Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.

Introduction: Endplate fractures are clinically important. They are very common, are associated with an increased risk of back pain, and can probably lead on to intervertebral disc degeneration. However, such fractures tend to damage the cranial endplate much more often than the caudal. In this study, we test the hypothesis that the vulnerability of cranial endplates arises from an underlying structural asymmetry in cortical and cancellous bone.

Methods: Sixty-two “motion segments” (two vertebrae and the intervening disc and ligaments) were obtained post-mortem from human spines aged 48–92 yrs. All levels were represented, from T8–9 to L4–L5. Specimens were compressed to failure while positioned in 2–6o of flexion, and the resulting damage characterised from radiographs and at dissection. 2mm-thick slices of 94 vertebral bodies (at least one from each motion segment) were cut in the mid-sagittal plane, and in a para-sagittal plane through the pedicles. Microradiographs of the slices were subjected to image analysis to determine the thickness of each endplate at 10 locations, and to measure the optical density of the endplates and adjacent trabecular bone. Comparisons between measurements obtained in cranial and caudal regions, and in mid-sagittal and pedicle slices, were made using repeated measures ANOVA, with age, level and gender as between-subject factors. Linear regression was used to determine significant predictors of compressive strength (yield stress).

Results: Fracture affected the cranial endplate in 55 specimens and caudal endplate in 2 specimens. Endplate thickness was low centrally and higher towards the periphery. Cranial endplates were thinner than caudal, by 14% and 11% in mid-sagittal and pedicle slices respectively (p=0.003). Differences were greater in central and posterior regions. Cranial endplates were supported by trabecular bone with 6% less optical density (p=0.004) with this difference also being greatest posteriorly. Caudal but not cranial endplates were thicker at lower spinal levels (p=0.01). Vertebral yield stress (mean 2.21 MPa, SD 0.78 MPa) was best predicted by the density of trabecular bone underlying the cranial endplate in the mid-sagittal slices of the fractured vertebral bodies (r2 = 0.67, p=0.0006).

Conclusions: When vertebrae are compressed by adjacent discs, cranial endplates usually fail before caudal endplates because they are thinner and supported by less dense trabecular bone. These asymmetries in vertebral structure may be explained by the location of back muscle attachments to vertebrae, and by the nutritional requirements of adjacent intervertebral discs.

Introduction: When the spine is subjected to compressive loading in-vivo and ex-vivo, there appears to be a predisposition for the cranial endplates to fracture before the caudal. We hypothesise that this fracture pattern arises from an underlying structural asymmetry. Endplate damage is common in elderly people, and closely related to disc degeneration and pain.

Methods: 47 human thoracolumbar motion segments aged 62–90 yrs were compressed to failure while positioned in moderate flexion. Damage was assessed from radiographs and at dissection. Two 2mm-thick slices were obtained from each vertebral body in the sagittal plane. Microradiographs were analysed to yield the following: thickness and image greyscale density (IGD) of the cranial and caudal cortex at 10 locations (94 vertebrae), and IGD of the cancellous bone in three regions adjacent to each endplate (34 vertebrae).

Results: Endplate damage occurred cranially in 39/47 vertebrae, and caudally in 4/47. Mean thickness of cranial and caudal endplates was 0.77mm (SD 0.27) and 0.90mm (SD 0.29) respectively (p=0.01). Thinnest regions were located centrally on cranial endplates. Endplate thickness increased at lower spinal levels for caudal (p< 0.01) but not cranial endplates. IGD was similar in cranial and caudal endplates, but IGD of trabecular bone adjacent to the endplate was 3–8% lower cranially than caudally (P< 0.01).

Discussion: In elderly spines, cranial endplates fracture more readily because they are thinner and supported by less dense trabecular bone. Endplate thickness may be minimised by the need to allow nutritional access to adjacent discs, and the vulnerability of cranial endplates may be associated with asymmetries in blood supply, or proximity to the pedicles.

Introduction: Back pain can be associated with erratic and/or excessive movements between adjacent vertebrae. Such movements are normally resisted by intervertebral ligaments, and yet few back pain patients report traumatic rupture of ligaments prior to their onset of symptoms. We suggest that two other mechanisms can lead to ligamentous slack and therefore to spinal instability. The first of these is the age-related dehydration of intervertebral discs, which reduces disc volume and height, bringing the vertebrae closer together. The second mechanism is disc decompression following vertebral endplate fracture, which is a common injury but one which is difficult to detect. Decompression allows the disc to bulge and lose height, increasing ligamentous laxity. In the present experiment, we simulated disc dehydration and endplate injury in cadaveric spines, and compared their effects on spinal (in)stability.

Methods: Cadaveric thoraco-lumbar motion segments were subjected to complex, continuous loading using a hydraulic materials testing machine (Zwick-Roell, Leominster, UK) to simulate full flexion and extension movements in vivo. Vertebral movements were recorded at 50 Hz using the optical “MacReflex” video capture system (Qualisys AB, Sweden). Experiments were repeated following 2 hours of compressive “creep” loading at 1500 N, which reduced disc water content by an amount similar to the aging process, and again following compressive overload sufficient to fracture a vertebral endplate. Bending moment-rotation curves were used to quantify the “neutral-zone” (NZ), range of motion (ROM), and bending stiffness (BS).

Results: Preliminary results (10 motion segments) showed that specimen height was reduced by 1.0 mm (STD 0.3 mm) following creep, and by a further 1.5 mm (STD 0.5 mm) following endplate fracture. Mean ROM in flexion increased from 6.5 deg initially, to 8.9 deg after creep and 12.6 deg after fracture. Corresponding values for NZ in flexion were 4.6 deg, 6.6 deg and 9.5 deg. BS decreased from 28.9 to 23.0 to 15.2 Nm/deg. All changes were statistically significant (p< 0.03). NZ, ROM and BS values in extension were initially 1.6 deg, 4.0 deg and 32.7 Nm, respectively, but no significant changes were noted following creep and endplate fracture. Total ROM (flexion + extension) increased from 10.5 deg to 16.7 deg degrees following both interventions.

Discussion: Results suggest that disc dehydration, which is a normal feature of aging, increases NZ and ROM in flexion, presumably because accompanying disc height loss allows more slack to the posterior intervertebral ligaments. Endplate fracture, which can occur under physiological loads in osteoporotic elderly spines, has an even greater effect. Extension movements were little affected, presumably because loss of disc height also increases the risk of impaction between neural arches.

Conclusion: We conclude that age-related disc dehydration, and relatively minor endplate injury, can increase segmental motion and cause substantial mechanical instability to the thoraco-lumbar spine.

Introduction : We have shown previously that, in the presence of severe disc degeneration, the neural arch can resist up to 80% of the compressive force acting on the spine. We hypothesise that the inferior articular processes can then act as a “pivot” during backward and lateral bending movements.

Materials and Methods: Twenty-one motion segments (T8–9 to L4–5) were obtained from spines aged 48–90yrs. Specimens were loaded rapidly to simulate flexion, extension and lateral bending, while vertebral movements were tracked using an optical MacReflex system. The varying position of the centre of rotation (CoR) during these movements was calculated. Experiments were repeated after a treatment designed to simulate two effects of severe disc degeneration: creep loading to dehydrate the disc, and compressive overload to fracture a vertebral endplate and decompress the nucleus.

Results: In flexion, the CoR was usually located just below the inferior endplate of the disc, close to the antero-posterior midline, and in extension it moved an average 4.6 mm posteriorly. The additional “disc degeneration” treatment increased the variability of the CoR within and between specimens. It also moved the CoR an average 10.7mm posteriorly during extension movements (P< 0.001), so that in some specimens it was near the tip of the inferior articular processes.

Discussion: Severe disc decompression and narrowing increase translational (gliding) movements between adjacent vertebrae so that the effective CoR becomes more variable. During extension movements, the CoR can move so far posteriorly that the vertebrae can effectively “pivot” about the inferior articular processes.

Introduction: We hypothesise that disc degeneration is a major cause of segmental instability in elderly spines. Accordingly, we simulated two mechanical features of disc degeneration on cadaveric spines, and measured their effects on spinal movements.

Methods: Twenty-one motion segments (T8–9 to L4–5) were obtained from spines aged 48–90yrs. Specimens were loaded rapidly to simulate full spinal bending movements in vivo, while vertebral movements were tracked using an optical MacReflex system. Intradiscal stresses were investigated using “stress profilometry”. Experiments were repeated following compressive creep loading (which reduced disc water content by an amount similar to the aging process) and again following a compressive overload cycle which fractured a vertebral endplate and decompressed the nucleus. MacReflex data were used to quantify the neutral-zone (NZ), the range of motion (ROM), and the range of translational (gliding) movements.

Results Creep and endplate fracture both reduced disc height, and generated stress concentrations within the posterior annulus. Both treatments increased NZ, ROM and translational movements in flexion and lateral bending, but not in extension. Endplate fracture markedly increased the “instability index” (NZ/ROM) in flexion.

Discussion Disc “degeneration” increased all measures of spinal instability during flexion and lateral bending. Disc decompression in particular created a large NZ in which the spine had negligible resistance to bending. In life, muscle action would prevent the spine “wobbling” within this range of movement. Results in extension suggest impaction between the neural arches. Back pain associated with spinal instability could arise from stress concentrations in the annulus and neural arches, or from abnormal muscle activity.

Introduction Vertebral fractures in the elderly frequently involve the anterior and superior regions of the vertebral body. We hypothesise that vertebral fracture patterns reflect regional variations in bone mineral density (BMD).

Methods Nineteen motion segments (aged 48–90 yrs) were obtained from thoracic and lumbar regions of cadaver spines. Specimens were compressed to failure while positioned in moderate flexion (to simulate someone lifting in a stooped posture). Superior and inferior vertebrae were dissected and the site of fracture identified by visual inspection. The volume of each vertebral body was measured by water immersion, and BMD was measured using dual X-ray absorptiometry (DXA). BMD was also calculated for the following regions: superior and inferior end-plates; upper, middle and lower thirds of the vertebral body between the end-plates; anterior, middle and posterior thirds of the vertebral body.

Results In 16 of the 19 specimens, an obvious fracture was located in the anterior or central region of the superior end-plate of the inferior vertebral body, accompanied by collapse of supporting trabeculae. BMD of the superior end-plate was significantly lower than that of the inferior end-plate. Similarly, BMD of the upper third of the vertebral body was less than that of the lower third, and BMD increased significantly from anterior to posterior regions in the vertebral body.

Discussion Low BMD in the superior and anterior regions of old vertebral bodies predisposes them to fracture. Altered load-sharing in old spines secondary to disc degeneration may explain these regions of low BMD.