Outcomes of Platelet-Rich Plasma Infiltration and Weightbearing Cast Immobilization in Distal Tibialis Anterior Tendinopathy: A Prospective Cohort Study.

BACKGROUND: Distal tibialis anterior tendinopathy (DTAT) is a chronic condition that may lead to functional impairment and secondary forefoot deformities when left untreated. Current clinical practice is mainly guided by case reports and small retrospective case series; little consensus exists on which treatment protocol is most effective. This study aims to assess a conservative treatment for DTAT consisting of PRP infiltration and walking cast immobilization. METHODS: This prospective study included 18 feet in 18 patients, recruited between September 2020 and September 2022 at a single institution. Ultrasonography was performed; leukocyte-poor PRP was infiltrated around the tibialis anterior tendon insertion. Walking cast immobilization was used for 3 weeks after infiltration, followed by eccentric exercises of the DTAT, and gastrocnemius-soleus muscle complex stretching. Clinical findings, visual analog scale (VAS), Foot Function Index (FFI), and American Orthopaedic Foot & Ankle Society (AOFAS) midfoot scores were recorded at inclusion, and 6 and 12 weeks after PRP infiltration. Minimal clinically important difference (MCID) limits were researched to assess clinical relevance of statistical outcomes. Means were determined for age, sex, and body mass index (BMI). One-way repeated measures ANOVA was performed over time for FFI, AOFAS, and VAS scores. RESULTS: Mean age was 65 years with a mean BMI of 25. Tendon thickening and hypoechogenicity were the most commonly reported ultrasonographic findings. Significant improvement from baseline VAS (VASrest: 4.71 ± 2.7, VASactivity: 5.66 ± 2.5) to 12 weeks follow-up (VASrest: 2.14 ± 2.7, VASactivity: 3.34 ± 2.5) was found. Both AOFAS and FFITotal improved significantly from baseline (AOFAS: 66.9 ± 3.3, FFITotal: 32.9 ± 3.3) to 6-week follow-up (AOFAS6w: 79.4 ± 3.3, P = .019; FFITotal: 19.4 ± 3.3, P = .011). No statistically significant further improvement was found at 12 weeks compared to 6 weeks' follow-up. Two (11%) patients chose operative treatment because of persisting symptoms. CONCLUSION: We found that PRP infiltration with walking cast immobilization as a first-line treatment was associated with general early symptom improvement. LEVEL OF EVIDENCE: Level IV, case series.

Bone marrow oedema syndrome of the foot and ankle in a paediatric population: a retrospective case series with serial MRI evaluation.

PURPOSE: By means of a case series we wanted to describe and correlate the clinical and imaging features of bone marrow oedema syndrome (BMOS) of the foot and ankle in children. METHODS: A retrospective data study was performed on patients born on or after 01 January 2001 who underwent multiple MRI scans of the foot and ankle for pain symptoms. Six patients who presented with increased signal intensity on T2-weighted MR imaging without any underlying causes or concomitant pathology were included. RESULTS: All patients, three boys and three girls with a mean age of 11 years (8 to 14), displayed patchy areas of increased signal intensity on T2-weighted and turbo inversion recovery magnitude (TIRM) images. On average, six tarsal bones were involved (4 to 8). In all patients, treatment consisted of rest and/or protected weight-bearing. The mean time for symptoms to improve during treatment was 6 months (1 to 16). The mean duration of treatment was nine months (3 to 16). In all patients clinical and imaging symptoms were strongly correlated and regressed in time. CONCLUSION: BMOS as a pathological entity should be considered in paediatric patients with foot and ankle pain without a clear underlying cause, and characteristic T2-weighted and TIRM signal intensity increase on MRI images. As BMOS is transient and self-limiting, conservative treatment is advised while the oedema regresses. An early diagnosis of this pathology could prevent unnecessary diagnostic investigations and invasive treatments. LEVEL OF EVIDENCE: IV.

Arthroscopic psoas release for iliopsoas impingement after total hip replacement.

Psoas impingement is a rare cause of persisting pain after hip arthroplasty. Diagnosis is based on clinical examination and exclusion of other complications after arthroplasty by radiographs, ultrasound, CT and blood analysis. The diagnosis is strongly supported by temporary pain relief after infiltration. When conservative measures fail, treatment can consist of a psoas tenotomy or a revision arthroplasty. When there is no obvious cause such as malpositioning for component impingement, psoas release reliably improves pain and function. This procedure is mostly performed through an open approach, which can give significant complications. An arthroscopic technique for psoas tenotomy after hip arthroplasty is described. This report shows that this minimal invasive technique is safe and effective and allows for inspection of the implant in the same session. However, the score used did not improve in a significant way.

Direct anti-cancer effect of oncostatin M on chondrosarcoma.

The cytokine Oncostatin M (OSM) is cytostatic, pro-apoptotic and induces differentiation of osteosarcoma cells into osteocytes, suggesting new adjuvant treatment for these bone-forming sarcomas. However, OSM systemic over-expression could lead to adverse side effects such as generalized inflammation, neoangiogenesis and osteolysis. We determine here the effect of OSM on chondrosarcoma, another primary bone sarcoma characterized by the production of cartilage matrix and altered bone remodelling. Chondrosarcomas are resistant to conventional chemotherapy and radiotherapy, and wide surgical excision remains the only available treatment. We found that OSM blocked the cell cycle in four of five chondrosarcoma cell lines, independently of p53 and presumably through the JAK3/STAT1 pathway. In two tested cell lines, OSM induced a hypertrophic chondrocyte differentiation, with an induced Cbfa1/SOX9 ratio and induced Coll10, matrix metalloproteinase 13 (MMP13) and RANKL expression. Adenoviral gene transfer of OSM (AdOSM) in the Swarm rat chondrosarcoma (SRC) model indicated that local intra-tumoral OSM over-expression reduces chondrosarcoma development not only with reduced tumor proliferation and enhanced apoptosis but also with enhanced RANKL expression, osteoclast formation and reduced bone volumes. Flu-like symptoms were induced by the AdOSM, but there was no effect on tumor angiogenesis. Therefore, OSM could be considered as a new adjuvant anti-cancer agent for chondrosarcomas. A local application of this cytokine is presumably needed to overcome the poor vascularization of these tumors and to limit the deleterious effect on other tissues. Its side effect on bone remodeling could be managed with anti-resorption agents, thus offering potential new lines of therapeutic interventions.

Interleukin-34 is expressed by giant cell tumours of bone and plays a key role in RANKL-induced osteoclastogenesis.

Interleukin-34 (IL-34) is a newly discovered regulator of myeloid lineage differentiation, proliferation, and survival, acting via the macrophage-colony stimulating factor receptor (M-CSF receptor, c-fms). M-CSF, the main ligand for c-fms, is required for osteoclastogenesis and has been already identified as a critical contributor of the pathogenesis of giant cell tumours of bone (GCTs), tumours rich in osteoclasts. According to the key role of M-CSF in osteoclastogenesis and GCTs, the expression of IL-34 in human GCTs was first assessed. Quantitative analysis of IL-34 mRNA expression in 14 human GCTs revealed expression of this cytokine in GCTs as well as M-CSF and c-fms. Immunohistochemistry demonstrated that osteoclast-like cells exhibited a huge immunostaining for IL-34 and that mononuclear stromal cells were slightly positive for this protein. In contrast to osteoblasts, bone-resorbing osteoclasts showed very strong staining for IL-34, suggesting its potential role in the pathogenesis of GCTs by facilitating osteoclast formation. The role of IL-34 in osteoclastogenesis was then studied in murine and human models. IL-34 was able to support RANKL-induced osteoclastogenesis in the absence of M-CSF in all models. Multinucleated cells generated in the presence of IL-34 and RANKL expressed specific osteoclastic markers and resorbed dentine. IL-34 induced phosphorylation of ERK 1/2 and Akt through the activation of c-fms, as revealed by the inhibition of signalling by a specific c-fms tyrosine kinase inhibitor. Furthermore, IL-34 stimulated RANKL-induced osteoclastogenesis by promoting the adhesion and proliferation of osteoclast progenitors, and had no effect on osteoclast survival. Overall, these data reveal that IL-34 can be entirely substituted for M-CSF in RANKL-induced osteoclastogenesis, thus identifying a new biological activity for this cytokine and a contribution to the pathogenesis of GCTs.

The McHale procedure in the treatment of the painful chronically dislocated hip in adolescents and adults with cerebral palsy.

We retrospectively studied the results achieved in adolescent and adult patients with cerebral palsy, following management of chronically painful dislocated hips with the McHale procedure. Thirteen patients with seventeen procedures were included in the study. The indication for surgery was pain in all patients. Limitation in sitting was also reported in eight cases and nursing care was difficult in ten of thirteen patients. All patients underwent clinical and radiological examination of the hips, and a questionnaire was answered by both parents and caretakers. Improvement was noted in all patients with respect to pain. In six patients sitting was tolerated for longer intervals and 10 out of 13 patients were easier to nurse owing to improved mobility of the hip. Although these results appear promising, the procedure had a high complication rate, including heterotopic ossification, residual pain caused by hardware, fracture and pulmonary complications, for which a second procedure was necessary in several cases. There was also in several cases a prolonged period of pain postoperatively, for which an additional procedure was needed in eight patients. The McHale procedure is a technique that can provide pain relief and improvement in motion. There is however a high incidence of failure and complications.

OPG, RANK and RANK ligand expression in thyroid lesions.

Receptor activator of NF-kappaB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG) play essential roles in bone metabolism. RANKL binds to RANK, which is expressed by osteoclasts whereas OPG acts as its decoy receptor blocking the RANK-RANKL interaction. OPG/RANK/RANKL are produced by variety of tissues including epithelial and mesenchymal cells. However, the role of RANKL/OPG in thyroid pathophysiology remains unclear. The aim of this study was to determine the expression pattern of RANK/RANKL/OPG in primary neoplastic thyroid lesions and in lymph node metastases. 27 specimens from total thyroidectomy were studied by immunohistochemistry: 9 papillary carcinomas (PC), 9 medullary carcinomas (MC), 9 macrovesicular adenomas (MA). Immunohistochemical evidence of RANKL was found in 30 % of MC, 22% of PC while RANKL has never been detected in PC. The expression of RANK is closely related to RANKL. OPG was restricted to the cytoplasm of epithelial in 1 MA and 1 MC. In contrast to pathological tissues, any expression of OPG/RANK/RANKL was detected in healthy thyroid tissue. This work reveals for the first time that OPG/RANK/RANKL are expressed in the pathological thyroid gland by follicular cells, by malignant parafollicular cells as well as in metastatic lymph node microenvironment. Thus OPG/RANK/RANKL molecular triad might play a role during pathogenesis of follicular and parafollicular tumors.

RANKL directly induces bone morphogenetic protein-2 expression in RANK-expressing POS-1 osteosarcoma cells.

The POS-1 murine model of osteolytic osteosarcoma was used to elucidate the molecular and cellular mechanisms involved in the development of primary bone tumors and associated lung metastasis. The POS-1 cell line is derived from an osteosarcoma tumor which develops spontaneously in C3H mice. The POS-1 cell line was characterized in vitro by mineralization capacity and expression of bone markers by semi-quantitative RT-PCR, compared to primary osteoblasts and bone marrow cells. POS-1 cells showed no mineralization capacity and exhibited an undifferentiated phenotype, expressing both osteoblastic and unexpected osteoclastic markers (TRAP, cathepsin K and RANK). Thereby, experiments were performed to determine whether RANK was functional, by studying the biological activity of murine RANKL through the receptor RANK expressed on POS-1 cells. Results revealed a RANKL-induced increase in ERK phosphorylation, as well as BMP-2 induction at the mRNA and protein levels, and a decrease of POS-1 cell proliferation in the presence of 10 ng/ml RANKL. BMP-2 induction is dependent on the ERK 1/2 signal transduction pathway, as its expression is abolished in the presence of UO126, a specific synthetic inhibitor of the ERK 1/2 pathway. Moreover, a 2-fold molar excess of soluble RANK blocks the RANKL-induced BMP-2 expression, demonstrating that the biological effects of RANKL observed in POS-1 cells are mediated by RANK. This is the first report describing a functional RANK expressed on osteosarcoma cells, as shown by its ability to induce signal transduction pathways and biological activity when stimulated by RANKL.