Purpose of study and background. Degeneration of the intervertebral disc is a strong contributor of low back pain. Studies have shown that both, mechanical unloading and overloading, lead to disc degeneration. This is intuitively clear if one considers that an intervertebral disc essentially is a poro-elastic material embedded with cells, which depend on fluid flow for the transport of nutrients and waste products. As such, mechanical loading is also required for regeneration. It is unclear, however, how much loading is beneficial or detrimental for the healthy or degenerated disc. Methods and Results. We developed a loaded disc culture system for the long-term study of disc physiology. This way we could control both the mechanical and biochemical conditions. If no loading was applied, about half of the cells died within a week. Cells died under a low dynamic loading regime after three weeks. A diurnal loading regime rescued cell viability, gene expression profile and mechanical behavior of the discs. Both static and dynamic overloading induced damage to the discs and led to catabolic and inflammatory gene expressions. Conclusion. Intervertebral discs need a certain dosage of mechanical loading to remain viable. Under overloading, cells deform, change gene expression and become degenerative. The matrix is also remodeled, thereby further decreasing the hydrostatic pressure on the cells and increasing their deformation. This induces a vicious circle of disc degeneration, which needs to be reversed in order to repair the disc. The loaded disc culture system also allows evaluating new therapies for disc degeneration. There are no conflicts of interest. Funded by ZonMW program “Alternatives for live animal testing”, grant #11400090;. BioMedical Materials Program, grant # P2.01 IDiDas; Dutch Arthritis Funds, personal grant KSE

This short contribution aims to explain how intervertebral disc ‘degeneration’ differs from normal ageing, and to suggest how mechanical loading and constitutional factors interact to cause disc degeneration and prolapse. We suggest that disagreement on these matters in medico-legal practice often arises from a misunderstanding of the nature of ‘soft-tissue injuries’

Introduction. The intervertebral disc (IVD) is a highly hydrated and hyperosmotic tissue, water and salt content fluctuate daily due to mechanical loading. Resident IVD cells must adapt to this ever-changing osmotic environment, to maintain normal behaviour. However, during IVD degeneration the disc becomes permanently dehydrated and cells can no longer perform their correct function. Here, we investigated how human nucleus pulposus (NP) cells respond to altered osmolality with regards to cell size and the rate of water permeability, along with the potential involvement of aquaporins (AQPs) and transient receptor potential vanilloid (TRPV) membrane channels. Methods. Water permeability of NP cells exposed to altered osmolality (225–525mOsm/kg) in the presence or absence of AQP and TRPV channel inhibitors was investigated with the cell-permeable calcein-AM fluorescent dye, and cell size determined using microscopy and flow cytometry. Results. Human NP cells modulate their size and water permeability in response to altered osmolality. Inhibiting channel proteins, specifically AQP4, modified NP cell responses to altered osmolality. Conclusion. IVD cells must regulate their size in order to survive and function within an osmotically challenging environment. Here, we demonstrated that NP cells alter their size and permeability in response to altered osmolality which enables them to adapt to their environment. Furthermore these processes were shown to be dependent at least in part by AQP4 expression, which we have previously shown to be decreased during disc degeneration. This potentially highlights novel ways to restore NP cell and overall IVD function by modulating AQPs in the disc. No conflicts of interest. Funded by BMRC, Sheffield Hallam University

Purpose and Background. Both overall spine shape and the size and shape of individual vertebrae undergo rapid growth and development during early childhood. Motor development milestones such as age of walking influence spine development, with delayed ambulation linked with spinal conditions including spondylolysis. However, it is unclear whether associations between motor development and spine morphology persist into older age. Therefore, these associations were examined using data from the MRC National Survey of Health and Development, a large nationally-representative British cohort, followed up since birth in 1946. Methods and Results. Statistical shape modelling was used to characterise spinal shape (L5-T10) and identify modes of variation in shape (SM) from dual energy x-ray absorptiometry images of the spine taken at age 60–64 years (N=1327 individuals; 51.8% female). Associations between walking age in months (reported by mothers at 2 years) and SMs were examined with adjustment for sex, birthweight, socioeconomic position, height, lean mass and fat mass. Later onset of independent walking was weakly associated with greater lordosis (SM1; P=0.05) and more uniform antero-posterior vertebral size along the spine (SM6, P=0.07). Later walking age was also associated with smaller relative anterior-posterior vertebral dimensions (SM3) among women whereas the opposite was found for men (P <0.01 for sex interaction). Conclusions. Spinal morphology in early old age was associated with the age that individuals began walking independently in childhood, potentially due to altered mechanical loading. This suggests that motor development may have a persisting effect on clinically-relevant features of spine morphology throughout life. Conflict of interest: None. Funded by the UK Medical Research Council (Grant MR/L010399/1) which supported FRS, SGM and AVP

Purpose. To investigate associations between sagittal thoracolumbar spine shape with sex and measures of adiposity throughout adulthood. Methods. Thoracolumbar spine shape was characterised using statistical shape modelling on lateral dual-energy x-ray absorptiometry images, recorded for vertebral fracture analysis, of the spine from 1529 participants of the MRC National Survey of Health and Development, acquired at age 60–64 years. Associations between spine shape modes (SM) and 1) sex, 2) contemporaneous measures of overall and central adiposity (indicated by body mass index and waist circumference, respectively), 3) changes in total and central adiposity during earlier stages of adulthood and age at onset of overweight, were investigated. Results. Four of the first eight spine modes (SM) describing lumbar spine shape differed by sex; on average, women had more lordotic spines than men with relatively smaller but caudally increasing anterior-posterior (a-p) vertebral diameters. Greater BMI and waist circumference and earlier onset of overweight were associated with uneven (or snaking) spinal curvatures (SM2) and larger a-p vertebral diameters (SM3). Central adiposity was also associated with larger caudal disc heights (SM4) in women, especially increases between 36–43 years. Conclusions. Sagittal spine shapes differed by sex and associations with overall and central adiposity also differed. Overweight and greater central adiposity earlier in adulthood were particularly important, and were associated with a straighter but more unevenly curved spine with larger vertebrae and caudal discs heights, possibly explained by a chronic effect of increased mechanical loading on the spine. Conflicts of interest: None. Funding received from MRC

Aims

This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

Objectives. Many studies have investigated the kinematics of the lumbar spine and the morphological features of the lumbar discs. However, the segment-dependent immediate changes of the lumbar intervertebral space height during flexion-extension motion are still unclear. This study examined the changes of intervertebral space height during flexion-extension motion of lumbar specimens. Methods. First, we validated the accuracy and repeatability of a custom-made mechanical loading equipment set-up. Eight lumbar specimens underwent CT scanning in flexion, neural, and extension positions by using the equipment set-up. The changes in the disc height and distance between adjacent two pedicle screw entry points (DASEP) of the posterior approach at different lumbar levels (L3/4, L4/5 and L5/S1) were examined on three-dimensional lumbar models, which were reconstructed from the CT images. Results. All the vertebral motion segments (L3/4, L4/5 and L5/S1) had greater changes in disc height and DASEP from neutral to flexion than from neutral to extension. The change in anterior disc height gradually increased from upper to lower levels, from neutral to flexion. The changes in anterior and posterior disc heights were similar at the L4/5 level from neutral to extension, but the changes in anterior disc height were significantly greater than those in posterior disc height at the L3/4 and L5/S1 levels, from neutral to extension. Conclusions. The lumbar motion segment showed level-specific changes in disc height and DASEP. The data may be helpful in understanding the physiologic dynamic characteristics of the lumbar spine and in optimising the parameters of lumbar surgical instruments. Cite this article: M. Fu, Q. Ye, C. Jiang, L. Qian, D. Xu, Y. Wang, P. Sun, J. Ouyang. The segment-dependent changes in lumbar intervertebral space height during flexion-extension motion. Bone Joint Res 2017;6:245–252. DOI: 10.1302/2046-3758.64.BJR-2016-0245.R1

Aims

The aim of this study was to investigate the impact of maturity status at the time of surgery on final spinal height in patients with an adolescent idiopathic scoliosis (AIS) using the spine-pelvic index (SPI). The SPI is a self-control ratio that is independent of age and maturity status.

Aims

To clarify the asymmetrical ossification of the epiphyseal ring between the convex and concave sides in patients with adolescent idiopathic scoliosis (AIS).

Mesenchymal stem-cell based therapies have been proposed as novel treatments for intervertebral disc degeneration, a prevalent and disabling condition associated with back pain. The development of these treatment strategies, however, has been hindered by the incomplete understanding of the human nucleus pulposus phenotype and by an inaccurate interpretation and translation of animal to human research. This review summarises recent work characterising the nucleus pulposus phenotype in different animal models and in humans and integrates their findings with the anatomical and physiological differences between these species. Understanding this phenotype is paramount to guarantee that implanted cells restore the native functions of the intervertebral disc.

Cite this article: Bone Joint Res 2013;2:169–78.

This article reviews the current knowledge of the intervertebral disc (IVD) and its association with low back pain (LBP). The normal IVD is a largely avascular and aneural structure with a high water content, its nutrients mainly diffusing through the end plates. IVD degeneration occurs when its cells die or become dysfunctional, notably in an acidic environment. In the process of degeneration, the IVD becomes dehydrated and vascularised, and there is an ingrowth of nerves. Although not universally the case, the altered physiology of the IVD is believed to precede or be associated with many clinical symptoms or conditions including low back and/or lower limb pain, paraesthesia, spinal stenosis and disc herniation.

New treatment options have been developed in recent years. These include biological therapies and novel surgical techniques (such as total disc replacement), although many of these are still in their experimental phase. Central to developing further methods of treatment is the need for effective ways in which to assess patients and measure their outcomes. However, significant difficulties remain and it is therefore an appropriate time to be further investigating the scientific basis of and treatment of LBP.

Vertebral compression fractures are the most prevalent complication of osteoporosis and percutaneous vertebroplasty (PVP) has emerged as a promising addition to the methods of treating the debilitating pain they may cause.

Since PVP was first reported in the literature in 1987, more than 600 clinical papers have been published on the subject. Most report excellent improvements in pain relief and quality of life. However, these papers have been based mostly on uncontrolled cohort studies with a wide variety of inclusion and exclusion criteria. In 2009, two high-profile randomised controlled trials were published in the New England Journal of Medicine which led care providers throughout the world to question the value of PVP. After more than two decades a number of important questions about the mechanism and the effectiveness of this procedure remain unanswered.