Aims

Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Interleukin-19 (IL-19), a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. The aim of our study was to investigate the effect of IL-19 on osteoporosis.

Aims. The aim of this study was to investigate the global and local impact of fat on bone in obesity by using the diet-induced obese (DIO) mouse model. Methods. In this study, we generated a diet-induced mouse model of obesity to conduct lipidomic and 3D imaging assessments of bone marrow fat, and evaluated the correlated bone adaptation indices and bone mechanical properties. Results. Our results indicated that bone mass was reduced and bone mechanical properties were impaired in DIO mice. Lipidomic sequencing and bioinformatic analysis identified 373 differential lipids, 176 of which were upregulated and 197 downregulated. Functional enrichment analysis revealed a significant downregulation of the pathways: fat digestion and absorption (ko04975) and lipolysis regulation in adipocytes (ko04923) in DIO mice, leading to local fat accumulation. The use of 3D imaging confirmed the increase in fat accumulation within the bone marrow cavity of obese mice. Conclusion. Our study sheds light on the intricate interplay between fat and bone, and provides a non-toxic and non-invasive method for measuring marrow adipose tissue. Cite this article: Bone Joint Res 2023;12(9):580–589

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.

Aims

Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models.

Aims

To verify whether secretory leucocyte protease inhibitor (SLPI) can promote early tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction.

Aims

Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named ‘tibial cortex transverse transport’ (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT animal model.

Aims

Femoral bone preparation using compaction technique has been shown to preserve bone and improve implant fixation in animal models. No long-term clinical outcomes are available. There are no significant long-term differences between compaction and broaching techniques for primary total hip arthroplasty (THA) in terms of migration, clinical, and radiological outcomes.

Aims

Acquired heterotopic ossification (HO) is a debilitating disease characterized by abnormal extraskeletal bone formation within soft-tissues after injury. The exact pathogenesis of HO remains unknown. It was reported that BRD4 may contribute to osteoblastic differentiation. The current study aims to determine the role of BRD4 in the pathogenesis of HO and whether it could be a potential target for HO therapy.

Aims

Surgeons and most engineers believe that bone compaction improves implant primary stability without causing undue damage to the bone itself. In this study, we developed a murine distal femoral implant model and tested this dogma.

Introduction. On the basis of a proposal by Noble, the marrow cavity form can be classified into three categories: normal, champagne-fluted and stovepipe. In the present study, three typical finite element femoral models were created using CT data based on Noble's three categories. The purpose was to identify the relationship of stress distribution of the surrounding areas between femoral bone marrow cavity form and hip stems. The results shed light on whether the distribution of the high-stress area reflects the stem design concept. In order to improve the results of THA, researchers need to consider the instability of a stem design based on the stress distributioin and give feedback on future stem selection. Methods. As analyzing object, we selected SL-PLUS and BiCONTACT stems. To develop finite element models, two parts (cortical bone and stem) were constructed using four-node tetrahedral elements. The model consisted of about 60,000 elements. The material characteristics were defined by the combination of mass density, elastic coefficient, and Poisson's ratio. Concerning the analysis system, HP Z800 Workstation was used as hardware and LS-DYNA Ver. 971 as software. The distal end of the femur was constrained in all directions. On the basis of ISO 7206 Part 4,8 that specifies a method of endurance testing for joint prostheses, the stem was tilted 10°, and a 1500 N resultant force in the area around the hip joint was applied to the head at an angle of 25° with the long axis. Automatic contact with a consideration of slip was used. Result. The maximum stress on femur implanted a SL-PLUS with marrow cavity form of normal, champagne-fluted and stovepipe were shown to be 90MPa, 90MPa and 45MPa. The maximum stress on a BiCONTACT with marrow cavity form of normal, champagne-fluted and stovepipe were shown to be 45MPa, 90MPa and 15MPa. Discussion. The design concept for aZweymüller-type stem can distribute load across a wide range of cortical bone from the middle position to the distal femur. It is determined using this concept that a wide range of stress was absorbed at the middle position and distal femur in the champagne-fluted and normal cases. On the other hand, the contact pressure zone of stovepipe could not meet the expected level at the distal femur. The method of this research involves controlling the stress conditions within the stem design. At this point, it is considered possible for the stability of various stem designs to be predicted and the stability to be assessed positively. On the basis of Noble's categories, three types of finite element model were made, and stress distribution measurement and finite element analyses were performed. The results indicate that Zweymüller stem has clinical validity for securing force in the champagne-fluted and stovepipe types from the stress distribution

Introduction. According to proposal of Noble, the femoral bone marrow cavity form of patients who underwent Total Hip Arthroplasty (THA) can be classified under 3 categories; those are Stovepipe, Normal and Champagne-fluted. We developed typical sodium chloride femoral model was created by 3D prototyping technique. The purpose was to identify the relationship of pressure zone of the surrounding areas between femoral bone marrow cavity form and hip stem. Materials and Method. As opponent clarified stem design concept Zweymüller type model was used. According to CT data with the patients who underwent THA, the sodium chloride femoral model was custom-made and selected as the representative model based on Noble's 3 categories. Eight models of each category were used to performed mechanical test. Result. In mechanics test, the result of comparison between the contact pressure zones of zone 1–7, significant differences of contact pressure zones were identified between the Stovepipe group and Normal group in zone 3, 4 and 5. In zone 3 and 5, such significant differences were also identified between Champagne-fluted group and Normal group. In Stovepipe group, a significant difference of the contact pressure zone was observed at the proximal and distal. In Champagne-fluted group and the Normal group, a significant difference was observed in the contact pressure in distal femur (3, 4, 5 Zone) and (Zone1, 2, 6, 7) proximal femur. Discussion. Although in most studies Sawbone® is used for femoral models, the focus of this research is of those who possess a characteristic femur with marrow cavity form. Therefore, sodium chloride bone model was used instead. In comparison in terms of applicability between sodium chloride bone model and regular model, the failure of all 24 joints of sodium chloride bone model were unconfirmed in mechanics test. Moreover, the possibility that its performance in mechanics test is equivalent to Sawbone®is considered. The design concept for Zweymüller type achieves the ability to load distribute within a wide range of cortical bone across the middle position to distal femur. It's determined by the concept that a wide range of contact pressure was admitted at middle position and distal femur in the Champagne-fluted group and the Normal group. On the other hand, the contact pressure zone of Stovepipe was not able to meet the expected level at distal femur. The method of this research is control its stress condition within the stem design. By this point, it is considered possible that the stability of various stem design was able to be forecasted and the assessment of stableness was positive. Conclusion. On the basis of Noble's categories, 3 types of bone models were created by 3D prototyping technique, and pressure distribution measurement were performed. The result from the pressure distribution indicated that even in Zweymüller stem had anxiety of securing force in Champagne-fluted type and Stovepipe type canal. We believe the method of in vivo study can develop to assess the stability of implant preoperatively

Introduction. On the basis of a proposal by Noble, the marrow cavity form can be classified into three categories: stovepipe, normal, and champagne-fluted. In the present study, three typical finite element femoral models were created using CT data based on Noble's three categories. The purpose was to identify the relationship of stress distribution of the surrounding areas between femoral bone marrow cavity form and hip stem. The results shed light on whether the distribution of the high-stress area reflects the stem design concept. In order to improve the results of THA, researchers need to consider the instability of a stem design based on the pressure zone and give feedback on future stem selection. Methods. To develop finite element models, two parts (cortical bone and stem) were constructed using four-node tetrahedral elements. The model consisted of about 40,000 elements. The material characteristics were defined by the combination of mass density, elastic coefficient, and Poisson's ratio. Concerning the analysis system, HP Z800 Workstation(HP, Japan) was used as hardware and LS-DYNA Ver. 971 (Livermore Software Technology Corporation, USA) as software. The distal end of the femur was constrained in all directions. On the basis of ISO 7206 Part 4,8 that specifies a method of endurance testing for joint prostheses, the stem was tilted 10°, and a 500 N resultant force in the area around the hip joint was applied to the head at an angle of 25° with the long axis. Automatic contact with a consideration of slip was used. Von Mises stress during a 1.0 s period after loading was analyzed, and stress distribution in the stem and its maximum value were calculated. Result. The maximum stress at marrow cavity form of normal was shown to be 72 MPa. The stress of champagne-fluted was evenly distributed from proximal to distal, and the maximum stress was 67 MPa. For stovepipe, the maximum proximal stress was shown to be 120 MPa; moreover, stress concentration was observed. Discussion. The design concept for a Zweymüller-type stem can distribute load across a wide range of cortical bone from the middle position to the distal femur. It is determined using this concept that a wide range of stress was absorbed at the middle position and distal femur in the champagne-fluted and normal cases. On the other hand, the contact pressure zone of stovepipe could not meet the expected level at the distal femur. The method of this research involves controlling the stress conditions within the stem design. At this point, it is considered possible for the stability of various stem designs to be predicted and the stability to be assessed positively. On the basis of Noble's categories, three types of finite element model were made, and stress distribution measurement and finite element analyses were performed. The results indicate that Zweymüller stem has clinical validity for securing force in the champagne-fluted and stovepipe types from the stress distribution

Objectives

The major problem with repair of an articular cartilage injury is the extensive difference in the structure and function of regenerated, compared with normal cartilage. Our work investigates the feasibility of repairing articular osteochondral defects in the canine knee joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate (ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells (BMSCs) and assesses its biological compatibility.

The treatment of osteochondral lesions and osteoarthritis remains an ongoing clinical challenge in orthopaedics. This review examines the current research in the fields of cartilage regeneration, osteochondral defect treatment, and biological joint resurfacing, and reports on the results of clinical and pre-clinical studies. We also report on novel treatment strategies and discuss their potential promise or pitfalls. Current focus involves the use of a scaffold providing mechanical support with the addition of chondrocytes or mesenchymal stem cells (MSCs), or the use of cell homing to differentiate the organism’s own endogenous cell sources into cartilage. This method is usually performed with scaffolds that have been coated with a chemotactic agent or with structures that support the sustained release of growth factors or other chondroinductive agents. We also discuss unique methods and designs for cell homing and scaffold production, and improvements in biological joint resurfacing. There have been a number of exciting new studies and techniques developed that aim to repair or restore osteochondral lesions and to treat larger defects or the entire articular surface. The concept of a biological total joint replacement appears to have much potential.

Cite this article: Bone Joint Res 2013;2:193–9.

To determine the gross structural alterations of the nailed bone (femur or tibia) after the removal of an intramedullary nail (IMN). Eighteen patients (14 femoral and 4 tibia nail) underwent an IMN removal from their femur or tibia. Every patient had a spiral computed tomography scan and a plain X-ray study, immediately after the nail removal and also at their latest follow-up (24–30 months). The 4 patients with a tibia nail were additionally examined using a peripheral quantitative computed tomography study at their latest follow-up. All patients were asymptomatic. An intramedullary shell of compact bone was demonstrated around the nail track. This new bone was apparent on plain radiographs in all of the patients. Peripheral quantitative computed tomography study revealed that the density of the bony ring was similar to that of subcortical bone. The histologic examination of the intra-medullary shell of one of our patients suggested that the bony ring was made of cortical bone. Intramedullary nailing may enhance new cortical bone formation within the bone marrow cavity. This “cortical bone” still exists more than 2 years after implant removal. Nail insertion also causes thickening of the normal cortex at the sites of nail–cortex contact where loads are transferred from the nail to the cortex. This new finding could probably lead the research of intramedullary nailing biomechanics toward new directions as to understand the body’s reaction to IMNs

Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 μm to 500 μm and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 μg/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks.

In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites.

In a rabbit model we investigated the efficacy of a silk fibroin/hydroxyapatite (SF/HA) composite on the repair of a segmental bone defect. Four types of porous SF/HA composites (SF/HA-1, SF/HA-2, SF/HA-3, SF/HA-4) with different material ratios, pore sizes, porosity and additives were implanted subcutaneously into Sprague-Dawley rats to observe biodegradation. SF/HA-3, which had characteristics more suitable for a bone substitite based on strength and resorption was selected as a scaffold and co-cultured with rabbit bone-marrow stromal cells (BMSCs). A segmental bone defect was created in the rabbit radius. The animals were randomised into group 1 (SF/HA-3 combined with BMSCs implanted into the bone defect), group 2 (SF/HA implanted alone) and group 3 (nothing implanted). They were killed at four, eight and 12 weeks for visual, radiological and histological study.

The bone defects had complete union for group 1 and partial union in group 2, 12 weeks after operation. There was no formation of new bone in group 3. We conclude that SF/HA-3 combined with BMSCs supports bone healing and offers potential as a bone-graft substitute.

Breast cancer is generally managed surgically with adjuvant agents which include hormone therapy, chemotherapy, radiotherapy and bisphosphonate therapy. However, some of these adjuvant therapies may cause adverse events, including wound infection, neutropenia, bone marrow suppression and fever. The simultaneous presentation of osteonecrosis and osteomyelitis has not previously been described in patients with breast cancer undergoing hormone therapy and chemotherapy.

We report a patient with breast cancer who developed bone infarcts in both legs as well as osteomyelitis in the right distal tibia after treatment which included a modified radical mastectomy, hormone therapy and chemotherapy. Simultaneous osteonecrosis and osteomyelitis should be considered in patients with breast cancer who are receiving chemotherapy and hormone therapy who present with severe bone pain, especially if there have been infective episodes during treatment.

Introduction: Osteoblasts precursors reside in the marrow and small numbers circulate in the blood. Our previous work demonstrated an increase in circulating cells following fracture in humans. Skeletal injury is recognised to stimulate a distant osteogenic response. We hypothesised that in response to fracture, some integral osteoblasts are recruited via the circulation from remote bone marrow sites. Method: We established a fracture union model in 3-month-old, male, New Zealand White rabbits and reimplanted labelled autologous osteoblast precursors. At date of submission we have 20 rabbits allocated into 4 groups. Three groups had labelled cells re-implanted, whilst the fourth control group did not receive cells. In groups I, II and III the cells were re-implanted into the fracture gap, into the circulation and into a remote bone marrow cavity respectively. There were six animals in groups I and IV, and four in both II and III. All animals had bone marrow harvested from their right tibia by saline flush. The mononuclear cells were isolated and culture-expanded in osteogenic medium for 3 weeks. Fluorescent reporter molecules were incorporated into the cell membranes, 24 hours prior to re-implantation of the cells into the fracture model. A 3 mm ulnar defect was preformed in all the animals. In groups I–III this was established 48 hours prior to cell re-implantation. The animals were sacrificed at least 3 weeks after fracture surgery. Representative samples of the fracture callous, lung, liver, spleen and kidney were harvested from all animals and cryo-sectioned. Using confocal microscopy, the labelled cells were expressed as the average in 5 high power fields for each solid tissue. In addition, cyto-spins were made from blood and marrow and the cell number expressed as a percentage of the total cells. Results: In group I, labelled cells were identified in the fracture callous, establishing their viability in vivo. Following intravenous re-implantation a smaller number of labelled cells were identified in the callous. When the cells were re-implanted into a remote marrow site, the number of cells in the callous was greater than after venous reimplantation, but less numerous than those in group I. In all sections, these labelled cells appeared on trabecular surfaces in an osteoblastic fashion, but occasionally they were surrounded by osteoid, corresponding to osteocytes. A small number of labelled cells were found in the blood, bone marrow, lung, liver and spleen of all animals in groups I–III. No labelled cells were identified in the kidney tissue. Discussion and Conclusions: We have demonstrated that cells from remote sites are integral in fracture healing. Their presence in callous following venous administration supports recruitment via the circulation. This preliminary data is a proof of concept. This is an exciting new phenomenon, which could provide alternatives for harvesting skeletal progenitor cells and for their delivery in the treatment of bony pathology