This edition of the Cochrane Corner looks at the three reviews that were published in the second half of 2023: surgical versus non-surgical interventions for displaced intra-articular calcaneal fractures; cryotherapy following total knee arthroplasty; and physical activity and education about physical activity for chronic musculoskeletal pain in children and adolescents

Cryotherapy is often applied after injuries of synovial joints. Although positive clinical effects on periarticular swelling and pain are well known, the effects on molecular processes of cartilage and synovial cells remained largely unknown so far. Therefore, the hypothesis was tested that hypothermia alleviates the synovial reaction and prevents chondrocyte death as well as cartilage destructive processes after blunt trauma. Human articular cartilage and synovial tissue was obtained with informed consent from patients undergoing knee joint replacement. Cartilage explants from macroscopically intact cartilage were impacted by a drop-tower apparatus with defined energy (0.59J) and cultivated for 24h or 7d at following temperature conditions: 2h, 16h or throughout at 27°C and afterwards or throughout at 37°C. Furthermore, human fibroblast-like synoviocytes (FLS) were stimulated with conditioned medium from traumatized cartilage (t-CM) and cultivated as indicated above up to 4d. Effects of hypothermia were evaluated by live/dead assay, gene expression (RQ-PCR), and type II collagen synthesis/cleavage as well as release of MMP-2, MMP-13 and IL-6 on protein level (ELISA, gelatin zymography). Statistical analysis was performed by 2-way ANOVA. The experimental study was performed in the research laboratory of the Orthopedic Department, University Hospital Ulm, Germany. Hypothermic treatment significantly improved chondrocyte viability 7d after blunt cartilage trauma (2h: p=0.016; 16h: p=0.036; throughout: p=0.039). 2h posttraumatic hypothermia attenuated expression of MMP-13 (m-RNA: p=0.012; protein: p=0.024). While type II collagen synthesis was significantly increased after 16h hypothermia, MMP-13 expression (mRNA: p=0.003; protein: p<0.001) and subsequent cleavage of type II collagen (p=0.049) were inhibited. Continuous hypothermia for 7d further significantly suppressed MMP release (proMMP-2, active MMP-2 and MMP-13) and type II collagen breakdown. On day 4 t-CM stimulated FLS revealed significantly suppressed gene expression of matrix-destructive enzymes (16h: ADAMTS-4; throughout: ADAMTS-4, MMP-3, MMP-13) and by trend reduced IL-6 expression in case of 16h or continuous hypothermia. Overall, hypothermia for only 2h and/or 16h after blunt cartilage trauma exhibited significant cell- and matrix-protective effects and promoted anabolic activity of surviving chondrocytes. Expression of matrix-destructive enzymes by FLS stimulated with Danger Associated Molecular Patterns (DAMPs) released from traumatized cartilage was attenuated by more prolonged hypothermia. These findings suggest that an optimized cryotherapy management after cartilage trauma might have the potential to ameliorate early molecular processes usually associated with the pathogenesis of posttraumatic osteoarthritis

Objectives

We studied subchondral intraosseous pressure (IOP) in an animal model during loading, and with vascular occlusion. We explored bone compartmentalization by saline injection.

Various chemicals are commonly used as adjuvant treatment to surgery for giant-cell tumour (GCT) of bone. The comparative effect of these solutions on the cells of GCT is not known. In this study we evaluated the cytotoxic effect of sterile water, 95% ethanol, 5% phenol, 3% hydrogen peroxide (H₂O₂) and 50% zinc chloride (ZnCI₂) on GCT monolayer tumour cultures which were established from six patients. The DNA content, the metabolic activity and the viability of the cultured samples of tumour cells were assessed at various times up to 120 hours after their exposure to these solutions.

Equal cytotoxicity to the GCT monolayer culture was observed for 95% ethanol, 5% phenol, 3% H₂O₂ and 50% ZnCI₂. The treated samples showed significant reductions in DNA content and metabolic activity 24 hours after treatment and this was sustained for up to 120 hours. The samples treated with sterile water showed an initial decline in DNA content and viability 24 hours after treatment, but the surviving cells were viable and had proliferated. No multinucleated cell formation was seen in these cultures.

These results suggest that the use of chemical adjuvants other than water could help improve local control in the treatment of GCT of bone.

Surgery is considered to be the most effective treatment for cartilaginous tumours. In recent years, a trend has emerged for patients with low-grade tumours to be treated less invasively using curettage followed by various forms of adjuvant therapy. We investigated the potential for phenol to be used as an adjuvant. Using a human chondrosarcoma-derived cartilage-producing cell line OUMS-27 as an in vitro model we studied the cytotoxic effect of phenol and ethanol. Since ethanol is the standard substance used to rinse phenol out of a bone cavity, we included an assessment of ethanol to see whether this was an important secondary factor with respect to cell death. The latter was assessed by flow cytometry.

A cytotoxic effect was found for concentrations of phenol of 1.5% and of ethanol of 42.5%. These results may provide a clinical rationale for the use of both phenol and ethanol as adjuvant therapy after intralesional curettage in low-grade central chondrosarcoma and justify further investigation.