Correlation of plain radiographic indices of the hip with quantitative bone mineral density.

UNLABELLED: Radiographic parameters of the hip can be useful as an indication of bone mineral density at the femoral neck. Measurements available from routine hip radiographs were correlated with DXA values. Although radiographs are not a test for osteoporosis, measurements of cortical thickness provide information useful for referral for osteoporosis assessment. INTRODUCTION: Plain hip radiographs are widely used for evaluation of hip pathology in osteoarthritis. A purpose of this study was to determine whether there are relationships between radiographic parameters of bone structure and bone mineral density T-scores, as assessed by dual energy x-ray absorptiometry (DXA). METHODS: Pre-operative radiographs of 32 postmenopausal, osteoarthritic women undergoing hip arthroplasty were evaluated. Radiographic parameters including the Singh index, Dorr classification, canal-to-calcar ratio, and cortical thickness indices (CTI) were measured and compared with T-score, serum 25 hydroxyvitamin D levels, body mass index (BMI), and body weight. RESULTS: The T-score at the femoral neck for type C bone was significantly lower than that of type A (p = 0.041). The CTIs were correlated positively with T-scores for anteroposterior radiographs (r = 0.5814, p = 0.0005), and for lateral radiographs (r = 0.571, p = 0.0006). A threshold for lateral CTI set at a value of < or =0.40 results in sensitivity of 0.85 and specificity of 0.79 to segregate the osteoporotic and non-osteoporotic patients. CONCLUSION: Femurs with small radiographic cortical thickness indices had lower T-scores. Finding a radiographic hip cortical thickness index (LAT) with a value of < or =0.40 should be an alert for referral for osteoporosis evaluation and bone mineral density testing.

Competition for BLyS-mediated signaling through Bcmd/BR3 regulates peripheral B lymphocyte numbers.

Striking cell losses occur during late B lymphocyte maturation, reflecting BcR-mediated selection coupled with requisites for viability promoting signals. How selection and survival cues are integrated remains unclear, but a key role for B lymphocyte stimulator (BLyS(TM); trademark of Human Genome Sciences, Inc.) is suggested by its marked effects on B cell numbers and autoantibody formation as well as the B lineage-specific expression of BLyS receptors. Our analyses of the B cell-deficient A/WySnJ mouse have established Bcmd as a gene controlling follicular B cell life span, and recent reports show Bcmd encodes a novel BLyS receptor. Here we show that A/WySnJ B cells are unresponsive to BLyS, affording interrogation of how Bcmd influences B cell homeostasis. Mixed marrow chimeras indicate A/WySnJ peripheral B cells compete poorly for peripheral survival. Moreover, in vivo BrdU labeling shows that (A/WySnJ x BALB/c)F(1) B cells have an intermediate but uniform life span, indicating viability requires continuous signaling via this pathway. Together, these findings establish the BLyS/Bcmd pathway as a dominant mediator of B cell survival, suggesting competition for BLyS/Bcmd signals regulates follicular B cell numbers.

xid mice reveal the interplay of homeostasis and Bruton's tyrosine kinase-mediated selection at multiple stages of B cell development.

Human X-linked agammaglobulinemia (XLA) and murine X-linked immune defect (XID) are both immunodeficiencies mediated by mutations in Bruton's tyrosine kinase (Btk), yet the developmental stage(s) affected remain controversial. To further refine the placement of the XID defect(s), we used bromodeoxyuridine labeling to determine turnover, production and transition rates of developing B cell subsets in normal, xid and xid mice expressing a human Bcl-2 transgene (xid/bcl-2). We find the xid mutation manifest at two stages of B cell development. The first is early, reducing pre-B cell production by restricting pro-B to pre-B cell transit. Surprisingly, this impairment is offset by increased survival of cells progressing from the pre- to immature B cell pool, suggesting that Btk-independent homeostatic mechanisms act to maintain this compartment. The second point of action is late, substantially reducing mature B cell production. Together, these findings reconcile apparent discrepancies in the developmental stage affected by the murine versus human lesions and suggest previously unappreciated homeostatic processes that act at the pre-B to immature B cell transition. Finally, Btk likely functions differently at these two checkpoints, since ectopic Bcl-2 expression fails to directly complement the early xid lesion, yet reverses the defect impeding final B cell maturation.

B cell production and turnover in CBA/Ca, CBA/N and CBA/N-bcl-2 transgenic mice: xid-mediated failure among pre B cells is unaltered by bcl-2 overexpression.

The CBA/N strain carries xid, a murine btk missense mutation that reduces peripheral B cell numbers. Using in vivo BrdU labeling and cytofluorimetry, we have compared the magnitude, production rates, and turnover rates of each B lineage subset in the marrow and periphery of CBA/Ca and CBA/N mice. Our results show the pro-B compartment is largely unaffected by xid. In contrast, the pre-B cell pool is markedly reduced, reflecting a diminished production rate and unaltered turnover time. Despite diminished pre-B cell formation, the size of the immature B cell pool is relatively normal in CBA/N mice, due to increased proportional survival of pre-B cells. In addition, we have assessed the marrow and peripheral B cell subsets of CBA/N mice transgenic for bcl-2. These results indicate that while the bcl-2 transgene promotes lengthened survival in most B cell subsets, the pro/pre-B cell losses mediated by xid are not abrogated by bcl-2 overexpression. Taken together, these findings suggest that the initial [not readable: see text] from the pro- to pre-B cell pools, and that anomalies in subsequent compartments likely reflects the action of homeostatic mechanisms compensating for compromised pre-B cell production.

B cell maturation and selection at the marrow-periphery interface.

More than 95% of newly formed B cells die in the short interval spanning sIgM acquisition in the bone marrow and entry into the long-lived pool, suggesting that selective events dictating B cell longevity occur at this stage. These likely include both ligand-induced deletion as well as discrete events that mediate recruitment to the long-lived recirculating pool. We are probing these events through the examination of normal B cell differentiation during this critical period: the characterization of a natural mutation that blocks late maturation, an irradiation/autoreconstitution model of marrow-derived B cell differentiation, and the identification of life span regulatory genes whose expression changes within this window.