The material properties of cancellous bone from patients with osteoporosis (OP) or osteoarthritis (OA) were determined and compared with normal controls. Samples were selected from defined sites in human femoral heads which are subjected to different loads in vivo. Overall, OP bone had the lowest stiffness and OA the highest, and this same order was reflected in the apparent densities of the bone, with OA being the most dense and OP the least. Normal and OP bone were found to have very similar stiffness-density relationships and composition. However, OA bone differed significantly from normal. The stiffness of OA bone increased more slowly with apparent density and its material density was significantly reduced. These findings were due to an altered composition of the bone in which the mass fraction of mineral is 12% less than normal. There was also greater site variation of both apparent and material density, suggesting an altered sensitivity to applied load. These results support the concept that osteoporosis is a loss of normal bone. They also provide evidence for the hypothesis that osteoarthritis is, at least partly, a bone disease in which proliferation of defective bone results in an increase in bone stiffness. (J Bone Miner Res 1997;12:641-651)

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Objective. Few methods exist to measure the progression of osteoarthritis (OA) or to identify people at high risk of developing OA. Striking radiographic changes include deformation of the femoral head and osteophyte growth, which are usually measured semiquantitatively following visual assessment. In this study, an active shape model (ASM) of the proximal femur was used to determine whether morphologic changes to the bone could be quantified and used as a marker of hip OA.Methods. One hundred ten subjects who had no signs of radiographic hip OA at baseline (Kellgren/ Lawrence [K/L] scores 0-1) were selected from the Rotterdam Study cohort of subjects ages >55 years. To measure the progression of OA, subjects were followed up with radiographic assessment after 6 years. At the 6-year followup, 55 subjects had established OA (K/L score 3), and in 12 of these OA subjects, the progression of the disease required a total hip replacement (THR). Age-and sex-matched control subjects had a K/L score of 0 at followup. Using the ASM, subjects were assessed for shape changes in the femoral head and neck before, during, and after the development of radiographic OA.Scores of shape variance, or mode scores, were assigned for 10 modes of variation in each subject, and differences in mode scores were determined.Results. During followup, significant changes in shape of the proximal femur occurred within the OA group from baseline to followup (P < 0.0001 for mode 1 and P ‫؍‬ 0.002 for mode 6) but not within the control group. At baseline (all subjects having K/L scores 0-1), there were significant differences in mode 6 between the OA group and the control group (P ‫؍‬ 0.020), and in modes 3 and 6 between the OA subjects who underwent THR and the remaining OA subjects (P ‫؍‬ 0.012 and P ‫؍‬ 0.019, respectively).Conclusion. Compared with traditional scoring methods, the ASM can be used more precisely to quantify the deforming effect of OA on the proximal femur and to identify, at an earlier stage of disease, those subjects at highest risk of developing radiographic OA or needing a THR. The ASM may therefore be useful as an imaging biomarker in the assessment of patients with hip OA.Osteoarthritis (OA) is one of the most common disorders in the elderly. It is estimated that by age 75 years, 85% of individuals show either clinical or radiologic evidence of OA (1). As OA of the hip progresses, changes in the shape of the femoral head develop, with flattened and irregular features becoming apparent. These changes can be observed on standard radiographs but are hard to quantify. The severity of OA is generally assessed using semiquantitative methods based on visual evaluation of a radiograph; for example, the Kellgren/ Lawrence (K/L) scoring method (2) is used to assess a Supported by the Dutch Arthritis Association.

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 sequencing (0.15X) with a novel 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 5% false discovery rate. Gene-level mapping resolution was achieved at about a fifth of loci, implicating Unc13c and Pgc1-alpha 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 GWAS can be extended via low-coverage sequencing to species with highly recombinant outbred populations.

Background: 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.Objective: 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.Design: Fifty men and women [men: n = 27, mean ± SD age: 70.6 ± 4.5 y, mean ± SD body mass index (BMI; in kg/m2): 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.Results: 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−1, 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.Conclusion: 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.

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.

Tendon ruptures are increasingly common, repair can be difficult, and healing is poorly understood. Tissue engineering approaches often require expansion of cell numbers to populate a construct, and maintenance of cell phenotype is essential for tissue regeneration. Here, we characterize the phenotype of human Achilles tenocytes and assess how this is affected by passaging. Tenocytes, isolated from tendon samples from 6 patients receiving surgery for rupture of the Achilles tendon, were passaged 8 times. Proliferation rates and cell morphology were recorded at passages 1, 4, and 8. Total collagen, the ratio of collagen types I and III, and decorin were used as indicators of matrix formation, and expression of the integrin beta1 subunit as a marker of cell-matrix interactions. With increasing passage number, cells became more rounded, were more widely spaced at confluence, and confluent cell density declined from 18,700/cm2 to 16,100/cm2 ( p = 0.009). No change to total cell layer collagen was observed but the ratio of type III to type I collagen increased from 0.60 at passage 1 to 0.89 at passage 8 ( p < 0.001). Decorin expression significantly decreased with passage number, from 22.9 +/- 3.1 ng/ng of DNA at passage 1, to 9.1 +/- 1.8 ng/ng of DNA at passage 8 ( p < 0.001). Integrin expression did not change. We conclude that the phenotype of tenocytes in culture rapidly drifts with progressive passage.

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