In Vivo Metacarpophalangeal Joint Kinematics After Silicone Implant Arthroplasty in Patients With Rheumatoid Arthritis.

PURPOSE: The aim of this study was to determine the potential mechanism of implant fracture using 3-dimensional motion analysis of patients with rheumatoid arthritis. METHODS: Active flexion motion in 9 hands (34 fingers) of 6 female patients with rheumatoid arthritis who previously underwent hinged silicone metacarpophalangeal joint arthroplasty was examined using 4-dimensional computed tomography. Positions of the proximal phalanges relative to the metacarpals were quantified using a surface registration method. The deformation of the silicone implant was classified in the sagittal plane in the maximum flexion frame. The longitudinal bone axis of the proximal phalanx and the helical axis of the proximal phalanx were evaluated in 3-dimensional coordinates based on the hinge of the silicone implant. RESULTS: Nineteen fingers were classified into group 1, in which the silicone implant moved volarly during flexion without buckling of the distal stem. Twelve fingers were classified into group 2, in which the distal stem of the silicone implant buckled. Three fingers were classified into group 3, in which the base of the distal stem had already fractured. Quantitatively, the longitudinal bone axes of the proximal phalanges were displaced from dorsal to volar in the middle stage of flexion and migrated in the proximal direction in the late phase of flexion. The helical axes of the proximal phalanges were located on the dorsal and proximal sides of the hinge, and these tended to move in the volar and proximal directions as the metacarpophalangeal joint flexed. CONCLUSIONS: Volar and proximal translation of the proximal phalange was observed on 4-dimensional computed tomography. CLINICAL RELEVANCE: Proximal displacement of the bone axis late in flexion appears to be a contributing factor inducing implant fractures, because the pistoning motion does not allow the implant to move in the proximal direction.

Tooth extraction in mice administered zoledronate increases inflammatory cytokine levels and promotes osteonecrosis of the jaw.

INTRODUCTION: Osteonecrosis of the jaw (ONJ) occurring after invasive dental treatment often adversely affects patients' activities of daily living. Long-term administration of strong anti-bone resorptive agents such as bisphosphonates prior to invasive dental treatment is considered an ONJ risk factor; however, pathological mechanisms underlying ONJ development remain unclear. MATERIALS AND METHODS: We developed an ONJ mouse model in which a tooth is extracted during treatment with the bisphosphonate zoledronate. RESULTS: We observed induction of apoptosis in osteocytes, resulting in formation of empty lacunae in jaw bones at sites of tooth extraction but not in other bones of the same mice. We also observed elevated levels of inflammatory cytokines such as TNFα, IL-6 and IL-1 in jaw bone at the extraction site relative to other sites in zoledronate-treated mice. We also report that treatment in vitro with either zoledronate or an extract from Porphyromonas gingivalis, an oral bacteria, promotes expression of inflammatory cytokines in osteoclast progenitor cells. We demonstrate that gene-targeting of either TNFα, IL-6 or IL-1 or treatment with etanercept, a TNFα inhibitor, or a neutralizing antibody against IL-6 can antagonize ONJ development caused by combined tooth extraction and zoledronate treatment. CONCLUSIONS: Taken together, the cytokine storm induced by invasive dental treatment under bisphosphonate treatment promotes ONJ development due to elevated levels of inflammatory cytokine-producing cells. Our work identifies novel targets potentially useful to prevent ONJ.

Machine Learning-Based Diagnosis in Laser Resonance Frequency Analysis for Implant Stability of Orthopedic Pedicle Screws.

Evaluation of the initial stability of implants is essential to reduce the number of implant failures of pedicle screws after orthopedic surgeries. Laser resonance frequency analysis (L-RFA) has been recently proposed as a viable diagnostic scheme in this regard. In a previous study, L-RFA was used to demonstrate the diagnosis of implant stability of monoaxial screws with a fixed head. However, polyaxial screws with movable heads are also frequently used in practice. In this paper, we clarify the characteristics of the laser-induced vibrational spectra of polyaxial screws which are required for making L-RFA diagnoses of implant stability. In addition, a novel analysis scheme of a vibrational spectrum using L-RFA based on machine learning is demonstrated and proposed. The proposed machine learning-based diagnosis method demonstrates a highly accurate prediction of implant stability (peak torque) for polyaxial pedicle screws. This achievement will contribute an important analytical method for implant stability diagnosis using L-RFA for implants with moving parts and shapes used in various clinical situations.

Potential Application of Protamine for Antimicrobial Biomaterials in Bone Tissue Engineering.

Bacterial infection of biomaterials is a serious problem in the field of medical devices. It is urgently necessary to develop new biomaterials with bactericidal activity. Antimicrobial peptides and proteins (AMPs), alternative antibacterial agents, are expected to overcome the bacterial resistance. The aim of this study was to develop a new intelligent material in bone tissue engineering based on protamine-loaded hydroxyapatite (protamine/HAp) that uses AMPs rather than antibiotics. It was found that the adsorption of protamine to HAp followed the Langmuir adsorption model and was due to electrostatic and/or hydrophobic interactions. In vitro bacterial adhesion and growth on protamine/HAp was inhibited in a protamine dose-dependent manner. Adherent bacteria exhibited an aberrant morphology for high dosages of protamine/HAp, resulting in the formation of large aggregates and disintegration of the membrane. The released protamine from protamine/HAp also prevented the growth of planktonic bacteria in vitro. However, a high dosage of protamine from powders at loading concentrations over 1000 µg·mL-1 induced a cytotoxic effect in vitro, although those exhibited no apparent cytotoxicity in vivo. These data revealed that protamine/HAp (less than 1000 µg·mL-1) had both antimicrobial activity and biocompatibility and can be applied for bone substitutes in orthopedic fields.

Bactericidal and Bioresorbable Calcium Phosphate Cements Fabricated by Silver-Containing Tricalcium Phosphate Microspheres.

Bacterial adhesion to the calcium phosphate surface is a serious problem in surgery. To prevent bacterial infection, the development of calcium-phosphate cements (CPCs) with bactericidal properties is indispensable. The aim of this study was to fabricate antibacterial CPCs and evaluate their biological properties. Silver-containing tricalcium phosphate (Ag-TCP) microspheres consisting of α/ß-TCP phases were synthesized by an ultrasonic spray-pyrolysis technique. The powders prepared were mixed with the setting liquid to fabricate the CPCs. The resulting cements consisting of ß-TCP and hydroxyapatite had a porous structure and wash-out resistance. Additionally, silver and calcium ions could be released into the culture medium from Ag-TCP cements for a long time accompanied by the dissolution of TCP. These data showed the bioresorbability of the Ag-TCP cement. In vitro antibacterial evaluation demonstrated that both released and immobilized silver suppressed the growth of bacteria and prevented bacterial adhesion to the surface of CPCs. Furthermore, histological evaluation by implantation of Ag-TCP cements into rabbit tibiae exhibited abundant bone apposition on the cement without inflammatory responses. These results showed that Ag-TCP cement has a good antibacterial property and good biocompatibility. The present Ag-TCP cements are promising for bone tissue engineering and may be used as antibacterial biomaterials.

Exploration for reliable radiographic assessment method for hinge-like hypermobility at atlanto-occipital joint.

PURPOSE: Hinge-like hyper-mobility is occasionally observed at the atlanto-occipital (O-C1) joint. However, it has not been clear if this kind of hinge-like hyper-mobility at the O-C1 joint should be regarded as "pathologic", or referred to as "instability". To solve this issue, we aimed to establish a reliable radiographic assessment method for this specific type of O-C1 instability and figure out the "standard value" for the range of motion (ROM) of the O-C1 joint. METHODS: To figure out the standard range of the O-C1 angle, we acquired magnetic resonance imaging (MRI) sagittal views of the cervical spine for 157 healthy volunteers [average: 37.4 year-old (yo)] without spine diseases, at neutral, maximum flexion and maximum extension positions. RESULTS: The average value (AVE) for ROM of O-C1 angle was 9.91°. The standard value for ROM of O-C1 angle was calculated as 0°-21°. There was no statistically significant gender difference. We also found that the older population (≧ 40 yo) significantly had a larger ROM of O-C1 angle (AVE: 11.72°) compared to the younger population (< 40 yo) (AVE: 8.99°). CONCLUSIONS: We consider that hinge-like instability at O-C1 joint, which cannot be assessed by measuring Powers ratio, can be assessed by measuring the range of O-C1 angles using dynamic-MRI. Evaluation of O-C1 instability is important especially when we perform surgical treatment for diseases with upper cervical instability (such as retro-odontoid pseudotumor). We consider that the current study provides important information in such a case.

Neural stem/progenitor cell-laden microfibers promote transplant survival in a mouse transected spinal cord injury model.

Previous studies have demonstrated that transplantation of neural stem/progenitor cells (NS/PCs) into the lesioned spinal cord can promote functional recovery following incomplete spinal cord injury (SCI) in animal models. However, this strategy is insufficient following complete SCI because of the gap at the lesion epicenter. To obtain functional recovery in a mouse model of complete SCI, this study uses a novel collagen-based microfiber as a scaffold for engrafted NS/PCs. We hypothesized that the NS/PC-microfiber combination would facilitate lesion closure as well as transplant survival in the transected spinal cord. NS/PCs were seeded inside the novel microfibers, where they maintained their capacity to differentiate and proliferate. After transplantation, the stumps of the transected spinal cord were successfully bridged by the NS/PC-laden microfibers. Moreover, the transplanted cells migrated into the host spinal cord and differentiated into three neural lineages (astrocytes, neurons, and oligodendrocytes). However, the NS/PC-laden scaffold could not achieve a neural connection between the rostral end of the injury and the intact caudal area of the spinal cord, nor could it achieve recovery of motor function. To obtain optimal functional recovery, a microfiber design with a modified composition may be useful. Furthermore, combinatorial therapy with rehabilitation and/or medications should also be considered for practical success of biomaterial/cell transplantation-based approaches to regenerative medicine.

Schwann cell-encapsulated chitosan-collagen hydrogel nerve conduit promotes peripheral nerve regeneration in rodent sciatic nerve defect models.

Chitosan has various tissue regeneration effects. This study was designed to investigate the nerve regeneration effect of Schwann cell (SC)-encapsulated chitosan-collagen hydrogel nerve conduit (CCN) transplanted into a rat model of sciatic nerve defect. We prepared a CCN consisting of an outer layer of chitosan hydrogel and an inner layer of collagen hydrogel to encapsulate the intended cells. Rats with a 10-mm sciatic nerve defect were treated with SCs encapsulated in CCN (CCN+), CCN without SCs (CCN-), SC-encapsulated silicone tube (silicone+), and autologous nerve transplanting (auto). Behavioral and histological analyses indicated that motor functional recovery, axonal regrowth, and myelination of the CCN+ group were superior to those of the CCN- and silicone+ groups. Meanwhile, the CCN- and silicone+ groups showed no significant differences in the recovery of motor function and nerve histological restoration. In conclusion, SC-encapsulated CCN has a synergistic effect on peripheral nerve regeneration, especially axonal regrowth and remyelination of host SCs. In the early phase after transplantation, SC-encapsulated CCNs have a positive effect on recovery. Therefore, using SC-encapsulated CCNs may be a promising approach for massive peripheral nerve defects.

Osteonecrosis development by tooth extraction in zoledronate treated mice is inhibited by active vitamin D analogues, anti-inflammatory agents or antibiotics.

Invasive dental treatment such as tooth extraction following treatment with strong anti-bone resorptive agents, including bisphosphonates and denosumab, reportedly promotes osteonecrosis of the jaw (ONJ) at the extraction site, but strategies to prevent ONJ remain unclear. Here we show that in mice, administration of either active vitamin D analogues, antibiotics or anti-inflammatory agents can prevent ONJ development induced by tooth extraction during treatment with the bisphosphonate zoledronate. Specifically, tooth extraction during treatment with zoledronate induced osteonecrosis in mice, but administration of either 1,25(OH)2D3 or ED71, both active vitamin D analogues, significantly antagonized osteonecrosis development, even under continuous zoledronate treatment. 1,25(OH)2D3 or ED71 administration also significantly inhibited osteocyte apoptosis induced by tooth extraction and bisphosphonate treatment. Administration of either active vitamin D analogue significantly inhibited elevation of serum inflammatory cytokine levels in mice in response to injection of lipopolysaccharide, an infection mimetic. Furthermore, administration of either anti-inflammatory or antibiotic reagents significantly blocked ONJ development following tooth extraction and zoledronate treatment. These findings suggest that administration of active vitamin D, anti-inflammatory agents or antibiotics could prevent ONJ development induced by tooth extraction in patients treated with zoledronate.

An ionic silver coating prevents implant-associated infection by anaerobic bacteria in vitro and in vivo in mice.

Currently, implants are utilized clinically for bone transplant procedures. However, if infectious osteomyelitis occurs at implant sites, removal of bacteria can be challenging. Moreover, altered blood flow at peri-implant infectious sites can create an anaerobic environment, making it more difficult to treat infection with antibiotics. Thus, it would be beneficial if implants could be modified to exhibit antibacterial activity, even in anaerobic conditions. Here, we show antibacterial activity of silver ions coated on titanium rods, even against the anaerobic bacteria Porphyromonas gingivalis (P. gingivalis), both in vitro and in vivo. Specifically, we implanted silver-coated or control uncoated titanium rods along with P. gingivalis in mouse femoral bone BM cavities and observed significantly inhibited P. gingivalis infection with silver-coated compared with non-coated rods, based on in vivo bio-imaging. Osteonecrosis by infectious osteomyelitis and elevation of the inflammatory factors C-reactive protein and IL-6 promoted by P. gingivalis s were also significantly reduced in the presence of silver-coated rods. Overall, our study indicates that silver ion coating of an implant represents a therapeutic option to prevent associated infection, even in anaerobic conditions or against anaerobic bacteria.

IL-27 abrogates receptor activator of NF-kappa B ligand-mediated osteoclastogenesis of human granulocyte-macrophage colony-forming unit cells through STAT1-dependent inhibition of c-Fos.

IL-27 was first discovered as a factor supporting initial Th1 immune responses. Subsequent studies revealed that this cytokine has pleiotropic effects, including inhibition of certain immune cells, a regulatory role in hemopoietic stem cell differentiation, and antitumor activities. However, the role of human IL (hIL)-27 in human osteoclast precursors and inflammatory bone disease is unclear. Here, we examined the direct effect of hIL-27 on human osteoclastogenesis. Human bone marrow cells cultured in MethoCult medium containing human (h) GM-CSF, human stem cell factor, and hIL-3 expressed Mac-1, c-kit, and c-Fms. These cells, called hCFU-GMs, also expressed the IL-27 receptor, an IL-27Ralpha (WSX-1)/gp130 heterodimer. Cultivation in hM-CSF and human receptor activator of NF-kappaB ligand induced the differentiation of tartrate-resistant acid phosphatase-positive multinucleated cells (osteoclasts) from hCFU-GMs, and hIL-27 inhibited this osteoclastogenesis in a dose-dependent manner. hIL-27 also repressed bone resorption by osteoclasts on a dentine slice. hIL-27 caused a remarkable increase in STAT1 phosphorylation and enhanced the STAT1 protein level. It also inhibited the expression of receptor activator of NF-kappaB ligand-induced c-Fos and cytoplasmic, calcineurin-dependent 1 NFAT (NFATc1), which are indispensable transcription factors for osteoclastogenesis. Fludarabine, a STAT1 inhibitor, and STAT1 small interfering RNA partially rescued the inhibition of osteoclastogenesis by IL-27. A WSX-1 deficiency caused severe inflammatory bone destruction primed by Escherichia coli cell wall lysate in vivo. Therefore, hIL-27 may act as an anti-inflammatory cytokine in human bone destruction, by inhibiting osteoclastogenesis from hCFU-GMs via STAT1-dependent down-regulation of the transcription factor c-Fos. Our results suggest that hIL-27 may prove useful as a therapeutic target for inflammatory bone destruction.

Cobalt-Chromium Alloy Has Superior Antibacterial Effect Than Titanium Alloy: In Vitro and In Vivo Studies.

STUDY DESIGN: In vitro and in vivo laboratory studies. OBJECTIVE: This study aimed to compare bacterial survival on titanium alloy (Ti) and cobalt-chromium alloy (CC) using in vitro and in vivo experiments. SUMMARY OF BACKGROUND DATA: Spinal implants are frequently manufactured from Ti and CC. These foreign materials are thought to be susceptible to biofilm formation that contributes to the development of surgical site infections. Certain metals (i.e., silver, cobalt) are known to have antibacterial properties. METHODS: In the in vitro study, discs made of Ti or CC were incubated with one of two common bacteria: Staphylococcus aureus (S. aureus) and Propionibacterium acnes (P. acnes). After incubation, discs were assessed to determine the number of viable bacterial cells. In the in vivo study, the discs that were made of CC or Ti were implanted into the subcutaneous layer of BALB/c mice. After skin closure, a suspension including either S. aureus or P. acnes was directly inoculated on the implanted discs. The discs were retrieved and analyzed to determine the number of viable bacteria at 0.5, 1, and 3 days after inoculation. RESULTS: The number of viable S. aureus cultured from the CC discs was 0.9 ±â€Š0.2 × 103 CFU/disc, which was significantly lower than the cultured Ti discs (114.8 ±â€Š18.3 × 103 CFU/disc). Moreover, a significantly lower mean number of P. acnes were cultured with CC (1.9 ±â€Š1.2 × 103 CFU/disc) compared with the Ti (180.0 ±â€Š72.1 × 103 CFU/disc). The in vivo infection model testing against S. aureus or P. acnes showed a significantly lower number of viable S. aureus or P. acnes on CC discs than Ti discs. The result was seen at all measured time points. CONCLUSION: CC suppressed S. aureus and P. acnes proliferation compared with Ti in vitro and in an in vivo infection model.Level of Evidence: N/A.

Laser resonance frequency analysis of pedicle screw stability: A cadaveric model bone study.

There is no evaluation method currently available to assess intraoperative pedicle screw fixation (PSF) strength. In this study, we established a laser-based resonance frequency analysis (RFA) system with high-speed, noncontact, quantitative measurements of PSF. Clinical investigations in the future can assess surgical failure risk of implants. We investigated the characteristics of the laser RFA and compared them with the conventional methods. We inserted a pedicle screw in the vertebral pedicle of human cadaver or model bone, followed by screw pull-out, peak torque, implant stability quotient (ISQ) value obtained by the magnetic dental RFA system, and fixation force of laser RFA. We compared the outcomes using best-fit linear or logarithmic approximations. For the model bone study, the resonance frequency (RF) versus peak torque/pull-out force (POF) demonstrated strong correlations using logarithmic approximation (vs. peak torque: R = 0.931, p < .001, vs. POF: R = 0.931, p < .001). RF strongly correlated with the ISQ value using linear approximation (R = 0.981, p < .001). For the cadaveric vertebrae study, the correlation coefficients between RF and the peak torque/POF were significant regardless of approximation method (peak torque: logarithmic: R = 0.716 vs. linear: R = 0.811; p < .001) (POF: logarithmic: R = 0.644 vs. linear: R = 0.548; p < .05). Thus, the results of this study revealed a constant correlation between RFA and conventional methods as a measurement validation, predicting favorable support for intraoperative PSF. RFA has the potential to be a new index for evaluating the implant fixation force.

A Novel Alaska Pollock Gelatin Sealant Shows Higher Bonding Strength and Nerve Regeneration Comparable to That of Fibrin Sealant in a Cadaveric Model and a Rat Model.

BACKGROUND: A novel biocompatible sealant composed of Alaska pollock-derived gelatin (ApGltn) has recently shown good burst strength and biocompatibility in a porcine aorta. The purpose of this study was to investigate the bonding strength and biocompatibility of the ApGltn sealant in transected digital nerves of fresh frozen cadavers and in the sciatic nerves of a rat model. METHODS: Eighty human digital nerves of fresh frozen cadavers were transected for biomechanical traction testing. They were treated with four surgical interventions: (1) suture plus ApGltn sealant; (2) suture; (3) ApGltn sealant; and (4) fibrin sealant. Forty-three sciatic nerves of male Wistar rats were used for functional and histopathologic evaluation. They were treated with six surgical interventions: (1) suture plus ApGltn sealant; (2) suture; (3) ApGltn sealant; (4) fibrin sealant; (5) resection with a 5-mm gap (10 rats per group); and (6) sham operation (three rats). Macroscopic confirmation, muscle weight measurement, and histopathologic findings including G-ratio were examined 8 weeks after the procedure. RESULTS: The maximum failure load of the ApGltn sealant was significantly higher than that of a fibrin sealant (0.22 ± 0.05 N versus 0.06 ± 0.04 N). The maximum failure load of the ApGltn sealant was significantly lower that of suture plus ApGltn sealant (1.37 N) and suture (1.27 N). Functional evaluation and histologic examination showed that sciatic nerves repaired with ApGltn sealant showed similar nerve recovery compared to repair with the suture and fibrin sealant. CONCLUSION: The ApGltn sealant showed higher bonding strength and equal effect of nerve regeneration when compared with the fibrin sealant.

An antibacterial coated polymer prevents biofilm formation and implant-associated infection.

To prevent infections associated with medical implants, various antimicrobial silver-coated implant materials have been developed. However, these materials do not always provide consistent antibacterial effects in vivo despite having dramatic antibacterial effects in vitro, probably because the antibacterial effects involve silver-ion-mediated reactive oxygen species generation. Additionally, the silver application process often requires extremely high temperatures, which damage non-metal implant materials. We recently developed a bacteria-resistant coating consisting of hydroxyapatite film on which ionic silver is immobilized via inositol hexaphosphate chelation, using a series of immersion and drying steps performed at low heat. Here we applied this coating to a polymer, polyetheretherketone (PEEK), and analyzed the properties and antibacterial activity of the coated polymer in vitro and in vivo. The ionic silver coating demonstrated significant bactericidal activity and prevented bacterial biofilm formation in vitro. Bio-imaging of a soft tissue infection mouse model in which a silver-coated PEEK plate was implanted revealed a dramatic absence of bacterial signals 10 days after inoculation. These animals also showed a strong reduction in histological features of infection, compared to the control animals. This innovative coating can be applied to complex structures for clinical use, and could prevent infections associated with a variety of plastic implants.

Chin on Chest Deformity Caused by Upper Cervical Kyphosis Associated With Ankylosing Spondylitis: A Case Report.

Chin on chest deformity caused by upper cervical kyphosis associated with ankylosing spondylitis is rare. A 66-year-old woman presented at our institute with chief complaints of difficulty in horizontal gaze and opening her mouth. Cervical radiographs showed a C0-2 angle of 1° on flexion and 7° on extension, and her chin-brow vertical angle was 49°. We planned fixation surgery at C0-5 posteriorly to prevent the progression of kyphosis, with slight correction of the kyphosis at C0-2. The correction was performed by pushing down the over lordotically contoured titanium rods connected to an occipital plate onto the C3-5 lateral mass screws, just like cantilever technique. No palpable cracking or loss of resistance was noticed during the correction. However, intraoperative radiographs revealed apparent anterior separation of the vertebral bodies between C3 and C4. Postoperative computed tomography images at the C3/4 level suggested hemorrhage from the fracture site. Tracheostomy was performed because of massive edema around the pharynx. To secure solid bone fusion, staged surgery to extend the fusion to T3 and to graft an additional iliac bone was performed. Fortunately, the C2-7 angle was corrected to 40°, and her chin-brow vertical angle was restored to 17° without any catastrophic complications. Although the patient finally obtained an ideal sagittal alignment, the surgeon should be aware that the technique had a higher perioperative risk for iatrogenic fracture, resulting in neurological and vascular injuries.

A study on the use of the Osstell apparatus to evaluate pedicle screw stability: An in-vitro study using micro-CT.

Pull-out force and insertion torque have not been generally used as intraoperative measures for the evaluation of pedicle screw stability because of their invasiveness. On the other hand, resonance frequency analysis is a non-invasive and repeatable technique that has been clinically used in dentistry to evaluate implant stability e.g. by the Osstell apparatus. In this study, the characteristics of the implant stability quotient (ISQ) value obtained by the Osstell apparatus in the field of spinal surgery were investigated. Biomechanical test materials simulating human bone were used to provide a comparative platform for evaluating each fixation strength measure, including pull-out force, insertion torque, and the ISQ value. To perform pull-out force measurement and to repeat pedicle screw insertion and removal, loosening was artificially created, and its effect was investigated. The grade of loosening was quantified on a micro-CT image after pedicle screw removal. In the comparison of the 3 fixation strength measures, the correlations of the ISQ value with the pull-out force (R2 = 0.339 p <0.0001) and the insertion torque (R2 = 0.337 p <0.0001) were lower than the correlation between pull-out force and insertion torque (R2 = 0.918 p <0.0001). On a micro-CT study, the material volume of the internal threads disappeared after destruction of its integrity due to repeated pedicle screw insertion and removal. Material integrity destruction of the internal threads decreased only the pull-out force and the insertion torque, but it did not affect the ISQ value. The ISQ value only decreased when the material volume of the internal threads disappeared, probably because the ISQ value reflects the resistance against a force in the perpendicular direction of the screw, unlike the conventional measures of fixation strength, such as pull-out force and insertion torque, which reflect axial load.

Elevation of pro-inflammatory cytokine levels following anti-resorptive drug treatment is required for osteonecrosis development in infectious osteomyelitis.

Various conditions, including bacterial infection, can promote osteonecrosis. For example, following invasive dental therapy with anti-bone resorptive agents, some patients develop osteonecrosis in the jaw; however, pathological mechanisms underlying these outcomes remain unknown. Here, we show that administration of anti-resorptive agents such as the bisphosphonate alendronate accelerates osteonecrosis promoted by infectious osteomyelitis. Potent suppression of bone turnover by these types of agents is considered critical for osteonecrosis development; however, using mouse models we found that acceleration of bone turnover by teriparatide injection did not prevent osteonecrosis but rather converted osteoclast progenitors to macrophages expressing inflammatory cytokines, which were required for osteonecrosis development. In fact, we demonstrate that TNFα-, IL-1α/ß- or IL-6-deficient mice as well as wild-type mice administered a TNFα-inhibitor were significantly resistant to development of osteonecrosis accompanying infectious myelitis, even under bisphosphonate treatment. Our data provide new insight into mechanisms underlying osteonecrosis and suggest new ways to prevent it.

A novel hydroxyapatite film coated with ionic silver via inositol hexaphosphate chelation prevents implant-associated infection.

Various silver-coated implants have been developed to prevent implant-associated infections, and have shown dramatic effects in vitro. However, the in vivo results have been inconsistent. Recent in vitro studies showed that silver exerts antibacterial activity by mediating the generation of reactive oxygen species in the presence of oxygen. To maintain its antibacterial activity in vivo, the silver should remain in an ionic state and be stably bound to the implant surface. Here, we developed a novel bacteria-resistant hydroxyapatite film in which ionic silver is immobilized via inositol hexaphosphate chelation using a low-heat immersion process. This bacteria-resistant coating demonstrated significant antibacterial activity both in vitro and in vivo. In a murine bioluminescent osteomyelitis model, no bacteria were detectable 21 days after inoculation with S. aureus and placement of this implant. Serum interleukin-6 was elevated in the acute phase in this model, but it was significantly lower in the ionic-silver group than the control group on day 2. Serum C-reactive protein remained significantly higher in the control group than the ionic-silver group on day 14. Because this coating is produced by a low-heat immersion process, it can be applied to complex structures of various materials, to provide significant protection against implant-associated infections.

Impact of interlaminar graft materials on the fusion status in atlantoaxial transarticular screw fixation.

OBJECT: Structural interlaminar graft materials were used for atlantoaxial transarticular screw fixation (TSF), and its impact on the fusion status was investigated. METHODS: Forty-two patients (10 men, 32 women, mean age 51 years, mean follow-up period 45 months; 30 with rheumatoid arthritis, and 12 with os odontoideum) underwent TSF and modified Brooks posterior wiring involving titanium cables. As interlaminar graft materials, autologous bone from posterior iliac crest alone was used in 20 patients (Group A), and a structural spacer (13 ceramic spacers, nine titanium mesh cages) in 22 (Group B). Lateral radiographs were evaluated to determine bone fusion, alignment of the cervical spine, and wire loosening. Solid osseous fusion was obtained in 95% of Group A and 96% of Group B patients. The mean atlantoaxial angle was 19.1+/-9.7 degrees and 16.7+/-10.4 degrees before surgery (p = 0.45), and 27.4+/-7.8 degrees and 22.1+/-5.5 degrees after surgery (p = 0.02) in Groups A and B, respectively. Atlantoaxial hyperlordosis (atlantoaxial angle > or = 30 degrees) was observed in 32% of Group A and 18% of Group B patients (p = 0.26). Postoperative kyphosis occurred in 40% of Group A and 23% of Group B patients (p = 0.28). Loosening of the cable was demonstrated in 50% of Group A and 36% of Group B patients(p = 0.37). In Group B patients maintenance of cervical lordosis was more likely than in those in Group A, although the differences did not reach statistical significance. CONCLUSIONS: These results indicate that structural interlaminar spacers can maintain proper cervical alignment without a decease in the fusion rate; the authors recommend their use in conjunction with TSF.