Aims

Symptomatic spinal stenosis is a very common problem, and decompression surgery has been shown to be superior to nonoperative treatment in selected patient groups. However, performing an instrumented fusion in addition to decompression may avoid revision and improve outcomes. The aim of the SpInOuT feasibility study was to establish whether a definitive randomized controlled trial (RCT) that accounted for the spectrum of pathology contributing to spinal stenosis, including pelvic incidence-lumbar lordosis (PI-LL) mismatch and mobile spondylolisthesis, could be conducted.

Abstract

Aims

The aims of this study were to compare the use of resources, costs, and quality of life outcomes associated with subacromial decompression, arthroscopy only (placebo surgery), and no treatment for subacromial pain in the United Kingdom National Health Service (NHS), and to estimate their cost-effectiveness.

Aims

A trial-based comparison of the use of resources, costs and quality of life outcomes of arthroscopic and open surgical management for rotator cuff tears in the United Kingdom NHS was performed using data from the United Kingdom Rotator Cuff Study (UKUFF) randomised controlled trial.

Purpose of the Study and Background

With a strong political agenda for change towards patient-centred healthcare, the notion of shared decision-making is reported to substantially improve patient experience, adherence to treatment and health outcomes. In clinical practice however, observational studies have shown shared decision-making is rarely implemented and patient preferences are seldom met.

The aim of this study was to measure the extent of shared decision-making in clinical encounters involving physiotherapists and patients with low back pain.

Despite the development of skeletal or mesenchymal stem cell (MSC) constructs aimed at creating viable cartilage and bone, few studies have examined the effects of cytokines present in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial tissues, or inhibition of these, on such constructs. This work addresses these issues using both in vitro and in vivo approaches and examines potential ways of overcoming the effects of cytokines on the integrity of cartilage and bone constructs.

Synovial samples were obtained from RA or OA (n=10) patients undergoing elective hip or knee arthroplasty at Southampton General Hospital. Full ethical approval was obtained. Control bone marrow-derived stromal cells were obtained from patients undergoing emergency fractured neck of femur repair, cultured in basal, osteogenic (ascorbate and dexamethasone) and chondrogenic (transforming growth factor beta (TGFbeta3)) conditions. Differentiation towards bone and cartilage was assessed using alkaline phosphatase (ALP) staining, ALP and DNA biochemical assays and analysis of osteogenic/chondrogenic gene expression using real time polymerase chain reaction (rt-PCR). Exogenous interleukin-1 (IL-1) (10ng/mL), tumour necrosis factor alpha (TNFalpha) (10ng/mL) or interleukin-6 (IL-6) (100ng/mL) was added and effects on differentiation noted. RA and OA synovial samples were digested, cultured for 48 hours then centrifuged to produce supernatants. Cytokine profiles were determined using ELISA. These supernatants were then added to MSCs and their effects on differentiation assessed.

Mesenchymal cultures in osteogenic media with IL-1 showed an additive osteogenic effect on biochemical assays. TNF exerted a less marked and IL-6 no apparent effect on osteogenic differentiation. ALP expression by rt-PCR correlated with these findings. Addition of supernatants to mesenchymal cultures produced a marked osteogenic profile that was IL-1 and TNFalpha concentration dependent, correlating with lower supernatant dilutions on initial ELISA analysis.

Preliminary studies indicate that exogenous IL-1 and TNFalpha modulate the osteogenic phenotype in MSCs in vitro. OA and RA synovial supernatants affect skeletal cell differentiation. Variations in cytokine profiles between supernatants require analysis for potential confounders. A larger study is underway to investigate these effects, the effects of cytokines on skeletal cell differentiation on commercially available scaffolds both in vitro and in an in vivo murine model of bone formation.

Background: Intrauterine protein restriction in rodent models is associated with low bone mass which persists into adulthood. This study examined how early nutritional compromise affects the mechanical and structural properties of spinal tissues in sheep throughout the lifecourse.

Methods: Lumbar spines were removed from 19 sheep; 5 control animals and 14 that received a restricted diet in-utero. Eight animals (2 control/6 diet) were sacrificed at a mean age of 2.7 years and eleven at a mean age of 4.4 yrs. Two motion segments from each spine were tested on a hydraulically-controlled materials testing machine to determine their mechanical properties. Vertebral bodies were assessed for a number of structural parameters including cortical thickness and area, and regional trabecular density.

Results: Younger animals in the diet group showed a 25% reduction in forward bending stiffness (p< 0.05) and a 32% reduction in extension strength (p< 0.05) compared to controls of the same age. Furthermore, these young animals showed a 25% reduction in the thickness of the anterior cortex (p< 0.001) and an 18% reduction in the thickness of the superior cortex (p< 0.02). In older animals, no differences were observed in any of the mechanical parameters examined between diet and control groups, although animals in the diet group showed an average increase in cortical thickness of 14%, across all regions (p< 0.01).

Conclusions: These results suggest that early nutritional challenge can have detrimental effects on the mechanical and structural properties of spinal tissues in young animals but that adaptation occurs over the lifecourse to compensate for these differences in older animals.

Conflicts of Interest: None

Source of Funding: None

Purpose: The aim of this study is to compare the long-term survival results of TKA in patients under the age of 60, using

revision surgery and

Method: From our knee database we identified a cohort of 60 total knee replacements that had been performed over 15 years previously. We identified those who had died, those who had been revised and established the Oxford Knee Score (OKS) for all those still surviving.

Results Using the following endpoint criteria the cumulative 15-year survival was (A) revision surgery alone = 78% (CI 12), (B) revision surgery or an OKS less than or equal to 24 (50% of total OKS) = 63% (CI 13), and (C) revision surgery or moderate pain = 48% (CI 14).

Conclusion The functional survival of TKA in patients under the age of 60 decreases in the second decade following implantation with a significant number of prostheses failing the patient due to knee pain

Introduction: Intrauterine protein restriction in rats is associated with low bone mass which persists with development through to adulthood. However, such adverse effects are not only restricted to bone. Intervertebral discs are the largest avascular structures in the body, and are particularly sensitive to their nutritional environment. We have examined the hypothesis that changes in the intervertebral disc (or ligaments), as a result of early nutritional compromise, affect the spine’s mechanical properties.

Material and methods: Lumbar spines were removed from 8 sheep (6 male, 2 female: mean age 2.7 yrs) that had received different diets early in their development: two animals received a control diet, three received low protein in utero (IU), and three received low protein both in utero and postnatally (PN). Fifteen motion segments (consisting of two vertebrae and the intervening disc and ligaments) were dissected from the spines and tested on a hydraulically-controlled materials testing machine. Compressive stiffness and bending stiffness were measured before and after creep loading, in both flexion and extension. Reflective markers attached to the specimens were tracked during loading, enabling intervertebral angles to be calculated. Bending moment-angular rotation curves were used to calculate bending stiffness. Repeated measures ANOVA was used to test for differences in stiffness with posture and creep, and between the dietary groups.

Results: Compressive stiffness increased after creep loading (p=0.002) but was unaffected by posture or dietary group. In contrast, bending stiffness was unaffected by creep but differed significantly between groups and with posture. When compared to controls, bending stiffness in the IU group was reduced by 35% in flexion and 26% in extension (p< 0.02). In the PN group, reductions of 28% in flexion and 15% in extension were observed (p=0.056).

Discussion: These results indicate that early protein restriction can affect the mechanical properties of the spine. These effects were evident in bending but not in compression, and tended to be greater in flexion than extension. These preliminary findings suggest that early protein restriction may affect the composition and mechanical function of the annulus fibrosus and the intervertebral ligaments which are the structures most involved in resisting flexion movements.

Introduction: Epidemiology suggests that an intrauterine nutrient restriction increases the likelihood of osteoporosis in later life, possibly due to differences in bone structure and strength. We hypothesise that, in an ovine model, early nutritional compromise reduces vertebral cancellous bone density and cortical thickness, and thereby reduces vertebral compressive strength.

Materials and methods: Lumbar spines were dissected from 8 sheep (6 male, 2 female: mean age 2.7 yrs). Spines were divided into different groups, based on the early diet of the sheep: group CC received a control diet, group IU received low protein in utero, and group PN received low protein both in utero and postnatally. Fifteen motion segments (consisting of two vertebrae and the intervening disc and ligaments) were prepared from the spines, and compressed to failure using a hydraulically-controlled materials testing machine to obtain yield strength. 1mm-thick bone slices were taken from the mid-sagittal and para-sagittal regions of each vertebral body and micro-radiographed. Digital images of the micro-radiographs were analysed to obtain the cancellous bone density in anterior and posterior regions, and the cortical thickness in the anterior, posterior, superior and inferior regions. Repeated measures ANOVA was used to test for differences in parameters at the different locations, and between the groups.

Results: The anterior cortex was 28% thinner for the IU group, and 23% thinner for the PN group compared to controls (both p< 0.001). In the PN group, the superior cortex was also 18% thinner than controls (p< 0.02). There was no significant difference between cancellous bone density in either region. Yield strength was 16% lower in the IU group compared to controls, but this did not reach significance.

Discussion: In the nutritionally compromised groups, cortical thickness was lower in regions of the vertebral body where fractures often occur in elderly people. However, the reduction in cortical thickness is not accompanied by a significant reduction in compressive strength in the sheep model. These findings suggest that the well-maintained cancellous bone protects the vertebra from fracture.

The growth plates of rapidly growing animals have been studied extensively. Nevertheless, several questions remain unanswered, partly because many events happen simultaneously, especially at the vascular front. Terminal chondrocytes are thought to undergo programmed cell death, but the fate of the cell remnants remains unclear. Are the dying cells released into the vascular space and phagocytosed by macrophages, as one would expect for apoptosis? Or are the cells eliminated prior to opening of the lacunae, leaving empty lacunae? Do all terminal chondrocytes die or do some become bone-forming cells? Rodents maintain a growth plate into old age, long after longitudinal growth has ceased. These stationary growth plates have several features not found in the growth plates of rapidly growing animals and closer study of these features may provide answers to the above questions. Femurs and tibiae from 4–16 week-old and 62–80 week-old rats were decalcified, processed into paraffin, and the morphological changes were documented.

Between 4–16 weeks, the heights of the growth plates decreased due to loss of the large hypertrophic chondrocytes, but the various zones were still present. In the aged rats, the growth plates were identifiable as a narrow cartilaginous band with some short columns of inactive cells. The vascular front was irregular, the narrow spicules of primary spongiosa were absent and the much thicker spicules, which are normally seen in secondary spongiosa, directly abutted to the cartilage. Horizontal apposition of bone matrix onto the cartilage edge was frequently present. In addition, the following features were noted. 1) Acellular areas: Nearly all growth plates contained regions of cartilage from which all cells and their lacunae had disappeared. In some cases, these acellular regions stretched from the reserve zone to the vascular front and even persisted as a relatively wide core within the spicules of spongiosa, indicating increased resistance of acellular cartilage to resorption. The absence of cells or cell debris was consistent with an autophagic mode of cell death and subsequent collapse of the lacunae. 2) Remodelling within the growth plate; in some growth plates, large regions of growth plate cartilage had been resorbed and new bone had been laid down in a pattern similar to the remodelling of cortical bone. This suggested that the normal resistance of cartilage to vascular invasion had been lost locally, but was maintained in adjacent non-remodelled regions. 3) Trans-differentiation of chondrocytes to bone-forming cells; extensive new medullary bone formation was noted in the diaphysis of approximately 30% of the aged rats, suggesting that they had received an (unknown) osteogenic stimulus. In these rats, bone matrix was identifiable inside chondrocytic lacunae, and spreading beyond the confines of the lacunae, thus directly replacing growth plate cartilage with bone matrix.

The results suggest that i) chondrocytes are capable of self-elimination, perhaps by a mechanism similar to the autophagic cell death that occurs during insect metamorphosis; ii) resorption of cartilage and vascular invasion requires the presence of the viable chondrocytes; and iii) chondrocytes have the capacity to transdifferentiate to bone-forming cells, but only do so when receiving an increased osteogenic stimulus.

Cohort studies in humans have suggested that the peak bone mass attained at skeletal maturity may be programmed in utero. To investigate which aspects of bone development might be influenced in utero, we utilised a rat model of maternal protein insufficiency, which has previously been used to demonstrate the fetal origin of adult hypertension. In rodents, a growth plate remains present throughout life, even after longitudinal growth ceases. Generally, the height of the growth plate is related to the rate of bone growth. Fast growing bones have maximal height growth plates, and as bone growth slows down the height decreases until it remains stationary.

The aim of this study was to compare the morphology of long bones in aged rats that had been subjected to protein insufficiency in utero with that of controls. Rat dams were fed either an 18% casein control diet or a 9% casein low protein diet from conception until the end of pregnancy. The offspring were fed a normal diet until death (~72 weeks), when bone density was measured by dual energy X-ray absorptiometry (DEXA) and the tibiae and femurs were processed for histology.

The offspring of rats from the low protein group had a significantly lower bone mass, as assessed by DEXA. The major differences in bone structure were found in the growth plates, which were very irregular without the usual zones of resting, proliferating and hypertrophic chondrocytes. A number of unusual cellular events were noted to have taken place subsequent to cessation of growth, including: a) elimination of all chondrocytes in a number of regions, resulting in vast acellular areas; b) formation of chondroid bone and/or transdifferentiation of chondrocytes to bone-forming cells in other regions; c) partial resorption of those latter regions while the acellular regions were not resorbed; d) ‘horizontal’ apposition of bone against a smooth metaphyseal edge of the growth plate.

To compare the growth plates from the low and high protein groups semi-quantitatively, the degrees of the above features were scored. In addition, the heights of the growth plates were were assessed by two independent measurements. In the low protein group, the height of the growth plate were found to be significantly greater (p< 0.001). Additionally, the growth plates from this group of animals were observed to be more irregular with regards to all the features outlined above.

These findings are consistent with the hypothesis that growth trajectory and bone mass are programmed in early life. The increased height of the growth plate in animals undernourished in utero may reflect the cessation of growth at an earlier age. The increased irregularity of the growth plate in this group of animals may infer an earlier onset of age-related changes within the growth cartilage.