Variaciones de la masa ósea en el trasplante de progenitores hematopoyéticos

Abstract

Previous: Osteoporosis is a common complication of hematopoietic stem cell transplantation. Its pathogenesis is complex, involving multiple factors, namely the immunosuppressive drugs that are used in the induction period and consolidation and particularly the changes in the stromal cells of the bone marrow as a consequence of the transplant. . This entails an uncoupling of bone remodeling with an increase of bone resorption and decreased bone formation. Hypothesis: Patients who receive stem cell transplantation have a decreased bone mass . There are differences in bone mineral density between patients receiving allogeneic and autologous transplantation. This reduction leads to an increase in the number of fractures. Objectives: To determine the changes in bone mineral density of patients who receive a transplant of hematopoietic progenitors. To study the differences in bone loss between autologous and allogeneic transplant. To establish the changes in bone remodeling as well as the concentration of osteoprotegerin serum and growth factor type I insulin in these patients and to correlate it with the bone mineral density and the rate of vertebral fractures. Design: Prospective study. We performed serial measurements of bone mineral density, bone turnover markers (aminoterminal propeptide of type I procollagen and telopeptide aminoterminal of type I collagen), hormones (thyrotropin, thyroxine unbound protein, cortisol, parathyroid, FSH, LH, estradiol, testosterone, testosterone binding protein), growth factor type I insulin, 25 and 1,25 hydroxyvitamin D and osteoprotegerin and thoracolumbar radiographs profile. Setting and subjects of study: Adult patients of age ≥ 18 years who have received hematopoietic stem cell transplantation at the University Hospital Germans Trias i Pujol. Instrumentation: Bone mineral density was investigated with densitometer LUNAR prodigy in all patients . Futhermore markers of bone formation and resorption, and osteoprotegerin by hormonal measurements enzimo techniques and radioimmunoassay were determined in all the patients. Results: 100 patients were recruited ; 46 (46%) were women; 53 (53%) received autologous and 47 (47%) allogeneic transplantation. Prior to the transplant 37 patients (38%) had a low (26 osteopenia and 11 osteoporosis) bone mass. The mean (SD) BMD were 1. 139 (0. 179) g/cm2 in lumbar spine and 0. 971 (0. 131) g / cm2 in femoral neck. A decrease in bone mineral density at 6 months in both lumbar spine (1. 132 vs. 1. 086 g / cm2, p 0. 001) and femoral neck (0. 964 vs. 0. 914 g / cm2 p 0. 001) was observed. At 12 months the bone mineral density was : at the lumbar spine (1,124 vs. 1,096 g / cm2, p 0. 001) and femoral neck (0. 962 vs. 0. 898 g / cm2, p 0. 001). When comparing bone mineral density by the type of the transplant, the change after 12 months at the lumbar spine, in the autologous was -1. 96% compared to -3. 18% in allogeneic and thew change at femoral neck was -8. 76 -5. 20% a respectively. Osteoprotegerin values increased after both autologous transplant group (4. 33 vs. 5. 35 pmol / l, p = 0. 016) and allogeneic (5. 08 vs. 5. 78 pmol / l, p = 0. 015 ). However, these values were not correlated with bone mineral density. A significant increase in the values of aminoterminal propeptide of type I procollagen at 3 months (80. 94 versus 79. 08 ng / mL, p = 0. 001) in the group of autologous transplantation was observed whereas the aminoterminal propeptide allogeneic type I procollagen was decreased at 3 months (81. 23 vs. 112. 47 ng / mL, p = 0. 034) , 6 months (127. 95 86. 893 versus ng / mL, p = 0. 021) and 12 months (90. 98 vs. 123. 07 ng / mL, p = 0. 048). A nonsignificant increase in values of aminoterminal telopeptide of type I collagen in both types of transplantation was observed. Patients who developed graft-versus-host disease (GVHD) Chronic showed a greater decrease in bone mineral density in L2-L4 segment than those who had not this complication. There was a negative correlation (close to be statistical significance) between the cumulative dose of glucocorticoids and the loss of mineral density in the lumbar spine. The fracture rate was 5. 2%. Conclusions: Patients candidates for hematopoietic stem cell transplant have low levels of bone mineral density ( one third of cases) prior to the transplant. Both autologous and allogeneic trasnplant groups showed a loss of bone mass, which was more marked in the femoral neck. Patients in the allogeneic transplant group have changes in markers of bone turnover ( a decrease in bone formation markers and a increase in resorption markers), this reflects the pathophysiological mechanism of bone loss. Serum osteoprotegerin is increased but it is not correlated with bone mineral density. Graft versus host disease is related to chronic loss of bone mass after allogeneic hematopoietic progenitors. The cumulative dose of glucocorticoids is negatively correlated with bone loss in that group, approaching a statistical significance.

Date of Award	3 Nov 2015
Original language	Spanish
Awarding Institution	Germans Trias i Pujol University Hospital
Supervisor	Jose Maria Ribera Santasusana (Director) & Alejandro Olive Marques (Director)