ABSTRACT:Introduction: Estrogen depletion after menopause is accompanied by bone loss and architectural deterioration of trabecular bone. The hypothesis underlying this work is that the MRI-based virtual bone biopsy can capture the temporal changes of scale and topology of the trabecular network and that estrogen supplementation preserves the integrity of the trabecular network. Materials and Methods: Subjects studied were early postmenopausal women, 45-55 yr of age (N ‫ס‬ 65), of whom 32 were on estrogen (estradiol group), and the remainder were not (control group). Early menopause was defined by amenorrhea for 6-24 mo and elevated serum follicle-stimulating hormone (FSH) concentration. The subjects were evaluated with three imaging modalities at baseline and 12 and 24 mo to determine the temporal changes in trabecular and cortical architecture and density. MRI of the distal radius and tibia was performed at 137 × 137 × 410-m 3 voxel size. The resulting bone volume fraction maps were Fourier interpolated to a final voxel size of 45.7 × 45.7 × 136.7 m 3 , binarized, skeletonized, and subjected to 3D digital topological analysis (DTA). Skeletonization converts trabecular rods to curves and plates to surfaces. Parameters quantifying scale included BV/TV, whereas DTA parameters included the volume densities of curves (C) and surface (S)-type voxels, as well as composite parameters: the surface/curve ratio (S/C), and erosion index (EI, ratio of the sum of parameters expected to increase with osteoclastic resorption divided by the sum of those expected to decrease). For comparison, pQCT of the same peripheral locations was conducted, and trabecular density and cortical structural parameters were measured. Areal BMD of the lumbar vertebrae and hip was also measured. Results: Substantial changes in trabecular architecture of the distal tibia, in particular as they relate to topology of the network, were detected after 12 mo in the control group. S/C decreased 5.6% (p < 0.0005), and EI increased 7.1% (p < 0.0005). Most curve-and profile-type voxels (representative of trabecular struts), increased significantly (p < 0.001). Curve and profile edges resulting from disconnection of rod-like trabeculae increased by 9.8% and 5.1% (p ‫ס‬ 0.0001 and <0.001, respectively). Similarly, DXA BMD in the spine and hip decreased 2.6% and 1.3% (p < 0.0001 and <0.005, respectively), and pQCT cortical area decreased 3.6% (p ‫ס‬ 0.0001). However, neither trabecular density nor BV/TV changed. Furthermore, none of the parameters measured in the estradiol group were significantly different after 12 mo. Substantial differences in the mean changes from baseline between the estradiol treatment and control groups, in particular after 24 mo, were observed, with relative group differences as large as 13% (S/C, p ‫ס‬ 0.005), and the relative changes in the two groups had the opposite sign for most parameters. The observed temporal alterations in architecture are consistent with remodeling changes that involve gradual conversion of plate-like to rod-...

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SUMMARYThe stimulatory effects of testosterone on erythropoiesis are very well known, but the mechanisms underlying the erythropoietic action of testosterone are still poorly understood, although erythropoietin has long been considered a potential mediator. A total of 108 healthy men >65 years old with serum testosterone concentration <475 ng/dL were recruited by direct mailings to alumni of the University of Pennsylvania and Temple University, and randomized to receive a 60-cm 2 testosterone or placebo patch for 36 months.Ninety-six subjects completed the trial. We used information and stored serum specimens from this trial to test the hypothesis that increasing testosterone increases haemoglobin by stimulating erythropoietin production. We used information of 67 men, 43 in the testosterone group and 24 in the placebo group who had banked specimens available for assays of testosterone, haemoglobin and erythropoietin at baseline and after 36 months. The original randomized clinical study was primarily designed to verify the effects of testosterone on bone mineral density. The primary outcome of this report was to investigate whether or not transdermal testosterone increases haemoglobin by increasing erythropoietin levels. The mean age ± SD of the 67 subjects at baseline was 71.8 ± 4.9 years. Testosterone replacement therapy for 36 months, as compared with placebo, induced a significant increase in haemoglobin (0.86 ± 0.31 g/dL, p = 0.01), but no change in erythropoietin levels (À0.24 ± 2.16 mIU/mL, p = 0.91). Included time-varying measure of erythropoietin did not significantly account for the effect of testosterone on haemoglobin (Treatment-by-time: b = 0.93, SE = 0.33, p = 0.01). No serious adverse effect was observed. Transdermal testosterone treatment of older men for 36 months significantly increased haemoglobin, but not erythropoietin levels. The haematopoietic effect of testosterone does not appear to be mediated by stimulation of erythropoietin production.

Testosterone concentrations in serum samples collected weekly over a 5-year period from a young adult male Asian elephant (Elephas maximus) and a young adult male African forest elephant (Loxodonta africana cyclotis) were measured by radioimmunoassay . Testosterone profiles during this maturational period were compared between the two species and related to the occurrence of musth, a recurring physiological and behavioral condition exhibited by most mature Asian, and some African, bull elephants. Musth is characterized by secretion from the bull's temporal glands, dribbling urine, and increased aggression. Serum testosterone concentrations in the Asian bull were elevated substantially between April and September each year, coincident with the presence of temporal gland secretion, urine dribbling, and aggressive behavior. Testosterone levels from April through September averaged (? SEM) 41.2 '-t 2.8 ng/ml, compared to 7.6 ? 1 .O ng/ml during the rest of the year. In contrast, the testosterone profile of the African bull showed greater variation and lower levels overall, the only pattern being a tendency for levels to be lowest from November to February (avg. 6.8 2 1.5 vs. 10.3 2 0.8 ngiml during the rest of the year). Temporal gland secretion and other signs of musth were first observed in this bull in 1988, at age 17. While his testosterone profile did not show a pattern comparable to that in the Asian bull, average testosterone values were significantly greater in 1988 compared to previous years.The Asian bull showed sexual attention to preovulatory (estrous) cows whether in musth or not, and exposure to estrous cows did not appear to alter the highly consistent, annual pattern of musth as evidenced in temporal gland flow.

Combined T and GH treatment of men with hypopituitarism for 2 years did not improve the measured structural or mechanical parameters of the distal tibia more than T alone. However, testosterone significantly increased the structural and mechanical properties of trabecular bone but decreased most of these properties of cortical bone, illustrating the potential importance of assessing trabecular and cortical bone separately in future studies of the effect of testosterone on bone.