Bone mass and microarchitecture of irradiated and bone marrow-transplanted mice: influences of the donor strain.
Total body irradiation and bone marrow transplantation induced dramatic trabecular bone loss and cortical thickening in mice. Transplanted cells were engrafted in bone marrow, along trabeculae, and in periosteal and endosteal envelopes. None of the osteocytes were of donor origin. Bone microarchitecture of transplanted mice changed to tend toward the donor phenotype.


BACKGROUND
Osteopenia and osteoporosis are complications of bone marrow transplants (BMT) attributed to related chemotherapy. However, the specific influence of total body irradiation (TBI) is unknown.


METHODS
We investigated the effects of TBI and BMT on bone mass and microarchitecture by micro-CT. Eighteen C57Bl/6 (B6) mice receiving lethal TBI had a BMT with marrow cells from green fluorescent protein--transgenic-C57Bl/6 (GFP) mice. Transplanted (T(GFP)B6), B6, and GFP mice were euthanized 1, 3, and 6 months after BMT or at a related age.


RESULTS
T(GFP)B6 presented a dramatic bone loss compared with B6 and did not restore their trabecular bone mass over time, despite a cortical thickening 6 months after BMT. Serum testosterone levels were not significantly reduced after BMT. During aging, GFP mice have less trabeculae, thicker cortices, but a narrower femoral shaft than B6 mice. From 3 months after BMT, cortical characteristics of T(GFP)B6 mice differed statistically from B6 mice and were identical to those of GFP mice. GFP(+) cells were located along trabecular surfaces and in periosteal and endosteal envelopes, but none of the osteocytes expressed GFP.


CONCLUSIONS
Our findings suggest that engrafted cells did not restore the irradiation-induced trabecular bone loss, but reconstituted a marrow microenvironment and bone remodeling similar to those of the donor. The effects of irradiation and graft on bone remodeling differed between cortical and trabecular bone.
INSERM, U922, "Remodelage osseux et biomatériaux", LHEA-Faculté de Médecine, 49045 Angers Cedex, France.
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Dumas
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Brigitte
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Moreau
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Chrétien
M F
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Baslé
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Chappard
D000818:Animals; D016026:Bone Marrow Transplantation / Q000473:pathology; D016723:Bone Remodeling / Q000528:radiation effects*; D016022:Case-Control Studies; D005269:Femur / Q000528:radiation effects* / Q000648:ultrastructure; D049452:Green Fluorescent Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010011:Osteocytes; D013045:Species Specificity; D013739:Testosterone / Q000097:blood; D014916:Whole-Body Irradiation / Q000009:adverse effects*
D049452:Green Fluorescent Proteins; D013739:Testosterone