Aims

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.

We developed a rat model of limb lengthening to study the basic mechanism of distraction osteogenesis, using a small monolateral external fixator. In 11-week-old male rats we performed a subperiosteal osteotomy in the midshaft of the femur with distraction at 0.25 mm every 12 hours from seven days after operation. Radiological and histological examinations showed a growth zone of constant thickness in the middle of the lengthened segment, with formation of new bone at its proximal and distal ends. Osteogenic cells were arranged longitudinally along the tension vector showing the origin and the fate of individual cells in a single section. Typical endochondral bone formation was prominent in the early stage of distraction, but intramembraneous bone formation became the predominant mechanism of ossification at later stages. We also showed a third mechanism of ossification, ‘transchondroid bone formation’. Chondroid bone, a tissue intermediate between bone and cartilage, was formed directly by chondrocyte-like cells, with transition from fibrous tissue to bone occurring gradually and consecutively without capillary invasion. In situ hybridisation using digoxigenin-11-UTP-labelled complementary RNAs showed that the chondroid bone cells temporarily expressed type-II collagen mRNA. They did not show the classical morphological characteristics of chondrocytes, but were assumed to be young chondrocytes undergoing further differentiation into bone-forming cells. We found at least three different modes of ossification during bone lengthening by distraction osteogenesis. We believe that this is the first report of such a rat model, and have shown the validity of in situ hybridisation techniques for the study of the cellular and molecular mechanisms involved in distraction osteogenesis

Aims

Developmental dysplasia of the hip (DDH) describes a pathological relationship between the femoral head and acetabulum. Periacetabular osteotomy (PAO) may be used to treat this condition. The aim of this study was to evaluate the results of PAO in adolescents and adults with persistent DDH.

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Osteofibrous dysplasia (OFD) is a rare benign lesion predominantly affecting the tibia in children. Its potential link to adamantinoma has influenced management. This international case series reviews the presentation of OFD and management approaches to improve our understanding of OFD.

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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.

Rheumatoid arthritis (RA) is an autoimmune disease that involves T and B cells and their reciprocal immune interactions with proinflammatory cytokines. T cells, an essential part of the immune system, play an important role in RA. T helper 1 (Th1) cells induce interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), and interleukin (IL)-2, which are proinflammatory cytokines, leading to cartilage destruction and bone erosion. Th2 cells primarily secrete IL-4, IL-5, and IL-13, which exert anti-inflammatory and anti-osteoclastogenic effects in inflammatory arthritis models. IL-22 secreted by Th17 cells promotes the proliferation of synovial fibroblasts through induction of the chemokine C-C chemokine ligand 2 (CCL2). T follicular helper (Tfh) cells produce IL-21, which is key for B cell stimulation by the C-X-C chemokine receptor 5 (CXCR5) and coexpression with programmed cell death-1 (PD-1) and/or inducible T cell costimulator (ICOS). PD-1 inhibits T cell proliferation and cytokine production. In addition, there are many immunomodulatory agents that promote or inhibit the immunomodulatory role of T helper cells in RA to alleviate disease progression. These findings help to elucidate the aetiology and treatment of RA and point us toward the next steps.

Cite this article: Bone Joint Res 2022;11(7):426–438.

Aims

Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have been reported to be a promising cellular therapeutic approach for various human diseases. The current study aimed to investigate the mechanism of BMSC-derived exosomes carrying microRNA (miR)-136-5p in fracture healing.

We evaluated the efficacy of Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E-BMP-2) in a mini-pig model of spinal anterior interbody fusion. A total of 14 male mini-pigs underwent three-level anterior lumbar interbody fusion using polyether etherketone (PEEK) cages containing porous hydroxyapatite (HA). Four groups of cages were prepared: 1) control (n = 10 segments); 2) 50 μg E-BMP-2 (n = 9); 3) 200 μg E-BMP-2 (n = 10); and 4) 800 μg E-BMP-2 (n = 9). At eight weeks after surgery the mini-pigs were killed and the specimens were evaluated by gross inspection and manual palpation, radiological evaluation including plain radiographs and micro-CT scans, and histological analysis. Rates of fusion within PEEK cages and overall union rates were calculated, and bone formation outside vertebrae was evaluated. One animal died post-operatively and was excluded, and one section was lost and also excluded, leaving 38 sites for assessment. This rate of fusion within cages was 30.0% (three of ten) in the control group, 44.4% (four of nine) in the 50 μg E-BMP-2 group, 60.0% (six of ten) in the 200 μg E-BMP-2 group, and 77.8% (seven of nine) in the 800 μg E-BMP-2 group. Fusion rate was significantly increased by the addition of E-BMP-2 and with increasing E-BMP-2 dose (p = 0.046). In a mini-pig spinal anterior interbody fusion model using porous HA as a carrier, the implantation of E-BMP-2-loaded PEEK cages improved the fusion rate compared with PEEK cages alone, an effect that was significantly increased with increasing E-BMP-2 dosage. Cite this article: Bone Joint J 2013;95-B:217–23

Aims

Giant cell tumour of bone (GCTB) treatment changed since the introduction of denosumab from purely surgical towards a multidisciplinary approach, with recent concerns of higher recurrence rates after denosumab. We evaluated oncological, surgical, and functional outcomes for distal radius GCTB, with a critically appraised systematic literature review.

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Despite the interest in the association of gut microbiota with bone health, limited population-based studies of gut microbiota and bone mineral density (BMD) have been made. Our aim is to explore the possible association between gut microbiota and BMD.

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A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing.

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Osteoarthritis (OA) is a common degenerative joint disease. The osteocyte transcriptome is highly relevant to osteocyte biology. This study aimed to explore the osteocyte transcriptome in subchondral bone affected by OA.

1. Ectopic ossification is commonest in, but not confined to, traumatic paraplegia. It occurs also in many other neurological disorders which have in common a gross disturbance of spinal cord reflex activity. It is a true ossification and must be distinguished from calcification. 2. The neurological lesion may lie anywhere from the cerebral cortex to the mixed peripheral nerve. It may involve motor tracts, sensory tracts or a mixture of both. 3. The ossification is localised and self-limiting. It occurs mainly in the lower limbs and is restricted to certain muscles or muscle groups, the nerve supply of which is always below the level of the central neurological lesion. 4. The blood chemistry is usually normal. 5. A true arthropathy is rare except as part of a secondary suppurative arthritis. 6. The resemblance to myositis ossificans progressiva or to ossifying haematoma is only superficial, although the pathological process at cellular level may be the same. 7. The period of onset after paraplegia is variable. The earliest recorded example is in one of our own cases in which ossification occurred nineteen days after injury. Other patients have developed ossification after several years. 8. The condition is commonest in acquired nervous disease rather than in congenital disorders, and so far as we know it has not been described in the myopathies. The presence of muscular spasticity or flaccidity is relevant only in that it indicates a disturbance of reflex activity. 9. Soft-tissue ulceration appears to be frequently associated with ectopic ossification. The type of new bone formation associated with large chronic ulcers is not to be compared with the new bone formation in the muscles of a paraplegic patient in otherwise good general condition. 10. The occurrence of urinary tract infections with calculi and generalised sepsis is not specifically related to the onset of new bone formation. 11. Localised soft-tissue oedema often precedes the formation of new bone. Its appearance is undoubtedly important, but the mechanism of its origin is obscure. 12. It is not yet known what initiates ectopic ossification, what limits its spread and what finally causes it to stop. 13. We have described 100 examples of ectopic ossification in 603 paraplegic patients. 14. Surgery has been required in only eight patients. The only indication for surgery is bony ankylosis of the hip in an unacceptable position

Aims

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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Unicompartmental and total knee arthroplasty (UKA and TKA) are successful treatments for osteoarthritis, but the solid metal implants disrupt the natural distribution of stress and strain which can lead to bone loss over time. This generates problems if the implant needs to be revised. This study investigates whether titanium lattice UKA and TKA implants can maintain natural load transfer in the proximal tibia.

Aims

With the ageing population, fragility fractures have become one of the most common conditions. The objective of this study was to investigate whether microbiological outcomes and fracture-healing in osteoporotic bone is worse than normal bone with fracture-related infection (FRI).

An experimental sheep model was used for impaction allografting of 12 hemiarthroplasty femoral components placed into two equal-sized groups. In group 1, a 50:50 mixture of ApaPore hydroxyapatite bone-graft substitute and allograft was used. In group 2, ApaPore and allograft were mixed in a 90:10 ratio. Both groups were killed at six months. Ground reaction force results demonstrated no significant differences (p > 0.05) between the two groups at 8, 16 and 24 weeks post-operatively, and all animals remained active. The mean bone turnover rates were significantly greater in group 1, at 0.00206 mm/day, compared to group 2 at 0.0013 mm/day (p < 0.05). The results for the area of new bone formation demonstrated no significant differences (p > 0.05) between the two groups. No significant differences were found between the two groups in thickness of the cement mantle (p > 0.05) and percentage ApaPore-bone contact (p > 0.05). The results of this animal study demonstrated that a mixture of ApaPore allograft in a 90:10 ratio was comparable to using a 50:50 mixture

We examined whether a selective cyclooxygenase-2 (COX-2) inhibitor (celecoxib) was as effective as a non-selective inhibitor (ibuprofen) for the prevention of heterotopic ossification following total hip replacement. A total of 250 patients were randomised to receive celecoxib (200 mg b/d) or ibuprofen (400 mg t.d.s) for ten days after surgery. Anteroposterior radiographs of the pelvis were examined for heterotopic ossification three months after surgery. Of the 250 patients, 240 were available for assessment. Heterotopic ossification was more common in the ibuprofen group (none 40.7% (50), Brooker class I 46.3% (57), classes II and III 13.0% (16)) than in the celecoxib group (none 59.0% (69), Brooker class I 35.9% (42), classes II and III 5.1% (6), p = 0.002). Celecoxib was more effective than ibuprofen in preventing heterotopic bone formation after total hip replacement

Impacted bone allograft is often used in revision joint replacement. Hydroxyapatite granules have been suggested as a substitute or to enhance morcellised bone allograft. We hypothesised that adding osteogenic protein-1 to a composite of bone allograft and non-resorbable hydroxyapatite granules (ProOsteon) would improve the incorporation of bone and implant fixation. We also compared the response to using ProOsteon alone against bone allograft used in isolation. We implanted two non-weight-bearing hydroxyapatite-coated implants into each proximal humerus of six dogs, with each implant surrounded by a concentric 3 mm gap. These gaps were randomly allocated to four different procedures in each dog: 1) bone allograft used on its own; 2) ProOsteon used on its own; 3) allograft and ProOsteon used together; or 4) allograft and ProOsteon with the addition of osteogenic protein-1. After three weeks osteogenic protein-1 increased bone formation and the energy absorption of implants grafted with allograft and ProOsteon. A composite of allograft, ProOsteon and osteogenic protein-1 was comparable, but not superior to, allograft used on its own. ProOsteon alone cannot be recommended as a substitute for allograft around non-cemented implants, but should be used to extend the volume of the graft, preferably with the addition of a growth factor

Two types of fracture, early and late, have been reported following limb lengthening in patients with achondroplasia (ACH) and hypochondroplasia (HCH). . We reviewed 25 patients with these conditions who underwent 72 segmental limb lengthening procedures involving the femur and/or tibia, between 2003 and 2011. Gender, age at surgery, lengthened segment, body mass index, the shape of the callus, the amount and percentage of lengthening and the healing index were evaluated to determine predictive factors for the occurrence of early (within three weeks after removal of the fixation pins) and late fracture (> three weeks after removal of the pins). The Mann‑Whitney U test and Pearson’s chi-squared test for univariate analysis and stepwise regression model for multivariate analysis were used to identify the predictive factor for each fracture. Only one patient (two tibiae) was excluded from the analysis due to excessively slow formation of the regenerate, which required supplementary measures. A total of 24 patients with 70 limbs were included in the study. There were 11 early fractures in eight patients. The shape of the callus (lateral or central callus) was the only statistical variable related to the occurrence of early fracture in univariate and multivariate analyses. Late fracture was observed in six limbs and the mean time between removal of the fixation pins and fracture was 18.3 weeks (3.3 to 38.4). Lengthening of the tibia, larger healing index, and lateral or central callus were related to the occurrence of a late fracture in univariate analysis. A multivariate analysis demonstrated that the shape of the callus was the strongest predictor for late fracture (odds ratio: 19.3, 95% confidence interval: 2.91 to 128). Lateral or central callus had a significantly larger risk of fracture than fusiform, cylindrical, or concave callus. Radiological monitoring of the shape of the callus during distraction is important to prevent early and late fracture of lengthened limbs in patients with ACH or HCH. In patients with thin callus formation, some measures to stimulate bone formation should be considered as early as possible. Cite this article: Bone Joint J 2014;96-B:1269–73