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

Abstract

Transplantation-associated bone loss is a well-known phenomenon, however, effects of hematopoietic stem cell transplantation are insufficiently characterized. We conducted a prospective, unicentric, longterm follow-up in 280 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Bone mineral density (BMD) was measured before transplantation and then yearly for at least 4 years. Patients received vitamin D plus calcium until steroid withdrawal. Mean baseline BMD was normal. We demonstrated significant bone loss with nadir BMD at month 6 for the spine and at month 24 for total body and femoral neck. Average annual bone loss was 0.6% for spine, 0.4% for total body, 2.3% for femoral neck, and 3.5% for Ward triangle. While spine and total body BMD returned to baseline, bone loss at femoral neck sites was attenuated, but BMD did not return to baseline until month 48 (P < . IntroductionOrgan transplant recipients benefit from greatly improved survival, however, long-term complications such as osteoporosis and osteoporotic fractures 1 adversely affect life quality and therefore have to be addressed. Transplantation of solid organs such as heart, 2 kidney, 3 liver, 4 and lung 5 is associated with rapid bone loss and increased susceptibility to osteoporotic fragility fractures. Transplantation-associated bone loss has been demonstrated to occur preferentially during the first year after transplantation, 6-8 with at least partial recovery during further follow-up. 9 Data on the temporal sequence of bone loss in long-term survivors following hematopoietic stem cell transplantation (HSCT) are sparse. 10-13 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. 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. 10,12,13,22 Ebeling 11 first evaluated likely mechanisms for bone loss in ...

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.…”

“…2,3 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.…”

“…Following allo-SCT, calcium, vitamin D and post-menopausal hormone replacement fail to prevent bone loss. 3,4 Encouragingly, small studies have demonstrated that prophylactic bisphosphonate administration prior to allo-SCT can prevent, 13 or at least ameliorate post-transplant bone loss. 14 In conclusion, we found rapid decline in BMD following allo-SCT despite calcium and vitamin D supplementation.…”

Post-Transplantation Osteoporosis

“…In a study of long term follow up of bone loss after BMT, Schulte and Beelen observed that lumbar spine BMD begins to recover after 12 months, returning to baseline at 48 months (24). High levels of bone marrow interleukin-6 during the immediate post-BMT period were related to the bone loss.…”