Moshe Salai

Carbon fiber reinforced PEEK Optima--a composite material biomechanical properties and wear/debris characteristics of CF-PEEK composites for orthopedic trauma implants.

BACKGROUND The advantageous properties of carbon fiber reinforced polyetheretherketone (CF-PEEK) composites for use as orthopedic implants include similar modulus to bone and ability to withstand prolonged fatigue strain. METHODS The CF-PEEK tibial nail, dynamic compression plate, proximal humeral plate and distal radius volar plate were compared biomechanically (by four-point bending, static torsion of the nail, and bending fatigue) and for wear/debris (by amount of the debris generated at the connection between the CF-PEEK plate and titanium alloy screws) to commercially available devices. RESULTS Four-point bending stress of the tibial nail and dynamic and distal radius plates yielded characteristics similar to other commercially available devices. The distal volar plate bending structural stiffness of the CF-PEEK distal volar plate was 0.542 Nm2 versus 0.376 Nm2 for the DePuys DVR anatomic volar plate. The PHILOS proximal humeral internal locking system stainless steel plate was much stronger (6.48 Nm2) than the CF-PEEK proximal humeral plate (1.1 Nm2). Tibial nail static torsion testing showed similar properties to other tested nails (Fixion, Zimmer and Synthes). All tested CF-PEEK devices underwent one million fatigue cycles without failure. Wear test showed a lower volume of generated particles in comparison to the common implants in use today. INTERPRETATION Thus, these tested implants were similar to commercially used devices and can be recommended for use as implants in orthopedic surgery.

Effects of commonly used medications on bone tissue mineralisation in SaOS-2 human bone cell line

We analysed the effects of commonly used medications on human osteoblastic cell activity in vitro, specifically proliferation and tissue mineralisation. A list of medications was retrieved from the records of patients aged > 65 years filed in the database of the largest health maintenance organisation in our country (> two million members). Proliferation and mineralisation assays were performed on the following drugs: rosuvastatin (statin), metformin (antidiabetic), metoprolol (β-blocker), citalopram (selective serotonin reuptake inhibitor [SSRI]), and omeprazole (proton pump inhibitor (PPI)). All tested drugs significantly stimulated DNA synthesis to varying degrees, with rosuvastatin 5 µg/ml being the most effective among them (mean 225% (SD 20)), compared with metformin 10 µg/ml (185% (SD 10)), metoprolol 0.25 µg/ml (190% (SD 20)), citalopram 0.05 µg/ml (150% (sd 10)) and omeprazole 0.001 µg/ml (145% (SD 5)). Metformin and metoprolol (to a small extent) and rosuvastatin (to a much higher extent) inhibited cell mineralisation (85% (SD 5)). Our results indicate the need to evaluate the medications prescribed to patients in terms of their potential action on osteoblasts. Appropriate evaluation and prophylactic treatment (when necessary) might lower the incidence and costs associated with potential medication-induced osteoporosis.

The Effects of Direct Factor Xa Inhibitor (Rivaroxaban) on the Human Osteoblastic Cell Line SaOS2

Thromboprophylaxis reduces the risk of surgery-related deep vein thrombosis, but anticoagulants were associated with systemic osteoporosis, a known risk factor for poor fracture healing. Rivaroxaban (XARELTO®) is a novel anticoagulant with specific ability to inhibit factor Xa, a serine endopeptidase, which plays a key role in coagulation. This study investigated the direct effects of rivaroxaban on bone biology using an in vitro cell culture model from the human female osteoblastic cell line SaOS2. Cells at subconfluence were treated for 24 hr with different concentrations of rivaroxaban and analyzed for DNA synthesis and creatine kinase- and alkaline phosphatase-specific activities, and were treated 21 days for analyzing mineralization. Rivaroxaban (0.01–50 μg/ml) dose-dependently inhibited up to 60% DNA synthesis of the cells. Creatine kinase-specific activity was also inhibited dose-dependently to a similar extent by the same concentrations. Alkaline phosphatase-specific activity was dose-dependently inhibited but only up to 30%. Cell mineralization was unaffected by 10 μg/ml rivaroxaban. This model demonstrated a significant rivaroxaban-induced reduction in osteoblastic cell growth and energy metabolism, and slight inhibition of the osteoblastic marker, alkaline phosphatase, while osteoblastic mineralization was unaffected. These findings might indicate that rivaroxaban inhibits the first stage of bone formation but does not affect later stages (i.e., bone mineralization).

Rivaroxaban, a direct inhibitor of the coagulation factor Xa interferes with hormonal-induced physiological modulations in human female osteoblastic cell line SaSO2

The use of anticoagulants has been associated with systemic osteoporosis and increased risk for poor fracture healing but is inevitable following major orthopedic surgery of lower limbs. Rivaroxaban A (R) is an anticoagulant recently introduced in the clinical setting, which is a specific factor Xa inhibitor. We reported previously that R significantly inhibited cell growth, energy metabolism and alkaline phosphatase activity in human osteoblastic cell line SaOS2, with no effect on mineralization, indicating transient inhibition of bone formation. We now investigated the effects of R on SaOS2 response to osteoblast-modulating hormones. At sub-confluence cells were treated with: estradiol-17β (E2), the phytoestrogens daidzein (D) and biochainin A (BA), the carboxy-pytoestrogenic derivative carboxy-D (cD), the estrogen receptor α (ERα) agonist PPT, the estrogen receptor β (ERβ) agonist DPN, parathyroid hormone (PTH) and several vitamin D metabolites and analogs with/without R for 24h. All hormones tested stimulated significantly DNA synthesis (DNA), creatine kinase (CK) and alkaline phosphatase (ALP) specific activities, but all these stimulations were totally inhibited when given together with R. R had no effect on mRNA expression of ERα, ERβ and 25 Hydroxy-vitamin D3-1α hydroxylase (1OHase), but inhibited hormonal modulations of mRNA expressions. In conclusion R inhibited significantly hormonal stimulation of different parameters indicating inhibition of not only the early stages of bone formation, but also the stimulatory effects of bone modulating hormones with a yet unclear mechanism. The relevance of these findings to human bone physiology is yet to be investigated.

The correlation between radiographic knee OA and clinical symptoms--do we know everything?

This study aims to evaluate the correlations between common clinical osteoarthritis (OA) diagnostic tools in order to determine the value of each. A secondary goal was to investigate the influence of gender differences on the findings. Five hundred and eighteen patients with knee OA were evaluated using the Western Ontario and McMaster Osteoarthritis Index (WOMAC) questionnaire, short form 36 (SF-36) Health Survey, and plain radiographs. Analysis of variance (ANOVA) was used to compare the different domains of the WOMAC and SF-36 questionnaires between genders and the radiographic scale. Higher knee OA x-ray grade were associated with worse clinical outcome: for women, higher scores for the WOMAC pain, function and final scores and lower scores in the SF-36 final score; in men, lower SF-36 overall and physical domains scores. Gender differences were found in all clinical scores that were tested, with women having worse clinical scores for similar radiographic grading (p values <0.001). Knee radiographs for OA have an important role in the clinical evaluation of the patient. Patients with higher levels of knee OA in x-ray have a higher probability of having a worse clinical score in the WOMAC and SF-36 scores. The gender differences suggest that for similar knee OA x-ray grade, women’s clinical scores are lower.Trial registration: NCT00767780

Ochrobactrum anthropi-Caused Osteomyelitis in the Foot Mimicking a Bone Tumor: Case Report and Review of the Literature

Osteomyelitis due to Ochrobactrum anthropi, a new genus Ochrobacterum widely distributed in the environment and occasionally associated with human infection, has been described in only a few case reports. We present a report of an unusual case of osteomyelitis caused by O. anthropi that was identified 9 years after a nail puncture to the lateral cuneiform bone. The patient was an 18-year-old male with a painful foot lesion that had originally been misdiagnosed as an osteolytic tumor. He underwent surgery and 2 firm pieces of rubber measuring 7 and 10 mm were removed from the lower portion of the lateral cuneiform bone, which appeared to be affected by an infection. After surgical debridement, O. anthropi was isolated from the bone cultures. The patient was successfully treated with a 6-week course of oral ciprofloxacin and clindamycin. At 1 year after the corrected diagnosis and appropriate treatment, he was symptom free and had resumed regular activities and an athletic lifestyle.

A double-plating approach to distal femur fracture: A clinical study

BACKGROUND Locked plating is one of the latest innovative options for treating supracondylar femur fractures with relatively low failure rates. Single lateral plating was often found to have a relative higher failure rate. No clinical studies of double-plating distal femur fixation have thus far been reported. The aim of this study is to present our clinical experience with this surgical approach. PATIENTS AND METHODS Thirty-two patients (26 females and 6 males, mean age 76 years, range 44-101) were included in the study. Eight of them patients had a periprosthetic stable implant fracture and two patients were treated for a nonunion. RESULTS All fractures, excluding one that needed bone grafting and one refracture, healed within 12 weeks. One patient needed bone grafting for delayed union and one patient needed fixation exchange due to femur re-fracture at the site of the most proximal screw. Two patients developed superficial wound infection and one patient required medial plate removal after union due to deep infection. CONCLUSIONS Based on these promising results, we propose that the double-plating technique should be considered in the surgeons armamentarium for the treatment of supracondylar femur fractures, particularly in patients with poor bone quality, comminuted fractures and very low periprosthetic fractures.

Pulsed electromagnetic fields increase osteogenetic commitment of MSCs via the mTOR pathway in TNF-α mediated inflammatory conditions: an in-vitro study

Pulsed electromagnetic fields (PEMFs) have been considered a potential treatment modality for fracture healing, however, the mechanism of their action remains unclear. Mammalian target of rapamycin (mTOR) signaling may affect osteoblast proliferation and differentiation. This study aimed to assess the osteogenic differentiation of mesenchymal stem cells (MSCs) under PEMF stimulation and the potential involvement of mTOR signaling pathway in this process. PEMFs were generated by a novel miniaturized electromagnetic device. Potential changes in the expression of mTOR pathway components, including receptors, ligands and nuclear target genes, and their correlation with osteogenic markers and transcription factors were analyzed. Involvement of the mTOR pathway in osteogenesis was also studied in the presence of proinflammatory mediators. PEMF exposure increased cell proliferation and adhesion and the osteogenic commitment of MSCs even in inflammatory conditions. Osteogenic-related genes were over-expressed following PEMF treatment. Our results confirm that PEMFs contribute to activation of the mTOR pathway via upregulation of the proteins AKT, MAPP kinase, and RRAGA, suggesting that activation of the mTOR pathway is required for PEMF-stimulated osteogenic differentiation. Our findings provide insights into how PEMFs influence osteogenic differentiation in normal and inflammatory environments.

Rivaroxaban significantly inhibits the stimulatory effects of bone-modulating hormones: In vitro study of primary female osteoblasts.

ABSTRACT Background: Anticoagulant therapy is a mainstay of treatment subsequent to major orthopedic surgeries. Evidence linking anticoagulant therapy, osteoporosis, and delayed fracture healing is not conclusive. We have previously reported that rivaroxaban significantly inhibited cell growth and energy metabolism in a human osteoblastic cell line. This study analyzed the response of primary female osteoblast cells to rivaroxaban in combination with various bone-modulating hormones. Methods: Bone samples were taken from both premenopausal (pre-Ob) and postmenopausal (post-Ob) women. Cells were isolated from each sample and cultured to sub-confluence. Each sample was then treated with Rivaroxaban (10 µg/ml) in combination with the following hormones or with the hormones alone for 24 hours: 30nM estradiol-17β (E2), 390nM estrogen receptor α (ERα) agonist PPT, 420nM estrogen receptor β (ERβ) agonist DPN, 50nM parathyroid hormone (PTH), and 1nM of vitamin D analog JKF. Results: No effects were observed after exposure to rivaroxaban alone. When pre-Ob and post-Ob cells were exposed to the bone-modulating hormones as a control experiment, DNA synthesis and creatine kinase (CK)-specific activity was significantly stimulated with a greater response in the pre-Ob cells. When the cells were exposed to rivaroxaban in combination with bone-modulating hormones, the increased DNA synthesis and CK-specific activity previously observed were completely attenuated. Conclusions: Rivaroxaban significantly inhibited the stimulatory effects of bone-modulating hormones in both pre-Ob and post-Ob primary human cell lines. This finding may have clinical relevance for patients at high risk of osteoporosis managed with rivaroxaban or other factor Xa inhibitors.