Purpose Low back pain (LBP) is the most disabling condition worldwide. Although LBP relates to different spinal pathologies, vertebral bone marrow lesions visualized as Modic changes on MRI have a high specificity for discogenic LBP. This review summarizes the pathobiology of Modic changes and suggests a disease model. Methods Non-systematic literature review. Results Chemical and mechanical stimulation of nociceptors adjacent to damaged endplates are likely a source of pain. Modic changes are adjacent to a degenerated intervertebral disc and have three generally interconvertible types suggesting that the different Modic change types represent different stages of the same pathological process, which is characterized by inflammation, high bone turnover, and fibrosis. A disease model is suggested where disc/ endplate damage and the persistence of an inflammatory stimulus (i.e., occult discitis or autoimmune response against disc material) create predisposing conditions. The risk to develop Modic changes likely depends on the inflammatory potential of the disc and the capacity of the bone marrow to respond to it. Bone marrow lesions in osteoarthritic knee joints share many characteristics with Modic changes adjacent to degenerated discs and suggest that damage-associated molecular patterns and marrow fat metabolism are important pathogenetic factors. There is no consensus on the ideal therapy. Non-surgical treatment approaches including intradiscal steroid injections, anti-TNF-α antibody, antibiotics, and bisphosphonates have some demonstrated efficacy in mostly non-replicated clinical studies in reducing Modic changes in the short term, but with unknown long-term benefits. New diagnostic tools and animal models are required to improve painful Modic change identification and classification, and to clarify the pathogenesis. Conclusion Modic changes are likely to be more than just a coincidental imaging finding in LBP patients and rather represent an underlying pathology that should be a target for therapy.

A new musculoskeletal model for the lumbar spine is described in this paper. This model features a rigid pelvis and sacrum, the five lumbar vertebrae, and a rigid torso consisting of a lumped thoracic spine and ribcage. The motion of the individual lumbar vertebrae was defined as a fraction of the net lumbar movement about the three rotational degrees of freedom: flexion-extension lateral bending, and axial rotation. Additionally, the eight main muscle groups of the lumbar spine were incorporated using 238 muscle fascicles with prescriptions for the parameters in the Hill-type muscle models obtained with the help of an extensive literature survey. The features of the model include the abilities to predict joint reactions, muscle forces, and muscle activation patterns. To illustrate the capabilities of the model and validate its physiological similarity, the model's predictions for the moment arms of the muscles are shown for a range of flexion-extension motions of the lower back. The model uses the OpenSim platform and is freely available on https://www.simtk.org/home/lumbarspine to other spinal researchers interested in analyzing the kinematics of the spine. The model can also be integrated with existing OpenSim models to build more comprehensive models of the human body.

This study explores the use of mesenchymal stem cells (MSCs) for intervertebral disc regeneration. We used an in vivo model to investigate the feasibility of exogenous cell delivery, retention, and survival in the pressurized disc space. MSC injection into rat coccygeal discs was performed using 15% hyaluronan gel as a carrier. Injections of gel with or without MSCs were performed. Immediately after injection, fluorescently labeled stem cells were visible on sections of cell-injected discs. Seven and 14 days after injection, stem cells were still present within the disc, but their numbers were significantly decreased. At 28 days, a return to the initial number of injected cells was observed, and viability was 100%. A trend of increased disc height compared to blank gel suggests an increase in matrix synthesis. The results indicate that MSCs can maintain viability and proliferate within the rat intervertebral disc.

The results of this study demonstrate the feasibility of developing a quantitative correlation between spinal loading and disc degeneration. Such a correlation may be coupled in the future to existing engineering models that predict spinal loading in response to physical exposures and lead to improved definition of the bounds of healthy and unhealthy spinal loading, and ultimately, refined guidelines for low back safety.

End plates serve as the interface between rigid vertebral bodies and pliant intervertebral disks. Because the lumbar spine carries significant forces and disks don't have a dedicated blood supply, end plates must balance conflicting requirements of being strong to prevent vertebral fracture and porous to facilitate transport between disk cells and vertebral capillaries. Consequently, end plates are particularly susceptible to damage, which can increase communication between proinflammatory disk constituents and vascularized vertebral bone marrow. Damaged end plate regions can be sites of reactive bone marrow lesions that include proliferating nerves, which are susceptible to chemical sensitization and mechanical stimulation. Although several lines of evidence indicate that innervated end plate damage can be a source of chronic low back pain, its role in patients is likely underappreciated because innervated damage is poorly visualized with diagnostic imaging. This literature review summarizes end plate biophysical function and aspects of pathologic degeneration that can lead to vertebrogenic pain. Areas of future research are identified in the context of unmet clinical needs for patients with chronic low back pain.

The rates of fracture at sites with different relative amounts of cortical and trabecular bone (hip, spine, distal radius) have been used to make inferences about the pathomechanics of bone loss and the existence of type I and type II osteoporosis. However, fracture risk is directly related to the ratio of tissue stress to tissue strength, which in turn is dependent not only on tissue composition but also tissue geometry and the direction and magnitude of loading. These three elements determine how the load is distributed within the tissue. As a result, assumptions on the relative structural importance of cortical and trabecular bone, and how these tissues are affected by bone loss, can be inaccurate if based on regional tissue composition and bone density alone. To investigate the structural significance of cortical and trabecular bone in the proximal femur, and how it is affected by bone loss, we determined the stress distributions in a normal and osteoporotic femur resulting from loadings representing: (1) gait; and (2) a fall to the side with impact onto the greater trochanter. A three-dimensional finite element model was generated based on a representative femur selected from a large database of femoral geometries. Stresses were analyzed throughout the femoral neck and intertrochanteric regions. We found that the percentage of total load supported by cortical and trabecular bone was approximately constant for all load cases but differed depending on location. Cortical bone carried 30% of the load at the subcapital region, 50% at the mid-neck, 96% at the base of the neck and 80% at the intertrochanteric region. These values differ from the widely held assumption that cortical bone carries 75% of the load in the femoral neck and 50% of the load at the intertrochanteric region. During gait, the principal stresses were concentrated within the primary compressive system of trabeculae and in the cortical bone of the intertrochanteric region. In contrast, during a fall, the trabecular stresses were concentrated within the primary tensile system of trabeculae with a peak magnitude 4.3 times that present during gait. While the distribution of stress for the osteoporotic femur was similar to the normal, the magnitude of peak stress was increased by between 33% and 45%. These data call into question several assumptions which serve as the basis for theories on the pathomechanics of osteoporosis. In addition, we expect that the insight provided by this analysis will result in the improved development and interpretation of non-invasive techniques for the quantification of in vivo hip fracture risk.

Tenascin-X is a large extracellular matrix protein of unknown function. Tenascin-X deficiency in humans is associated with Ehlers-Danlos syndrome, a generalized connective tissue disorder resulting from altered metabolism of the fibrillar collagens. Because TNXB is the first Ehlers-Danlos syndrome gene that does not encode a fibrillar collagen or collagen-modifying enzyme, we suggested that tenascin-X might regulate collagen synthesis or deposition. To test this hypothesis, we inactivated Tnxb in mice. Tnxb-/- mice showed progressive skin hyperextensibility, similar to individuals with Ehlers-Danlos syndrome. Biomechanical testing confirmed increased deformability and reduced tensile strength of their skin. The skin of Tnxb-/- mice was histologically normal, but its collagen content was significantly reduced. At the ultrastructural level, collagen fibrils of Tnxb-/- mice were of normal size and shape, but the density of fibrils in their skin was reduced, commensurate with the reduction in collagen content. Studies of cultured dermal fibroblasts showed that although synthesis of collagen I by Tnxb-/- and wildtype cells was similar, Tnxb-/- fibroblasts failed to deposit collagen I into cell-associated matrix. This study confirms a causative role for TNXB in human Ehlers-Danlos syndrome and suggests that tenascin-X is an essential regulator of collagen deposition by dermal fibroblasts.

Anular fibrochondrocytes in degenerated discs are responsive to some growth factors in vivo. The results have implications in the early intervention of disc degeneration to arrest or slow the degenerative process.