Axial rotation and pain are associated with facet joint osteoarthritis in adolescent idiopathic scoliosis.

OBJECTIVE: Facet joints are crucial for spinal stability but develop premature osteoarthritis in patients with adolescent idiopathic scoliosis (AIS). Here, we evaluated the association between facet joint cartilage and subchondral bone homeostasis, perceived back pain and 3-dimensional spinal deformity to better understand the role of facet joint degeneration in AIS progression and pain. METHOD: The osteoarthritic state of cartilage and bone of AIS facet joint surgical samples were characterized using histological OARSI scoring, visual morphological grading and µCT analysis, respectively. Back pain was self-reported using a numerical rating scale and expressed relative to the location on the patient's back. The scoliotic curves from our patient cohort were digitally reconstructed using biplanar radiographs and the eOS system (EOS imaging). The deformity was then reduced to three intervertebral angles (coronal, sagittal and axial) for each pair of bilateral facet joints. Statistical associations between the intervertebral angles, osteoarthritis parameters and pain intensity were performed using the Spearman method and Friedman test. RESULTS: Facet joint cartilage degeneration was associated with decreased subchondral bone volume and quality. Most importantly, asymmetrical, and overall degeneration of facet joints was strongly correlated to intervertebral axial rotation. Additionally, kyphotic intervertebral segments in the sagittal plane were good predictors of increased facet joint degeneration and back pain. CONCLUSION: Facet joint degeneration is associated with axial deformity, kyphotic intervertebral angle and back pain intensity in AIS. These results suggest that facet joints are important features to consider for rotational instability in AIS spines and related disease progression and perceived back pain.

Psychosocial and psychophysical assessment in paediatric patients and young adults with chronic back pain: A cluster analysis.

BACKGROUND: Identifying subgroups with different clinical profiles may inform tailored management and improve outcomes. The objective of this study was to identify psychosocial and psychophysical profiles of children and adolescents with chronic back pain. METHODS: One hundred and ninety-eight patients with chronic back pain were recruited for the study. Pain assessment was mainly conducted in the form of an interview and with the use of validated pain-related questionnaires assessing their psychosocial factors and disability. All patients underwent mechanical and thermal quantitative sensory tests assessing detection and pain thresholds, and conditioned pain modulation efficacy. RESULTS: Hierarchal clustering partitioned our patients into three clusters accounting for 34.73% of the total variation of the data. The adaptive cluster represented 45.5% of the patients and was characterized to display high thermal and pressure pain thresholds. The high somatic symptoms cluster, representing 19.2% of patients, was characterized to use more sensory, affective, evaluative and temporal descriptors of pain, more likely to report their pain as neuropathic of nature, report a more functional disability, report symptoms of anxiety and depression and report poor sleep quality. The pain-sensitive cluster, representing 35.4% of the cohort, displayed deep tissue sensitivity and thermal hyperalgesia. CONCLUSIONS: This study identified clinical profiles of children and adolescents experiencing chronic back pain based on specific psychophysical and psychosocial characteristics highlighting that chronic pain treatment should address underlying nociceptive and non-nociceptive mechanisms. SIGNIFICANCE: To our current knowledge, this study is the first to conduct cluster analysis with youth experiencing chronic back pain and displays clinical profiles based on specific physical and psychosocial characteristics. This study highlights that in a clinical context, chronic pain assessment should include multiple elements contributing to pain which can be assessed in a clinical context and addressed when pathoanatomical symptoms are unidentifiable.

Craniocervical abnormalities in osteogenesis imperfecta type V.

Craniocervical abnormalities in osteogenesis imperfecta (OI) such as basilar invagination or cervical kyphosis can cause severe neurological morbidity. These abnormalities may be more frequent in OI type V compared with other OI subtypes of similar disease severity, underlining the importance of screening in this group. INTRODUCTION: Craniocervical abnormalities in osteogenesis imperfecta (OI) can cause severe neurological morbidity. Although radiological cranial base abnormalities in OI have been well described in the literature, there are limited data on these abnormalities in OI type V and their association with clinical sequelae. METHODS: A retrospective case series on patients with craniocervical abnormalities in OI type V at our institution. RESULTS: Craniocervical abnormalities were present in 7 of 37 patients with OI type V (19%). For 5 patients (age at last follow-up: 5 to 26 years; 2 females), sufficient information was available for inclusion in the case series. All had genetically confirmed OI type V. Age range at diagnosis of the craniocervical abnormality was 1 day to 18 years. Basilar invagination was present in 3 patients; 2 had cervical kyphosis. Dysplasia of upper cervical vertebrae or base of skull was seen in 3 patients. The severity of the craniocervical abnormality did not clearly correlate with the severity of the OI phenotype. Three patients required surgical intervention (ages 7, 11, and 26 years) due to compression of the spinal cord or brainstem. Craniocervical abnormalities were detected incidentally or on screening in 3 patients, and only 2 had significant positive findings on neurological examination. CONCLUSION: A variety of craniocervical abnormalities are seen in OI type V including dysplasia of the cervical vertebrae. These cases highlight the importance of screening patients with OI type V with lateral skull and cervical spine x-rays throughout childhood and after skeletal maturity.

Thermoreversible hyaluronan-hydrogel and autologous nucleus pulposus cell delivery regenerates human intervertebral discs in an ex vivo, physiological organ culture model.

Numerous studies show promise for cell-based tissue engineering strategies aiming to repair painful intervertebral disc (IVD) degeneration. However, clinical translation to human IVD repair is slow. In the present study, the regenerative potential of an autologous nucleus pulposus (NP)-cell-seeded thermoresponsive hyaluronic acid hydrogel in human lumbar IVDs was assessed under physiological conditions. First, agarose-encased in vitro constructs were developed, showing greater than 90 % NP cell viability and high proteoglycan deposition within HA-pNIPAM hydrogels following 3 weeks of dynamic loading. Second, a bovine-induced IVD degeneration model was used to optimise and validate T1ρ magnetic resonance imaging (MRI) for detection of changes in proteoglycan content in isolated intact IVDs. Finally, isolated intact human lumbar IVDs were pre-scanned using the established MRI sequence. Then, IVDs were injected with HA-pNIPAM hydrogel alone or autologous NP-cell-seeded. Next, the treated IVDs were cultured under cyclic dynamic loading for 5 weeks. Post-treatment T1ρ values were significantly higher as compared to pre-treatment scans within the same IVD and region of interest. Histological evaluation of treated human IVDs showed that the implanted hydrogel alone accumulated proteoglycans, while those that contained NP cells also displayed neo-matrix-surrounded cells within the gel. The study indicated a clinical potential for repairing early degenerative human IVDs using autologous cells/hydrogel suspensions. This unique IVD culture set-up, combined with the long-term physiological culture of intact human IVDs, allowed for a more clinically relevant evaluation of human tissue repair and regeneration, which otherwise could not be replicated using the available in vitro and in vivo models.

Spinal infections in children: a multicentre retrospective study.

Aims: This multicentre, retrospective study aimed to improve our knowledge of primary pyogenic spinal infections in children by analyzing a large consecutive case series. Patients and Methods: The medical records of children with such an infection, treated at four tertiary institutions between 2004 and 2014, were analyzed retrospectively. Epidemiological, clinical, paraclinical, radiological, and microbiological data were evaluated. There were 103 children, of whom 79 (76.7%) were aged between six months and four years. Results: We confirmed a significant male predominance in the incidence of primary pyogenic spinal infections in children (65%). The lumbar spine was the most commonly affected region, and 27 infections (26.2%) occurred at L4/5. The white blood cell count was normal in 61 children (59%), and the CRP level was normal in 43 (42%). Blood cultures were performed in 95 children, and were positive in eight (8%). A total of 20 children underwent culture of biopsy or aspiration material, which was positive in eight (40%). Methicillin-sensitive Staphylococcus aureus (MSSA) and Kingella ( K.) kingae were the most frequently isolated pathogens. Conclusion: MSSA remains the most frequently isolated pathogen in children with primary pyogenic infection of the spine, but K. kingae should be considered as an important pathogen in children aged between six months and four years. Therefore, an empirical protocol for antibiotic treatment should be used, with consideration being made for the triphasic age distribution and specific bacteriological aetiology. In the near future, the results of polymerase chain reaction assay on throat swabs may allow the indirect identification of K. kingae spondylodiscitis in young children and thus aid early treatment. However, these preliminary results require validation by other prospective multicentre studies. Cite this article: Bone Joint J 2018;100-B:542-8.

Comparative analysis in continuous expansion of bovine and human primary nucleus pulposus cells for tissue repair applications.

Autologous NP cell implantation is a potential therapeutic avenue for intervertebral disc (IVD) degeneration. However, monolayer expansion of cells isolated from surgical samples may negatively impact matrix production by way of dedifferentiation. Previously, we have used a continuous expansion culture system to successfully preserve a chondrocyte phenotype. In this work, we hypothesised that continuous expansion culture could also preserve nucleus pulposus (NP) phenotype. We confirmed that serial passaging drove NP dedifferentiation by significantly decreasing collagen type II, aggrecan and chondroadherin (CHAD) gene expression, compared to freshly isolated cells. Proliferation, gene expression profile and matrix production in both culture conditions were compared using primary bovine NP cells. Both standard culture and continuous culture produced clinically relevant cell populations. However, continuous culture cells maintained significantly higher collagen type II, aggrecan and CHAD transcript expression levels. Also, continuous expansion cells generated greater amounts of proteoglycan, collagen type II and aggrecan protein deposition in pellet cultures. To our surprise, continuous expansion of human intervertebral disc cells - isolated from acute herniation tissue - produced less collagen type II, aggrecan and CHAD genes and proteins, compared to standard culture. Also, continuous culture of cells isolated from young non-degenerate tissue did not preserve gene and protein expression, compared to standard culture. These data indicated that primary bovine and human NP cells responded differently to continuous culture, where the positive effects observed for bovine cells did not translate to human cells. Therefore, caution must be exercised when choosing animal models and cell sources for pre-clinical studies.

Dynamic loading, matrix maintenance and cell injection therapy of human intervertebral discs cultured in a bioreactor.

Low back pain originating from intervertebral disc (IVD) degeneration affects the quality of life for millions of people, and it is a major contributor to global healthcare costs. Long-term culture of intact IVDs is necessary to develop ex vivo models of human IVD degeneration and repair, where the relationship between mechanobiology, disc matrix composition and metabolism can be better understood. A bioreactor was developed that facilitates culture of intact human IVDs in a controlled, dynamically loaded environment. Tissue integrity and cell viability was evaluated under 3 different loading conditions: low 0.1-0.3, medium 0.1-0.3 and high 0.1-1.2 MPa. Cell viability was maintained > 80 % throughout the disc at low and medium loads, whereas it dropped to approximately 70 % (NP) and 50 % (AF) under high loads. Although cell viability was affected at high loads, there was no evidence of sGAG loss, changes in newly synthesised collagen type II or chondroadherin fragmentation. Sulphated GAG content remained at a stable level of approximately 50 µg sGAG/mg tissue in all loading protocols. To evaluate the feasibility of tissue repair strategies with cell supplementation, human NP cells were transplanted into discs within a thermoreversible hyaluronan hydrogel. The discs were loaded under medium loads, and the injected cells remained largely localised to the NP region. This study demonstrates the feasibility of culturing human IVDs for 14 days under cyclic dynamic loading conditions. The system allows the determination a safe range-of-loading and presents a platform to evaluate cell therapies and help to elucidate the effect of load following cell-based therapies.

Acute mechanical injury of the human intervertebral disc: link to degeneration and pain.

Excessive mechanical loading or acute trauma to intervertebral discs (IVDs) is thought to contribute to degeneration and pain. However, the exact mechanisms by which mechanical injury initiates and promotes degeneration remain unclear. This study investigates biochemical changes and extracellular matrix disruption in whole-organ human IVD cultures following acute mechanical injury. Isolated healthy human IVDs were rapidly compressed by 5% (non-injured) or 30% (injured) of disc height. 30% strain consistently cracked cartilage endplates, confirming disc trauma. Three days post-loading, conditioned media were assessed for proteoglycan content and released cytokines. Tissue extracts were assessed for proteoglycan content and for aggrecan integrity. Conditioned media were applied to PC12 cells to evaluate if factors inducing neurite growth were released. Compared to controls, IVD injury caused significant cell death. Injury also caused significantly reduced tissue proteoglycan content with a reciprocal increase of proteoglycan content in culture media. Increased aggrecan fragmentation was observed in injured tissue due to increased matrix metalloproteinase and aggrecanase activity. Injured-IVD conditioned media contained significantly elevated interleukin (IL)-5, IL-6, IL-7, IL-8, MCP-2, GROα, and MIG, and ELISA analysis showed significantly increased nerve growth factor levels compared to non-injured media. Injured-disc media caused significant neurite sprouting in PC12 cells compared to non-injured media. Acute mechanical injury of human IVDs ex vivo initiates release of factors and enzyme activity associated with degeneration and back pain. This work provides direct evidence linking acute trauma, inflammatory factors, neo-innervation and potential degeneration and discogenic pain in vivo.

Treatment of metastatic spinal cord compression: cepo review and clinical recommendations.

BACKGROUND: Metastatic spinal cord compression (mscc) is an oncologic emergency that, unless diagnosed early and treated appropriately, can lead to permanent neurologic impairment. After an analysis of relevant studies evaluating the effectiveness of various treatment modalities, the Comité de l'évolution des pratiques en oncologie (cepo) made recommendations on mscc management. METHOD: A review of the scientific literature published up to February 2011 considered only phase ii and iii trials that included assessment of neurologic function. A total of 26 studies were identified. RECOMMENDATIONS: Considering the evidence available to date, cepo recommends that cancer patients with mscc be treated by a specialized multidisciplinary team.dexamethasone 16 mg daily be administered to symptomatic patients as soon as mscc is diagnosed or suspected.high-loading-dose corticosteroids be avoided.histopathologic diagnosis and scores from scales evaluating prognosis and spinal instability be considered before treatment.corticosteroids and chemotherapy with radiotherapy be offered to patients with spinal cord compression caused by myeloma, lymphoma, or germ cell tumour without sign of spinal instability or compression by bone fragment.short-course radiotherapy be administered to patients with spinal cord compression and short life expectancy.long-course radiotherapy be administered to patients with inoperable spinal cord compression and good life expectancy.decompressive surgery followed by long-course radiotherapy be offered to appropriate symptomatic mscc patients (including spinal instability, displacement of vertebral fragment); andpatients considered for surgery have a life expectancy of at least 3-6 months.

Effect of dexrazoxane and amifostine on the vertebral bone quality of Doxorubicin treated male rats.

Doxorubicin (DOX) is widely used in combination cocktails for treatment of childhood hematological cancers and solid tumors. A major factor limiting DOX usage is DOX-induced cardiotoxicity. However, it is not known whether protectants like dexrazoxane (DXR) and amifostine (AMF) can prevent DOX-mediated bone damage. The present study investigated whether administration of AMF alone or in combination with DXR would prevent any DOX-mediated bone damage. Male rat pups were treated with DOX, DXR, AMF, and their combinations. On neonate day 38, the bone mineral density (BMD), bone mineral content (BMC) and the micro-architecture of the lumbar vertebrae were analyzed. We have shown that when male rats are treated with DOX, DXR, DOX+DXR, AMF, DOX+AMF or DOX+DXR+AMF, there is a decrease in lumbar vertebral BMD (p<0.05). Furthermore, the relative bone volume (BV/TV) was decreased by DXR, DOX+DXR, and DOX+AMF treatments. Interestingly, DOX+AMF significantly increased BV/TV when compared to DXR treatment (p<0.04). The trabecular number (Tb.N) decreased with DXR and DOX+DXR and increased with DOX+AMF treatments. This information will be useful in designing better cancer combination therapies that do not lead to vertebrae deterioration.

The locked flexible intramedullary humerus nail in pediatric femur and tibia shaft fractures: a feasibility study.

There are several options for the treatment of long bone fractures in skeletally immature patients. Surgeon experience, type of fracture, and the possibility of damage to the physeal area dictate individual fracture management patterns. Notably, nail devices have not gained popularity in this patient group. Intramedullary locking nails have become the standard of care in adult patients due to decreased morbidity and mortality. A novel nail has been developed for humeral shaft fractures that uses a lateral starting position to avoid damage to the rotator cuff in humeral fracture fixation. This is possible because of the nail's transient flexibility during insertion. This study illustrates that it is feasible to insert this type of nail through multiple entry portals for both tibial and femoral fracture fixation, without damaging the physeal blood supply or growth areas.