Aims. This study investigated the effects of β-caryophyllene (BCP) on protecting bone from vitamin D deficiency in mice fed on a diet either lacking (D-) or containing (D+) vitamin D. Methods. A total of 40 female mice were assigned to four treatment groups (n = 10/group): D+ diet with propylene glycol control, D+ diet with BCP, D-deficient diet with control, and D-deficient diet with BCP. The D+ diet is a commercial basal diet, while the D-deficient diet contains 0.47% calcium, 0.3% phosphorus, and no vitamin D. All the mice were housed in conditions without ultraviolet light. Bone properties were evaluated by X-ray micro-CT. Serum levels of klotho were measured by enzyme-linked immunosorbent assay. Results. Under these conditions, the D-deficient diet enhanced the length of femur and tibia bones (p < 0.050), and increased bone volume (BV; p < 0.010) and trabecular bone volume fraction (BV/TV; p < 0.010) compared to D+ diet. With a diet containing BCP, the mice exhibited higher BV and bone mineral density (BMD; p < 0.050) than control group. The trabecular and cortical bone were also affected by vitamin D and BCP. In addition, inclusion of dietary BCP improved the serum concentrations of klotho (p < 0.050). In mice, klotho regulates the expression level of cannabinoid type 2 receptor (Cnr2) and fibroblast growth factor 23 (Fgf23) through CD300a. In humans, data suggest that klotho is connected to BMD. The expression of klotho is also associated with bone markers. Conclusion. These data indicate that BCP enhances the serum level of klotho, leading to improved bone properties and mineralization in an experimental mouse model. Cite this article: Bone Joint Res 2022;11(8):528–540

Objectives. Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls. Methods. Trabecular bone from hip fracture patients treated with BP (n = 10) was compared with naïve fractured (n = 14) and non-fractured controls (n = 6). Trabecular cores were synchrotron scanned and micro-CT scanned for microstructural analysis, including quantification of bone volume fraction, microarchitecture and microcracks. The specimens were then mechanically tested in compression. Results. BP bone was 28% lower in strength than untreated hip fracture bone, and 48% lower in strength than non-fractured control bone (4.6 MPa vs 6.4 MPa vs 8.9 MPa). BP-treated bone had 24% more microcracks than naïve fractured bone and 51% more than non-fractured control (8.12/cm. 2. vs 6.55/cm. 2. vs 5.25/cm. 2. ). BP and naïve fracture bone exhibited similar trabecular microarchitecture, with significantly lower bone volume fraction and connectivity than non-fractured controls. Conclusion. BP therapy had no detectable mechanical benefit in the specimens examined. Instead, its use was associated with substantially reduced bone strength. This low strength may be due to the greater accumulation of microcracks and a lack of any discernible improvement in bone volume or microarchitecture. This preliminary study suggests that the clinical impact of BP-induced microcrack accumulation may be significant. Cite this article: A. Jin, J. Cobb, U. Hansen, R. Bhattacharya, C. Reinhard, N. Vo, R. Atwood, J. Li, A. Karunaratne, C. Wiles, R. Abel. The effect of long-term bisphosphonate therapy on trabecular bone strength and microcrack density. Bone Joint Res 2017;6:602–609. DOI: 10.1302/2046-3758.610.BJR-2016-0321.R1

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

Aims. To investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities. Methods. We cultured osteoblasts isolated from trabecular bone explants taken from the femoral head and the intertrochanteric region of patients with idiopathic ONFH, or from the intertrochanteric region of patients with osteoarthritis (OA), and compared their viability, mineralization capacity, and secretion of paracrine factors. Results. Osteoblasts from the intertrochanteric region of patients with ONFH showed lower alkaline phosphatase (ALP) activity and mineralization capacity than osteoblasts from the same skeletal site in age-matched patients with OA, as well as lower messenger RNA (mRNA) levels of genes encoding osteocalcin and bone sialoprotein and higher osteopontin expression. In addition, osteoblasts from patients with ONFH secreted lower osteoprotegerin (OPG) levels than those from patients with OA, resulting in a higher receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) ligand (RANKL)-to-OPG ratio. In patients with ONFH, osteoblasts from the femoral head showed reduced viability and mineralized nodule formation compared with osteoblasts from the intertrochanteric region. Notably, the secretion of the pro-resorptive factors interleukin-6 and prostaglandin E. 2. as well as the RANKL-to-OPG ratio were markedly higher in osteoblast cultures from the femoral head than in those from the intertrochanteric region. Conclusion. Idiopathic ONFH is associated with a reduced mineralization capacity of osteoblasts and increased secretion of pro-resorptive factors. Cite this article: Bone Joint Res 2021;10(9):619–628

The relationship between post-operative bone density and subsequent failure of total knee replacement (TKR) is not known. This retrospective study aimed to determine the relationship between bone density and failure, both overall and according to failure mechanism. All 54 aseptic failures occurring in 50 patients from 7760 consecutive primary cemented TKRs between 1983 and 2004 were matched with non-failing TKRs, and 47 failures in 44 patients involved tibial failures with the matching characteristics of age (65.1 for failed and 69.8 for non-failed), gender (70.2% female), diagnosis (93.6% OA), date of operation, bilaterality, pre-operative alignment (0.4 and 0.3 respectively), and body mass index (30.2 and 30.0 respectively). In each case, the density of bone beneath the tibial component was assessed at each follow-up interval using standardised, calibrated radiographs. Failing knees were compared with controls both overall and, as a subgroup analysis, by failure mechanism. Knees were compared with controls using univariable linear regression.

Significant and continuous elevation in tibial density was found in knees that eventually failed by medial collapse (p < 0.001) and progressive radiolucency (p < 0.001) compared with controls, particularly in the medial region of the tibia. Knees failing due to ligamentous instability demonstrated an initial decline in density (p = 0.0152) followed by a non-decreasing density over time (p = 0.034 for equivalence). Non-failing knees reported a decline in density similar to that reported previously using dual-energy x-ray absorptiometry (DEXA). Differences between failing and non-failing knees were observable as early as two months following surgery. This tool may be used to identify patients at risk of failure following TKR, but more validation work is needed.

Cite this article: Bone Joint J 2014;96-B:1503–9.

We aimed to highlight the relationship between age and the architectural properties of trabecular bone, to outline the patterns in which the variations in these properties take place, and to investigate the influence of the architecture on the mechanical properties of trabecular bone in growing animals. We studied 30 lambs in three age groups and 20 sheep in two age groups. Cubes of subchondral bone were cut from the proximal tibia according to a standardised protocol. They were serially sectioned and their architectural properties were determined. Similar cubes were obtained from the identical anatomical position of the contralateral tibia and their compressive mechanical properties measured. The values obtained from the skeletally immature and mature individuals were compared. Multiple regression analyses were performed between the architectural and the mechanical properties. The bone volume fraction, the mean trabecular volume, the architectural and the mechanical anisotropy, the elastic modulus, the bone strength, the energy absorption to failure, and the elastic energy correlated positively with increasing age whereas the connectivity density, the bone surface density, the ultimate strain, the absorption of viscoelastic energy and the relative loss of energy correlated inversely. The values of all variables were significantly different in the skeletally mature and immature groups. We determined the patterns in which the variations took place. The bone volume fraction of the trabecular bone tissue was found to be the major predictor of its compressive mechanical properties. Together with the mean trabecular volume and the bone surface density, it explained 81% of the variations in the compressive elastic modulus of specimens obtained from the contralateral tibiae

Our aim was to determine the relationship between age and the mechanical and physical properties of trabecular bone, to describe the patterns in which the variations in these properties take place, and to investigate the influence of the physical properties on the mechanical characteristics of trabecular bone during growth. We used 30 lambs in three age groups and 20 sheep in two age groups. Cubes of subchondral bone were cut from the proximal tibia according to a standardised protocol. We performed non-destructive compression tests of the specimens in three orthogonal directions and compression tests to failure in the axial direction. The physical properties of the specimens were also determined. The data were correlated with age and compared in skeletally immature and mature animals. Multiple regression analyses were performed between the mechanical and the physical properties. Age correlated positively with elastic modulus, bone strength, energy absorption to failure, elastic energy, mechanical anisotropy ratio, tissue density, apparent density, apparent ash density, and bone mineral content, and inversely with ultimate strain, viscoelastic energy absorption, relative energy loss, the collagen content of bone and the percentage porosity. The values of all variables were significantly different in the skeletally mature and immature groups. The apparent density of trabecular bone tissue was found to be the major predictor of its compressive mechanical properties. Together with the content of bone muscle and bone collagen, the apparent density could explain 84% of the variation in the elastic modulus, whereas only a small portion of the variation in ultimate strain could be explained by the variation in apparent density

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. Methods. Blood and femoral bone marrow suspension IL-19 levels were first measured in the lipopolysaccharide (LPS)-induced bone loss model. Small interfering RNA (siRNA) was applied to knock down IL-19 for further validation. Thereafter, osteoclast production was stimulated with IL-19 in combination with mouse macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). The effect of IL-19 was subsequently evaluated using tartrate-resistant acid phosphatase (TRAP) staining and quantitative real-time polymerase chain reaction (RT-qPCR). The effect of IL-19 on osteoprotegerin (OPG) was then assessed using in vitro recombinant IL-19 treatment of primary osteoblasts and MLO-Y4 osteoblast cell line. Finally, transient transfection experiments and chromatin immunoprecipitation (ChIP) experiments were used to examine the exact mechanism of action. Results. In the LPS-induced bone loss mouse model, the levels of IL-19 in peripheral blood serum and femoral bone marrow suspension were significantly increased. The in vivo results indicated that global IL-19 deletion had no significant effect on RANKL content in the serum and bone marrow, but could increase the content of OPG in serum and femoral bone marrow, suggesting that IL-19 inhibits OPG expression in bone marrow mesenchymal stem cells (BMSCs) and thus increases bone resorption. Conclusion. IL-19 promotes bone resorption by suppressing OPG expression in BMSCs in a LPS-induced bone loss mouse model, which highlights the potential benefits and side effects of IL-19 for future clinical applications. Cite this article: Bone Joint Res 2023;12(11):691–701

Aims. This study examined whether systemic administration of melatonin would have different effects on osseointegration in ovariectomized (OVX) rats, depending on whether this was administered during the day or night. Methods. In this study, a titanium rod was implanted in the medullary cavity of one femoral metaphysis in OVX rats, and then the rats were randomly divided into four groups: Sham group (Sham, n = 10), OVX rat group (OVX, n = 10), melatonin day treatment group (OVX + MD, n = 10), and melatonin night treatment group (OVX + MN, n = 10). The OVX + MD and OVX + MN rats were treated with 30 mg/kg/day melatonin at 9 am and 9 pm, respectively, for 12 weeks. At the end of the research, the rats were killed to obtain bilateral femora and blood samples for evaluation. Results. Micro-CT and histological evaluation showed that the bone microscopic parameters of femoral metaphysis trabecular bone and bone tissue around the titanium rod in the OVX + MD group demonstrated higher bone mineral density, bone volume fraction, trabecular number, connective density, trabecular thickness, and lower trabecular speculation (p = 0.004) than the OVX + MN group. Moreover, the biomechanical parameters of the OVX + MD group showed higher pull-out test and three-point bending test values, including fixation strength, interface stiffness, energy to failure, energy at break, ultimate load, and elastic modulus (p = 0.012) than the OVX + MN group. In addition, the bone metabolism index and oxidative stress indicators of the OVX + MD group show lower values of Type I collagen cross-linked C-telopeptide, procollagen type 1 N propeptide, and malondialdehyde (p = 0.013), and higher values of TAC and SOD (p = 0.002) compared with the OVX + MN group. Conclusion. The results of our study suggest that systemic administration with melatonin at 9 am may improve the initial osseointegration of titanium rods under osteoporotic conditions more effectively than administration at 9 pm. Cite this article: Bone Joint Res 2022;11(11):751–762

Aims. The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI. Methods. Periprosthetic femoral trabecular bone specimens were obtained from patients suffering from chronic PJI of the hip and knee (n = 20). Microbiological analysis was performed on preoperative joint aspirates and tissue specimens obtained during revision surgery. Microstructural and cellular bone parameters were analyzed in bone specimens by histomorphometry on undecalcified sections complemented by tartrate-resistant acid phosphatase immunohistochemistry. Data were compared with control specimens obtained during primary arthroplasty (n = 20) and aseptic revision (n = 20). Results. PJI specimens exhibited a higher bone volume, thickened trabeculae, and increased osteoid parameters compared to both control groups, suggesting an accelerated bone turnover with sclerotic microstructure. On the cellular level, osteoblast and osteoclast parameters were markedly increased in the PJI cohort. Furthermore, a positive association between serum (CRP) but not synovial (white blood cell (WBC) count) inflammatory markers and osteoclast indices could be detected. Comparison between different pathogens revealed increased osteoclastic bone resorption parameters without a concomitant increase in osteoblasts in bone specimens from patients with Staphylococcus aureus infection, compared to those with detection of Staphylococcus epidermidis and Cutibacterium spp. Conclusion. This study provides insights into the local bone metabolism in chronic PJI, demonstrating osteosclerosis with high bone turnover. The fact that Staphylococcus aureus was associated with distinctly increased osteoclast indices strongly suggests early surgical treatment to prevent periprosthetic bone alterations. Cite this article: Bone Joint Res 2023;12(10):644–653

Aims. Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid hormone (PTH) ameliorated OA in papain-induced and anterior cruciate ligament transection-induced OA models; therefore, we hypothesized that PTH improved OA in a preclinical age-related OA model. Methods. Guinea pigs aged between six and seven months of age were randomized into control or treatment groups. Three- or four-month-old guinea pigs served as the young control group. The knees were administered 40 μl intra-articular injections of 10 nM PTH or vehicle once a week for three months. Their endurance as determined from time on the treadmill was evaluated before kill. Their tibial plateaus were analyzed using microcalculated tomography (μCT) and histological studies. Results. PTH increased the endurance on the treadmill test, preserved glycosaminoglycans, and reduced Osteoarthritis Research Society International score and chondrocyte apoptosis rate. No difference was observed in the subchondral plate bone density or metaphyseal trabecular bone volume and bone morphogenetic 2 protein staining. Conclusion. Subchondral bone is crucial in the initiation and progression of OA. Although previous studies have shown that subcutaneous PTH alleviates knee OA by improving subchondral and metaphyseal bone mass, we demonstrated that intra-articular PTH injections improved spontaneous OA by directly affecting the cartilage rather than the subchondral or metaphyseal bone in a preclinical age-related OA model. Cite this article: Bone Joint Res 2021;10(8):514–525

Despite worldwide clinical use of bio-absorbable devices for internal fixation in orthopaedic surgery, the degradation behaviour and tissue replacement of these implants are not fully understood. In a long-term experimental study, we have determined the patterns of tissue restoration 36 and 54 months after implantation of polyglycolic acid and poly-laevo-lactic acid screws in the distal femur of the rabbit. After 36 months in the polyglycolic acid group the specimens showed no remaining polymer and loose connective tissue occupied 80% of the screw track. Tissue restoration remained poor at 54 months, the amounts of trabecular bone and haematopoietic elements being significantly lower than those in the intact control group. The amount of trabecular bone within the screw track at 54 months in the polyglycolic acid group was less than in the empty drill holes (p = 0.04). In the poly-laevo-lactic acid group, polymeric material was present in abundance after 54 months, occupying 60% of the cross-section of the core area of the screw track. When using absorbable internal fixation implants we should recognise that the degradation of the devices will probably not be accompanied by the restoration of normal trabecular bone

Aims. Loosening is a well-known complication in the fixation of fractures using devices such as locking plates or unilateral fixators. It is believed that high strains in the bone at the bone-screw interface can initiate loosening, which can result in infection, and further loosening. Here, we present a new theory of loosening of implants. The time-dependent response of bone subjected to loads results in interfacial deformations in the bone which accumulate with cyclical loading and thus accentuates loosening. Methods. We used an ‘ideal’ bone-screw system, in which the screw is subjected to cyclical lateral loads and trabecular bone is modelled as non-linear viscoelastic and non-linear viscoelastic-viscoplastic material, based on recent experiments, which we conducted. Results. We found that the interfacial deformation in the bone increases with the number of cycles, and the use of a non-linear viscoelastic-viscoplastic model results in larger deformations, some of which are irrecoverable. There is an apparent trend in which interfacial deformations increase with increasing porosity of bone. Conclusion. The developed time-dependent model of the mechanical behaviour of bone permits prediction of loosening due to cyclical loads, which has not been possible previously. Application of this model shows that implant loosening will be accentuated by cyclical loading due to physiological activities, and the risks of loosening are greater in osteoporotic patients. Cite this article: S. Xie, K. Manda, P. Pankaj. Time-dependent behaviour of bone accentuates loosening in the fixation of fractures using bone-screw systems. Bone Joint Res 2018;7:580–586. DOI: 10.1302/2046-3758.710.BJR-2018-0085.R1

Objectives. The primary stability of the cementless Oxford Unicompartmental Knee Replacement (OUKR) relies on interference fit (or press fit). Insufficient interference may cause implant loosening, whilst excessive interference could cause bone damage and fracture. The aim of this study was to identify the optimal interference fit by measuring the force required to seat the tibial component of the cementless OUKR (push-in force) and the force required to remove the component (pull-out force). Materials and Methods. Six cementless OUKR tibial components were implanted in 12 new slots prepared on blocks of solid polyurethane foam (20 pounds per cubic foot (PCF), Sawbones, Malmo, Sweden) with a range of interference of 0.1 mm to 1.9 mm using a Dartec materials testing machine HC10 (Zwick Ltd, Herefordshire, United Kingdom) . The experiment was repeated with cellular polyurethane foam (15 PCF), which is a more porous analogue for trabecular bone. Results. The push-in force progressively increased with increasing interference. The pull-out force was related in a non-linear fashion to interference, decreasing with higher interference. Compared with the current nominal interference, a lower interference would reduce the push-in forces by up to 45% (p < 0.001 One way ANOVA) ensuring comparable (or improved) pull-out forces (p > 0.05 Bonferroni post hoc test). With the more porous bone analogue, although the forces were lower, the relationship between interference and push-in and pull-out force were similar. Conclusions. This study suggests that decreasing the interference fit of the tibial component of the cementless OUKR reduces the push-in force and can increase the pull-out force. An optimal interference fit may both improve primary fixation and decrease the risk of fracture. Cite this article: S. Campi, S. J. Mellon, D. Ridley, B. Foulke, C. A. F. Dodd, H. G. Pandit, D. W. Murray. Optimal interference of the tibial component of the cementless Oxford Unicompartmental Knee Replacement. Bone Joint Res 2018;7:226–231. DOI: 10.1302/2046-3758.73.BJR-2017-0193.R1

Objectives. The biomembrane (induced membrane) formed around polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone defect reconstruction. Few studies have evaluated its cellular, molecular or stem cell features. Our objective was to characterise induced membrane morphology, molecular features and osteogenic stem cell characteristics. Methods. Following Institutional Review Board approval, biomembrane specimens were obtained from 12 patient surgeries for management of segmental bony defects (mean patient age 40.7 years, standard deviation 14.4). Biomembranes from nine tibias and three femurs were processed for morphologic, molecular or stem cell analyses. Gene expression was determined using the Affymetrix GeneChip Operating Software (GCOS). Molecular analyses compared biomembrane gene expression patterns with a mineralising osteoblast culture, and gene expression in specimens with longer spacer duration (> 12 weeks) with specimens with shorter durations. Statistical analyses used the unpaired student t-test (two tailed; p < 0.05 was considered significant). Results. Average PMMA spacer in vivo time was 11.9 weeks (six to 18). Trabecular bone was present in 33.3% of the biomembrane specimens; bone presence did not correlate with spacer duration. Biomembrane morphology showed high vascularity and collagen content and positive staining for the key bone forming regulators, bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2). Positive differentiation of cultured biomembrane cells for osteogenesis was found in cells from patients with PMMA present for six to 17 weeks. Stem cell differentiation showed greater variability in pluripotency for osteogenic potential (70.0%) compared with chondrogenic or adipogenic potentials (100% and 90.0%, respectively). Significant upregulation of BMP2 and 6, numerous collagens, and bone gla protein was present in biomembrane compared with the cultured cell line. Biomembranes with longer resident PMMA spacer duration (vs those with shorter residence) showed significant upregulation of bone-related, stem cell, and vascular-related genes. Conclusion. The biomembrane technique is gaining favour in the management of complicated bone defects. Novel data on biological mechanisms provide improved understanding of the biomembrane’s osteogenic potential and molecular properties. Cite this article: Dr H. E. Gruber. Osteogenic, stem cell and molecular characterisation of the human induced membrane from extremity bone defects. Bone Joint Res 2016;5:106–115. DOI: 10.1302/2046-3758.54.2000483

Aims

Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown.

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.

Aims

cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect.

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain.

Cite this article: Bone Joint Res 2022;11(7):439–452.

Aims

Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects.

Aims

Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss.

Aims. Idiopathic scoliosis is the most common spinal deformity in adolescents and children. The aetiology of the disease remains unknown. Previous studies have shown a lower bone mineral density in individuals with idiopathic scoliosis, which may contribute to the causation. The aim of the present study was to compare bone health in adolescents with idiopathic scoliosis with controls. Methods. We included 78 adolescents with idiopathic scoliosis (57 female patients) at a mean age of 13.7 years (8.5 to 19.6) and 52 age- and sex-matched healthy controls (39 female patients) at a mean age of 13.8 years (9.1 to 17.6). Mean skeletal age, estimated according to the Tanner-Whitehouse 3 system (TW3), was 13.4 years (7.4 to 17.8) for those with idiopathic scoliosis, and 13.1 years (7.4 to 16.5) for the controls. Mean Cobb angle for those with idiopathic scoliosis was 29° (SD 11°). All individuals were scanned with dual energy x-ray absorptiometry (DXA) and peripheral quantitative CT (pQCT) of the left radius and tibia to assess bone density. Statistical analyses were performed with independent-samples t-test, the Mann-Whitney U test, and the chi-squared test. Results. Compared with controls, adolescents with idiopathic scoliosis had mean lower DXA values in the left femoral neck (0.94 g/cm. 2. (SD 0.14) vs 1.00 g/cm. 2. (SD 0.15)), left total hip (0.94 g/cm. 2. (SD 0.14) vs 1.01 g/cm. 2. (SD 0.17)), L1 to L4 (0.99 g/cm. 2. (SD 0.15) vs 1.06 g/cm. 2. (SD 0.17)) and distal radius (0.35 g/cm. 2. (SD 0.07) vs 0.39 g/cm. 2. (SD 0.08; all p ≤ 0.024), but not in the mid-radius (0.72 g/cm. 2. vs 0.74 g/cm. 2. ; p = 0.198, independent t-test) and total body less head (1,559 g (SD 380) vs 1,649 g (SD 492; p = 0.0.247, independent t-test). Compared with controls, adolescents with idiopathic scoliosis had lower trabecular volume bone mineral density (BMD) on pQCT in the distal radius (184.7 mg/cm. 3. (SD 40.0) vs 201.7 mg/cm. 3. (SD 46.8); p = 0.029), but not in other parts of the radius or the tibia (p ≥ 0.062, Mann-Whitney U test). Conclusion. In the present study, idiopathic scoliosis patients seemed to have lower BMD at central skeletal sites and less evident differences at peripheral skeletal sites when compared with controls. Cite this article: Bone Joint J 2020;102-B(2):268–272

Aims

To examine the long-term outcome of arthrodesis of the hip undertaken in a paediatric population in treating painful arthritis of the hip. In our patient population, most of whom live rurally in hilly terrain and have limited healthcare access and resources, hip arthrodesis has been an important surgical option for the monoarticular painful hip in a child.

Aims

To evaluate whether low-intensity pulsed ultrasound (LIPUS) accelerates bone healing at osteotomy sites and promotes functional recovery after open-wedge high tibial osteotomy (OWHTO).

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.

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.

Cite this article: Bone Joint Res 2023;12(9):536–545.

Aims

Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing.

There is an increased risk of fracture following osteoplasty of the femoral neck for cam-type femoroacetabular impingement (FAI). Resection of up to 30% of the anterolateral head–neck junction has previously been considered to be safe, however, iatrogenic fractures have been reported with resections within these limits. We re-evaluated the amount of safe resection at the anterolateral femoral head–neck junction using a biomechanically consistent model. In total, 28 composite bones were studied in four groups: control, 10% resection, 20% resection and 30% resection. An axial load was applied to the adducted and flexed femur. Peak load, deflection at time of fracture and energy to fracture were assessed using comparison groups. There was a marked difference in the mean peak load to fracture between the control group and the 10% resection group (p < 0.001). The control group also tolerated significantly more deflection before failure (p < 0.04). The mean peak load (p = 0.172), deflection (p = 0.547), and energy to fracture (p = 0.306) did not differ significantly between the 10%, 20%, and 30% resection groups. . Any resection of the anterolateral quadrant of the femoral head–neck junction for FAI significantly reduces the load-bearing capacity of the proximal femur. After initial resection of cortical bone, there is no further relevant loss of stability regardless of the amount of trabecular bone resected. Based on our findings we recommend any patients who undergo anterolateral femoral head–neck junction osteoplasty should be advised to modify their post-operative routine until cortical remodelling occurs to minimise the subsequent fracture risk. Cite this article: Bone Joint J 2015;97-B:1214–19

The cause of fracture of the femoral neck after hip resurfacing is poorly understood. In order to evaluate the role of avascular necrosis we compared 19 femoral heads retrieved at revision for fracture of the femoral neck and 13 retrieved for other reasons. We developed a new technique of assessing avascular necrosis in the femoral head by determining the percentage of empty osteocyte lacunae present. Femoral heads retrieved as controls at total hip replacement for osteoarthritis and avascular necrosis had 9% (. sd. 4; n = 13) and 85% (. sd. 5; n = 10, p < 0.001) empty lacunae, respectively. In the fracture group the percentage of empty lacunae was 71% (. sd. 22); in the other group it was 21% (. sd. 13). The differences between the groups were highly significant (p < 0.001). We conclude that fracture after resurfacing of the hip is associated with a significantly greater percentage of empty osteocyte lacunae within the trabecular bone. This indicates established avascular necrosis and suggests that damage to the blood supply at the time of surgery is a potent risk factor for fracture of the femoral neck after hip resurfacing

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To develop an early implant instability murine model and explore the use of intermittent parathyroid hormone (iPTH) treatment for initially unstable implants.

Cite this article: Bone Joint Res 2023;12(1):5–8.

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Osteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth hormone (GH) signalling, thus mice deficient in SOCS2 (Socs2^-/-) display accelerated bone growth.

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The localization of necrotic areas has been reported to impact the prognosis and treatment strategy for osteonecrosis of the femoral head (ONFH). Anteroposterior localization of the necrotic area after a femoral neck fracture (FNF) has not been properly investigated. We hypothesize that the change of the weight loading direction on the femoral head due to residual posterior tilt caused by malunited FNF may affect the location of ONFH. We investigate the relationship between the posterior tilt angle (PTA) and anteroposterior localization of osteonecrosis using lateral hip radiographs.

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The aim of this study was to report the patterns of symptoms and insufficiency fractures in patients with tumour-induced osteomalacia (TIO) to allow the early diagnosis of this rare condition.

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Manual impaction, with a mallet and introducer, remains the standard method of installing cementless acetabular cups during total hip arthroplasty (THA). This study aims to quantify the accuracy and precision of manual impaction strikes during the seating of an acetabular component. This understanding aims to help improve impaction surgical techniques and inform the development of future technologies.

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The evidence demonstrating the superiority of early MRI has led to increased use of MRI in clinical pathways for acute wrist trauma. The aim of this study was to describe the radiological characteristics and the inter-observer reliability of a new MRI based classification system for scaphoid injuries in a consecutive series of patients.

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The aim of this retrospective study was to assess the incidence of early periprosthetic femoral fracture (PFF) associated with Charnley-Kerboull (CK) femoral components cemented according to the ‘French paradox’ principles through the Hueter anterior approach (HAA) in patients older than 70 years.

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The aim of this study was to analyze how proximal radial neck resorption (PRNR) starts and progresses radiologically in two types of press-fit radial head arthroplasties (RHAs), and to investigate its clinical relevance.

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Pelvic discontinuity is a rare but increasingly common complication of total hip arthroplasty (THA). This single-centre study evaluated the performance of custom-made triflange acetabular components in acetabular reconstruction with pelvic discontinuity by determining: 1) revision and overall implant survival rates; 2) discontinuity healing rate; and 3) Harris Hip Score (HHS).

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Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice.

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Disorders of bone integrity carry a high global disease burden, frequently requiring intervention, but there is a paucity of methods capable of noninvasive real-time assessment. Here we show that miniaturized handheld near-infrared spectroscopy (NIRS) scans, operated via a smartphone, can assess structural human bone properties in under three seconds.

Aternatives to autogenous bone graft for spinal fusion have been investigated for many years. It has been shown that osteoconductive materials alone do not give a rate of fusion which is comparable to that of autogenous bone graft. We analysed the effectiveness of porous ceramic loaded with cultured mesenchymal stem cells as a new graft material for spinal fusion in an animal model. Posterolateral fusion was carried out at the L4/L5 level in 40 White New Zealand rabbits using one of the following graft materials: porous ceramic granules plus cultured mesenchymal stem cells (group I); ceramic granules plus fresh autogenous bone marrow (group II); ceramic granules alone (group III); and autogenous bone graft (group IV). The animals were killed eight weeks after surgery and the spines were evaluated radiographically, by a manual palpation test and by histological analysis. The rate of fusion was significantly higher in group I compared with group III and higher, but not significantly, in group I compared with groups II and IV. In group I histological analysis showed newly formed bone in contact with the implanted granules and highly cellular bone marrow between the newly formed trabecular bone. In group II, thin trabeculae of newly formed bone were present in the peripheral portion of the fusion mass. In group III, there was a reduced mount of newly formed bone and abundant fibrous tissue. In group IV, there were thin trabeculae of newly formed bone close to the decorticated transverse processes and dead trabecular bone in the central portion of the fusion mass. In vitro cultured mesenchymal stem cells may be loaded into porous ceramic to make a graft material for spinal fusion which appears to be more effective than porous ceramic alone. Further studies are needed to investigate the medium- to long-term results of this procedure, its feasibility in the clinical setting and the most appropriate carrier for mesenchymal stem cells

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.

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Gap junction intercellular communication (GJIC) in osteocytes is impaired by oxidative stress, which is associated with age-related bone loss. Ageing is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, it is still unknown whether AOPP accumulation is involved in the impairment of osteocytes’ GJIC. This study aims to investigate the effect of AOPP accumulation on osteocytes’ GJIC in aged male mice and its mechanism.

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Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood.

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Treatment outcomes for methicillin-resistant Staphylococcus aureus (MRSA) periprosthetic joint infection (PJI) using systemic vancomycin and antibacterial cement spacers during two-stage revision arthroplasty remain unsatisfactory. This study explored the efficacy and safety of intra-articular vancomycin injections for PJI control after debridement and cement spacer implantation in a rat model.

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The association of auraptene (AUR), a 7-geranyloxycoumarin, on osteoporosis and its potential pathway was predicted by network pharmacology and confirmed in experimental osteoporotic mice.

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Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut microbiome in PTOA remains elusive.

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The distal radius is a major site of osteoporotic bone loss resulting in a high risk of fragility fracture. This study evaluated the capability of a cortical index (CI) at the distal radius to predict the local bone mineral density (BMD).