Arthritis Research UK published a report in 2009 entitled "Osteoarthritis and obesity" in which they highlight the severe consequences of obesity for musculoskeletal health. Throughout the report, ...however, the mechanical effect of excess body weight is assumed to be the direct cause of osteoarthritis (OA). Although this assumption is common, is it supported by the evidence? A survey of the studies associating OA with obesity is inconclusive on whether body weight is the causative factor. The increase in direct-loading on joints due to weight-gain is not as great as is often believed, and compensatory gait patterns ameliorate much of the kinematic effects. One manifestation of obesity, however, is increased adipose tissue--a rich source of proinflammatory endocrine factors. I propose that body weight might not be the main problem in OA pathogenesis, but that increased adipose tissue itself might be both an indicator and a driver of widespread disease.
Resistance exercise increases muscle mass and function in older adults, but responses are attenuated compared with younger people. Data suggest that long-chain n-3 polyunsaturated fatty acids (PUFAs) ...may enhance adaptations to resistance exercise in older women. To our knowledge, this possibility has not been investigated in men.
We sought to determine the effects of long-chain n-3 PUFA supplementation on resistance exercise training-induced increases in muscle mass and function and whether these effects differ between older men and women.
Fifty men and women men: n = 27, mean ± SD age: 70.6 ± 4.5 y, mean ± SD body mass index (BMI; in kg/m
): 25.6 ± 4.2; women: n = 23, mean ± SD age: 70.7 ± 3.3 y, mean ± SD BMI: 25.3 ± 4.7 were randomly assigned to either long-chain n-3 PUFA (n = 23; 3 g fish oil/d) or placebo (n = 27; 3 g safflower oil/d) and participated in lower-limb resistance exercise training twice weekly for 18 wk. Muscle size, strength, and quality (strength per unit muscle area), functional abilities, and circulating metabolic and inflammatory markers were measured before and after the intervention.
Maximal isometric torque increased after exercise training to a greater (P < 0.05) extent in the long-chain n-3 PUFA group than in the placebo group in women, with no differences (P > 0.05) between groups in men. In both sexes, the effect of exercise training on maximal isokinetic torque at 30, 90, and 240° s
, 4-m walk time, chair-rise time, muscle anatomic cross-sectional area, and muscle fat did not differ (P > 0.05) between groups. There was a greater (P < 0.05) increase in muscle quality in women after exercise training in the long-chain n-3 PUFA group than in the placebo group, with no such differences in men (P > 0.05). Long-chain n-3 PUFAs resulted in a greater decrease (P < 0.05) than the placebo in plasma triglyceride concentrations in both sexes, with no differences (P > 0.05) in glucose, insulin, or inflammatory markers.
Long-chain n-3 PUFA supplementation augments increases in muscle function and quality in older women but not in older men after resistance exercise training. This trial was registered at clinicaltrials.gov as NCT02843009.
The importance, and the difficulty, of generating biosynthetic articular cartilage is widely recognized. Problems arise from obtaining sufficient stiffness, toughness and longevity in the material ...and integration of new material into existing cartilage and bone. Much work has been done on chondrocytes and tissue macromolecular components while water, which comprises the bulk of the tissue, is largely seen as a passive component; the ‘solid matrix’ is believed to be the main load-bearing element most of the time. Water is commonly seen as an inert filler whose restricted flow through the tissue is believed to be sufficient to generate the properties measured. We propose that this model should be turned on its head. Water comprises 70–80% of the matrix and has a bulk modulus considerably greater than that of cartilage. We suggest that the macromolecular components structure the water to support the loads applied. Here, we shall examine the structure and organization of the main macromolecules, collagen, aggrecan and hyaluronan, and explore how water interacts with their polyelectrolyte nature. This may inform the biosynthetic process by identifying starting points to enable developing tissue properties to guide the cells into producing the appropriate macromolecular composition and structure.
Articular cartilage is known to be a viscoelastic material, however little research has explored the impact of cartilage water content and bone density on its viscoelasticity. This study aimed to ...isolate subchondral bone density and hydration of articular cartilage and analyse their effects on the viscoelastic properties of articular cartilage.
Dynamic mechanical analysis was used to test samples at frequencies of 1, 8, 12, 29, 49, 71, and 88 Hz. Synthetic bone material with densities of 663.7 kg/m
and 156.8 kg/m
were used to mimic the bone mineral density (BMD). Dehydration occurred in a stepwise manner at relative humidity (RH) levels of 100%, 30%, and 1%. These relative humidity levels led to water contents of approximately 76%, 8.5%, and ≈ 0% by mass, respectively.
Samples from eight bovine femoral heads were tested under a sinusoidal load. Storage stiffness was lower on the lower substrate density. Storage stiffness, though, increased as cartilage samples were dehydrated from a water content of 76% to 8.5%; decreasing again as the water content was further reduced. Loss stiffness was lower on a lower density substrate and decreased as the water content decreased.
In conclusions, a decrease in hydration decreases the loss stiffness, but a non-linear relationship between hydration and storage stiffness may exist. Additionally, higher BMD values led to greater storage and loss stiffnesses.
Two bottlenecks impeding the genetic analysis of complex traits in rodents are access to mapping populations able to deliver gene-level mapping resolution and the need for population-specific ...genotyping arrays and haplotype reference panels. Here we combine low-coverage (0.15×) sequencing with a new method to impute the ancestral haplotype space in 1,887 commercially available outbred mice. We mapped 156 unique quantitative trait loci for 92 phenotypes at a 5% false discovery rate. Gene-level mapping resolution was achieved at about one-fifth of the loci, implicating Unc13c and Pgc1a at loci for the quality of sleep, Adarb2 for home cage activity, Rtkn2 for intensity of reaction to startle, Bmp2 for wound healing, Il15 and Id2 for several T cell measures and Prkca for bone mineral content. These findings have implications for diverse areas of mammalian biology and demonstrate how genome-wide association studies can be extended via low-coverage sequencing to species with highly recombinant outbred populations.
Abstract
Objectives
Responsive biomarkers are needed to assess the progression of OA and their lack has hampered previous clinical trials. Statistical shape modelling (SSM) from radiographic images ...identifies those at greatest risk of fast-progression or joint replacement, but its sensitivity to change has not previously been measured. This study evaluates the responsiveness of SSM in knee OA in a 12-month observational study.
Methods
A total of 109 people were recruited who had undergone knee radiographs in the previous 12 months, and were grouped based on severity of radiographic OA (Kellgren–Lawrence grading). An SSM was built from three dual-energy X-ray absorptiometry scans at 6-month intervals. Change-over-time and OA were assessed using generalized estimating equations, standardized response means (SRM) and reliable change indices
Results
Mode 1 showed typical features of radiographic OA and had a strong link with Kellgren–Lawrence grading but did not change significantly during the study. Mode 3 showed asymmetrical changes consistent with medial cartilage loss, osteophytes and joint malalignment, and was responsive to change, with a 12-month SRM of 0.63. The greatest change was observed in the moderate radiographic OA group (SRM 0.92) compared with the controls (SRM 0.21), and the reliable change index identified 14% of this group whose progression was clinically significant.
Conclusion
Shape changes linked the progression of osteophytosis with increasing malalignment within the joint. Modelling of the whole joint enabled quantification of change beyond the point where bone-to-bone contact has been made. The knee SSM is, therefore, a responsive biomarker for radiographic change in knees over 12 months.
Faced with reduced levels of food, animals must adjust to the consequences of the shortfall in energy. We explored how C57BL/6 mice withdrew energy from different body tissues during three months of ...food restriction at graded levels up to 40% (calorie restriction: CR). We compared this to the response to equivalent levels of protein restriction (PR) without a shortfall in calories. Under CR there was a dynamic change in body mass over 30 days and thereafter it stabilized. The time to reach stability was independent of the level of restriction. At the end of three months whole body dissections revealed differential utilization of the different tissues. Adipose tissue depots were the most significantly utilized tissue, and provided 55.8 to 60.9% of the total released energy. In comparison, reductions in the sizes of structural tissues contributed between 29.8 and 38.7% of the energy. The balance was made up by relatively small changes in the vital organs. The components of the alimentary tract grew slightly under restriction, particularly the stomach, and this was associated with a parallel increase in assimilation efficiency of the food (averaging 1.73%). None of the changes under CR were recapitulated by equivalent levels of PR.
Hip shape is an important determinant of hip osteoarthritis (OA), which occurs more commonly in women. However, it remains unclear to what extent differences in OA prevalence are attributed to sex ...differences in hip shape. Here, we explore sex differences in proximal femur shape in a cohort of adolescents. Hip morphology was quantified using hip DXA scans from the Avon Longitudinal Study of Parents and Children. Independent modes of variation (hip shape mode (HSM) scores) were generated for each image using an adult reference statistical shape model (N = 19,379). Linear regression was used to examine sex differences for the top ten HSMs, adjusting for age, height, lean and fat mass. Complete outcome and covariate data were available for 4,428 and 4,369 participants at ages 14 and 18 years, respectively. Several HSMs showed sex differences at both time points. The combined effect of sex on hip shape at age 14 reflected flatter femoral head and smaller lesser trochanter in females compared with males and, following adjustment for age and body size, these differences became more pronounced. At age 18, smaller lesser trochanter and femoral neck width (FNW) in females still remained although differences in femoral head, femoral shaft and FNW were largely attenuated following adjustment. Sexual dimorphism in proximal femur shape can be discerned in adolescence and early adulthood. Observed differences in proximal femur shape, particularly at age 14 were largely independent of body size, however to what extent differences in hip shape in early life play a role in predisposing to hip OA in later life remains to be determined.
Abstract Cortical and trabecular bone are both produced and maintained by the same cell types. At the microscopic scale they have a similar lamellar structure but at a macroscopic scale they are very ...different. Raman microscopy has been used to investigate compositional differences in the two bone types using bone from standard laboratory mice in physiological conditions. Clear differences were observed when complete spectra were compared by principal component analysis (PCA). Analysis of individual bands showed cortical bone to have compositional characteristics of older bone when compared with trabecular material, possibly due to the higher bone turnover traditionally reported in the trabecular compartment.
It remains unclear how the different features of radiographic hip osteoarthritis (rHOA) contribute to hip pain. We examined the relationship between rHOA, including its individual components, and hip ...pain using a novel dual-energy x-ray absorptiometry (DXA)-based method.
Hip DXAs were obtained from UK Biobank. A novel automated method obtained minimum joint space width (mJSW) from points placed around the femoral head and acetabulum. Osteophyte areas at the lateral acetabulum, superior and inferior femoral head were derived manually. Semi-quantitative measures of osteophytes and joint space narrowing (JSN) were combined to define rHOA. Logistic regression was used to examine the relationships between these variables and hip pain, obtained via questionnaires.
6807 hip DXAs were examined. rHOA was present in 353 (5.2%) individuals and was associated with hip pain OR 2.42 (1.78–3.29) and hospital diagnosed OA 6.01 (2.98–12.16). Total osteophyte area but not mJSW was associated with hip pain in mutually adjusted models 1.31 (1.23–1.39), 0.95 (0.87–1.04) respectively. On the other hand, JSN as a categorical variable showed weak associations between grade ≥ 1 and grade ≥ 2 JSN with hip pain 1.30 (1.06–1.60), 1.80 (1.34–2.42) respectively. Acetabular, superior and inferior femoral osteophyte areas were all independently associated with hip pain 1.13 (1.06–1.20), 1.13 (1.05–1.24), 1.10 (1.03–1.17) respectively.
In this cohort, the relationship between rHOA and prevalent hip pain was explained by 2-dimensional osteophyte area, but not by the apparent mJSW. Osteophytes at different locations showed important, potentially independent, associations with hip pain, possibly reflecting the contribution of distinct biomechanical pathways.
•Radiographic hip OA, derived from DXA images, is associated with hip pain in UK Biobank.•Osteophyte size, as reflected by osteophyte area on the DXA image, shows strong associations with hip pain.•In contrast, joint space width is only weakly associated with hip pain.
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