Recovery of bone mass and normalization of bone turnover in long-term survivors of allogeneic bone marrow transplantation

Abstract

Summary:Osteoporotic fractures are potential long-term complications of bone marrow transplantation (BMT). We previously reported that bone mineral density (BMD) of patients undergoing allogeneic BMT decreased by 6% to 9% during the first 6 months after BMT and that bone turnover rate was still increased 1 year after BMT. BMT patients do not need lifelong immunosuppressive treatment, which should offer favorable circumstances for the recovery of BMD. Thus, 27 (14 women, 13 men) of 29 long-term survivors of our previous study were invited to a follow-up study at a median of 75 months after BMT. From 12 months after BMT the BMD of the lumbar spine had increased by 2.4% (P ‫؍‬ 0.002). The respective changes in femoral sites were ؉4.1% in the femoral neck (P ‫؍‬ 0.087), 4.0% in the trochanter (P ‫؍‬ 0.095), ؉4.7% in Ward's triangle (P ‫؍‬ 0.072) and ؉1.4% in the total hip (P ‫؍‬ 0.23). The markers of bone formation, serum osteocalcin and type I procollagen aminoterminal propeptide (PINP) had returned to control levels, but out of the markers of bone resorption the mean level of serum type I carboxyterminal telopeptide (ICTP) was 41% higher (P ‫؍‬ 0.0001) and that of urinary type I collagen N-terminal telopeptide/creatinine (NTx) 41% lower (P ‫؍‬ 0.0002) in patients than in con Keywords: bone marrow transplantation; osteoporosis; bone mineral density; bone markers; vitamin D Osteoporosis and osteoporotic fractures are potential longterm complications of not only solid organ transplants 1 but also of the bone marrow. 2,3 In our prospective study of 44 patients undergoing allogeneic bone marrow transplantation (BMT) bone mineral density (BMD) decreased by 6% in the lumbar spine and by 7% to 9% in the three femoral sites during the first 6 post-transplant months; no significant further decline occurred between 6 and 12 months. 2 Shortly after BMT bone loss was explained by uncoupling between increased bone resorption and decreased bone formation. 2 At the end of 1-year follow-up both resorption and formation markers were elevated, indicating accelerated bone turnover in survivors. 2 Unlike transplant recipients of solid organs, recipients of hemopoietic transplants do not need lifelong immunosuppression, and glucocorticoids and cyclosporine A can usually be stopped. This fact, together with a relatively young age of BMT recipients offer the bone favourable circumstances to recover, the magnitude of which has not been addressed in previous studies. Thus, we invited the long-term survivors of our original patient population to a follow-up study, in which their BMD and bone turnover state were re-evaluated at a median of 6 years after BMT. The values were compared to those obtained at the end of the previous 1-year follow-up, and biochemical data were compared to those produced by sex-matched controls. The vitamin D status of the patients was also evaluated. Patients and methods PatientsTwenty-nine of 44 patients who had received an allogeneic bone marrow transplant and taken part in our previous study were still alive and...

Decreased bone mineral density in young adults treated with SCT in childhood: the role of 25-hydroxyvitamin D

“…Even though decreased levels of 25(OH) vitamin D have been documented in adults after SCT, to our knowledge this is the first study to show this in longterm survivors after childhood SCT. 8,9 In contrast, Daniels et al 12 and Taskinen et al 14 found no relationship between BMD and calciotropic hormones in survivors after childhood SCT. As production in the skin through UVB light exposure is an important source of vitamin D, one potential pitfall when interpreting vitamin D data is the seasonal variation with lower levels during winter at our latitudes.…”

“…25 For the sake of comparison we chose the lower limit to be 37 nmol/L, which was used in two studies of BMD after SCT performed in Finland, and thus from similar latitudes to ours. 8,14 The cause of decreased 25(OH) vitamin D in our patients is not readily apparent. 26 One possible explanation may be that SCT survivors are prone to a more sedentary lifestyle than their peers, including less outdoor activities and consequently less sun exposure.…”

“…However, patients who have undergone allo-SCT might theoretically have lower BMD compared with auto-SCT even in the absence of cGVHD, as they have received post-SCT CYA (here tapered over 6 months). 4 Kananen et al 8 found that in adult survivors after allo-SCT including TBI, BMD had recovered and bone turnover had normalized a median of 75 months after SCT compared with the situation 12 months after SCT, when CyA was tapered off. Also, in the only previous study of BMD in postpubertal survivors of childhood SCT, Taskinen et al 14 reported on 16 patients aged 15-34 years after allo-SCT including TBI.…”

“…6,7 Furthermore, low levels of 25-hydroxy (25(OH)) vitamin D have been documented in long-term adult survivors, but only in the short term after SCT in childhood. [8][9][10] Decreased bone mineral density (BMD) has been reported after childhood SCT, but there are few long-term studies and consequently a limited number of patients who have been studied after attaining peak bone mass. 5,[11][12][13][14] The aim of the present study was to investigate the long-term effects of TBI-based SCT on BMD in a group of young adults and to explore potential risk factors for reduced BMD.…”

Bone metabolism in patients more than five years after bone marrow transplantation

“…13 The published literature reveals only one investigation with a follow-up of about 6 years after allogeneic BMT. 14 The study showed that seven of 26 patients had osteopenia, while no patient had osteoporosis. Bone mineral density (BMD) measurements about 4 years after autologous blood or marrow transplantation showed that 26 and 2% of patients had osteopenia and osteoporosis at the lumbar spine, respectively, and 46 and 8% of patients had osteopenia and osteoporosis at the femoral neck, respectively.…”