Our findings suggest that G-RBX-C may be useful in the treatment of chronic osteomyelitis

Immobilisation causes denervation-like changes in the motor endplates, decreases the content of IGF-I, and increases the number of IGF-I receptors in the spinal cord. In the rat we investigated whether similar changes occur after a fracture of the midshaft of the femur which had been treated by intramedullary fixation with adequate or undersized pins. A more pronounced reduction in muscle wet weight was seen after fixation by undersized pins as well as decreased ash density of the ipsilateral tibia which did not completely return to normal within the 12-week experimental period. The nicotinic cholinergic receptors in the motor endplates of tibialis anterior were increased (p < 0.01) and there was a significant increase (p < 0.02) in IGF-I receptors in the lumbar spinal cord ipsilateral to the fracture after treatment by undersized nails. These changes may be associated with the impaired proprioception, co-ordination and motor activity which are sometimes seen after fractures

Objectives

There are various pin-in-plaster methods for treating fractures of the distal radius. The purpose of this study is to introduce a modified technique of ‘pin in plaster’.

Objective. To study the effect of hyaluronic acid (HA) on local anaesthetic chondrotoxicity in vitro. Methods. Chondrocytes were harvested from bovine femoral condyle cartilage and isolated using collagenase-containing media. At 24 hours after seeding 15 000 cells per well onto a 96-well plate, chondrocytes were treated with media (DMEM/F12 + ITS), PBS, 1:1 lidocaine (2%):PBS, 1:1 bupivacaine (0.5%):PBS, 1:1 lidocaine (2%):HA, 1:1 bupivacaine (0. 5%):HA, or 1:1 HA:PBS for one hour. Following treatment, groups had conditions removed and 24-hour incubation. Cell viability was assessed using PrestoBlue and confirmed visually using fluorescence microscopy. Results. Media-treated groups had a mean of 1.55×10. 4. cells/well (. sem. 783). All treated cells showed statistically significant reduced viability when compared with media alone (all p < 0.003). Cells treated with bupivacaine + HA (6.70×10. 3. cells/well (. sem. 1.10×10. 3. )) survived significantly more than bupivacaine (2.44×10. 3. cells/well (. sem . 830)) (p < 0.001). Lidocaine + HA (1.45×10. 3. cells/well (. sem. 596)) was not significantly more cytotoxic than lidocaine (2.24×10. 3. cells/well (. sem. 341)) (p = 0.999). There was no statistical difference between the chondrotoxicities of PBS (8.49×10. 3. cells/well (. sem. 730) cells/well) and HA (4.75×10. 3. cells/well (. sem. 886)) (p = 0.294). Conclusions. HA co-administration reduced anaesthetic cytotoxicity with bupivacaine but not lidocaine, suggesting different mechanisms of injury between the two. Co-administered intra-articular injections of HA with bupivacaine, but not lidocaine, may protect articular chondrocytes from local anaesthetic-associated death. Cite this article: Bone Joint Res 2013;2:270–5

In a series of 12 patients with inoperable gastric carcinoma who had treatment with a synthetic matrix metalloproteinase inhibitor (Marimastat) for more than one month, six developed a frozen shoulder or a condition resembling Dupuytren’s disease. This suggests that the matrix metalloproteinases, a family of naturally occurring proteinases, may be involved in the pathogenesis of these two conditions. Our observation opens avenues for further research which could lead to local or systemic therapeutic interventions for frozen shoulder and Dupuytren’s disease

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.

The use of a composite osteochondral device for simulating partial hemiarthroplasty was examined. The device was composed of a polyvinyl alcohol hydrogel and a titanium fibre mesh, acting as artificial cartilage and as porous artificial bone, respectively. The titanium fibre mesh was designed to act as an interface material, allowing firm attachment to both the polyvinyl alcohol gel (through injection moulding) and the femoral joint surface (through bony ingrowth). We implanted 22 of these devices into canine femoral heads. Histological findings from the acetabular cartilage and synovial membrane, as well as the attachment of the prosthesis to bone, were examined up until one year after operation.

No marked pathological changes were found and firm attachment of the device to the underlying bone was confirmed. The main potential application for this device is for partial surface replacement of the femoral head after osteonecrosis. Other applications could include articular resurfacing and the replacement of intervertebral discs.

The efficacy of β-tricalcium phosphate (β-TCP) loaded with bone morphogenetic protein-2 (BMP-2)-gene-modified bone-marrow mesenchymal stem cells (BMSCs) was evaluated for the repair of experimentally-induced osteonecrosis of the femoral head in goats.

Bilateral early-stage osteonecrosis was induced in adult goats three weeks after ligation of the lateral and medial circumflex arteries and delivery of liquid nitrogen into the femoral head. After core decompression, porous β-TCP loaded with BMP-2 gene- or β-galactosidase (gal)-gene-transduced BMSCs was implanted into the left and right femoral heads, respectively. At 16 weeks after implantation, there was collapse of the femoral head in the untreated group but not in the BMP-2 or β-gal groups. The femoral heads in the BMP-2 group had a normal density and surface, while those in the β-gal group presented with a low density and an irregular surface. Histologically, new bone and fibrous tissue were formed in the macropores of the β-TCP. Sixteen weeks after implantation, lamellar bone had formed in the BMP-2 group, but there were some empty cavities and residual fibrous tissue in the β-gal group. The new bone volume in the BMP-2 group was significantly higher than that in the β-gal group. The maximum compressive strength and Young’s modulus of the repaired tissue in the BMP-2 group were similar to those of normal bone and significantly higher than those in the β-gal group.

Our findings indicate that porous β-TCP loaded with BMP-2-gene-transduced BMSCs are capable of repairing early-stage, experimentally-induced osteonecrosis of the femoral head and of restoring its mechanical function.

We have investigated the anatomy of the proximal part of the ulna to assess its influence on the use of plates in the management of fractures at this site. We examined 54 specimens from cadavers. The mean varus angulation in the proximal third was 17.5° (11° to 23°) and the mean anterior deviation 4.5° (1° to 14°). These variations must be considered when applying plates to the dorsal surface of the ulna for Monteggia-type fractures. A pre-operative radiograph of the contralateral elbow may also be of value.

We have developed a new drug delivery system using porous apatite-wollastonite glass ceramic (A-W GC) to treat osteomyelitis. A-W GC (porosity, 70% and 20% to 30%), or porous hydroxyapatite (HA) blocks (porosity 35% to 48%) used as controls, were soaked in mixtures of two antibiotics, isepamicin sulphate (ISP) and cefmetazole (CMZ) under high vacuum.

We evaluated the release concentrations of the antibiotics from the blocks. The bactericidal concentration of ISP from A-W GC was maintained for more than 42 days, but that from HA decreased to below the detection limit after 28 days. The concentrations of CMZ from both materials were lower than those of ISP. An in vivo study using rabbit femora showed that an osseous concentration of ISP was maintained at eight weeks after implantation. Osteoconduction of the A-W GC block was good.

Four patients with infected hip arthroplasties and one with osteomyelitis of the tibia have been treated with the new delivery system with excellent results.

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. Methods. In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload. Results. Utilizing an OVX rat model, we observed significant alterations in bone mass and osseointegration due to VIT administration in aged rats with iron overload. The observed effects were concomitant with reductions in bone metabolism, oxidative stress, and inflammation. To elucidate whether these effects are associated with osteoclast and osteoblast activity, we conducted in vitro experiments using MC3T3-E1 cells and RAW264.7 cells. Our findings indicate that iron accumulation suppressed the activity of MC3T3-E1 while enhancing RAW264.7 function. Furthermore, iron overload significantly decreased oxidative stress levels; however, these detrimental effects can be mitigated by VIT treatment. Conclusion. Collectively, our data provide compelling evidence that VIT has the potential to reverse the deleterious consequences of iron overload on osseointegration and bone mass during ageing. Cite this article: Bone Joint Res 2024;13(9):427–440

This edition of Cochrane Corner looks at some of the work published by the Cochrane Collaboration, covering pharmacological interventions for the prevention of bleeding in people undergoing definitive fixation or joint replacement for hip, pelvic, and long bone fractures; interventions for reducing red blood cell transfusion in adults undergoing hip fracture surgery: an overview of systematic reviews; and pharmacological treatments for low back pain in adults: an overview of Cochrane Reviews