Comparison of forces generated using compression plating versus a magnetic lengthening nail in a sawbones femur model.

BACKGROUND: The purpose of this study is to compare compression generated by a Precice magnetic lengthening intramedullary nail and a 5.0 mm limited contact dynamic compression plate. METHODS: Transverse osteotomy sites were created in the femoral shaft of ten Sawbones fourth generation composite femurs. Antegrade 10-degree trochanteric Precice nails and 8-hole, 5.0 mm plates were used for fixation. The plates were compressed by placing a neutral screw and three eccentrically drilled compression screws on alternating sides of the osteotomy. Average compression and distribution of compression were compared, and P-values <0.05 were considered statistically significant. FINDINGS: The Precice nail generated an average of 2.38 megapascal across the osteotomy sites. The plate generated an average of 0.70 megapascal (P < 0.001) with the initial compression screw, 0.93 megapascal (P < 0.001) after the second screw, and 1.04 megapascal (p < 0.001) after the final screw. The distribution of compression was assessed utilizing a polar transformation to compare pressure values. We found that the distribution of compression was more circumferentially uniform in the Precice nail group (P = 0.046). INTERPRETATION: This study demonstrates that an electromagnetic intramedullary device is capable of generating significantly higher compression, in a more uniform distribution, than a 5.0 mm limited contact dynamic compression plate in a Sawbones model. The results indicate that electromagnetic intramedullary nail systems may be an ideal alternative to compression plating for treatment of at-risk fractures, nonunions, delayed unions, and intercalary allograft reconstruction.

Bupivacaine and Lidocaine Induce Apoptosis in Osteosarcoma Tumor Cells.

BACKGROUND: Osteosarcoma is the most common type of bone cancer in adolescents. There have been no significant improvements in outcomes since chemotherapy was first introduced. Bupivacaine and lidocaine have been shown to be toxic to certain malignancies. This study evaluates the effect of these medications on two osteosarcoma cell lines. QUESTIONS/PURPOSES: (1) Does incubation of osteosarcoma cells with bupivacaine or lidocaine result in cell death? (2) Does this result from an apoptotic mechanism? (3) Is a specific apoptotic pathway implicated? METHODS: Two cell lines were chosen to account for the inherent heterogeneity of osteosarcoma. UMR-108 is a transplantable cell line that has been used in multiple studies as a primary tumor. MNNG/HOS has a high metastatic rate in vivo. Both cell lines were exposed bupivacaine (0.27, 0.54, 1.08, 2.16, 4.33 and 8.66 mM) and lidocaine (0.66, 1.33, 5.33, 10.66, 21.32 and 42.64 mM) for 24 hours, 48 hours, and 72 hours. These concentrations were determined by preliminary experiments that found the median effective dose was 1.4 mM for bupivacaine and 7.0 mM for lidocaine in both cell lines. Microculture tetrazolium and colony formation assay determined whether cell death occurred. Apoptosis induction was evaluated by phase-contrast micrographs, flow cytometry, DNA fragmentation and reactive oxygen species (ROS). The underlying pathways were analyzed by protein electrophoresis and Western blot. All testing was performed in triplicate and compared with pH-adjusted controls. Quantitative results were analyzed without blinding. RESULTS: Both medications caused cell death in a dose- and time-dependent manner. Exposure to bupivacaine for 24 hours reduced viability of UMR-108 cells by 6 ± 0.75% (95% CI 2.9 to 9.11; p = 0.01) at 1.08 mM and 89.67 ± 1.5% (95% CI 82.2 to 95.5; p < 0.001) at 2.16 mM. Under the same conditions, MNNG/HOS viability was decreased in a similar fashion. After 24 hours, the viability of UMR-108 and MNNG/HOS cells exposed to 5.33 mM of lidocaine decreased by 25.33 ± 8.3% (95% CI 2.1 to 48.49; p = 0.03) and 39.33 ± 3.19% (95% CI 30.46 to 48.21; p < 0.001), respectively, and by 90.67 ± 0.66% (95% CI 88.82 to 92.52; p < 0.001) and 81.6 ± 0.47% (95% CI 79.69 to 82.31; p < 0.001) at 10.66 mM, respectively. After 72 hours, the viability of both cell lines was further reduced. Cell death was consistent with apoptosis based on cell morphology, total number of apoptotic cells and DNA fragmentation. The percentage increase of apoptotic UMR-108 and MNNG/HOS cells confirmed by Annexin-V positivity compared with controls was 21.3 ± 2.82 (95% CI 16.25 to 26.48; p < 0.001) and 21.23 ± 3.23% (95% CI 12.2 to 30.2; p = 0.003) for bupivacaine at 1.08 mM and 25.15 ± 4.38 (95% CI 12.9 to 37.3; p = 0.004) and 9.11 ± 1.74 (95% CI 4.35 to 13.87; p = 0.006) for lidocaine at 5.33 mM. The intrinsic apoptotic pathway was involved as the expression of Bcl-2 and survivin were down-regulated, and Bax, cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase-1 were increased. ROS production increased in the UMR-108 cells but was decreased in the MNNG/HOS cells. CONCLUSION: These findings provide a basis for evaluating these medications in the in vivo setting. Studies should be performed in small animals to determine if clinically relevant doses have a similar effect in vivo. In humans, biopsies could be performed with standard doses of these medications to see if there is a difference in biopsy tract contamination on definitive resection. CLINICAL RELEVANCE: Bupivacaine and lidocaine could potentially be used for their ability to induce and enhance apoptosis in local osteosarcoma treatment. Outcome data when these medications are used routinely during osteosarcoma treatment can be evaluated compared with controls. Further small animal studies should be performed to determine if injection into the tumor, isolated limb perfusion, or other modalities of treatment are viable.

Antiproliferative effect of bupivacaine on patient-derived sarcoma cells.

Sarcomas are rare tumors with limited treatment options. Although chemotherapy is standard for certain subtypes, overall survival has not improved in several decades. Bupivacaine has been shown to induce apoptosis and prevent cell growth in multiple different types of malignancies but has not been studied in sarcoma. The current study evaluated the effects of bupivacaine on multiple patient-derived sarcoma cells and a commercial sarcoma cell line. Multiple patient-derived sarcoma cell subtypes and a commercial synovial cell sarcoma cell line were exposed to bupivacaine for different durations and at different concentrations. The patient-derived cells included a high-grade conventional osteosarcoma, a high-grade undifferentiated pleomorphic sarcoma of bone, and a high-grade synovial sarcoma. Flow cytometry and an MTT assay were used to evaluate whether a treatment effect was observed. Treatment of all the subtypes of sarcomas in this study with bupivacaine demonstrated a time- and dose-dependent increase in apoptosis and decrease in cell viability. A cell viability assay demonstrated that the IC50 was between 0.04 and 0.05% and that the treatment effect occurred at clinically relevant doses in vitro. Bupivacaine was toxic to both the patient-derived cells and the commercial cell line at doses commonly used in the clinical setting. These findings provide a foundation for further in vivo studies to evaluate whether these effects will translate to the clinical setting. Although further research is necessary, bupivacaine shows promise as not only an adjunct for pain management but as a treatment modality for sarcoma.

Focal Periphyseal Edema: An Uncommon Cause of Adolescent Knee Pain: A Report of Three Cases.

CASE: Focal periphyseal edema (FOPE) zones have only recently been described as a cause of joint pain in adolescence. The literature is limited to a few case reports and radiologic studies describing this symptomatic physeal pathology. This series describes 3 adolescent patients with magnetic resonance imaging (MRI) confirmed FOPE zones of the distal femur. Repeat MRI of 2 of the 3 patients showed improvement yet incomplete resolution of the bone edema, corresponding with persistent knee pain. CONCLUSIONS: FOPE zones usually improve with conservative treatment, but may be a cause of persistent knee pain in adolescents.

Short tau inversion recovery magnetic resonance imaging for staging and screening in myxoid liposarcoma.

PURPOSE: Myxoid liposarcoma has a propensity to metastasize to bone. MRI is the preferred modality for detecting bone disease. We evaluated multiple MRI sequences to determine an optimal screening method. METHODS: Whole body MRI was performed on all patients. The number and locations of metastases found by imaging and round cell component of the sites sampled were evaluated. RESULTS: We found a total of 68 osseous lesions. Whole body MRI utilizing STIR only sequences decreased imaging time by 83.6% and demonstrated the lesions the best. CONCLUSIONS: STIR sequences can be exclusively used during staging and screening of myxoid liposarcoma.

Surgical Treatment of Insufficiency Fractures of the Knee.

Bone marrow lesions (BMLs) in the knee represent focal edema caused by subchondral bone attrition and microfractures to the trabecular bone. These lesions are poor prognostic indicators for several orthopaedic procedures but also have been associated with the progression of osteoarthritis. Current research is aimed at treating BMLs with the intent to improve the overall structural integrity of the subchondral bone and delay the need for arthroplasty. The injection of calcium phosphate bone substitute has been proposed to treat BMLs because animal models have shown its potential to stimulate bone repair. This technical note describes the key steps involved in performing percutaneous fixation of BMLs with a hard-setting bone substitute, as well as associated pearls and pitfalls. Although continued research with prospective comparative cohorts and long-term follow-up is needed to determine the efficacy of this procedure, this intervention holds promise in delaying the need for total knee replacement in the arthritic patient with a focal lesion.

Use of Magnetic Growing Intramedullary Nails in Compression During Intercalary Allograft Reconstruction.

Traditionally, intercalary allograft reconstruction after tumor resection has had a high rate of complications, particularly nonunion. Plate and intramedullary nail fixation have been used alone and in combination to improve union rates. This study sought to evaluate a new technique that uses a magnetic growing intramedullary nail to compress the osteotomy sites to aid in healing and to answer 2 questions: (1) What is the union rate and the time to union when using magnetic growing intramedullary nails? (2) What complications occur with this technique? Eight patients with 15 osteotomy sites with a minimum follow-up of 14 months were retrospectively reviewed. Seven of the 8 patients underwent initial reconstruction with the magnetic nail, whereas 1 patient underwent treatment of a nonunion that occurred with prior carbon fiber nail fixation. Twelve of the 15 osteotomy sites had healed by an average of 9 months. Nonunions occurred in 2 patients with an associated failure of the hardware. One of these patients healed after revision surgery. Of the patients who healed at both sites, 1 had a fracture through the allograft, 1 had backing out of a locking screw that required removal, and 1 required a manipulation under anesthesia of the knee. Two patients underwent successful limb lengthening needed because of an expected limb-length discrepancy after healing occurred. Use of growing intramedullary nails in compression mode led to an 87% union rate at final follow-up with acceptable complications. This technique provides a viable alternative to standard nail and plate fixation when intercalary allografts are used. [Orthopedics. 2018; 41(6):330-335.].