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.

Using the United States Nationwide Inpatient Sample, we identified national trends in revision spinal fusion along with a comprehensive comparison of comorbidities, inpatient complications and surgical factors of revision spinal fusion compared to primary spinal fusion.

In 2009, there were 410 158 primary spinal fusion discharges and 22 128 revision spinal fusion discharges. Between 2002 and 2009, primary fusion increased at a higher rate compared with revision fusion (56.4% vs 51.0%; p < 0.001). In 2009, the mean length of stay and hospital charges were higher for revision fusion discharges than for primary fusion discharges (4.2 days vs 3.8 days, p < 0.001; USD $91 909 vs. $87 161, p < 0.001). In 2009, recombinant human bone morphogenetic protein (BMP) was used more in revision fusion than in primary fusion (39.6% vs 27.6%, p < 0.001), whereas interbody devices were used less in revision fusion (41.8% vs 56.6%, p < 0.001).

In the multivariable logistic regression model for all spinal fusions, depression (odds ratio (OR) 1.53, p < 0.001), psychotic disorders (OR 1.49, p < 0.001), deficiency anaemias (OR 1.35, p < 0.001) and smoking (OR 1.10, p = 0.006) had a greater chance of occurrence in revision spinal fusion discharges than in primary fusion discharges, adjusting for other variables. In terms of complications, after adjusting for all significant comorbidities, this study found that dural tears (OR 1.41; p < 0.001) and surgical site infections (OR 3.40; p < 0.001) had a greater chance of occurrence in revision spinal fusion discharges than in primary fusion discharges (p < 0.001). A p-value < 0.01 was considered significant in all final analyses.

Cite this article: Bone Joint J 2014;96-B:807–16.

Aims. The aim of this study was to identify the risk factors for adverse events following the surgical correction of cervical spinal deformities in adults. Methods. We identified adult patients who underwent corrective cervical spinal surgery between 1 January 2007 and 31 December 2015 from the MarketScan database. The baseline comorbidities and characteristics of the operation were recorded. Adverse events were defined as the development of a complication, an unanticipated deleterious postoperative event, or further surgery. Patients aged < 18 years and those with a previous history of tumour or trauma were excluded from the study. Results. A total of 13,549 adults in the database underwent primary corrective surgery for a cervical spinal deformity during the study period. A total of 3,785 (27.9%) had a complication within 90 days of the procedure, and 3,893 (28.7%) required further surgery within two years. In multivariate analysis, male sex (odds ratio (OR) 0.90 (95% confidence interval (CI) 0.8 to 0.9); p = 0.019) and a posterior approach (compared with a combined surgical approach, OR 0.66 (95% CI 0.5 to 0.8); p < 0.001) significantly decreased the risk of complications. Osteoporosis (OR 1.41 (95% CI 1.3 to 1.6); p < 0.001), dyspnoea (OR 1.48 (95% CI 1.3 to 1.6); p < 0.001), cerebrovascular accident (OR 1.81 (95% CI 1.6 to 2.0); p < 0.001), a posterior approach (compared with an anterior approach, OR 1.23 (95% CI 1.1 to 1.4); p < 0.001), and the use of bone morphogenic protein (BMP) (OR 1.22 (95% CI 1.1 to 1.4); p = 0.003) significantly increased the risks of 90-day complications. In multivariate regression analysis, preoperative dyspnoea (OR 1.50 (95% CI 1.3 to 1.7); p < 0.001), a posterior approach (compared with an anterior approach, OR 2.80 (95% CI 2.4 to 3.2; p < 0.001), and postoperative dysphagia (OR 2.50 (95% CI 1.8 to 3.4); p < 0.001) were associated with a significantly increased risk of further surgery two years postoperatively. A posterior approach (compared with a combined approach, OR 0.32 (95% CI 0.3 to 0.4); p < 0.001), the use of BMP (OR 0.48 (95% CI 0.4 to 0.5); p < 0.001) were associated with a significantly decreased risk of further surgery at this time. Conclusion. The surgical approach and intraoperative use of BMP strongly influence the risk of further surgery, whereas the comorbidity burden and the characteristics of the operation influence the rates of early complications in adult patients undergoing corrective cervical spinal surgery. These data may aid surgeons in patient selection and surgical planning. Cite this article: Bone Joint J 2021;103-B(4):734–738

External fixation of distal tibial fractures is often associated with delayed union. We have investigated whether union can be enhanced by using recombinant bone morphogenetic protein-7 (rhBMP-7). Osteoinduction with rhBMP-7 and bovine collagen was used in 20 patients with distal tibial fractures which had been treated by external fixation (BMP group). Healing of the fracture was compared with that of 20 matched patients in whom treatment was similar except that rhBMP-7 was not used. Significantly more fractures had healed by 16 (p = 0.039) and 20 weeks (p = 0.022) in the BMP group compared with the matched group. The mean time to union (p = 0.002), the duration of absence from work (p = 0.018) and the time for which external fixation was required (p = 0.037) were significantly shorter in the BMP group than in the matched group. Secondary intervention due to delayed healing was required in two patients in the BMP group and seven in the matched group. RhBMP-7 can enhance the union of distal tibial fractures treated by external fixation

Periosteum is important for bone homoeostasis through the release of bone morphogenetic proteins (BMPs) and their effect on osteoprogenitor cells. Smoking has an adverse effect on fracture healing and bone regeneration. The aim of this study was to evaluate the effect of smoking on the expression of the BMPs of human periosteum. Real-time polymerase chain reaction was performed for BMP-2,-4,-6,-7 gene expression in periosteal samples obtained from 45 fractured bones (19 smokers, 26 non-smokers) and 60 non-fractured bones (21 smokers, 39 non-smokers). A hierarchical model of BMP gene expression (BMP-2 > BMP-6 > BMP-4 > BMP-7) was demonstrated in all samples. When smokers and non-smokers were compared, a remarkable reduction in the gene expression of BMP-2, -4 and -6 was noticed in smokers. The comparison of fracture and non-fracture groups demonstrated a higher gene expression of BMP-2, -4 and -7 in the non-fracture samples. Within the subgroups (fracture and non-fracture), BMP gene expression in smokers was either lower but without statistical significance in the majority of BMPs, or similar to that in non-smokers with regard to BMP-4 in fracture and BMP-7 in non-fracture samples. In smokers, BMP gene expression of human periosteum was reduced, demonstrating the effect of smoking at the molecular level by reduction of mRNA transcription of periosteal BMPs. Among the BMPs studied, BMP-2 gene expression was significantly higher, highlighting its role in bone homoeostasis

Ossification of the ligamentum flavum and secondary spinal-cord compression were produced experimentally in mice by implanting bone morphogenetic protein (BMP) in the lumbar extradural space. The ligamentum flavum became hypertrophied and ossified, and protruded into the spinal canal. The thickness of the ossified ligament increased gradually with time, leading to compression and deformation of the spinal cord which showed various degrees of degeneration. Demyelination occurred in the posterior and lateral white columns and neuronal loss or chromatolysis in the grey matter. The pathological findings in the experimental animals closely resemble those found in the human disease and suggest that BMP may be a causative factor of ossification of the ligamentum flavum in man. This experimental model may be useful for the study of myelopathy caused by gradual spinal-cord compression

In dogs, resection of a length of the ulna equal to twice the diameter of the mid-shaft leaves a defect which consistently fails to unite. In response to an implant of 100 mg of bovine bone morphogenetic protein (BMP), the defect becomes filled by callus consisting of fibrocartilage, cartilage and woven bone within four weeks. The cartilage is resorbed and replaced by new bone in four to eight weeks. Woven bone is then resorbed, colonised by bone marrow cells and remodelled into lamellar bone. Union of the defect is produced by 12 weeks. Control defects filled with autogeneic cortical bone chips unite after the same period. In regeneration induced by bone morphogenetic protein (BMP) and in repair enhanced by bone graft, union depends upon the proliferation of cells within and around the bone ends. Our working hypothesis is that BMP induces the differentiation of perivascular connective tissue cells into chondroblasts and osteoprogenitor cells and thereby augments the process of bone regeneration from the cells already present in the endosteum and periosteum

Since bone morphogenetic proteins (BMPs) are highly homologous, we investigated the hypothesis that recombinant BMP-4 of the genome of Xenopus laevis (rxBMP-4) may influence the proliferation or differentiation of human primary osteoblast-like cells (HPOC), as occurs with recombinant human BMP (rhBMP-2). HPOC were incubated in the presence of either rxBMP-4, rhBMP-2 or basic fibroblast growth factor (rh-bFGF). The last two were used as positive controls and are known to induce differentiation or proliferation of HPOC, respectively. rxBMP-4 (50 ng/ml and 100 ng/ml) induced a differentiation of HPOC to almost the same extent as rhBMP-2, whereas the addition of rh-bFGF, applied in the same concentration, failed to have any influence on cell differentiation. rh-bFGF however, provoked an increase in cell proliferation of up to 150% when compared with non-stimulated HPOC, while rhBMP-2 and rxBMP-4 had no such effect. Our results indicate an equipotent effect of rhBMP-2 and rxBMP-4 obtained from Xenopus laevis on the differentiation and proliferation of human primary osteoblast-like cells

Aims

Osteopetrosis (OP) is a rare hereditary disease that causes reduced bone resorption and increased bone density as a result of osteoclastic function defect. Our aim is to review the difficulties, mid-term follow-up results, and literature encountered during the treatment of OP.

Aims

The purpose of this study was to: review the efficacy of the induced membrane technique (IMT), also known as the Masquelet technique; and investigate the relationship between patient factors and technique variations on the outcomes of the IMT.

Aims

Despite declining frequency of blood transfusion and electrolyte supplementation following total joint arthroplasty, postoperative blood analyses are still routinely ordered for these patients. This study aimed to determine the rate of blood transfusion and electrolyte restoration in arthroplasty patients treated with a perioperative blood conservation protocol and to identify risk factors that would predict the need for transfusion and electrolyte supplementation.

Aims

This study reviews the use of a titanium mesh cage (TMC) as an adjunct to intramedullary nail or plate reconstruction of an extra-articular segmental long bone defect.

Aims

The success of anterior cruciate ligament reconstruction (ACLR) depends on osseointegration at the graft-tunnel interface and intra-articular ligamentization. Our aim was to conduct a systematic review of clinical and preclinical studies that evaluated biological augmentation of graft healing in ACLR.

The continual cycle of bone formation and resorption is carried out by osteoblasts, osteocytes, and osteoclasts under the direction of the bone-signaling pathway. In certain situations the host cycle of bone repair is insufficient and requires the assistance of bone grafts and their substitutes. The fundamental properties of a bone graft are osteoconduction, osteoinduction, osteogenesis, and structural support. Options for bone grafting include autogenous and allograft bone and the various isolated or combined substitutes of calcium sulphate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. Not all bone grafts will have the same properties. As a result, understanding the requirements of the clinical situation and specific properties of the various types of bone grafts is necessary to identify the ideal graft. We present a review of the bone repair process and properties of bone grafts and their substitutes to help guide the clinician in the decision making process.

Cite this article: Bone Joint J 2016;98-B(1 Suppl A):6–9.

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.

Congenital pseudarthrosis of the tibia (CPT) is a rare but well recognised condition. Obtaining union of the pseudarthrosis in these children is often difficult and may require several surgical procedures. The treatment has changed significantly since the review by Hardinge in 1972, but controversies continue as to the best form of surgical treatment. This paper reviews these controversies.

Cite this article: Bone Joint J 2013;95-B:1027–34.

In order to investigate the osteoinductive properties of allograft used in impaction grafting and the effect of strain during impaction on these properties, we designed an in vitro experiment to measure strain-related release of bone morphogenetic protein-7 (BMP-7) from fresh-frozen femoral head allograft. A total of 40 10 mm cubes of cancellous bone were cut from ten samples of fresh-frozen femoral head. The marrow was removed from the cubes and the baseline concentrations of BMP-7 were measured. Specimens from each femoral head were allocated to four groups and subjected to different compressive strains with a material testing machine, after which BMP-7 activity was reassessed. It was present in all groups. There was a linear increase of 102.1 pg/g (95% confidence interval 68.6 to 135.6) BMP-7 for each 10% increase in strain. At 80% strain the mean concentration of BMP-7 released (830.3 pg/g bone) was approximately four times that released at 20% strain. Activity of BMP-7 in fresh-frozen allograft has not previously been demonstrated. This study shows that the freezing and storage of femoral heads allows some maintenance of biological activity, and that impaction grafting provides a source of osteoinductive bone for remodelling.

We have shown that BMP-7 is released from fresh-frozen femoral head cancellous bone in proportion to the strain applied to the bone. This suggests that the impaction process itself may contribute to the biological process of remodelling and bony incorporation.

Aims

We aimed to assess the influence of ethnicity on the incidence of heterotopic ossification (HO) after total hip arthroplasty (THA).

The presacral retroperitoneal approach for axial lumbar interbody fusion (presacral ALIF) is not widely reported, particularly with regard to the mid-term outcome. This prospective study describes the clinical outcomes, complications and rates of fusion at a follow-up of two years for 26 patients who underwent this minimally invasive technique along with further stabilisation using pedicle screws. The fusion was single-level at the L5-S1 spinal segment in 17 patients and two-level at L4–5 and L5-S1 in the other nine. The visual analogue scale for pain and Oswestry Disability Index scores were recorded pre-operatively and during the 24-month study period. The evaluation of fusion was by thin-cut CT scans at six and 12 months, and flexion-extension plain radiographs at six, 12 and 24 months. Significant reductions in pain and disability occurred as early as three weeks postoperatively and were maintained. Fusion was achieved in 22 of 24 patients (92%) at 12 months and in 23 patients (96%) at 24 months. One patient (4%) with a pseudarthrosis underwent successful revision by augmentation of the posterolateral fusion mass through a standard open midline approach.

There were no severe adverse events associated with presacral ALIF, which in this series demonstrated clinical outcomes and fusion rates comparable with those of reports of other methods of interbody fusion.