We applied MDCT for in vivo evaluation of the microarchitecture of human vertebrae. Microstructure parameters, such as structure model index, Euler's number, and bone volume fraction, revealed higher relative risk for prevalent vertebral fracture than did BMD obtained by DXA. Thus, microstructure analysis by MDCT, together with simultaneously obtained volumetric BMD values, is useful for clinical assessment of fracture risk.Introduction: BMD measurement by DXA alone has limitations in predicting fracture, and methods for clinical assessment of bone quality, such as microstructure, are awaited. This study was undertaken to examine the applicability of multidetector row CT (MDCT) for in vivo evaluation of trabecular microstructure. Materials and Methods: Optimal conditions for MDCT scanning were determined at a spatial resolution of 250 × 250 × 500 m, using CT data of excised human vertebra specimens as a reference. We analyzed the trabecular microstructure of the vertebrae of 82 postmenopausal women (55-76 years old), including 39 women with and 43 without a recent vertebral fracture. Results: Microstructure indices obtained by MDCT scanning revealed higher relative risk for prevalent vertebral fracture (OR: 16.0 for structure model index, 13.6 for bone volume fraction, and 13.1 for Euler's number) than did spinal BMD obtained by DXA (OR: 4.8). MDCT could also provide volumetric BMD data, which had higher diagnostic value (OR: 12.7) than did DXA. Conclusion: Vertebral microarchitecture can be visualized by MDCT, and microstructure parameters obtained by MDCT, together with volumetric BMD, provided better diagnostic performance for assessing fracture risk than DXA measurement.

Over the past 10 years (1992-2002) the physical activity of healthy elderly (over 65) has been more youthful by 7.5 years in men and 10 years in women. Functional independence in elderly diabetic patients (over 65) has been more youthful by 15 years. pathological examination revealed that the cerebral arteries have been more youthful by 20 years in men and 10 years in women during the past 14 years (1986-2000). Based on these data, the current definition of elderly (65 year over) should be changed to those over 75 years. Changing the social system (retirement, pension, medical care etc.) to harmonize with the coming aging society is a matter of great urgency.

Interleukin-6 (IL6) has come to be regarded as a potential osteoporotic factor because it has stimulatory effects on cells of the osteoclast lineage, and, thus, may play a role in the pathogenesis of bone loss associated with estrogen deficiency. We previously described association of the IL6 microsatellite with bone mineral density (BMD), as well as genetic linkage of the IL6 locus to human osteoporosis, by means of sib-pair analysis. However, the molecular mechanism by which this locus regulates BMD remains unknown. Accordingly, we searched for polymorphisms in the 5Ј and 3Ј flanking regions and in all five exons of the IL6 gene in a Japanese population sample. We identified three single-nucleotide sequence variations: a C/G substitution at nucleotide (nt) Ϫ634 in the promoter region, a G/A substitution at nt 4391 in the 3Ј noncoding region, and a variation in the AnTn tract around nt Ϫ447. The last of these had already been observed in Caucasians, as well as in Japanese. The single-nucleotide polymorphism at Ϫ634 created a restriction site for the BsrBI endonuclease, and the frequency of the minor (G) allele was 0.184. Five haplotypes were constructed among three variations examined in the population. Linkage disequilibrium was observed between the variation at Ϫ634 and the variation at 4391, as well as between the variation at Ϫ634 and the AnTn tract variation. We found a significant correlation, in 470 subjects, between the presence of the G allele and decreased BMD, by analysis of variance. When BMD values were compared among the three genotypic groups (G/G, G/C, C/C) at nt Ϫ634, BMD was lowest among the G/G homozygotes (mean Ϯ SD; 0.284 Ϯ 0.062 g/cm 2 ), highest among the C/C homozygotes (0.314 Ϯ 0.059 g/cm 2 ), and intermediate among the heterozygotes (0.303 Ϯ 0.066 g/cm 2 ; P Ͻ 0.05).Given the several lines of evidence from different genetic studies, we suggest that IL6 is, indeed, one of the genes affecting bone metabolism, in which variations can lead to osteoporosis.

Senescence-accelerated mouse (SAM) has been characterized as a unique animal model to investigate spontaneous aging as well as age-related disorders. However, little is known about the properties of the lung. We examined age-related morphologic and functional changes of the lung in SAM P2, as the senescence-prone strain, and in SAM R1, as the senescence-resistant strain. On morphologic examination, the earlier (starting at 6 mo) and more severe change in airspace size (mean linear intercept: MLI) was observed in SAM P2 (MLI [micron]; 3 mo: 72.1 +/- 2.4; 6 mo: 80.8 +/- 2.9; 12 mo: 91.1 +/- 3.1; 18 mo: 143.4 +/- 6.6), compared with SAM R1 (MLI [micron]; 3 mo: 68.9 +/- 1.8; 6 mo: 70.8 +/- 2.6; 12 mo: 76.1 +/- 2.8; 18 mo: 101.2 +/- 4.7). The destructive index was not remarkably changed through life in both strains, suggesting that the alveolar wall was relatively intact in SAM. On functional examination, the left-sided shift of the pressure-volume (P-V) curves observed in SAM P2 at an early stage of aging (starting at 9 mo) compared with SAM R1. The shape constant (K) obtained from the P-V curve was increased with aging in SAM P2 (K; 3 mo: 0.124 +/- 0.004; 9 mo: 0.142 +/- 0.003; 18 mo: 0.183 +/- 0.008), and also increased at a late stage of aging in SAM R1 (K; 3 mo: 0.123 +/- 0.005; 9 mo: 0.135 +/- 0.004; 18 mo: 0.148 +/- 0.007). This study demonstrates that SAM P2 manifested most of the characteristic changes in senile lung.(ABSTRACT TRUNCATED AT 250 WORDS)

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