Objectives. The aim of this systematic literature review was to assess the clinical level of evidence of commercially available demineralised bone matrix (DBM) products for their use in trauma and orthopaedic related surgery. Methods. A total of 17 DBM products were used as search terms in two available databases: Embase and PubMed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement. All articles that reported the clinical use of a DBM-product in trauma and orthopaedic related surgery were included. Results. The literature search resulted in 823 manuscripts of which 64 manuscripts met the final inclusion criteria. The included manuscripts consisted of four randomised controlled trials (level I), eight cohort studies (level III) and 49 case-series (level IV). No clinical studies were found for ten DBM products, and most DBM products were only used in combination with other grafting materials. DBM products were most extensively investigated in spinal surgery, showing limited level I evidence that supports the use Grafton DBM (Osteotech, Eatontown, New Jersey) as a bone graft extender in posterolateral lumbar fusion surgery. DBM products are not thoroughly investigated in trauma surgery, showing mainly level IV evidence that supports the use of Allomatrix (Wright Medical, London, United Kingdom), DBX (DePuy Synthes, Zuchwil, Switzerland), Grafton DBM, or OrthoBlast (Citagenix Laval, Canada) as bone graft extenders. Conclusions. The clinical level of evidence that supports the use of DBM in trauma and orthopaedic surgery is limited and consists mainly of poor quality and retrospective case-series. More prospective, randomised controlled trials are needed to understand the clinical effect and impact of DBM in trauma and orthopaedic surgery. Cite this article: J. van der Stok, K. A. Hartholt, D. A. L. Schoenmakers, J. J. C. Arts. The available evidence on demineralised bone matrix in trauma and orthopaedic surgery: A systemati c review. Bone Joint Res 2017;6:423–432. DOI: 10.1302/2046-3758.67.BJR-2017-0027.R1

Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment. Cite this article: Bone Joint Res 2024;13(12):725–740

Extraskeletal bone formation can be induced in rodents by implantation of demineralised bone matrix and such implantation has been used to treat bone defects in man, but it is uncertain if induction or merely conduction occurs. We studied bone induction in primates by excising segments of the fibulae of adult squirrel monkeys, defatting and demineralising them before reimplanting them into the quadriceps of the same animal. As a control experiment, rat matrix was prepared in exactly the same way and implanted in rats. After six weeks the implants were harvested and either ashed and analysed for calcium content or prepared for histology. In the rats, the calcium content indicated that about 20% of the original matrix had been replaced by new bone. In the monkeys the calcium content was about the same as that in normal body fluid and no bone was seen in histological sections. This result casts doubt on the use of demineralised human bone matrix as a bone inductor, although it may function by other mechanisms

1. The appearance of decalcified bone matrix in the electron microscope is described. 2. In the matrix two types of collagen fibril have been distinguished. Differences observed are in solubility, x-ray diffraction pattern and appearance. In infant bone the form which appears as fine fibrils predominates. In adult bone the form which appears as tubular fibrils of larger diameter predominates. 3. In bones from elderly subjects the chemical reaction employed to convert collagen into eucollagen sometimes hydrolyses fatty acid esters, and lines due to the free fatty acid are found on the x-ray diffraction patterns of the insoluble residue after citrate extraction. 4. In ancient bones and fossils the stable tubular form of collagen survives, but not the fine fibrils. 5. When decalcified, the matrix in osteoporotic bones loses its architecture and fibrillar form. Under conditions in which only a small fraction is dissolved from normal bone most of the collagen in osteoporotic bone disperses in citric acid. The insoluble residue then gives a modified x-ray diffraction pattern. 6. Evidence has been produced to suggest that the immediate cause of many forms of osteoporosis is some local factor affecting the osteocytes, rather than a general chemical effect

We used demineralised bone matrix (DBM) to augment re-attachment of tendon to a metal prosthesis in an in vivo ovine model of reconstruction of the extensor mechanism at the knee. We hypothesised that augmentation of the tendon-implant interface with DBM would enhance the functional and histological outcomes as compared with previously reported control reconstructions without DBM. Function was assessed at six and 12 weeks postoperatively, and histological examination was undertaken at 12 weeks. A significant increase of 23.5% was observed in functional weight-bearing at six weeks in the DBM-augmented group compared with non-augmented controls (p = 0.004). By 12 weeks augmentation with DBM resulted in regeneration of a more direct-type enthesis, with regions of fibrocartilage, mineralised fibrocartilage and bone. In the controls the interface was predominantly indirect, with the tendon attached to the bone graft-hydroxyapatite base plate by perforating collagen fibres

Demineralised homologous bone-matrix implant was used to bridge a large circumferential osteoperiosteal gap in the diaphysis of the ulna of rabbits. Periodic observations of the graft were made clinically, radiologically, histologically and by tetracycline fluorescence up to forty-two weeks. By the twelfth week after operation 81 per cent of the animals revealed bone formation in the implant and complete bridging of the gap. The new bone was laid on the surface and in the substance of the matrix, suggesting that the inductive principle was acting locally. The bone, once formed, remodelled to the texture of a mature tubular bone and did not undergo absorption during a long follow-up period. Demineralise bone-matrix proved to be a highly osteoinductive and readily osteoconductive material. The graft did not evoke any appreciable local foreign-body or immunogenic reaction. The high degree of success in bridging massive bone defects justifies further serious studies and hopes for a useful substitute for massive autologous bone grafts.

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. Methods. The network of AUR was constructed and a potential pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms enrichment. Female ovariectomized (OVX) Institute of Cancer Research mice were intraperitoneally injected with 0.01, 0.1, and 1 mM AUR for four weeks. The bone mineral density (BMD) level was measured by dual-energy X-ray absorptiometry. The bone microstructure was determined by histomorphological changes in the femora. In addition, biochemical analysis of the serum and assessment of the messenger RNA (mRNA) levels of osteoclastic markers were performed. Results. In total, 65.93% of the genes of the AUR network matched with osteoporosis-related genes. Osteoclast differentiation was predicted to be a potential pathway of AUR in osteoporosis. Based on the network pharmacology, the BMD and bone mineral content levels were significantly (p < 0.05) increased in the whole body, femur, tibia, and lumbar spine by AUR. AUR normalized the bone microstructure and the serum alkaline phosphatase (ALP), bone-specific alkaline phosphatase (bALP), osteocalcin, and calcium in comparison with the OVX group. In addition, AUR treatment reduced TRAP-positive osteoclasts and receptor activator of nuclear factor kappa-B ligand (RANKL). +. nuclear factor of activated T cells 1 (NFATc1). +. expression in the femoral body. Moreover, the expressions of initiators for osteoclastic resorption and bone matrix degradation were significantly (p < 0.05) regulated by AUR in the lumbar spine of the osteoporotic mice. Conclusion. AUR ameliorated bone loss by downregulating the RANKL/NFATc1 pathway, resulting in improvement of osteoporosis. In conclusion, AUR might be an ameliorative cure that alleviates bone loss in osteoporosis via inhibition of osteoclastic activity. Cite this article: Bone Joint Res 2022;11(5):304–316

We carried out a prospective study to determine whether the addition of a recombinant human bone morphogenetic protein (rhBMP-2) to a machined allograft spacer would improve the rate of intervertebral body fusion in the spine. We studied 77 patients who were to undergo an interbody fusion with allograft and instrumentation. The first 36 patients received allograft with adjuvant rhBMP-2 (allograft/rhBMP-2 group), and the next 41, allograft and demineralised bone matrix (allograft/demineralised bone matrix group). Each patient was assessed clinically and radiologically both pre-operatively and at each follow-up visit using standard methods. Follow-up continued for two years. Every patient in the allograft/rhBMP-2 group had fused by six months. However, early graft lucency and significant (> 10%) subsidence were seen radiologically in 27 of 55 levels in this group. The mean graft height subsidence was 27% (13% to 42%) for anterior lumbar interbody fusion, 24% (13% to 40%) for transforaminal lumbar interbody fusion, and 53% (40% to 58%) for anterior cervical discectomy and fusion. Those who had undergone fusion using allograft and demineralised bone matrix lost only a mean of 4.6% (0% to 15%) of their graft height. Although a high rate of fusion (100%) was achieved with rhBMP-2, significant subsidence occurred in more than half of the levels (23 of 37) in the lumbar spine and 33% (6 of 18) in the cervical spine. A 98% fusion rate (62 of 63 levels) was achieved without rhBMP-2 and without the associated graft subsidence. Consequently, we no longer use rhBMP-2 with allograft in our practice if the allograft has to provide significant structural support

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

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.

A common situation presenting to the orthopaedic surgeon today is a worn acetabular liner with substantial acetabular and pelvic osteolysis. The surgeon has many options for dealing with osteolytic defects. These include allograft, calcium based substitutes, demineralised bone matrix, or combinations of these options with or without addition of platelet rich plasma. To date there are no clinical studies to determine the efficacy of using bone-stimulating materials in osteolytic defects at the time of revision surgery and there are surprisingly few studies demonstrating the clinical efficacy of these treatment options. Even when radiographs appear to demonstrate incorporation of graft material CT studies have shown that incorporation is incomplete. The surgeon, in choosing a graft material for a surgical procedure must take into account the efficacy, safety, cost and convenience of that material. Cite this article: Bone Joint J 2014;96-B (11 Suppl A):70–2

Aims

Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders.

Sterilisation of demineralised bone matrix with ethylene oxide has been claimed to destroy the ability of bone matrix to induce new bone formation on intramuscular implantation. Other workers have routinely used ethylene oxide sterilised bone matrix for assays in rodents without detrimental effects. We studied the effects of various lengths of exposure to ethylene oxide gas, and found that bone induction properties are destroyed in a dose-dependent manner. After a short exposure, bone induction properties were moderately diminished. However, this short ethylene oxide treatment did not kill Bacillus subtilis spores. A sterilisation procedure that killed these spores rendered the implants incapable of bone-induction

In fully-grown mongrel dogs, diaphyseal ulnar defects 25 mm long were stabilised by screws and plates, and were temporarily filled with silicone rubber blocks. After eight weeks the block was replaced either by fresh autogeneic cancellous bone, allogeneic deep-frozen cancellous bone, allogeneic decalcified bone matrix, or bone matrix gelatin. After 24 weeks the implants were evaluated by radiography, histology, and measurements of new bone volume, using computer-assisted density registration on microradiographs. Only the autogeneic bone grafts led to healing in all instances. Bone regeneration in the other groups was not significantly better than in the sham group in which no graft was employed. Decalcified bone matrix proved ineffective

Aims. Demineralised bone matrix (DBM) is rarely used for the local delivery of prophylactic antibiotics. Our aim, in this study, was to show that a graft with a bioactive glass and DBM combination, which is currently available for clinical use, can be loaded with tobramycin and release levels of antibiotic greater than the minimum inhibitory concentration for Staphylococcus aureus without interfering with the bone healing properties of the graft, thus protecting the graft and surrounding tissues from infection. Materials and Methods. Antibiotic was loaded into a graft and subsequently evaluated for drug elution kinetics and the inhibition of bacterial growth. A rat femoral condylar plug model was used to determine the effect of the graft, loaded with antibiotic, on bone healing. Results. We found that tobramycin loaded into a graft composed of bioglass and DBM eluted antibiotic above the minimum inhibitory concentration for three days in vitro. It was also found that the antibiotic loaded into the graft produced no adverse effects on the bone healing properties of the DBM at a lower level of antibiotic. Conclusion. This antibiotic-loaded bone void filler may represent a promising option for the delivery of local antibiotics in orthopaedic surgery. Cite this article: Bone Joint J 2016;98-B:1126–31

Aims

This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes.

The December 2014 Research Roundup. 360 . looks at: demineralised bone matrix not as good as we thought?; trunk control following ACL reconstruction; subclinical thyroid dysfunction: not quite subclinical?; establishing musculoskeletal function in mucopolysaccharidosis; starting out: a first year in consultant practice under the spotlight; stroke and elective surgery; sepsis and clots; hip geometry and arthritis incidence; and theatre discipline and infection

Aims

The purpose of this study was to assess the success rate and functional outcomes of bone grafting for periprosthetic bone cysts following total ankle arthroplasty (TAA). Additionally, we evaluated the rate of graft incorporation and identified associated predisposing factors using CT scan.

Aims

The present study investigated receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) gene expressions in giant cell tumour of bone (GCTB) patients in relationship with tumour recurrence. We also aimed to investigate the influence of CpG methylation on the transcriptional levels of RANKL and OPG.

Bone defects are frequently observed in anterior shoulder instability. Over the last decade, knowledge of the association of bone loss with increased failure rates of soft-tissue repair has shifted the surgical management of chronic shoulder instability. On the glenoid side, there is no controversy about the critical glenoid bone loss being 20%. However, poor outcomes have been described even with a subcritical glenoid bone defect as low as 13.5%. On the humeral side, the Hill-Sachs lesion should be evaluated concomitantly with the glenoid defect as the two sides of the same bipolar lesion which interact in the instability process, as described by the glenoid track concept. We advocate adding remplissage to every Bankart repair in patients with a Hill-Sachs lesion, regardless of the glenoid bone loss. When critical or subcritical glenoid bone loss occurs in active patients (> 15%) or bipolar off-track lesions, we should consider anterior glenoid bone reconstructions. The techniques have evolved significantly over the last two decades, moving from open procedures to arthroscopic, and from screw fixation to metal-free fixation. The new arthroscopic techniques of glenoid bone reconstruction procedures allow precise positioning of the graft, identification, and treatment of concomitant injuries with low morbidity and faster recovery. Given the problems associated with bone resorption and metal hardware protrusion, the new metal-free techniques for Latarjet or free bone block procedures seem a good solution to avoid these complications, although no long-term data are yet available.

Cite this article: Bone Joint J 2024;106-B(10):1100–1110.