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The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 12 | Pages 1617 - 1622
1 Dec 2008
Axelrad TW Steen B Lowenberg DW Creevy WR Einhorn TA

Heterotopic ossification occurring after the use of commercially available bone morphogenetic proteins has not been widely reported. We describe four cases of heterotopic ossification in patients treated with either recombinant bone morphogenetic protein 2 or recombinant bone morphogenetic protein 7. We found that while some patients were asymptomatic, heterotopic ossification which had occurred around a joint often required operative excision with good results


Bone & Joint Research
Vol. 5, Issue 4 | Pages 106 - 115
1 Apr 2016
Gruber HE Ode G Hoelscher G Ingram J Bethea S Bosse MJ

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


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 488 - 488
1 Sep 2012
Chan O Coathup M Hing K Buckland T Campion C Blunn G
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INTRODUCTION. Autologous bone grafts are considered gold standard in the repair of bone defects. However they are limited in supply and are associated with donor site morbidity. This has led to the development of synthetic bone graft substitute (BGS) materials, many of which have been reported as being osteoinductive. The structure of the BGS is important and bone formation has been observed in scaffolds with a macroporous morphology. Smaller pores termed ‘strut porosity’ may also be important for osteoinduction. The aim of this study was to compare the osteoinductive ability of one silicate-substituted calcium phosphate (SiCaP) with differing strut porosities in an ectopic ovine model. Our hypothesis was that SiCaP with greater strut porosity would be more osteoinductive. METHODS. The osteoinduction of SiCaP BGS with two different strut porosities (AF and AF++) was investigated. The materials had an identical chemical composition and morphological structure but differing strut porosity (AF=22.5%, AF++=47%). Implants were inserted into the paraspinal muscles in skeletally mature sheep. Procedures were carried out in compliance with UK Home Office regulations. There were 12 implants in each group. Implants remained in vivo for 8 and 12 weeks and on retrieval were prepared for undecalcified histology. Sections were stained and examined using light microscopy. A line intersection method was used to quantify bone, implant and implant surface/bone contact within seven random regions of interest along each implant. A Mann-Whitney U test was used for statistical analysis where p values < 0.05 were considered significant. RESULTS. Bone formation was observed to be greater in the AF++ group at 8 (AF=0.2%+/−0.15; AF++=0.44%+/−0.12) and significantly higher at 12 weeks (AF=1.33% +/−0.84; AF++=6.17%+/−1.51) (p=0.04). Significantly higher implant surface/bone contact was observed in the AF++ group at 8 (AF=0.67%+/−0.52; AF++=3.30%+/−1.17) (p=0.04) and 12 weeks (AF=3.06%+/−1.89; AF++=21.82%+/−5.59) (p=0.01). The % implant measured was less in the AF++ group at 8 (AF=39.06%+/−1.26; AF++=33.09%+/−2.14) and 12 weeks (AF=36.05% +/−3.55; AF++=30.60%+/−2.29) but this was not significant. Histology revealed bone formation within BGS strut pores measuring < 50um. Endochondral and intramembranous ossification were also observed in both groups. DISCUSSION. The results indicate that higher strut porosity promotes greater osteoinduction in SiCaP materials. This could be attributed to the micropores providing a greater surface area for the action of growth factors and osteoblasts leading to the formation of bone at an earlier time point. Endochondral ossification was an unusual finding as this is usually associated with bone formation secondary to Bone Morphogenetic proteins (BMPs). This suggests that the osteoinductive mechanisms by SiCaP may involve cytokines such as BMPs


The Bone & Joint Journal
Vol. 102-B, Issue 12 | Pages 1723 - 1734
1 Dec 2020
Fung B Hoit G Schemitsch E Godbout C Nauth A

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.

Methods

A systematic search was performed in CINAHL, The Cochrane Library, Embase, Ovid MEDLINE, and PubMed. We included articles from 1 January 1980 to 30 September 2019. Studies with a minimum sample size of five cases, where the IMT was performed primarily in adult patients (≥ 18 years old), in a long bone were included. Multivariate regression models were performed on patient-level data to determine variables associated with nonunion, postoperative infection, and the need for additional procedures.


The Bone & Joint Journal
Vol. 100-B, Issue 4 | Pages 646 - 651
1 Apr 2018
Attias N Thabet AM Prabhakar G Dollahite JA Gehlert RJ DeCoster TA

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.

Patients and Methods

A total of 17 patients (aged 17 to 61 years) treated for a segmental long bone defect by nail or plate fixation and an adjunctive TMC were included. The bone defects treated were in the tibia (nine), femur (six), radius (one), and humerus (one). The mean length of the segmental bone defect was 8.4 cm (2.2 to 13); the mean length of the titanium mesh cage was 8.3 cm (2.6 to 13). The clinical and radiological records of the patients were analyzed retrospectively.


Bone & Joint Research
Vol. 6, Issue 7 | Pages 423 - 432
1 Jul 2017
van der Stok J Hartholt KA Schoenmakers DAL Arts JJC

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.


The Bone & Joint Journal
Vol. 95-B, Issue 5 | Pages 583 - 597
1 May 2013
Kurien T Pearson RG Scammell BE

We reviewed 59 bone graft substitutes marketed by 17 companies currently available for implantation in the United Kingdom, with the aim of assessing the peer-reviewed literature to facilitate informed decision-making regarding their use in clinical practice. After critical analysis of the literature, only 22 products (37%) had any clinical data. Norian SRS (Synthes), Vitoss (Orthovita), Cortoss (Orthovita) and Alpha-BSM (Etex) had Level I evidence. We question the need for so many different products, especially with limited published clinical evidence for their efficacy, and conclude that there is a considerable need for further prospective randomised trials to facilitate informed decision-making with regard to the use of current and future bone graft substitutes in clinical practice.

Cite this article: Bone Joint J 2013;95-B:583–97.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 7 | Pages 928 - 932
1 Jul 2006
Patil S Montgomery R

We reviewed 78 femoral and tibial nonunions treated between January 1992 and December 2003. Of these, we classified 41 in 40 patients as complex cases because of infection (22), bone loss (6) or failed previous surgery (13). The complex cases were all treated with Ilizarov frames. At a mean time of 14.1 months (4 to 38), 39 had healed successfully.

Using the Association for the Study and Application of the Methods of Ilizarov scoring system we obtained 17 excellent, 14 good, four fair and six poor bone results. The functional results were excellent in 14 patients, good in 14, fair in two and poor in two. A total of six patients were lost to follow-up and two had amputations so were not evaluated for final functional assessment. All but two patients were very satisfied with the results. The average cost of treatment to the treating hospital was approximately £30 000 per patient.

We suggest that early referral to a tertiary centre could reduce the morbidity and prolonged time off work for these patients. The results justify the expense, but the National Health Service needs to make financial provision for the reconstruction of this type of complex nonunion.