Long-lasting bone damage detected by dual-energy x-ray absorptiometry, phalangeal osteosonogrammetry, and in vitro growth of marrow stromal cells after allogeneic stem cell transplantation.
Bone complications after allogeneic stem cell transplant (allo-SCT) include osteoporosis, fractures, and osteonecrosis. We investigated bone abnormalities in long-term survivors after busulfan cyclophosphamide-conditioning regimen, followed by human leukocyte antigen-identical sibling SCT. Bone density was measured by dual-energy x-ray absorptiometry at lumbar spine (LS) and femoral neck (FN) and phalangeal osteosonogrammetry (OSG) in 41 patients 1-10 yr after allo-SCT. Using colony-forming units-fibroblast (CFU-F) assay, we analyzed the repopulating capacity of clonogenic fibroblast progenitors belonging to the osteogenic stromal lineage. LS and FN bone mineral density (BMD) and phalangeal densitometric values were significantly reduced, compared with 188 healthy controls (P < 0.001). Decrease in T-score less than 1 SD was documented in 29% and 52% of patients at the LS and FN, respectively. OSG detected densitometric values with a T-score less than 1 SD in 68% of transplanted patients. The patients examined within the first 3 yr after transplant showed low BMD, which remained stable at FN and improved at LS. Phalangeal densitometry was low up to 10 yr after transplant. CFU-F was found permanently depressed and unable to give rise to a confluent stroma. Low serum osteocalcin levels were present throughout the whole follow-up period. A significant correlation was found between densitometric values detected by both techniques and CFU-F growth in vitro. Osteonecrosis was associated with lower FN BMD, and phalangeal densitometry correlated inversely with duration of amenorrhea and chronic graft vs. host disease requiring long-lasting steroid therapy. In conclusion, dual-energy x-ray absorptiometry and phalangeal OSG may provide complementary information on bone density after allo-SCT. Prolonged severe impairment of femoral BMD and phalangeal densitometry suggest that bone loss may persist for many years after transplant. Inability to regenerate a normal number of osteoblastic precursors in the stromal stem cell compartment may in part account for severe long-lasting posttransplant decrease in bone mass.
Tauchmanovà
Libuse
L
Department of Endocrinology, Division of Rheumatology, Federico II University of Naples, Via S. Pansini 5, 80131 Naples, Italy.
Serio
Bianca
B
Del Puente
Antonio
A
Risitano
Antonio Maria
AM
Esposito
Antonella
A
De Rosa
Gennaro
G
Lombardi
Gaetano
G
Colao
Annamaria
A
Rotoli
Bruno
B
Selleri
Carmine
C
D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D015519:Bone Density; D001847:Bone Diseases / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000209:etiology; D001854:Bone Marrow Cells / Q000166:cytology*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003430:Cross-Sectional Studies; D016572:Cyclosporine / Q000009:adverse effects; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D008297:Male; D009336:Necrosis; D033581:Stem Cell Transplantation; D017154:Stromal Cells / Q000166:cytology*; D014184:Transplantation, Homologous; D014463:Ultrasonography
D007166:Immunosuppressive Agents; D016572:Cyclosporine