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.
{"title":"Interleukin-19 promotes bone resorption by suppressing osteoprotegerin expression in BMSCs in a lipopolysaccharide-induced bone loss mouse model.","authors":"Zhicheng Dai, Yanan Chen, Enjun He, Hongjie Wang, Weihong Guo, Zhenkai Wu, Kai Huang, Qinghua Zhao","doi":"10.1302/2046-3758.1211.BJR-2023-0101.R1","DOIUrl":"10.1302/2046-3758.1211.BJR-2023-0101.R1","url":null,"abstract":"<p><strong>Aims: </strong>Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. <i>Interleukin-19</i> (<i>IL-19</i>), 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 <i>IL-19</i> on osteoporosis.</p><p><strong>Methods: </strong>Blood and femoral bone marrow suspension <i>IL-19</i> levels were first measured in the lipopolysaccharide (LPS)-induced bone loss model. Small interfering RNA (siRNA) was applied to knock down <i>IL-19</i> for further validation. Thereafter, osteoclast production was stimulated with <i>IL-19</i> in combination with mouse macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). The effect of <i>IL-19</i> was subsequently evaluated using tartrate-resistant acid phosphatase (TRAP) staining and quantitative real-time polymerase chain reaction (RT-qPCR). The effect of <i>IL-19</i> on osteoprotegerin (OPG) was then assessed using in vitro recombinant <i>IL-19</i> 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.</p><p><strong>Results: </strong>In the LPS-induced bone loss mouse model, the levels of <i>IL-19</i> in peripheral blood serum and femoral bone marrow suspension were significantly increased. The in vivo results indicated that global <i>IL-19</i> 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 <i>IL-19</i> inhibits OPG expression in bone marrow mesenchymal stem cells (BMSCs) and thus increases bone resorption.</p><p><strong>Conclusion: </strong><i>IL-19</i> 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 <i>IL-19</i> for future clinical applications.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10622185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-01DOI: 10.1302/2046-3758.1211.BJR-2022-0425.R3
Xiaochuan Wang, Wen Jiang, Kexin Pan, Lin Tao, Yue Zhu
Aims: Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis.
Methods: The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the Bmal1 gene. We established a postmenopausal mouse model and verified the effect of melatonin on the bone mass of postmenopausal osteoporosis in mice via micro-CT. Bmal1 lentiviral activation particles were used to establish an in vitro model of overexpression of the bmal1 gene.
Results: Melatonin promoted apoptosis of RAW264.7 cells and increased the expression of BMAL1 to inhibit the activation of ROS and phosphorylation of mitogen-activated protein kinase (MAPK)-p38. Silencing the bmal1 gene weakened the above effects of melatonin. After that, we used dehydrocorydaline (DHC) to enhance the activation of MAPK-p38, and the effects of melatonin on reducing ROS levels and promoting apoptosis of RAW264.7 cells were also blocked. Then, we constructed a mouse model of postmenopausal osteoporosis and administered melatonin. The results showed that melatonin improves bone loss in ovariectomized mice. Finally, we established a model of overexpression of the bmal1 gene, and these results suggest that the bmal1 gene can regulate ROS activity and change the level of the MAPK-p38 signalling pathway.
Conclusion: Our study confirmed that melatonin promotes the apoptosis of RAW264.7 cells through BMAL1/ROS/MAPK-p38, and revealed the therapeutic effect and mechanism of melatonin in postmenopausal osteoporosis. This finding enriches BMAL1 as a potential target for the treatment of osteoporosis and the pathogenesis of postmenopausal osteoporosis.
{"title":"Melatonin induces RAW264.7 cell apoptosis via the BMAL1/ROS/MAPK-p38 pathway to improve postmenopausal osteoporosis.","authors":"Xiaochuan Wang, Wen Jiang, Kexin Pan, Lin Tao, Yue Zhu","doi":"10.1302/2046-3758.1211.BJR-2022-0425.R3","DOIUrl":"https://doi.org/10.1302/2046-3758.1211.BJR-2022-0425.R3","url":null,"abstract":"<p><strong>Aims: </strong>Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis.</p><p><strong>Methods: </strong>The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the <i>Bmal1</i> gene. We established a postmenopausal mouse model and verified the effect of melatonin on the bone mass of postmenopausal osteoporosis in mice via micro-CT. <i>Bmal1</i> lentiviral activation particles were used to establish an in vitro model of overexpression of the bmal1 gene.</p><p><strong>Results: </strong>Melatonin promoted apoptosis of RAW264.7 cells and increased the expression of BMAL1 to inhibit the activation of ROS and phosphorylation of mitogen-activated protein kinase (MAPK)-p38. Silencing the bmal1 gene weakened the above effects of melatonin. After that, we used dehydrocorydaline (DHC) to enhance the activation of MAPK-p38, and the effects of melatonin on reducing ROS levels and promoting apoptosis of RAW264.7 cells were also blocked. Then, we constructed a mouse model of postmenopausal osteoporosis and administered melatonin. The results showed that melatonin improves bone loss in ovariectomized mice. Finally, we established a model of overexpression of the bmal1 gene, and these results suggest that the bmal1 gene can regulate ROS activity and change the level of the MAPK-p38 signalling pathway.</p><p><strong>Conclusion: </strong>Our study confirmed that melatonin promotes the apoptosis of RAW264.7 cells through BMAL1/ROS/MAPK-p38, and revealed the therapeutic effect and mechanism of melatonin in postmenopausal osteoporosis. This finding enriches BMAL1 as a potential target for the treatment of osteoporosis and the pathogenesis of postmenopausal osteoporosis.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-19DOI: 10.1302/2046-3758.1210.BJR-2023-0109.R1
Maria A Forteza-Genestra, Miquel Antich-Rosselló, Guillem Ramis-Munar, Javier Calvo, Antoni Gayà, Marta Monjo, Joana M Ramis
Aims Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants. Methods pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 109 particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs. Results Significantly higher content of DNA and collagen was observed for the pEV-treated group compared to control and cEV groups. No differences were found in GAG quantification nor in EVs uptake within any treated group. Conclusion In conclusion, pEVs showed better performance than cEVs in our in vitro OA model. Although further studies are needed, pEVs are shown as a potential alternative to cEVs for cell-free regenerative medicine. Cite this article: Bone Joint Res 2023;12(10):667–676.
{"title":"Comparative effect of platelet- and mesenchymal stromal cell-derived extracellular vesicles on human cartilage explants using an ex vivo inflammatory osteoarthritis model.","authors":"Maria A Forteza-Genestra, Miquel Antich-Rosselló, Guillem Ramis-Munar, Javier Calvo, Antoni Gayà, Marta Monjo, Joana M Ramis","doi":"10.1302/2046-3758.1210.BJR-2023-0109.R1","DOIUrl":"https://doi.org/10.1302/2046-3758.1210.BJR-2023-0109.R1","url":null,"abstract":"Aims Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants. Methods pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 109 particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs. Results Significantly higher content of DNA and collagen was observed for the pEV-treated group compared to control and cEV groups. No differences were found in GAG quantification nor in EVs uptake within any treated group. Conclusion In conclusion, pEVs showed better performance than cEVs in our in vitro OA model. Although further studies are needed, pEVs are shown as a potential alternative to cEVs for cell-free regenerative medicine. Cite this article: Bone Joint Res 2023;12(10):667–676.","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/30/12/BJR-12-2046-3758.1210.BJR-2023-0109.R1.PMC10584413.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49674223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-17DOI: 10.1302/2046-3758.1210.BJR-2023-0062.R1
Jonghoo Sung, Kate R Barratt, Stephen M Pederson, Chantal Chenu, Ines Reichert, Gerald J Atkins, Paul H Anderson, Peter J Smitham
Aims Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy. Methods Zucker rats, WT and homozygous for leptin receptor mutation (ZDF), were fed a moderately high-fat diet to induce T2DM only in the ZDF animals. At ten weeks of age, open femoral fractures were simulated using a unilateral osteotomy stabilized with an external fixator. At three weeks post-surgery, the fractured femur from each animal was retrieved for analysis. Callus formation and the extent of healing were assessed by radiograph and histology. Bone tissue was processed for total RNA extraction and messenger RNA (mRNA) sequencing (mRNA-Seq). Results Radiographs and histology demonstrated impaired fracture healing in ZDF rats with incomplete bony bridge formation and an influx of intramedullary inflammatory tissue. In comparison, near-complete bridging between cortices was observed in Sham WT animals. Of 13,160 genes, mRNA-Seq analysis identified 13 that were differentially expressed in ZDF rat callus, using a false discovery rate (FDR) threshold of 10%. Seven genes were upregulated with high confidence (FDR = 0.05) in ZDF fracture callus, most with known roles in inflammation. Conclusion These findings suggest that elevated or prolonged inflammation contributes to delayed fracture healing in T2DM. The identified genes may be used as biomarkers to monitor and treat delayed fracture healing in diabetic patients. Cite this article: Bone Joint Res 2023;12(10):657–666.
{"title":"Unbiased gene expression analysis of the delayed fracture healing observed in Zucker diabetic fatty rats.","authors":"Jonghoo Sung, Kate R Barratt, Stephen M Pederson, Chantal Chenu, Ines Reichert, Gerald J Atkins, Paul H Anderson, Peter J Smitham","doi":"10.1302/2046-3758.1210.BJR-2023-0062.R1","DOIUrl":"10.1302/2046-3758.1210.BJR-2023-0062.R1","url":null,"abstract":"Aims Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy. Methods Zucker rats, WT and homozygous for leptin receptor mutation (ZDF), were fed a moderately high-fat diet to induce T2DM only in the ZDF animals. At ten weeks of age, open femoral fractures were simulated using a unilateral osteotomy stabilized with an external fixator. At three weeks post-surgery, the fractured femur from each animal was retrieved for analysis. Callus formation and the extent of healing were assessed by radiograph and histology. Bone tissue was processed for total RNA extraction and messenger RNA (mRNA) sequencing (mRNA-Seq). Results Radiographs and histology demonstrated impaired fracture healing in ZDF rats with incomplete bony bridge formation and an influx of intramedullary inflammatory tissue. In comparison, near-complete bridging between cortices was observed in Sham WT animals. Of 13,160 genes, mRNA-Seq analysis identified 13 that were differentially expressed in ZDF rat callus, using a false discovery rate (FDR) threshold of 10%. Seven genes were upregulated with high confidence (FDR = 0.05) in ZDF fracture callus, most with known roles in inflammation. Conclusion These findings suggest that elevated or prolonged inflammation contributes to delayed fracture healing in T2DM. The identified genes may be used as biomarkers to monitor and treat delayed fracture healing in diabetic patients. Cite this article: Bone Joint Res 2023;12(10):657–666.","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cc/18/BJR-12-2046-3758.1210.BJR-2023-0062.R1.PMC10578971.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-16DOI: 10.1302/2046-3758.1210.BJR-2023-0237
Navnit S Makaram, A H R W Simpson
Cite this article: Bone Joint Res 2023;12(10):654–656.
{"title":"Disease-modifying agents in osteoarthritis: where are we now and what does the future hold?","authors":"Navnit S Makaram, A H R W Simpson","doi":"10.1302/2046-3758.1210.BJR-2023-0237","DOIUrl":"10.1302/2046-3758.1210.BJR-2023-0237","url":null,"abstract":"Cite this article: Bone Joint Res 2023;12(10):654–656.","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8a/ba/BJR-12-2046-3758.1210.BJR-2023-0237.PMC10577043.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-10DOI: 10.1302/2046-3758.1210.BJR-2023-0071.R1
Nico Hinz, Sebastian Butscheidt, Nico M Jandl, Holger Rohde, Johannes Keller, Frank T Beil, Jan Hubert, Tim Rolvien
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.
{"title":"Increased local bone turnover in patients with chronic periprosthetic joint infection.","authors":"Nico Hinz, Sebastian Butscheidt, Nico M Jandl, Holger Rohde, Johannes Keller, Frank T Beil, Jan Hubert, Tim Rolvien","doi":"10.1302/2046-3758.1210.BJR-2023-0071.R1","DOIUrl":"10.1302/2046-3758.1210.BJR-2023-0071.R1","url":null,"abstract":"<p><strong>Aims: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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 <i>Staphylococcus aureus</i> infection, compared to those with detection of <i>Staphylococcus epidermidis</i> and <i>Cutibacterium</i> spp.</p><p><strong>Conclusion: </strong>This study provides insights into the local bone metabolism in chronic PJI, demonstrating osteosclerosis with high bone turnover. The fact that <i>Staphylococcus aureus</i> was associated with distinctly increased osteoclast indices strongly suggests early surgical treatment to prevent periprosthetic bone alterations.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/63/76/BJR-12-2046-3758.1210.BJR-2023-0071.R1.PMC10562080.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41182070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-10DOI: 10.1302/2046-3758.1210.BJR-2023-0028.R1
Victoria Hamilton, Sadiyah Sheikh, Alicja Szczepanska, Nick Maskell, Fergus Hamilton, Jonathan P Reid, Bryan R Bzdek, James R D Murray
Aims: Orthopaedic surgery uses many varied instruments with high-speed, high-impact, thermal energy and sometimes heavy instruments, all of which potentially result in aerosolization of contaminated blood, tissue, and bone, raising concerns for clinicians' health. This study quantifies the aerosol exposure by measuring the number and size distribution of the particles reaching the lead surgeon during key orthopaedic operations.
Methods: The aerosol yield from 17 orthopaedic open surgeries (on the knee, hip, and shoulder) was recorded at the position of the lead surgeon using an Aerodynamic Particle Sizer (APS; 0.5 to 20 μm diameter particles) sampling at 1 s time resolution. Through timestamping, detected aerosol was attributed to specific procedures.
Results: Diathermy (electrocautery) and oscillating bone saw use had a high aerosol yield (> 100 particles detected per s) consistent with high exposure to aerosol in the respirable range (< 5 µm) for the lead surgeon. Pulsed lavage, reaming, osteotome use, and jig application/removal were medium aerosol yield (10 to 100 particles s-1). However, pulsed lavage aerosol was largely attributed to the saline jet, osteotome use was always brief, and jig application/removal had a large variability in the associated aerosol yield. Suctioning (with/without saline irrigation) had a low aerosol yield (< 10 particles s-1). Most surprisingly, other high-speed procedures, such as drilling and screwing, had low aerosol yields.
Conclusion: This work suggests that additional precautions should be recommended for diathermy and bone sawing, such as enhanced personal protective equipment or the use of suction devices to reduce exposure.
{"title":"Diathermy and bone sawing are high aerosol yield procedures.","authors":"Victoria Hamilton, Sadiyah Sheikh, Alicja Szczepanska, Nick Maskell, Fergus Hamilton, Jonathan P Reid, Bryan R Bzdek, James R D Murray","doi":"10.1302/2046-3758.1210.BJR-2023-0028.R1","DOIUrl":"10.1302/2046-3758.1210.BJR-2023-0028.R1","url":null,"abstract":"<p><strong>Aims: </strong>Orthopaedic surgery uses many varied instruments with high-speed, high-impact, thermal energy and sometimes heavy instruments, all of which potentially result in aerosolization of contaminated blood, tissue, and bone, raising concerns for clinicians' health. This study quantifies the aerosol exposure by measuring the number and size distribution of the particles reaching the lead surgeon during key orthopaedic operations.</p><p><strong>Methods: </strong>The aerosol yield from 17 orthopaedic open surgeries (on the knee, hip, and shoulder) was recorded at the position of the lead surgeon using an Aerodynamic Particle Sizer (APS; 0.5 to 20 μm diameter particles) sampling at 1 s time resolution. Through timestamping, detected aerosol was attributed to specific procedures.</p><p><strong>Results: </strong>Diathermy (electrocautery) and oscillating bone saw use had a high aerosol yield (> 100 particles detected per s) consistent with high exposure to aerosol in the respirable range (< 5 µm) for the lead surgeon. Pulsed lavage, reaming, osteotome use, and jig application/removal were medium aerosol yield (10 to 100 particles s<sup>-1</sup>). However, pulsed lavage aerosol was largely attributed to the saline jet, osteotome use was always brief, and jig application/removal had a large variability in the associated aerosol yield. Suctioning (with/without saline irrigation) had a low aerosol yield (< 10 particles s<sup>-1</sup>). Most surprisingly, other high-speed procedures, such as drilling and screwing, had low aerosol yields.</p><p><strong>Conclusion: </strong>This work suggests that additional precautions should be recommended for diathermy and bone sawing, such as enhanced personal protective equipment or the use of suction devices to reduce exposure.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41182069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-04DOI: 10.1302/2046-3758.1210.BJR-2022-0457.R1
Conrad J Harrison, Constantin Y Plessen, Gregor Liegl, Jeremy N Rodrigues, Shiraz A Sabah, David J Beard, Felix Fischer
Aims: To map the Oxford Knee Score (OKS) and High Activity Arthroplasty Score (HAAS) items to a common scale, and to investigate the psychometric properties of this new scale for the measurement of knee health.
Methods: Patient-reported outcome measure (PROM) data measuring knee health were obtained from the NHS PROMs dataset and Total or Partial Knee Arthroplasty Trial (TOPKAT). Assumptions for common scale modelling were tested. A graded response model (fitted to OKS item responses in the NHS PROMs dataset) was used as an anchor to calibrate paired HAAS items from the TOPKAT dataset. Information curves for the combined OKS-HAAS model were plotted. Bland-Altman analysis was used to compare common scale scores derived from OKS and HAAS items. A conversion table was developed to map between HAAS, OKS, and the common scale.
Results: We included 3,329 response sets from 528 patients undergoing knee arthroplasty. These generally met the assumptions of unidimensionality, monotonicity, local independence, and measurement invariance. The HAAS items provided more information than OKS items at high levels of knee health. Combining both instruments resulted in higher test-level information than either instrument alone. The mean error between common scale scores derived from the OKS and HAAS was 0.29 logits.
Conclusion: The common scale allowed more precise measurement of knee health than use of either the OKS or HAAS individually. These techniques for mapping PROM instruments may be useful for the standardization of outcome reporting, and pooling results across studies that use either PROM in individual-patient meta-analysis.
{"title":"Overcoming floor and ceiling effects in knee arthroplasty outcome measurement.","authors":"Conrad J Harrison, Constantin Y Plessen, Gregor Liegl, Jeremy N Rodrigues, Shiraz A Sabah, David J Beard, Felix Fischer","doi":"10.1302/2046-3758.1210.BJR-2022-0457.R1","DOIUrl":"https://doi.org/10.1302/2046-3758.1210.BJR-2022-0457.R1","url":null,"abstract":"<p><strong>Aims: </strong>To map the Oxford Knee Score (OKS) and High Activity Arthroplasty Score (HAAS) items to a common scale, and to investigate the psychometric properties of this new scale for the measurement of knee health.</p><p><strong>Methods: </strong>Patient-reported outcome measure (PROM) data measuring knee health were obtained from the NHS PROMs dataset and Total or Partial Knee Arthroplasty Trial (TOPKAT). Assumptions for common scale modelling were tested. A graded response model (fitted to OKS item responses in the NHS PROMs dataset) was used as an anchor to calibrate paired HAAS items from the TOPKAT dataset. Information curves for the combined OKS-HAAS model were plotted. Bland-Altman analysis was used to compare common scale scores derived from OKS and HAAS items. A conversion table was developed to map between HAAS, OKS, and the common scale.</p><p><strong>Results: </strong>We included 3,329 response sets from 528 patients undergoing knee arthroplasty. These generally met the assumptions of unidimensionality, monotonicity, local independence, and measurement invariance. The HAAS items provided more information than OKS items at high levels of knee health. Combining both instruments resulted in higher test-level information than either instrument alone. The mean error between common scale scores derived from the OKS and HAAS was 0.29 logits.</p><p><strong>Conclusion: </strong>The common scale allowed more precise measurement of knee health than use of either the OKS or HAAS individually. These techniques for mapping PROM instruments may be useful for the standardization of outcome reporting, and pooling results across studies that use either PROM in individual-patient meta-analysis.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10547565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41096916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-03DOI: 10.1302/2046-3758.1210.BJR-2023-0019.R1
Omer Helwa-Shalom, Faris Saba, Elad Spitzer, Salem Hanhan, Koby Goren, Shany I Markowitz, Dekel Shilo, Nissim Khaimov, Yechiel N Gellman, Dan Deutsch, Anat Blumenfeld, Hani Nevo, Amir Haze
Aims: Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model.
Methods: A reproducible large OCI was created in the right leg femoral trochlea of 93 rats. The OCIs were treated with 0.1, 0.5, 1.0, 2.5, or 5.0 μg/μl recombinant human amelogenin protein (rHAM+) dissolved in propylene glycol alginate (PGA) carrier, or with PGA carrier alone. The degree of healing was evaluated 12 weeks after treatment by morphometric analysis and histological evaluation. Cell recruitment to the site of injury as well as the origin of the migrating cells were assessed four days after treatment with 0.5 μg/μl rHAM+ using immunohistochemistry and immunofluorescence.
Results: A total of 12 weeks after treatment, 0.5 μg/μl rHAM+ brought about significant repair of the subchondral bone and cartilage. Increased expression of proteoglycan and type II collagen and decreased expression of type I collagen were revealed at the surface of the defect, and an elevated level of type X collagen at the newly developed tide mark region. Conversely, the control group showed osteoarthritic alterations. Recruitment of cells expressing the mesenchymal stem cell (MSC) markers CD105 and STRO-1, from adjacent bone marrow toward the OCI, was noted four days after treatment.
Conclusion: We found that 0.5 μg/μl rHAM+ induced in vivo healing of injured articular cartilage and subchondral bone in a rat model, preventing the destructive post-traumatic osteoarthritic changes seen in control OCIs, through paracrine recruitment of cells a few days after treatment.
{"title":"Regeneration of injured articular cartilage using the recombinant human amelogenin protein.","authors":"Omer Helwa-Shalom, Faris Saba, Elad Spitzer, Salem Hanhan, Koby Goren, Shany I Markowitz, Dekel Shilo, Nissim Khaimov, Yechiel N Gellman, Dan Deutsch, Anat Blumenfeld, Hani Nevo, Amir Haze","doi":"10.1302/2046-3758.1210.BJR-2023-0019.R1","DOIUrl":"https://doi.org/10.1302/2046-3758.1210.BJR-2023-0019.R1","url":null,"abstract":"<p><strong>Aims: </strong>Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model.</p><p><strong>Methods: </strong>A reproducible large OCI was created in the right leg femoral trochlea of 93 rats. The OCIs were treated with 0.1, 0.5, 1.0, 2.5, or 5.0 μg/μl recombinant human amelogenin protein (rHAM<sup>+</sup>) dissolved in propylene glycol alginate (PGA) carrier, or with PGA carrier alone. The degree of healing was evaluated 12 weeks after treatment by morphometric analysis and histological evaluation. Cell recruitment to the site of injury as well as the origin of the migrating cells were assessed four days after treatment with 0.5 μg/μl rHAM<sup>+</sup> using immunohistochemistry and immunofluorescence.</p><p><strong>Results: </strong>A total of 12 weeks after treatment, 0.5 μg/μl rHAM<sup>+</sup> brought about significant repair of the subchondral bone and cartilage. Increased expression of proteoglycan and type II collagen and decreased expression of type I collagen were revealed at the surface of the defect, and an elevated level of type X collagen at the newly developed tide mark region. Conversely, the control group showed osteoarthritic alterations. Recruitment of cells expressing the mesenchymal stem cell (MSC) markers CD105 and STRO-1, from adjacent bone marrow toward the OCI, was noted four days after treatment.</p><p><strong>Conclusion: </strong>We found that 0.5 μg/μl rHAM<sup>+</sup> induced in vivo healing of injured articular cartilage and subchondral bone in a rat model, preventing the destructive post-traumatic osteoarthritic changes seen in control OCIs, through paracrine recruitment of cells a few days after treatment.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1d/a7/BJR-12-2046-3758.1210.BJR-2023-0019.R1.PMC10545453.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41108898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-21DOI: 10.1302/2046-3758.129.BJR-2023-0232
A H R W Simpson, Navnit S Makaram, Ewen Harrison, John Norrie
Cite this article: Bone Joint Res 2023;12(9):598–600.
{"title":"Decision-making in surgical study designs: a proposed decision algorithm to aid in the selection of an appropriate research study design for a given surgical intervention: the PERFECT tool.","authors":"A H R W Simpson, Navnit S Makaram, Ewen Harrison, John Norrie","doi":"10.1302/2046-3758.129.BJR-2023-0232","DOIUrl":"https://doi.org/10.1302/2046-3758.129.BJR-2023-0232","url":null,"abstract":"Cite this article: Bone Joint Res 2023;12(9):598–600.","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/c7/BJR-12-2046-3758.129.BJR-2023-0232.PMC10512865.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41103058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}