Platelet-released supernatant induces osteoblastic differentiation of human mesenchymal stem cells: potential role of BMP-2.

Platelet-rich preparations have recently gained popularity in maxillofacial and dental surgery, but their beneficial effect is still under debate. Furthermore, very little is known about the effect of platelet preparations at the cellular level, and the underlying mechanisms. In this study, we tested the effect of platelet-released supernatant (PRS) on human mesenchymal stem cell (MSC) differentiation towards an osteoblastic phenotype in vitro. Cultures of MSC were supplemented with PRS and typical osteoblastic markers were assessed at up to 28 days post-confluence. PRS showed an osteoinductive effect on MSC, as shown by an increased expression of typical osteoblastic marker genes such as collagen Ialpha1, bone sialoprotein II, BMP-2 and MMP-13, as well as by increased 45Ca²+ incorporation. Our results suggest that the effect of PRS on human MSC could be at least partially mediated by BMP-2. Activated autologous PRS could therefore provide an alternative to agents like recombinant bone growth factors by increasing osteoblastic differentiation of bone precursor cells at bone repair sites, although further studies are needed to fully support our observations.

[Vertebroplasty: an update: value of percutaneous cement augmentation after randomized, placebo-controlled trials]. / Vertebroplastie: ein Update : Stellenwert der perkutanen Zementaugmentation nach randomisierten, placebokontrollierten Studien.

Percutaneous cement augmentation (kyphoplasty and vertebroplasty) has become established as a procedure for treatment of painful osteoporotic vertebral fractures and certain neoplastic changes. The injection of cement ensures rapid stabilization of the vertebra and prevents further sintering. This also results in pain improvement. Nonetheless, based on two placebo-controlled trials, this treatment approach has been called into question. However, these studies did not take the technical aspects of the treatment into consideration, and it appears probable that the amount of filler material chosen was too small so that the treatment group also received placebo. Furthermore, it is likely that mostly older fractures were treated so that the effect can no longer be expected to be as pronounced. A randomized, controlled trial comparing kyphoplasty to conservative management provided good evidence that cement augmentation is of benefit within the first year. Newer procedures for kyphoplasty are very promising, but their clinical significance still needs verification.

Clinical investigations of polymethylmethacrylate cement viscosity during vertebroplasty and related in vitro measurements.

Percutaneous vertebroplasty, comprising an injection of polymethylmethacrylate (PMMA) into vertebral bodies, is a practical procedure for the stabilization of osteoporotic compression fractures as well as other weakening lesions. Cement leakage is considered to be one of the major and most severe complications during percutaneous vertebroplasty. The viscosity of the material plays a key role in this context. In order to enhance the safety for the patient, a rheometer system was developed to measure the cement viscosity intraoperatively. For this development, it is of great importance to know the proper viscosity to start the procedure determined by experienced surgeons and the relation between the time period when different injection devices are used and the cement viscosity. The purpose of the study was to investigate the viscosity ranges for different injection systems during conventional vertebroplasty. Clinically observed viscosity values and related time periods showed high scattering. In order to get a better understanding of the clinical observations, cement viscosity during hardening at different ambient temperatures and by simulation of the body temperature was investigated in vitro. It could be concluded, that the direct viscosity assessment with a rheometer during vertebroplasty can help clinicians to define a lower threshold viscosity and thereby decrease the risk of leakage and make adjustments to their injection technique in real time. Secondly, the acceleration in hardening of PMMA-based cements at body temperature can be useful in minimizing leakages by addressing them with a short injection break.

Differences in endplate deformation of the adjacent and augmented vertebra following cement augmentation.

Vertebral cement augmentation can restore the stiffness and strength of a fractured vertebra and relieve chronic pain. Previous finite element analysis, biomechanical tests and clinical studies have indirectly associated new adjacent vertebral fractures following augmentation to altered loading. The aim of this repeated measures in situ biomechanical study was to determine the changes in the adjacent and augmented endplate deformation following cement augmentation of human cadaveric functional spine units (FSU) using micro-computed tomography (micro-CT). The surrounding soft tissue and posterior elements of 22 cadaveric human FSU were removed. FSU were assigned to two groups, control (n = 8) (loaded on day 1 and day 2) and augmented (n = 14) (loaded on day 1, augmented 20% cement fill, and loaded on day 2). The augmented group was further subdivided into a prophylactic augmentation group (n = 9), and vertebrae which spontaneously fractured during loading on day 1 (n = 5). The FSU were axially loaded (200, 1,000, 1,500-2,000 N) within a custom made radiolucent, saline filled loading device. At each loading step, FSUs were scanned using the micro-CT. Endplate heights were determined using custom software. No significant increase in endplate deformation following cement augmentation was noted for the adjacent endplate (P > 0.05). The deformation of the augmented endplate was significantly reduced following cement augmentation for both the prophylactic and fracture group (P < 0.05, P < 0.01, respectively). Endplate deformation of the controls showed no statistically significant differences between loading on day 1 and day 2. A linear relationship was noted between the applied compressive load and endplate deflection (R (2) = 0.58). Evidence of significant endplate deformation differences between unaugmented and augmented FSU, while evident for the augmented endplate, was not present for the adjacent endplate. This non-invasive micro-CT method may also be useful to investigate endplate failure, and parameters that predict vertebral failure.

[Cement injection for spinal metastases (vertebroplasty and kyphoplasty)]. / Zementaugmentation bei Wirbelmetastasen (Vertebro- und Kyphoplastie).

Osteolytic lesions of the spine (metastasis, myeloma) can be treated extremely efficiently by percutaneous cement injection. The treatment should be restricted to osteolytic lesions of the vertebral body, and only if a relevant mechanical deterioration is present. If the pedicles and/or the lamina are involved and if there is compression of the spinal canal, the treatment is no longer appropriate. The surgical technique is similar to the treatment of osteoporotic fractures; however, there is definitely a higher risk for cement leakage and the clinical outcome is not as predictable as in osteoporotic fracture treatment. It is important to realize that cement injection per se has no impact on the tumor itself, but provides stability to the vertebral body. An osteolytic lesion without mechanical compromise does not need a vertebroplasty. Patients with tumorous lesions of the spine should be followed by an interdisciplinary team of spine surgeon, oncologist and radio-oncologist.

Femoroplasty--augmentation of the proximal femur with a composite bone cement--feasibility, biomechanical properties and osteosynthesis potential.

BACKGROUND: Analogous to vertebroplasty, cement-augmentation of the proximal femur ("femoroplasty") could reinforce osteoporotic bones. This study was to evaluate (i) the feasibility of femoroplasty with a composite cement (Cortoss), (ii) its influence on femoral strength by mechanical testing and (iii) the feasibility of stable osteosynthesis of the augmented fractured bones. METHODS: Nine human cadaveric femora were augmented with a composite bone cement, the surface heat generation monitored, and then tested biomechanically against their native contralateral control to determine fracture strength. Subsequently, thirteen reinforced and fractured femora were osteosynthetized by different implants and tested against their osteosynthetisized, non-augmented contralateral control. FINDINGS: Cement could be injected easily, with a moderate temperature rise. A positive correlation between BMD and fracture load and a significant increase in fracture load (+43%) of the augmented femora compared to their native controls (6324 N and 4430 N, respectively) as well as a significant increase in energy-to-failure (+187%, 86 N m and 30 N m, respectively) was found. Osteosynthesis was possible in cement-augmented femora. Osteosynthetisized femora showed equivalent strength to the intact controls. INTERPRETATION: Augmentation of the proximal femur with composite bone cement could be of use in prophylaxis of fractures in osteoporotic femurs. Osteosynthesis of the fractured augmented bones is a challenging procedure but has a good chance to restore strength.

Theoretical and experimental model to describe the injection of a polymethylmethacrylate cement into a porous structure.

A theoretical approach was used to determine the distribution of a poly(methylmethacrylate) cement after its injection into a porous structure. The predictions of the model were then compared to experimental results obtained by injecting a polymethylmethacrylate cement into an open-porous ceramic filter. The goal was to define a model that could predict what factors affect the risk of cement extravasation and hence how the risk of cement extravasation can be minimized. The calculations were based on two important rheological laws: the law of Hagen-Poiseuille and the law of Darcy. The law of Hagen-Poiseuille describes the flow of a fluid in a cylindrical tube. The law of Darcy describes the flow of a fluid through a porous media. The model predicted that the extravasation risk was decreased when the cement viscosity, the bone pore size, the bone permeability and the bone porosity were increased, and when the diameter of the extravasation path and the viscosity of the marrow were decreased. Experimentally, the effect of the marrow viscosity and extravasation path could be evidenced. Therefore, the model was believed to be an adequate approximation of the experimental behavior. In conclusion, the experimental results demonstrated that the model was adequate and that the best practical way to decrease the risk of extravasation is to increase the cement viscosity.

Adjacent vertebral failure after vertebroplasty. A biomechanical investigation.

Vertebroplasty, which is the percutaneous injection of bone cement into vertebral bodies has recently been used to treat painful osteoporotic compression fractures. Early clinical results have been encouraging, but very little is known about the consequences of augmentation with cement for the adjacent, non-augmented level. We therefore measured the overall failure, strength and structural stiffness of paired osteoporotic two-vertebra functional spine units (FSUs). One FSU of each pair was augmented with polymethylmethacrylate bone cement in the caudal vertebra, while the other served as an untreated control. Compared with the controls, the ultimate failure load for FSUs treated by injection of cement was lower. The geometric mean treated/untreated ratio of failure load was 0.81, with 95% confidence limits from 0.70 to 0.92, (p < 0.01). There was no significant difference in overall FSU stiffness. For treated FSUs, there was a trend towards lower failure loads with increased filling with cement (r2 = 0.262, p = 0.13). The current practice of maximum filling with cement to restore the stiffness and strength of a vertebral body may provoke fractures in adjacent, non-augmented vertebrae. Further investigation is required to determine an optimal protocol for augmentation.

Injection biomechanics of bone cements used in vertebroplasty.

The incidence of osteoporotic bone fractures is growing exponentially as the western population ages and as life expectancy increases. Vertebroplasty, where acrylic or calcium phosphate cement is injected into the weakened vertebrae to augment them, is an emerging procedure for treating spinal fragility fractures. However, cement injection is currently limited because there are no clear standards for a safe, reproducible and predictable procedure. The purpose of this paper is to examine the role that bone cements play in the underlying bio-mechanisms that affect the outcomes of cement injection. Our most important finding after combining clinical, laboratory and theoretical research is that the process of cement injection poses conflicting demands on bone cements. The cements are required to be more viscous and less viscous at the same time. The challenge therefore is to develop biomaterials, techniques and/or devices that can overcome or manage the conflicting demands on cement viscosity.

[What must the family practitioner know about spinal injuries]. / Was muss der Hausarzt wissen über Wirbelsäulenverletzungen?

Spine injuries in a general practitioner's environment are mainly related to osteoporosis fractures in the elderly as well as cervical spine injuries in the elderly especially fractures of the odontoid process that need to be excluded if there is any suspicion. For osteoporotic spine fractures the invention of vertebroplasty offers a new treatment option and therefore patients should be transferred to a spine surgeon for further evaluation. The fracture of the odontoid process can end up in a non-union problem if not treated early; therefore this injury must be excluded in patients after sustaining any head contusion and complaints of neck pain afterwards.

[Percutaneous cementing techniques in treatment of osteoporotic spinal sintering]. / Perkutane Zementierungstechniken zur Behandlung osteoporotischer Wirbelkörpersinterungen.

During the last years minimal-invasive augmentation techniques of vertebral bodies have been established to stabilize painful height losses. A vertebroplasty fills the vertebral body with cement, whereas a kyphoplasty intends to achieve a reduction of kyphosis prior to cementing. The present review describes both techniques and summarizes in vivo and in vitro experiences.

Bone substitutes in vertebroplasty.

Vertebroplasty--percutaneous cement augmentation of vertebral bodies--is an efficient procedure for the treatment of painful vertebral fractures in osteoporosis. At the present time, polymethylmethacrylate (PMMA) is the only available cement with reports of clinical application and experience. The material is easy to handle, the radiopacity can be adapted by adding contrast dye, and it is mechanically efficient. Composite cements (acrylic cements in conjunction with ceramics) are bioactive, highly radiopaque, and feature excellent mechanical properties. One such cement, Cortoss, is currently undergoing clinical trials for vertebroplasty and has so far been shown to be a potentially valuable alternative to PMMA. Several in vitro studies with injectable calcium phosphate (CaP) cements show their feasibility and mechanical effectiveness. Animal studies confirm their biocompatibility and osteoconductivity. However, handling problems and the limited radiopacity of these cements currently preclude their clinical use.

[Vertebroplasty in severe osteoporosis. Technique and experience with multi-segment injection]. / Vertebroplastik bei hochgradiger Osteoporose. Technik und Erfahrung mit plurisegmentalen Injektionen.

In severe osteoporosis progressive collapse of multiple vertebrae is an unsolved problem. Medical treatment appears to be too slow to prevent the course. The evolving experience with vertebroplasty led us to treat these problems with more extensive cement injections. Of 362 patients who were treated with percutaneous cement injection over a 5-year period, 100 were injected at five and more levels (average 7.3, maximum 14). The surgical technique has been refined, allowing six levels to be injected monolaterally under local anesthesia. No more than six levels or 25-30 cc of cement should be injected per session. The outcome of the procedure is favorable in 84% of patients with a significant pain decrease (from 7.6 to 2.7 VAS). More impressive is the subjective report of the patients about better posture and increased force in their back, allowing them to become more active again. The radiological follow-up for 1 year shows a stable situation without further sintering of the reinforced vertebrae and maintained disc space in between these vertebrae. Vertebroplasty on multiple levels is efficient and can prevent further collapse. Due the risk of fat embolism the injections should be limited to six levels per session.

Percutaneous transpedicular vertebroplasty with PMMA: operative technique and early results. A prospective study for the treatment of osteoporotic compression fractures.

Vertebroplasty-percutaneous cement augmentation of osteoporotic vertebrae is an efficient procedure for the treatment of painful vertebral fractures. From a prospectively monitored series of 70 patients with 193 augmented vertebrae for osteoporotic and metastatic lesions, we analysed a group of 17 patients suffering from back pain due to osteoporotic fractures. The reinforcement of 45 vertebral bodies in these patients led to a significant and lasting pain reduction (P < 0.01 ). The presented technique is useful, as, in one session, at least four injections can be performed when required, allowing the prophylactic reinforcement of adjacent vertebrae as well. The use of a low-viscosity polymethyl methacrylate (PMMA) in combination with a non-ionic liquid contrast dye provides a reliable and safe procedure. Extraosseous cement leakage was seen in 20% of the interventions; however, none of them had clinical sequelae.

Load shift of the intervertebral disc after a vertebroplasty: a finite-element study.

Infiltrating osteoporotic cancellous bone with bone cement (vertebroplasty) is a novel surgical procedure to stabilize and prevent osteoporotic vertebral fractures. Short-term clinical and biomechanical results are encouraging; however, so far no reports on long-term results have been published. Our clinical observations suggest that vertebroplasty may induce subsequent fractures in the vertebrae adjacent to the ones augmented. At this point, there is only a limited understanding of what causes these fractures. We have previously hypothesized that adjacent fractures may result from a shift in stiffness and load following rigid augmentation. The purpose of this study is to determine the load shift in a lumbar motion segment following vertebroplasty. A finite-element (FE) model of a lumbar motion segment (L4-L5) was used to quantify and compare the pre- and post-augmentation stiffness and loading (load shift) of the intervertebral (IV) disc adjacent to the augmented vertebra in response to quasi-static compression. The results showed that the rigid cement augmentation underneath the endplates acted as an upright pillar that severely reduced the inward bulge of the endplates of the augmented vertebra. The bulge of the augmented endplate was reduced to 7% of its value before the augmentation, resulting in a stiffening of the IV joint by approximately 17%, and of the whole motion segment by approximately 11%. The IV pressure accordingly increased by approximately 19%, and the inward bulge of the endplate adjacent to the one augmented (L4 inferior) increased considerably, by approximately 17%. This increase of up to 17% in the inward bulge of the endplate adjacent to the one augmented may be the cause of the adjacent fractures.

Augmentation of mechanical properties in osteoporotic vertebral bones--a biomechanical investigation of vertebroplasty efficacy with different bone cements.

Recent clinical trials have reported favorable early results for transpedicular vertebral cement reinforcement of osteoporotic vertebral insufficiencies. There is, however, a lack of basic data on the application, safety and biomechanical efficacy of materials such as polymethyl-methacrylate (PMMA) and calciumphospate (CaP) cements. The present study analyzed 33 vertebral pairs from five human cadaver spines. Thirty-nine vertebrae were osteoporotic (bone mineral density < 0.75 g/cm2), 27 showed nearly normal values. The cranial vertebra of each pair was augmented with either PMMA (Palacos E-Flow) or experimental brushite cement (EBC), with the caudal vertebra as a control. PMMA and EBC were easy to inject, and vertebral fillings of 20-50% were achieved. The maximal possible filling was inversely correlated to the bone mineral density (BMD) values. Cement extrusion into the spinal canal was observed in 12% of cases. All specimens were subjected to axial compression tests in a displacement-controlled mode. From load-displacement curves, the stiffness, S, and the maximal force before failure, Fmax, were determined. Compared with the native control vertebrae, a statistically significant increase in vertebral stiffness and Fmax was observed by the augmentation. With PMMA the stiffness increased by 174% (P = 0.018) and Fmax by 195% (P = 0.001); the corresponding augmentation with EBC was 120% (P = 0.03) and 113% (P = 0.002). The lower the initial BMD, the more pronounced was the augmentation effect. Both PMMA and EBC augmentation reliably and significantly raised the stiffness and maximal tolerable force until failure in osteoporotic vertebral bodies. In non-porotic specimens, no significant increase was achieved.