Mechanical initiation of intervertebral disc degeneration

STUDY DESIGN: Mechanical testing of cadaveric lumbar motion segments. OBJECTIVES: To test the hypothesis that minor damage to a vertebral body can lead to progressive disruption of the adjacent intervertebral disc. SUMMARY OF BACKGROUND DATA: Disc degeneration involves gross structural disruption as well as cell-mediated changes in matrix composition, but there is little evidence concerning which comes first. Comparatively minor damage to a vertebral body is known to decompress the adjacent discs, and this may adversely affect both structure and cell function in the disc. METHODS: In this study, 38 cadaveric lumbar motion segments (mean age, 51 years) were subjected to complex mechanical loading to simulate typical activities in vivo while the distribution of compressive stress in the disc matrix was measured using a pressure transducer mounted in a needle 1.3 mm in diameter. "Stress profiles" were repeated after a controlled compressive overload injury had reduced motion segment height by approximately 1%. Moderate repetitive loading, appropriate for the simulation of light manual labor, then was applied to the damaged specimens for approximately 4 hours, and stress profilometry was repeated a third time. Discs then were sectioned and photographed. RESULTS: Endplate damage reduced pressure in the adjacent nucleus pulposus by 25% +/- 27% and generated peaks of compressive stress in the anulus, usually posteriorly to the nucleus. Discs 50 to 70 years of age were affected the most. Repetitive loading further decompressed the nucleus and intensified stress concentrations in the anulus, especially in simulated lordotic postures. Sagittal plane sections of 15 of the discs showed an inwardly collapsing anulus in 9 discs, extreme outward bulging of the anulus in 11 discs, and complete radial fissures in 2 discs, 1 of which allowed posterior migration of nucleus pulposus. Comparisons with the results from tissue culture experiments indicated that the observed changes in matrix compressive stress would inhibit disc cell metabolism throughout the disc, and could lead to progressive deterioration of the matrix. CONCLUSIONS: Minor damage to a vertebral body endplate leads to progressive structural changes in the adjacent intervertebral discs.     

Intervertebral disc cell death is dependent on the magnitude and duration of spinal loading

STUDY DESIGN: An in vivo study of the toxic consequences of static compressive stress on the intervertebral disc. OBJECTIVES: To determine whether disc cell death is correlated with the magnitude and duration of spinal compressive loading. SUMMARY OF BACKGROUND DATA: Static compression in vivo has been demonstrated to induce cell death. Cell death, in turn, has been associated with disc degeneration in humans. There are currently no tolerance criteria for the intervertebral disc that combine both biomechanical and biologic factors, although both have been implicated in cases of accelerated degeneration. METHODS: Mouse tail discs were loaded in vivo with an external compression device. Compressive stress was applied at one of two magnitudes (0.4 and 0.8 MPa) for 7 days, and at one additional magnitude (1.3 MPa) for 1, 3, and 7 days. Midsagittal sections of the discs were stained for apoptosis using the TdT-dUTP terminal nick-end labeling (TUNEL) reaction. Quantal analysis was used to correlate the extent of cell death to the magnitude and duration of loading. RESULTS: The probit transformation of the percentage of dying cells was proportional to the sum of the logarithmic transformations of the compressive stress and the time of loading. CONCLUSIONS: 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.     

The effect of static in vivo bending on the murine intervertebral disc.

BACKGROUND CONTEXT: Intervertebral disc cell function in vitro has been linked to features of the local environment that can be related to deformation of the extracellular matrix. Epidemiologic data suggest that certain regimens of spinal loading accelerate disc degeneration in vivo. Yet, the direct association between disc cell function, spinal loading and ultimately tissue degeneration is poorly characterized. PURPOSE: To examine the relationships between tensile and compressive matrix strains, cell activity and annular degradation. STUDY DESIGN/SETTING: An in vivo study of the biologic, morphologic and biomechanical consequences of static bending applied to the murine intervertebral disc. SUBJECT SAMPLE: Twenty-five skeletally mature Swiss Webster mice (12-week-old males) were used in this study. OUTCOME MEASURES: Bending neutral zone, bending stiffness, yield point in bending, number of apoptotic cells, annular matrix organization, cell shape, aggrecan gene expression, and collagen II gene expression.METHODS: Mouse tail discs were loaded for 1 week in vivo with an external device that applied bending stresses. Mid-sagittal sections of the discs were analyzed for cell death, collagen II and aggrecan gene expression, and tissue organization. Biomechanical testing was also performed to measure the bending stiffness and strength. RESULTS: Forceful disc bending induced increased cell death, decreased aggrecan gene expression and decreased tissue organization preferentially on the concave side. By contrast, collagen II gene expression was symmetrically reduced. Asymmetric loading did not alter bending mechanical behavior of the discs. CONCLUSIONS: In this model, annular cell death was related to excessive matrix compression (as opposed to tension). Collagen II gene expression was most negatively influenced by the static nature of the loading (immobilization), rather than the specific state of stress (tension or compression).     

颈脊柱姿势及预负荷史对压缩强度影响的生物力学研究

目的研究颈脊柱姿势及预负荷对颈脊柱压缩强度的影响。方法选用12具成人健康新鲜尸体颈段脊柱,解剖出C3,4、C5,6共24个运动单位(包括上下两个椎体和椎间盘)。施以压缩负荷,观察两种预负荷状态(脱水和高度水化状态)和两种姿势(中立位和屈曲位)下,颈段脊柱的极限压缩强度。通过解剖和x线检查来明确颈椎的损伤。结果标本屈曲位时极限压缩强度比中立位时小(P<0001),在中立位损伤负荷下,高度水化状态标本的极限压缩强度比脱水状态标本低29%(P<001)。结论晨起椎间盘高度水化状态下以及颈脊柱屈曲位时,受到外伤负荷颈脊柱更易损伤。     

Intervertebral disc degeneration can predispose to anterior vertebral fractures in the thoracolumbar spine.

Mechanical experiments on cadaveric thoracolumbar spine specimens showed that intervertebral disc degeneration was associated with reduced loading of the anterior vertebral body in upright postures. Reduced load bearing corresponded to locally reduced BMD and inferior trabecular architecture as measured by histomorphometry. Flexed postures concentrated loading on the weakened anterior vertebral body, leading to compressive failure at reduced load. INTRODUCTION: Osteoporotic fractures are usually attributed to age-related hormonal changes and inactivity. However, why should the anterior vertebral body be affected so often? We hypothesized that degenerative changes in the adjacent intervertebral discs can alter load bearing by the anterior vertebral body in a manner that makes it vulnerable to fracture. MATERIALS AND METHODS: Forty-one thoracolumbar spine "motion segments" (two vertebrae and the intervertebral disc) were obtained from cadavers 62-94 years of age. Specimens were loaded to simulate upright standing and flexed postures. A pressure transducer was used to measure the distribution of compressive "stress" inside the disc, and stress data were used to calculate how compressive loading was distributed between the anterior and posterior halves of the vertebral body and the neural arch. The compressive strength of each specimen was measured in flexed posture. Regional volumetric BMD and histomorphometric parameters were measured. RESULTS: In the upright posture, compressive load bearing by the neural arch increased with disc degeneration, averaging 63 +/- 22% (SD) of applied load in specimens with severely degenerated discs. In these specimens, the anterior half of the vertebral body resisted only 10 +/- 8%. The anterior third of the vertebral body had a 20% lower trabecular volume fraction, 16% fewer trabeculae, and 28% greater intertrabecular spacing compared with the posterior third (p < 0.001). In the flexed posture, flexion transferred 53-59% of compressive load bearing to the anterior half of the vertebral body, regardless of disc degeneration. Compressive strength measured in this posture was proportional to BMD in the anterior vertebral body (r2 = 0.51, p < 0.001) and inversely proportional to neural arch load bearing in the upright posture (r2 = 0.28, p < 0.001). CONCLUSIONS: Disc degeneration transfers compressive load bearing from the anterior vertebral body to the neural arch in upright postures, reducing BMD and trabecular architecture anteriorly. This predisposes to anterior fracture when the spine is flexed.     

Low-intensity vibrations partially maintain intervertebral disc mechanics and spinal muscle area during deconditioning

Background contextReduced spinal loading degrades the intervertebral disc and alters the muscle size.PurposeTo determine the ability of high-frequency and low-intensity vibrations to maintain disc biomechanics and prevent muscle changes during hindlimb unloading.Study designThree groups of Sprague-Dawley rats were hindlimb unloaded for 4 weeks. In two hindlimb unloaded groups, unloading was interrupted for 15 min/d and the rats were positioned upright on a 90 Hz vertically oscillating plate or a sham control inactive plate. One author owns (provisional) patents regarding the application of vibrations to the musculoskeleton.MethodsThe motion segments L4–L5 were mechanically evaluated in compression-tension, axial creep, and torsion loading. In vivo microcomputed tomography was used to determine longitudinal psoas and paraspinal muscle area. This work was supported by National Institutes of Health, National Aeronautics and Space Administration (NASA), Alliance for Graduate Education and the Professoriate, and NASA-Harriett G. Jenkins Predoctoral and W. Burghardt Turner Fellowships. The author (SJ) holds (provisional) patents regarding the application of vibrations.ResultsThere were no differences between the discs of uninterrupted unloading and sham animals and these groups were pooled. Compared with normally ambulating age-matched controls, hindlimb unloaded discs had altered properties in every loading modality. Psoas area of the unloaded rats increased at L4 and L5 and the paraspinal area decreased at L4. Vibrations (90 Hz) maintained compression-tension properties, partially maintained creep properties, but did not mitigate torsional weakening because of unloading. Low-intensity vibrations prevented the increase in psoas area but did not abate paraspinal muscle loss.ConclusionsIn support of clinical studies, unloading deconditioned the rodent disc and altered the muscle area. Although brief exposures to upright posture provided only limited benefits, low-intensity vibrations superimposed on upright posture served to preserve disc mechanics during unloading.     

Stress in lumbar intervertebral discs during distraction: a cadaveric study

Background contextThe intervertebral disc is a common source of low back pain (LBP). Prospective studies suggest that treatments that intermittently distract the disc might be beneficial for chronic LBP. Although the potential exists for distraction therapies to affect the disc biomechanically, their effect on intradiscal stress is debated.PurposeTo determine if distraction alone, distraction combined with flexion, or distraction combined with extension can reduce nucleus pulposus pressure and posterior annulus compressive stress in cadaveric lumbar discs compared with simulated standing or lying.Study designLaboratory study using single cadaveric motion segments.Outcome measuresStrain gauge measures of nucleus pulposus pressure and compressive stress in the anterior and posterior annulus fibrosus.MethodsIntradiscal stress profilometry was performed on 15 motion segments during 5 simulated conditions: standing, lying, and 3 distracted conditions. Disc degeneration was graded by inspection from 1 (normal) to 4 (severe degeneration).ResultsAll distraction conditions markedly reduced nucleus pressure compared with either simulated standing or lying. There was no difference between distraction with flexion and distraction with extension in regard to posterior annulus compressive stress. Discs with little or no degeneration appeared to distribute compressive stress differently than those with moderate or severe degeneration.ConclusionsDistraction appears to predictably reduce nucleus pulposus pressure. The effect of distraction therapy on the distribution of compressive stress may be dependent in part on the health of the disc.     

The internal mechanical properties of cervical intervertebral discs as revealed by stress profilometry

Extensive anatomical differences suggest that cervical and lumbar discs may have functional differences also. We investigated human cervical discs using “stress profilometry”. Forty-six cadaveric cervical motion segments aged 48-90 years were subjected to a compressive load of 200 N for 20 s, while compressive ‘stress’ was recorded along the posterior-anterior midline of the disc using a pressure transducer, side-mounted in a 0.9 mm diameter needle. Stress profiles were repeated with the transducer orientated horizontally and vertically, and with the specimen in neutral, flexed and extended postures. Profiles were repeated again following creep loading (150 N, 2 h) which simulated diurnal water loss in vivo. Stress profiles were reproducible, and measured “stress” at each location was proportional to applied load. Stress profiles usually showed a hydrostatic nucleus with regions of higher compressive stress concentrated anteriorly in flexion, and posteriorly in extension. Stress concentrations increased in degenerated discs and following creep. Some features were unique to cervical discs: many showed a stress gradient across their central regions, even though vertical and horizontal stresses were equal to each other, and stress concentrations in the posterior annulus were generally small. Central regions of many cervical discs show the characteristics of a “tethered fluid” which can equalise stress over small distances, but not large. This may be attributable to their fibrous texture. The small radial diameter of the cervical posterior annulus may facilitate buckling and thereby prevent it from sustaining high compressive stresses.     

A mechanochemical hypothesis for bone remodeling induced by mechanical stress

A new mechanism is presented to explain how increased or decreased mechanical stresses applied to bone are translated into osteoblastic and/or osteoclastic activity. A mechano-chemical hypothesis for bone remodeling induced by mechanical stress is presented in an attempt to explain this phenomenon. Bone responds to mechanical stress by differential growth so as to resist the applied stress; therefore mechanically induced bone remodeling is probably regulated by a negative feedback system. The hypothesis is that a change in the loading of bone results in an altered straining of the hydroxyapatite crystals in bone. This in turn alters the solubility of the crystals, providing the required negative feedback message to the bone cells in the form of a mechanically induced chemical change. The cells then take appropriate action to compensate for the alteration in the localized calcium activity either by building up bone to redistribute an increased stress, or by removing bone which is surplus to the structural needs imposed by a reduced stress. In order to test the hypothesis, synthetic hydroxyapatite crystals were stressed and changes in calcium ion activity were recorded from a divalent cation activity electrode. The results show that a mechanochemical effect can be detected in hydroxyapatite crystals which, when stressed, generate a calcium activity of 9×10^?5 moles/l compared to 7×10^?5 moles/l when unstressed. The experimental results in this study and evidence from cellular physiology are consistent with the mechanochemical hypothesis proposed here.     

Variables affecting disc size in the lumbar spine of rabbits: anesthesia, paralysis, and disc injury

Methods have been developed that permit repetitive radiographic measurement of the lumbar intervertebral disc space in a rostral-caudal direction (width) in the anesthetized laboratory rabbit. Using isolated control discs and injured discs in which narrowing has been induced for chronic and acute periods, the widths of the lumbar intervertebral disc spaces determined ratio-graphically correlate with widths determined histologically (p less than 0.000, r = 0.75). Both an increase (widening) and a decrease (narrowing) in disc width were observed using radiography after different experimental treatments. Anesthesia and lower-body paralysis (an experimentally induced inability to bear weight on and to perceive a pinch stimulus in hind limbs) caused widening of the discs: anesthesia causing a general widening throughout the lumbar spine and lower-body paralysis causing a specific widening low in the lumbar spine. Both disc injection and piercing the disc with needles to recover nucleus pulposus material caused narrowing of the discs. Acridine-orange injection induced a narrowing accompanied by osteophytosis. Experimentally induced narrowing at L4-5 (the result of injury to the disc) resulted in narrowing also at L2-3. These findings are consistent with the hypothesis that in vivo disc-width size in the young rabbit depends on both the quantity of nucleus pulposus material and the force-generating activities of the adjacent spinal muscles, and that disc injury at one level stimulates narrowing at other levels.     

Abnormal stress concentrations in lumbar intervertebral discs following damage to the vertebral bodies: a cause of disc failure?

Summary The purpose of this investigation was to test the hypothesis that damage to a lumbar vertebral body can lead to abnormal stress concentrations in the adjacent intervertebral discs. Twenty-three cadaveric lumbar motion segments, from persons who had died aged between 19 and 87 years, were subjected to substantial compressive loading while in the neutral, lordotic and flexed postures. During the loading period, a miniature pressure transducer was pulled through the disc along its mid-sagittal diameter and graphs of horizontal and vertical compressive stress against distance were obtained. Measurements were repeated after each motion segment had been compressed up to the point of mechanical failure: at this point the vertebral bodies suffered minor damage to the trabecular arcades, and sometimes to the end-plate, but the structure remained essentially intact and motion segment height was reduced by only 1%–2%. After damage, the stress in the nucleus and anterior annulus fell by about 30%, and high stress peaks appeared in the inner posterior annulus. These changes were more pronounced in lordotic posture and less pronounced in flexion. The youngest discs showed the smallest changes. It is concluded that minor compressive damage to the vertebral body can lead to high stress concentrations in the posterior annulus. Since the vertebral body is the weak link of the lumbar spine, this may be a frequent precipitating cause of isolated disc failure in living people.AcroMed Prize of the European Spine Society 1992     

Characterization of Bone Cements

Thirty-seven patients with fractures of the thoracic and lumbar spine treated with Harrington instrumentation were reviewed. Twenty-seven patients with a follow-up time of more than 2 years were summoned for a clinical and radiographic examination. This report presents the results related to reduction, stabilization, return of neural function, spinal posture and mobility, and residual disability. It is concluded that Harrington instrumentation can be performed without a substantial number of complications. Its major advantages are early mobilization and ambulation. The operative technique is discussed with special reference to the preservation of the normal configuration of the back. The value of computerized tomography in the preoperative assessment is stressed.     

Harrington instrumentation for thoracic and lumbar vertebral fractures

Thirty-seven patients with fractures of the thoracic and lumbar spine treated with Harrington instrumentation were reviewed. Twenty-seven patients with a follow-up time of more than 2 years were summoned for a clinical and radiographic examination. This report presents the results related to reduction, stabilization, return of neural function, spinal posture and mobility, and residual disability. It is concluded that Harrington instrumentation can be performed without a substantial number of complications. Its major advantages are early mobilization and ambulation. The operative technique is discussed with special reference to the preservation of the normal configuration of the back. The value of computerized tomography in the preoperative assessment is stressed.     

Peak stresses observed in the posterior lateral anulus

STUDY DESIGN: The stress distributions within cadaveric lumbar intervertebral discs were measured for a range of loading conditions. OBJECTIVES: To examine the distribution of stress across the area of the intervertebral disc and to compare regional variations in peak stress during compression loading with various flexion angles. SUMMARY OF BACKGROUND DATA: The rate of disc degeneration and the occurrence of low back disorders increase with higher mechanical loading of the spine. The largest peak stresses occur in the anulus. METHODS: Human lumbar L2--L3 and L4--L5 cadaver functional spinal units were obtained and tested. The distribution of disc stress was measured using a pressure probe with loads applied, pure compression and compression with 5 degrees of either flexion or extension. RESULTS: Stress profiles were recorded across the intervertebral disc at a compressive force of 1000 N and each of the three flexion-extension angles. The highest values (2.99 +/- 1.31 MPa) were measured during extension-compression lateral to the midline of the disc in the posterior anulus. The pressure in the nucleus was relatively unchanged by flexion angle remaining about 1.00 MPa for a 1000-N compression. CONCLUSIONS: Pressure measurements of the cadaveric nucleus have been used to validate models of lumbar spine loading and to evaluate the risk of low back injury and disc herniation. Previous observations limited to midsagittal measurements of the nucleus did not identify the regions of highest stress. The highest values observed here within the posterolateral anulus correspond to common sites of disc degeneration and herniation.     

Olfactory stem cells can be induced to express chondrogenic phenotype in a rat intervertebral disc injury model

BackgroundIn humans, lower back pain is one of the most common causes of morbidity. Many studies implicate degeneration of intervertebral discs as the cause. In the normal intervertebral disc, the nucleus pulposus exerts a hydrostatic pressure against the constraining annulus fibrosus, which allows the disc to maintain flexibility between adjacent vertebrae, while absorbing necessary compressive forces. The nucleus pulposus performs this role because of its hydrophilic gel-like structure. The extracellular matrix of the nucleus pulposus is up to 80% hydrated, as a result of large amounts of the aggregating proteoglycan, chondroitin sulfate proteoglycan (CSPG). This proteoglycan is enmeshed in a randomly orientated network of fine collagen Type II (CT2) fibers.Study design and purposeA useful adult tissue-derived stem cell is that from the olfactory mucosa, the organ of smell. These cells, accessible in humans from nasal biopsies, are multipotent and are able to make many cell types from all germ layers. They are easily grown in vitro and can be expanded to large numbers and stored frozen. These qualities indicate the potential for autologous transplantation for disc repair. In this article, using a rat model, we explore the hypothesis that olfactory stem cells can differentiate into a nucleus pulposus chondrocyte phenotype in vitro, as well as in vivo after transplantation into the injured intervertebral disc.Patient sampleFemale rats (14 weeks) were anesthetized with xylazine/ketamine. The abdominal wall was shaved and injected with local anesthetic (lidocaine) before incision. The ventral part of the lumbar spine, including two intervertebral discs, was exposed. Disc degeneration was then induced in the two exposed discs by needle aspiration of the nucleus pulposus. The prominent spina iliaca posterior superior was used as an anatomical landmark for identification of the first disc. Two weeks later, one injured intervertebral disc was exposed in a second, similar, surgery and 20,000 olfactory neurosphere-derived cells were transplanted with a 25-G needle.Outcome measuresIn vitro induction of nucleus pulposus chondrocyte phenotype is measured by the percentage of cells expressing CT2 and CSPG. In vivo, a successful outcome is evidence of engraftment of donor-derived cells and their expression of CT2 and CSPG.MethodsIn this article, we tested two hypotheses: the first that progenitor cells within olfactory neurospheres could be induced to express markers distinctive of the nucleus pulposus when placed in vitro in a coculture experiment. The second hypothesis tested the same induction in genetically labeled transplanted cells within damaged vertebral discs in vivo. The two markers measured are those held by current literature to engender the necessary cushioning characteristics of nucleus pulposus, CT2 and CSPG.ResultsOur experiments demonstrated virtually 100% induction of these two markers in vitro. Also, this induction was achieved in donor-derived cells after delivery to the nucleus pulposus region of animals whose discs had previously been lesioned 2 weeks before transplant.ConclusionsThese results provide a rationale for moving toward more extensive larger animal studies for assessment of regeneration before human trials where relief of symptoms can be more easily assessed.     

Analysis and simulation of progressive adolescent scoliosis by biomechanical growth modulation

Scoliosis is thought to progress during growth because spinal deformity produces asymmetrical spinal loading, generating asymmetrical growth, etc. in a ‘vicious cycle.’ The aim of this study was to test quantitatively whether calculated loading asymmetry of a spine with scoliosis, together with measured bone growth sensitivity to altered compression, can explain the observed rate of scoliosis progression in the coronal plane during adolescent growth. The simulated spinal geometry represented a lumbar scoliosis of different initial magnitudes, averaged and scaled from measurements of 15 patients’ radiographs. Level-specific stresses acting on the vertebrae were estimated for each of 11 external loading directions (‘efforts’) from published values of spinal loading asymmetry. These calculations assumed a physiologically plausible muscle activation strategy. The rate of vertebral growth was obtained from published reports of growth of the spine. The distribution of growth across vertebrae was modulated according to published values of growth sensitivity to stress. Mechanically modulated growth of a spine having an initial 13° Cobb scoliosis at age 11 with the spine subjected to an unweighted combination of eleven loading conditions (different effort direction and magnitude) was predicted to progress during growth. The overall shape of the curve was retained. The averaged final lumbar spinal curve magnitude was 32° Cobb at age 16 years for the lower magnitude of effort (that produced compressive stress averaging 0.48 MPa at the curve apex) and it was 38° Cobb when the higher magnitudes of efforts (that produced compressive stress averaging 0.81 MPa at the apex). An initial curve of 26° progressed to 46° and 56°, respectively. The calculated stresses on growth plates were within the range of those measured by intradiscal pressures in typical daily activities. These analyses predicted that a substantial component of scoliosis progression during growth is biomechanically mediated. The rationale for conservative management of scoliosis during skeletal growth assumes a biomechanical mode of deformity progression (Hueter-Volkmann principle). The present study provides a quantitative basis for this previously qualitative hypothesis. The findings suggest that an important difference between progressive and non-progressive scoliosis might lie in the differing muscle activation strategies adopted by individuals, leading to the possibility of improved prognosis and conservative or less invasive interventions.     

Sudden and unexpected loading generates high forces on the lumbar spine

STUDY DESIGN: A cross-sectional study of spinal loading in healthy volunteers. OBJECTIVES: To measure the bending and compressive forces acting on the lumbar spine, in a range of postures, when unknown loads are delivered unexpectedly to the hands. SUMMARY OF BACKGROUND DATA: Epidemiologic studies suggest that sudden and unexpected loading events often lead to back injuries. Such incidents have been shown to increase back muscle activity, but their effects on the compressive force and bending moment acting on the spine have not been fully quantified. Furthermore, previous investigations have focused on the upright posture only. METHODS: In this study, 12 volunteers each stood on a force plate while weights of 0, 2, 4, and 6 kg (for men, 40% less for women) were delivered into their hands in one of three ways: 1) by the volunteer holding an empty box with handles, into which an unknown weight was dropped; 2) by the same way as in 1, but with volunteer wearing a blindfold and earphones to eliminate sensory cues; or 3) by the volunteer sliding a box of unknown weight off a smooth table. Experiments were carried out with participants standing in upright, partially flexed, and moderately flexed postures. Spinal compression resulting from muscular activity was quantified using electromyographic signals recorded from the back and abdominal muscles. The axial inertial force acting up the long axis of the spine was calculated from the vertical ground reaction force. The bending moment acting on the osteoligamentous spine was quantified by comparing measurements of lumbar curvature with the bending stiffness properties of cadaveric lumbar spines. RESULTS: The contribution from abdominal muscle contraction to overall spinal compression was small (average, 8%), as was the axial inertial force (average, 2.5%), and both were highest in the upright posture. Peak bending moments were higher in flexed postures, but did not increase much at the moment of load delivery in any posture. Peak spinal compressive forces were increased by 30% to 70% when loads were suddenly and unexpectedly dropped into the box, and by 20% to 30% when they were slid off the table, as compared with loads simply held statically in the same posture (P < 0.001). The removal of audiovisual cues had little effect. CONCLUSIONS: Sudden and alarming events associated with manual handling cause a reflex overreaction of the back muscles, which substantially increases spine compressive loading. Manual handling regulations should aim to prevent such events and limit the weight of objects to be lifted.     

Alterations of ADAMTSs and TIMP‐3 in human nucleus pulposus cells subjected to compressive load: Implications in the pathogenesis of human intervertebral disc degeneration

Intervertebral disc degeneration (IDD) pertains to the loss of extracellular matrix (ECM), particularly the early loss of aggrecan, the turnover of which is regulated by ADAMTSs. Amongst the etiological factors of IDD, mechanical stress plays an important role in the physiological and pathological processes of nucleus pulposus (NP) cells. However, the role of ADAMTSs and their inhibitor in human NP cells under mechanical stress has not been elucidated to date. The purpose of this study was to investigate the role of ADAMTSs and TIMP‐3 in NP cells under mechanical stress. Human NP cells isolated from non‐degenerative and degenerative discs were subjected to dynamic compressive load. The expression of ADAMTSs, aggrecan, and TIMP‐3 was detected by quantitative real‐time PCR and/or Western blot. Consequently, the gene expression of ADAMTS‐1, 4, and 5 increased significantly in loaded NP cells compared with not‐loaded cells from either non‐degenerative or degenerative discs, whereas the gene expression of aggrecan decreased significantly. Moreover, Western blot indicated increased protein levels of ADAMTSs‐1, 4, and 5. However, the expression of TIMP‐3 altered insignificantly. Together, this study is the first addressing the underlying mechanisms of compressive load as a contributing factor to IDD in terms of ADAMTSs. Our results suggest that compressive load leads to the increase in ADAMTS‐1, 4, and 5 that contributes to the decrease of aggrecan and IDD via TIMP‐3 independent machinery. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:267–273, 2012     

Biological and mechanical consequences of transient intervertebral disc bending

Degenerative mechanisms for the intervertebral disc are unclear, particularly those associated with cumulative trauma. This research focuses on how mechanical loading at levels below those known to cause acute trauma can lead to cellular injury. Mouse-tail discs were subjected to static bending for 1 week, then allowed to recover unloaded for 3 weeks and 3 months. Discs were analyzed using histology, in situ hybridization (collagen and aggrecan gene expression), TUNEL assay for apoptotic cell death, and biomechanics. The bent discs demonstrated loss of annular cellularity on the concave (compressed) side, while the nucleus and convex annulus appeared normal. Chondrocyte-like cells were apparent within the inner, concave annulus on the recovered discs, with evidence of proliferation at the annulus/endplate interface. However, annular architecture and biomechanical properties for the recovered discs were not different from controls, suggesting that restoration of physiologic tissue stress prevents the inner annular degradation noted in previous compression-induced degeneration models. These data demonstrate that cellular injury can be induced by transient compressive stress, and that recellularization is slow in this avascular tissue. Taken together, this suggests that cellular damage accumulation may be an important injury mechanism that is distinct from acute mechanical failure.