The Skeletal Site-Differential Changes in Bone Mineral Density Following Bone Marrow Transplantation: 3-Year Prospective Study

Abstract

INTRODUCTIONWith improved survival following transplantation, increasing importance is now being placed upon the long-term effects of therapy including osteoporosis. Several reviews regarding bone complications in transplanted patients have appeared in the literature (1-5). Most of these works refer to renal, hepatic, and cardiac transplants, whereas references to bone marrow transplantation (BMT) remain scarce, especially about the long-term changes in bone mineral metabolism. Bone diseases following BMT show several differences from those following other organ transplants. BMT recipients are relatively young and the duration of immunosuppressive therapy is usually short. The duration from diagnosis to BMT is relatively short, and thus pre-transplant bone mineral density (BMD) in BMT is higher than those in other solid organ transplantation (6). However, loss of bone mineral density is usually detected following BMT in short-term studies (6-9).We previously reported one-year change of bone mineral metabolism in which early bone loss is significant after BMT (7). However, data on the long-term change of BMD following BMT are rare. We observed the changes of yearly BMD during the post-BMT 3 yr and found a unique pattern in the bone loss and recovery according to the skeletal sites. PATIENTS AND METHODSWe prospectively investigated 11 patients (5 females and 6 males) undergoing allogeneic BMT for hematologic diseases (7 with leukemia, 3 with severe aplastic anemia, and 1 with myelodysplastic syndrome). The mean age of patients was 28.7 ±8.6 yr at the time of BMT (Table 1). Each patient received high dose cyclophosphamide (60 mg/kg/day) for two to four days. Six patients also received total body irradiation (TBI, 10-13.2 Gy) as a conditioning regimen. Intravenous cyclosporin A was administered at a dose of 5 mg/kg/day one day before BMT and at 3 mg/kg/day until the 20th day after BMT to the patients in order to prevent graft-versus-host disease (GVHD). Thereafter, oral cyclosporin A at 6 mg/kg/day was begun and continued for 6 to 12 months. Chronic GVHD developed in 3 patients. Established GVHD was treated with a combination of intravenous methylprednisolone or oral prednisolone and cyclosporin A. Doses were tapered when GVHD was controlled clinically.During the 3-yr study period, pre-BMT and yearly BMD were measured. BMDs of the lumbar spine (lumbar vertebrae L2-L4) and of the total proximal femur were measured by dual-energy radiography absorptiometry (DEXA) using a Lunar Expert (Lunar, Madison, WI, U.S.A. Loss of bone mass is usually detected after bone marrow transplantation (BMT) during the early post-transplant period. However, little is known about the long-term effects of BMT on bone metabolism. We have prospectively investigated 11 patients undergoing BMT. Bone mineral density (BMD) was measured before BMT, and 1, 2, and 3 yr after BMT. Serum markers of bone turnover were serially measured before BMT and 1, 2, 3, 4, and 12 weeks, 6 months, and 1 yr after BMT. The mean change in the lumbar spine (L2-4) BMD,...

Impact of circulating bone-resorbing cytokines on the subsequent bone loss following bone marrow transplantation

“…It was previously reported that bone disease is one of the complications of a BMT. 1,5 According to Castaneda et al, 9 33 and 18% of BMT recipients had osteopenia and osteoporosis in the lumbar spine when examined 33.6 months after BMT. The main causes of bone loss following a BMT include the use of immunosuppressants and hypogonadism induced by TBI or chemotherapy.…”

“…The post-BMT bone loss is mainly related to the immunosuppressants and the gonadal dysfunctions secondary to myeloablative therapy and/or total body irradiation (TBI). [1][2][3][4][5] The rapid impairment in bone formation and the increase in bone resorption, as mirrored by the biochemical markers, might play a role in bone loss, particularly during the early post-BMT period. 1 The pathogenic role of the cytokines is well known in the development of postmenopausal osteoporosis and other forms of secondary osteoporosis.…”

Bone loss following hematopoietic stem cell transplantation: a long-term follow-up

“…9 Data on the temporal sequence of bone loss in long-term survivors following hematopoietic stem cell transplantation (HSCT) are sparse. [10][11][12][13] However, these patients are exposed to numerous bone toxic factors: induction and consolidation therapy of the underlying hematological disease; malignancy-related changes in bone structure, especially in acute leukemia 14 ; dose-dependent toxicity of high-dose chemotherapy to bone marrow osteoprogenitors 15 ; conditioning regimen for transplantation, including total body irradiation (TBI) 16 ; graftversus-host disease (GVHD) and its treatment with steroids and cyclosporine A 17 ; immobilization; and hypogonadism following TBI. Cross-sectional studies of bone loss after HSCT revealed conflicting data: 5 of 25 patients, examined at least one year after HSCT (mean, 3; range, 1-10 years) showed osteoporotic bone mineral density (BMD) 18 ; 29 long-term survivors with a median survival of 5 years (minimum, 3 years) showed BMD within normal limits (Z-score Ͼ Ϫ1.5) except 2 male patients with hypogonadism.…”

“…Cross-sectional studies of bone loss after HSCT revealed conflicting data: 5 of 25 patients, examined at least one year after HSCT (mean, 3; range, 1-10 years) showed osteoporotic bone mineral density (BMD) 18 ; 29 long-term survivors with a median survival of 5 years (minimum, 3 years) showed BMD within normal limits (Z-score Ͼ Ϫ1.5) except 2 male patients with hypogonadism. 19 Prospective studies of bone loss are sparse; [10][11][12][13][20][21][22] the study with longest observation time presents follow-up of 11 patients observed for 3 years. 13 Data demonstrate rapid bone loss during the first 6 months after transplantation (5.7% at the lumbar spine and 6.9% to 8.7% at the femoral neck sites) with no further decline between months 6 and 12 21 and even recovery of bone mass during further follow-up.…”

High prevalence of early-onset osteopenia/osteoporosis after allogeneic stem cell transplantation and improvement after bisphosphonate therapy

“…6 It has been described after hematopoietic stem cell transplantation (SCT) as well, with the majority of cases reported in alloSCT recipients. [7][8][9][11][12][13][14][15][16][17][18][19][20][21][22][24][25][26][27][28][29][30][31][32][33][34][35] AlloSCT-associated BMD loss is usually described in the first 6-12 months after the transplantation, but varies widely from 40 days 17 to 4-6 years after the transplantation, 30,31,34 and in some instances can persist for 10-12 years. 26,28 Baseline BMD pre-SCT is usually within the normal limits; [15][16][17]24,[27][28][29][30]33 the few exceptions noting high O/O prevalence pre-SCT are probably due to the underlying diseases or intensive chemotherapy prior to the transplantation.…”