Aims

Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice.

Aims

Distraction osteogenesis (DO) is a useful orthopaedic procedure employed to lengthen and reshape bones by stimulating bone formation through controlled slow stretching force. Despite its promising applications, difficulties are still encountered. Our previous study demonstrated that pulsed electromagnetic field (PEMF) treatment significantly enhances bone mineralization and neovascularization, suggesting its potential application. The current study compared a new, high slew rate (HSR) PEMF signal, with different treatment durations, with the standard Food and Drug Administration (FDA)-approved signal, to determine if HSR PEMF is a better alternative for bone formation augmentation.

The range of allograft products for spinal fusion has been extended with the development of cellular bone matrices (CBMs). Most of these combine demineralized bone with viable cancellous bone prepared in a manner that retains cells with differentiation potential. The purpose of this study was to compare commercially-available human CBMs in the athymic rat model of posterolateral spinal fusion. The products compared were Trinity ELITE® (TEL, OrthoFix), ViviGen (VIV, DePuy Synthes), Cellentra (CEL, Zimmer Biomet), Osteocel® Pro (OCP, NuVasive), Bio4 (BIO, Stryker) and map3 (MAP, RTI Surgical). Bone from the ilia of syngeneic rats was used as a control to approximate the human gold standard.

All implants were stored, thawed, and prepared per manufacturer's instructions and all implantations occurred within the manufacturer's time allowance for use after preparation. In total, fifteen 9–10 week old male rats were implanted per implant type, with three different lots of each implant used per five rats to account for lot-to-lot variability. Under anesthesia, a posterior midline longitudinal skin and subcutaneous incision was made, followed by bilateral longitudinal paraspinal myofascial incisions to expose the transverse processes at the L4–5 level. Implants (0.3 cc of allograft or freshly harvested syngeneic iliac bone graft) were placed bilaterally. Surgeons were blinded as to CBM implant type. Incisions were closed with sutures and in vivo microCT scans performed within 48 hours of surgery. A second microCT scan was taken at euthanasia, six weeks after surgery, and the lumbar spines harvested. Fusion was evaluated by manual palpation by three independent, blinded reviewers. MicroCT analysis was performed by an independent CRO (ImageIQ, Cleveland OH). Anonymity of implant type was rigorously kept to avoid bias.

By manual palpation, 5/15 (33%) spines of the syngeneic bone group were fused at 6 weeks. The TEL (8/15, 53%) and CEL (11/15, 73%) groups were not significantly different from each other but were from all other CBM groups. Only 2/15 (13%) of VIV-implanted spines fused and none (0/15, 0%) of the OCP, BIO and MAP CBMs produced stable fusion. The mineralized cancellous bone component of the allografts confounded radiographic analysis but microCT analysis indicated bone volume increased over six weeks for all groups except the syngeneic bone (−4.3%). TEL (+65%) and CEL (+73%) were not different from each other but were significantly increased over all other groups (VIV 29%, OCP 37%, BIO 19%, and MAP 45%, respectively).

CBMs have distinct formulations and are likely processed differently. The claimed live cell and stem cell contents differ between products. Additionally, map3 has cells added at the time of surgery, whereas the other CBMs are processed to retain matrix-adherent cells. Given the wide range of formulations, differences in performance were not surprising, and Trinity ELITE and Cellentra did significantly better than other implants at both forming new bone and achieving fusion. The other CBMs did not have greater bone formation than the control and were very poor at forming a solid fusion. These findings suggest more careful consideration of these allograft products is needed at the clinical level.

PEMF is currently approved by the FDA for adjunctive treatment of lumbar/cervical spine fusion and for treatment of long-bone non-unions. Soft tissues are a potential new therapeutic application for PEMF due to pre-clinical studies showing a reduction of inflammatory markers following PEMF exposure. The aim was therefore to investigate the structural/functional effects of PEMFs on tendon-to-bone and tendon-to-tendon healing in a rotator-cuff (RC) and Achilles tendon (AT) repair model, respectively. RC study: Adult male rats (n=280), underwent bi-lateral supraspinatus tendon transections with immediate repair followed by cage activity until sacrifice (4, 8, and 16 weeks). Non-controls received PEMF for 1, 3, or 6 hours daily. AT study: Male rats underwent acute, complete transection and repair of the Achilles tendon (FULL, n=144) or full thickness, partial width injury (PART, n=160) followed by immobilization for 1 week. Sacrifice was at 1, 3, and 6 weeks. Outcome measures included passive joint mechanics, gait analysis, biomechanical assessments, histological analysis of the repair site and mCT (humerus) assessment (FULL only). RC study: Significant increases in modulus, stiffness, bone mineral content and improved collagen organization was observed for the PEMF groups. No differences in joint mechanics and ambulation were observed. AT study: A decrease in stiffness and limb-loading rate was observed for the PEMF groups for the FULL groups, whereas an increase in stiffness with no change in range-of-motion was seen for the PART groups. The combined studies show that PEMF can be effective for soft tissue repair but is dependent on the location of application.

Introduction

The crescent sign is thought to be an early indicator of collapse in osteonecrosis of the femoral head. However, the formation mechanism of the crescent sign is still not quite clear. The purpose of this study was to utilize the two-dimensional finite element model analysis (FEA) technique to analyze mechanical function of different structures and intraosseous fluid in the femoral head under the stress of physiological loading. We wished to answer the following question: which structure or structures' failure are the main causes of collapse in osteonecrosis of the femoral head (ONFH)?

Introduction

Multifocal osteonecrosis (ON) was defined by Mont et al. as a disease involving three or more anatomic sites. Few papers have been published on the Chinese experience. The purpose of this study was to characterize the experience with multifocal ON in order to make an earlier diagnosis for more patients with this disorder.

This study prospectively compared the efficacy of kyphoplasty using a Jack vertebral dilator and balloon kyphoplasty to treat osteoporotic compression fractures between T10 and L5. Between 2004 and 2009, two groups of 55 patients each underwent vertebral dilator kyphoplasty and balloon kyphoplasty, respectively. Pain, function, the Cobb angle, and the anterior and middle height of the vertebral body were assessed before and after operation. Leakage of bone cement was recorded. The post-operative change in the Cobb angle was significantly greater in the dilator kyphoplasty group than in the balloon kyphoplasty group (−9.51° (sd 2.56) vs −7.78° (sd 1.19), p < 0.001)). Leakage of cement was less in the dilator kyphoplasty group. No other significant differences were found in the two groups after operation, and both procedures gave equally satisfactory results in terms of all other variables assessed. No serious complications occurred in either group.

These findings suggest that vertebral dilator kyphoplasty can facilitate better correction of kyphotic deformity and may ultimately be a safer procedure in reducing leakage of bone cement.

Introduction: The formation mechanism of the “crescent sign” in the ONFH is not quite clear. We sought to find the formation mechanism of the “crescent sign”.

Methods: We observed the pathologic structure changes of femoral heads with “crescent signs” in general, using coronal sections and X-ray films. We used the principle of effective stress and stress concentration theory to analyze and explain the reasons of pathologic changes occurring in the ONFH with the “crescent sign”.

Results: The concentrated stress accumulated in the junction between the subchondral plate and the unrepaired necrotic cancellous bone brings on the fracture line right beneath the subchondral plate. Increased effective stress causes the stress-to-strength ratio to increase progressively until reaching the critical level of collapse onset. The volume decrease of unrepaired necrotic cancellous bone leads to the formation of the crescent cavum.

Discussion: Bones are a kind of living porous media. The principle of effective stress is one of the important fundamental concepts in porous media mechanics. The principle of effective stress and stress concentration theory could clearly explain phenomena occurring in ONFH. This is the first time an explanation of the formation mechanism of the “crescent sign” has been done with the principle of effective stress. The results are useful for prediction and prevention collapse of ONFH.

Severe acute respiratory syndrome (SARS) is a newly described infectious disease caused by the SARS coronavirus which attacks the immune system and pulmonary epithelium. It is treated with regular high doses of corticosteroids. Our aim was to determine the relationship between the dosage of steroids and the number and distribution of osteonecrotic lesions in patients treated with steroids during the SARS epidemic in Beijing, China in 2003.

We identified 114 patients for inclusion in the study. Of these, 43 with osteonecrosis received a significantly higher cumulative and peak methylprednisolone-equivalent dose than 71 patients with no osteonecrosis identified by MRI. We confirmed that the number of osteonecrotic lesions was directly related to the dosage of steroids and that a very high dose, a peak dose of more than 200 mg or a cumulative methylprednisolone-equivalent dose of more than 4000 mg, is a significant risk factor for multifocal osteonecrosis with both epiphyseal and diaphyseal lesions. Patients with diaphyseal osteonecrosis received a significantly higher cumulative methylprednisolone-equivalent dose than those with epiphyseal osteonecrosis. Multifocal osteonecrosis should be suspected if a patient is diagnosed with osteonecrosis in the shaft of a long bone.