Magnetic resonance arthrography, a procedure through which contrast agents containing gadolinium and/or iopromide are administered intra-articularly, has become a useful tool in musculoskeletal diagnosis. Nevertheless, despite being considered safe for systemic use, certain tissue toxicities have been identified for both drugs. In this study, the effects of short-term exposure of human primary chondrocyte cell cultures to gadolinium and/or iopromide contrast agents were examined by assaying for stage-specific embryonic antigen-1 (SSEA-1) protein expression (a chondrogenic differentiation marker), cell viability, toxicity, and proliferation. Human articular chondrocytes were grown in monolayer culture and were exposed to iopromide and/or gadolinium diethylenetriamine-pentaacetate (Gd-DPT) for 2 and 6 h. Cell cultures with no drug exposure were used as the control group. Cell differentiation status was assessed according to SSEA-1 protein expression. Contrast agent effects on cell viability and proliferation were analyzed using MTT analysis. Further, changes in cell morphology in relation to the control group were evaluated using inverted light microscopy, environmental scanning electron microscopy (ESEM), and 3-tesla magnetic resonance imaging. The obtained data were statistically compared. When compared with the control group, both SSEA-1 protein expression and cell proliferation were lowest in the Gd-DPT group (P = 0.000). There was a statistically significant correlation between SSEA-1 expression and MTT results (rho = 0.351; P = 0.003). Nevertheless, the data obtained from in vitro experiments may not directly correspond to clinical applications. However, the mere fact that a drug used solely for diagnostic purposes may repress chondrocyte cell proliferation should be carefully considered by clinicians.

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed to relieve pain and inflammation. These NSAIDs have also analgesic effects and can be administered via oral, injectable, and topical routes. During inflammation, a number of synovial mediators and cytokines are released which decrease the pH level of the synovial fluid. Administration of acidic NSAIDs further decreases the pH levels and hence contributes to the destruction of the cartilage. To our knowledge, no cellular-based study regarding the chondrotoxicity of phenyl alkanoic acid derivatives on NSAIDs was conducted before. Thus, the aim of this pioneering study was to examine the effect of frequently prescribed NSAIDs, a phenyl alkanoic acid derivative, flurbiprofen, on the proliferation and differentiation of human primer chondrocyte cultures in vitro. Primer chondrocyte cultures were prepared from osteochondral tissue obtained during surgery for gonarthrosis. Samples not exposed to the pharmacological agent were used as the control group. The samples were treated with 1, 10, 100, 250, 500, or 1000 μM of the agent for 24, 48, and 72 h. The cell viability, toxicity, and proliferation were assessed with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) analysis and prechondrocytic precursor stage-specific embryonic antigen-1 (SSEA-1) expression using a commercial ELISA kit spectrophotometrically. The surface morphology of the samples in each group was compared using an inverted light microscope and an environmental scanning electron microscope (ESEM). An analysis of variance was used to compare between-group differences. Tukey’s honest significant difference (HSD) method (95 % confidence interval) was used to evaluate the differences and significance in averages. The alpha significance value was considered <0.01. Statistically significant cytotoxicity was observed in the treatment groups. NSAID had a significant negative effect on the proliferation and differentiation of chondrocytes as compared to the control group (p < 0.01). Before administering phenyl alkanoic acid derivatives in the clinical setting, their role in suppressing the proliferation and differentiation of chondrocytes should be taken into account. Thus, caution should be given when prescribing these drugs.

Background and objective Bone marrow edema (BME) is a rare condition caused by insufficient osseous blood supply and may result in severe pain that has adverse effects on patients' life. To date, various conservative treatments have been recommended for the treatment of BME, including analgesics, immobilization of the affected extremity, and iloprost infusion. The aim of this retrospective study was to investigate the effectiveness of parenteral iloprost therapy in the treatment of BME detected in different skeletal locations. Materials and methods This retrospective study included 23 patients (17 men and six women) with BME who were classified as stage I-III according to the Association Research Circulation Osseous (ARCO) classification. BME was localized to the proximal femur in 13 (56.5%), the distal femur in four (17.4%), tarsal bone in four (17.4%), and tibial plateau in two (8.7%) patients. The mean age of the patients was 46.7 years and all the patients were evaluated with the Visual Analog scale (VAS), Functional Mobility Scale (FMS), and MRI. Results A significant improvement was observed in the post-treatment VAS and FMS scores of all patients compared to their pre-treatment scores. Moreover, the edema regressed completely in 60.9% of the patients at three months of MRI control. No serious side effects were observed during the treatment in any of the patients. However, transient side effects including headache, arrhythmia, and flushing were observed in five patients. Conclusion The present study indicated that iloprost therapy is an effective and safe option in the treatment of BME patients, particularly in the reduction of severe pain that has adverse effects on patients' social life, regardless of ARCO staging. Moreover, this therapy could be particularly useful in reducing pain, improving functional recovery, and achieving complete regression of the edema on MRI in ARCO stage I-II patients.