Intractable autoimmune diseases in chimeric resistant MRL/lpr mice were treated by a new bone marrow transplantation (BMT) method consisting of fractionated irradiation, 5.5 Gy ؋ 2, followed by intrabone marrow (IBM) injection of whole bone marrow cells (BMCs) from allogeneic normal C57BL/6 (B6) mice (5.5 Gy ؋ 2 ؉ IBM). In MRL/lpr mice treated with this method, the number of donor-derived cells in the bone marrow, spleen, and liver rapidly increased (almost 100% donor-derived cells by 14 days after the treatment), and the number of donorderived hemopoietic progenitor cells concomitantly increased. Furthermore, donorderived stromal cells were clearly detected in the cultured bone pieces from MRL/lpr mice treated with 5.5 Gy ؋ 2 ؉ IBM. All the recipients thus treated survived more than 1 year (> 60 weeks after birth) and remained free from autoimmune diseases. Autoantibodies decreased to almost normal levels, and abnormal T cells (

The SAMP6 mouse (a substrain of senescenceaccelerated mice) spontaneously develops osteoporosis early in life and is, therefore, a useful model for examining the mechanisms underlying osteoporosis. We have recently established a new bone marrow transplantation (BMT) method: the bone marrow cells (BMCs) of normal allogeneic mice are directly injected into the bone marrow (BM) cavity of irradiated (5.5 Gy × 2) recipients (IBM-BMT). Using IBM-BMT, we attempted to prevent osteoporosis in SAMP6 mice. The hematolymphoid system was completely reconstituted with donor-type cells after IBM-BMT. Thus-treated SAMP6 mice showed marked increases in trabecular bones even at 12 months of age, and the bone mineral density remained similar to that of normal B6 mice. In concordance with these findings, urinary deoxypyridinoline also remained continuously low until 10 months of age, indicating that IBM-BMT was effective in the prevention of bone absorption.In addition to the above, BM stromal cells in the treated SAMP6 mice were replaced with donor stromal cells, and the message level of interleukin-11 (IL-11), which is produced by the BM stromal cells and is known as an important factor in the regulation of bone remodeling, was restored to a level similar to that observed in normal B6 mice. Furthermore, the message level of IL-6, which is known to enhance osteoclastogenesis, was also restored to normal. These results indicate that the BM microenvironment was normalized after IBM-BMT and that the increased production of IL-11 and IL-6 ameliorated the imbalance between bone absorption and formation, resulting in the prevention of osteoporosis in SAMP6 mice.

Trunk and lower extremity loss of muscle mass and central obesity may be risk factors for chronic low back pain without a positive straight leg raise test result in women aged 45 to 69 years. Arch Intern Med. 2000;160:3265-3269.

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