Bone Loss in Long-Term Survivors after Transplantation of Hematopoietic Stem Cells: A Prospective Study

Abstract

Organ transplantation is associated with relevant bone loss. Bone loss of up to 20% of pretransplant bone mineral density (BMD) values within the first year after kidney, liver, heart and lung transplantation has been reported. Patients undergoing transplantation of hematopoietic stem cells provide an interesting model to study transplantation-induced bone loss, especially because most patients do not have preexisting bone disease. A longitudinal study was performed in 81 patients undergoing bone marrow or peripheral blood stem cell transplantation. BMD was determined by dual-energy X-ray absorptiometry before transplantation, at discharge from the hospital, and at 6 and 12 months after transplantation in all 81 patients. In 35 patients BMD was re-evaluated 24 months after transplantation. Vitamin D and parathyroid hormone, bone alkaline phosphatase as a marker of bone formation, and N-terminal telopeptide of type I collagen as a marker of bone resorption were assessed before transplantation and in the short-term follow-up 14 and 28 days after transplantation. The majority of patients (72%) showed normal BMD before transplantation. However, lower BMD was observed in patients who had received high-dose cytoreductive chemotherapy before transplantation compared with those who had received no chemotherapy or only hydroxyurea. Despite supplementation with elemental calcium (1000 mg/day) and vitamin D (1000 IU/day), the mean rate of bone loss during the first year was 7.2 +/- 6.3% at the lumbar spine, 11.9 +/- 8.1% at the femoral neck and 3.8 +/- 2.5% at the total body compartment. Evaluation of the pattern of bone loss during the first year demonstrated that the amount of bone loss was largest within the first 40 days after transplantation and small during the second half of the first year after transplantation. The majority of patients showed vitamin D deficiency and secondary hyperparathyroidism. Bone formation was normal before and after transplantation, whereas bone resorption was dramatically increased before and after transplantation. Exposure to glucocorticoids was associated with higher bone loss at spine and femoral neck but not at the total body compartment. Our data demonstrate rapid bone loss in patients undergoing transplantation of hematopoietic stem cells. Bone turnover is characterized by biochemical uncoupling of bone resorption and bone formation, changes interestingly pre-existing before transplantation. The observed alterations in bone mass and metabolism emphasize the importance of clinical trials with antiresorptive agents to prevent and treat post-transplantation osteoporosis in this group of patients.

Early changes in bone mineral density and trabecular bone score following allogeneic stem cell transplant

“…The association between glucocorticoids and bone loss at various sites has been inconsistent in previous studies. [1][2][3][4][5] The lack of association with spine BMD loss in our study is unexpected as trabecular bone loss occurs most rapidly in glucocorticoid-induced osteoporosis. 8 At the more cortical site, the femoral neck, the lack of association suggests that cortical bone loss occurs by a distinct mechanism.…”

“…2 Previous studies have shown that the most profound bone mineral density (BMD) decline occurs within the first 6 months following allo-SCT 3,4 but information regarding earlier change is limited. 2,3 Declines in BMD are greater at the femoral neck, a site rich in cortical bone, than lumbar spine, a site rich in trabecular bone, and this may suggest disproportionate cortical bone loss. 1,[3][4][5] This pattern is unlike the early spine BMD decline generally seen in postmenopausal and glucocorticoid-induced osteoporosis and suggests a unique mechanism.…”

“…2,3 Declines in BMD are greater at the femoral neck, a site rich in cortical bone, than lumbar spine, a site rich in trabecular bone, and this may suggest disproportionate cortical bone loss. 1,[3][4][5] This pattern is unlike the early spine BMD decline generally seen in postmenopausal and glucocorticoid-induced osteoporosis and suggests a unique mechanism. In addition, qualitative microstructural properties also affect bone strength and fracture risk.…”

“…9 Therefore, cytokine driven osteoclast differentiation may account for the large cortical bone loss seen by us and others. 1,[3][4][5] In addition, the impressive femoral neck bone loss observed following allo-SCT is reminiscent of cortical bone loss in patients with hyperparathyroidism, except the loss appears quite early. Translational studies have reported that lymphoid cells express parathyroid hormone (PTH) receptors and mice lacking T cells cannot induce osteoclast formation in response to PTH infusion and are resistant to cortical bone resorption.…”

Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long‐term follow‐up of a prospective study

“…Prospective studies have demonstrated that bone mineral density (BMD) is reduced in recipients of allogeneic haematopoietic stem cell transplants (alloSCT) (Stern et al, 1996;Ebeling et al, 1999;Kang et al, 2000;Schulte et al, 2000). This may increase the susceptibility to fragility fractures in these patients, although fracture data in this group of patients are limited.…”