Intervertebral disc (IVD) degeneration is inadequately understood due to the lack of in vitro systems that fully mimic the mechanical and biological complexity of this organ. We have recently made an advancement by developing a bioreactor able to simulate physiological, multiaxial IVD loading and maintain the biological environment in ex vivo IVD models [1].

To validate this new bioreactor system, we simulated natural spine movement by loading 12 bovine IVDs under a combination of static compression (0.1 MPa), cyclic flexion/extension (±3˚, ±6˚ or 0-6˚) and cyclic torsion (±2˚, ±4˚ or 0-4˚) for more than 10’000 (0.2 Hz) or 100’000 (1 Hz) cycles over 14 days. A higher number of cycles increased the release of glycosaminoglycans and nitric oxide, as an inflammation marker, whereas fewer cycles maintained these two factors at physiological levels. All applied protocols upregulated the expression of MMP13 in the outermost annulus fibrosus (AF), indicating a collagen degradation response. This was supported by fissures observed in the AF after a longer loading duration. Increasing loading cycles induced high cell death in the nucleus pulposus and inner AF, while with fewer cycles, high cell viability was maintained in all IVD regions, irrespective of the magnitude of rotation.

Less frequent multiaxial loading maintains IVD homeostasis while more frequent loading initiates an IVD degenerative profile. Specifically, the morphological and molecular changes were localized in the AF, which can be associated with combined flexion/extension and torsion. More loading cycles induced region-specific cell death and a higher release of extracellular matrix molecules from the innermost IVD regions, likely associated with longer exposure to static compression. Altogether, we demonstrated the advantages of the multiaxial bioreactor to study region-specific response in the IVD, which will allow a more profound investigation of IVD degeneration under different combinations of motions.

Purpose: The average age of people suffering spinal cord injuries in many countries is shifting toward an older population, with a disproportionate number occurring in the spondylotic cervical spine. These injuries are typically due to low energy impacts, such as a fall from standing height. Since a stenotic spinal canal (a common feature of a spondylotic cervical spine) can cause myelopathy when the spine is flexed or extended, traumatic flexion or extension likely causes the injury during the low energy impact. However, this injury mechanism has not been observed experimentally.

Method: To better understand this injury mechanism an in-vitro study, using six whole cervical porcine spines, was conducted. The following techniques were combined to directly observe spinal cord compression in a stenotic spine during physiologic and super-physiologic motion:

A radio-opaque surrogate cord, with material properties matched to in-vivo specimens, replaced the real spinal cord.

Results: Initial results show that a stenotic occlusion that removes all extra space in the canal in the neutral posture, without compressing the cord, can lead to spinal cord compression within physiologic ranges of flexion and extension. The spinal cord can also be compressed during slightly super-physiologic flexion and extension with only 25% canal occlusion. Physiologic loads and motions in the same spines did not cause cord compression when canal occlusion was 0%.

Conclusion: These results support the hypothesis that cervical spinal canal stenosis increases the risk of spinal cord injury because spinal cord compression was observed during motions and loads that would be safe for a non-stenotic spine. These results are limited primarily due to the use of a porcine spine. However, this new stenosis model and experimental technique will be applied to in-vitro human spine specimens in future work.

Introduction Vertebroplasty and kyphoplasty have been gaining popularity for treating vertebral fractures. Current reviews provide an overview of the procedures but are not comprehensive and tend to rely heavily on personal experience. This paper aimed to compile all available data and evaluate the clinical outcome of the two procedures. The objective was to evaluate the safety and efficacy of vertebroplasty and kyphoplasty using the data presented in published clinical studies, with respect to patient pain relief, restoration of mobility and vertebral body height, complication rate, and incidence of new adjacent vertebral fractures.

Methods This is a systematic review of all the available data presented in peer reviewed published clinical trials (69 papers). Where possible a quantitative aggregation of the data was performed. Data was collected for each study under the headings: general information, participants, intervention, outcomes, complications, and follow-up. Outcome data was collected detailing: pain relief, general health, functional improvements, satisfaction with treatment, and reduction in kyphosis. Complications included: cement leakage (asymptomatic and symptomatic), neurological deficits, cardiovascular, pulmonary and any other clinically relevant complication. Long term follow-up information included all the items recorded under the heading “outcome” with the addition of new fracture details.

Results A large proportion of subjects experienced some pain relief (87% vertebroplasty, 92% kyphoplasty). Vertebral height restoration was possible using kyphoplasty (average 6.6°) and for a subset of patients using vertebroplasty. Cement leaks occurred for 41% and 9% of treated vertebrae for vertebroplasty and kyphoplasty respectively. New fractures of adjacent vertebrae occurred for both procedures at rates that are greater than the general osteoporotic population but approximately equivalent to the general osteoporotic population that had a previous vertebral fracture.

Discussion The pain relief experienced by patients is promising for both kyphoplasty and vertebroplasty in the short term (< 1 year). Leakage of the PMMA is the most common complication and may pose significant danger. Higher leakage rates have been reported for vertebroplasty studies compared to kyphoplasty studies. Particularly kyphoplasty has the ability to reduce the kyphotic angle and restore vertebral height. The critical factor for the restoration of vertebral height would appear to be fracture age.

Introduction Cement leakage into adjacent structures is the main complication during vertebroplasty. The majority of these leaks are asymptomatic, but pulmonary cement embolism has been reported to cause cardiovascular disturbances and even death (1,2). Furthermore, the use of calcium phosphate (CaP) cements for vertebroplasty may aggravate cardiovascular deterioration in the event of cement embolism by stimulating coagulation [3].

The cardiovascular effects of pulmonary cement embolism were investigated using an animal model.

Methods In 18 skeletally mature sheep, 2.0ml cement was injected into the pulmonary trunk during general anaesthesia (approved by Animal Ethics Committee). Three different cements were used: 1) PMMA (Simplex P, Stryker); 2) PMMA with 10% hydroxyapatite (PMMA & HA) (Vertecem, Synthes); 3) Experimental injectable CaP cement (Synthes). The following cardiovascular parameters were recorded continuously (endpoint: 60min post-injection): arterial, central venous, pulmonary arterial pressures and cardiac output. Blood gases and coagulation parameters (antithrombin, D-dimer, prothrombin fragments I & II) were measured pre-injection, 10, 30 and 60min post-injection. Postmortem, lungs were removed intact and submitted to computer tomography (CT) imaging.

Results There were no fatalities. After 1min, mean pulmonary arterial pressure had increased by 9%, 14% and 21% from pre-injection value in the PMMA, PMMA & HA and CaP group respectively. Differences in pulmonary arterial pressure between the three material groups were not statistically significant. Pulmonary arterial pressure stayed elevated for the duration of the experiment (i.e. 60min post-injection). There were no other significant changes in cardiovascular, blood gas or coagulation parameters from pre- to post-injection values. Three dimensional reconstructions of the CT images showed a tendency of the CaP cement to break up into multiple smaller pieces whereas the two other cements did not.

Discussion Cement embolism led to mild pulmonary hypertension in all material groups. Present results are in contrast to earlier reports (pig model) of fulminant cardiovascular deterioration after CaP cement embolism (3). Present changes were not as severe and there was no evidence of thromboembolism. This discrepancy may have been due to differences in the cement formulations or the animal model.

Pulmonary hypertension was more severe in the CaP cement group. This may have been due to the disintegration of the CaP cement resulting in blockage of more pulmonary vessels compared to the PMMA cements.

Introduction Reported clinical results suggest that vertebroplasty is a safe and effective technique for providing pain relief. However, information about the long-term effect of PMMA on the adjacent intervertebral discs and the augmented bone is lacking. Adjacent intervertebral discs may be at higher risk of degeneration due to nutritional constraints. Bone loss in augmented vertebrae may occur due to mechanical stress-shielding or toxicological effects.

The aim of the present study was therefore to investigate the effect of PMMA augmentation on intervertebral disc and bone tissue after 6 and 12 months, using an animal model.

Methods In 12 skeletally mature sheep, 2.0ml PMMA (Simplex P) was injected into three lumbar vertebrae (approved by Animal Ethics Committee). Two injection holes were drilled into the middle of three vertebrae at a distance of 5.0mm from the cranial and caudal endplate and 1.0ml PMMA was injected into each hole. Four weeks before euthanasia, animals received an injection of tetracycline for bone labeling.

Postmortem, T1- and T2-weighted sagittal and axial MR images were taken prior to fixation in 80% ethanol. Spines were cut into specimens containing one intervertebral disc and half of the two adjacent vertebrae. The discs which were two levels above the first augmented vertebra served as controls. Microsections were stained with H& E, Goldner, Alcian blue-PAS and Safranin O. MRI signal intensity and morphology of discs were evaluated qualitatively. Histomorphological analysis of discs and endplates was conducted using published criteria [1]. Presence of bone remodeling, fibrous tissue and foreign body reaction in the vertebrae was also recorded.

Results There was no distinguishable loss of MRI signal intensity in the discs in between augmented vertebrae. Cement injection resulted in blocking 50–75% of the endplate lengths. Most discs that were in between augmented vertebrae showed signs of degeneration (chondrocyte proliferation, necrosis) after 6 (80%) and 12 months (88%). Inflammatory reaction to PMMA was observed in some specimens (approximately 25%). Cement had been covered with fibrous tissue in all augmented vertebrae, but tetracycline labeling revealed new bone formation in the vicinity of PMMA.

Discussion Augmentation of three adjacent vertebrae initiated degenerative changes of intervertebral discs in between two augmented vertebrae. This is in contrast to previous animal studies [2] where no degenerative changes after cementing endplates were observed. Current investigations were performed with the specific aim to block the endplates. Clinically, endplates may not get blocked as effectively. On the other hand, discs in older patients are nutritionally constrained due to end-plate calcification and even partial blockage may lead to degenerative changes as documented presently.

The risk of degenerative changes of intervertebral discs should be considered in patients undergoing vertebroplasty.

Minimal-invasive augmentation techniques have been advocated to treat osteoporotic vertebral body fractures (VBFs). Kyphoplasty is designed to address both fracture-related pain as well as the kyphotic deformity usually associated with the fracture. Previous studies have indicated the potential of the technique for immediate pain relief and reduction of vertebral height, but whether this is a lasting effect, has not been well investigated. The current prospective study reports on our experience and the one-year results in 27 kyphoplasty procedures in 24 patients with PMMA for osteoporotic VBFs.

Pain was assessed on a 0–10 VAS. Deformity and reduction of the vertebral body was measured as the angulation between the two endplates on standing lateral radiographs. All parameters were taken pre-op, one day and two months post-operatively and after one year. Multiple regression analysis was conducted to determine the importance of independent factors as predictors of the achieved fracture reduction.

All but one patient experienced pain relief directly following the procedure with a lasting effect after 2 months and also one year in 25 cases. An average vertebral kyphosis reduction of 47.7% was achieved with no loss of reduction after one year. Pain relief was not related to the amount of reduction. The potential for reduction was related to pre-op kyphosis, level treated, and fracture age, but not to the age of the patient.

In this series, kyphoplasty was an effective treatment of VBFs in terms of pain relief and durable reduction of deformity. However, whether spinal realignment results in an improved long-term clinical outcome remains to be investigated.