Long-Term Bone Mineral Density Loss Following Autologous and Allogeneic Hematopoietic Cell Transplantation and Effectiveness of Bone Loss Therapies to Combat the Loss
Croudy, Christopher M.
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Background. Following hematopoietic cell transplantation (HCT), patients experience a sudden, significant loss of bone mineral density (BMD), measured by dual-energy X-ray absorptiometry (DXA) which is most dramatic in the first 100 days (D100). Long term follow-up has shown that recovery to pre-HCT BMD levels does not occur in myeloablative (MA) allogeneic recipients, but no studies have examined the persistence of BMD loss after autologous or reduced-intensity (RI)/non-myeloablative (NMA) allogeneic HCT. Standard therapy of BMD loss includes bisphosphonate, calcium, and/or vitamin D; however, their impact on the severe post-HCT BMD loss is not well studied. Hypothesis and specific aims. It is hypothesized that recipients of autologous HCT and RI/NMA allogeneic HCT experience similar incidence of the long-term persistence of acute BMD loss following HCT as described previously in MA allogeneic patients. Additionally, it is hypothesized that bisphosphonate therapy will significantly decrease the time to return to pre-HCT BMD levels. The study aims are: Specific Aim 1: To validate the previous study of acute BMD loss, and related clinical factors, following autologous and allogeneic HCT. Specific Aim 2: To examine the persistence of HCT associated BMD loss following both autologous and allogeneic HCT. Specific Aim 3: To estimate the effectiveness of various bone loss therapies to attenuate or reverse HCT associated BMD loss in autologous and allogeneic HCT patients. Study population and methods. We conducted a prospective study following autologous and allogeneic HCT in patients transplanted at Roswell Park Cancer Institute (RPCI) between January 25, 2006 and July 15, 2011. In autologous HCT patients, we were able to analyze acute (D100 or 4 months post-HCT) and long-term (1 year post-HCT) BMD change in 148 and 41 patients, respectively. In allogeneic HCT patients, we had more extensive follow-up data available and were able to perform analyses to 2 years post-HCT. Our sample sizes were: 132 at D100, 90 at 1 year, and 39 at 2 years post-HCT. Results. In aim 1, we validated all significant factors in autologous HCT patients at the spine and femur. We found an additional significant association where patients receiving melphalan containing conditioning regimens lost less BMD than those treated with any other regimens at both spinal and femoral BMD change. In allogeneic HCT patients, all significant factors were validated except baseline weight (kg.) for change in spine BMD. In aim 2, we found most autologous HCT patients had no change in BMD between D100 and 1 year DXA scans at the spine and dual femur. Osteopenia and osteoporosis rates were not significantly different between D100 and 1 year DXA scans. In allogeneic HCT patients, we found a significant increase in osteopenia and osteoporosis rates at the femur between D100 and 1 year DXA scans but no change between scans at 1 year and 2 years post-HCT. D100 BMD at the spine and femur were significantly associated with change by 1 year post-HCT. Steroid dose was increased BMD loss at the femur between D100 and 1 year and between 1 year and 2 years post-HCT. Higher pre-HCT BMD was significant for increased BMD loss in both the spine and femur out to 2 years post-HCT. In aim 3, we found that autologous HCT patients receiving bisphosphonate therapy lost significantly less BMD between 1 year post-HCT and pre-HCT than those not treated. No association between patients treated with high dose vitamin D replacement therapy and those not treated was found. In allogeneic HCT patients, bisphosphonates prevented BMD loss at the spine and femur between D100 and 1 year post-HCT DXA scans. Conclusion. We validated the findings in our previous study of acute BMD change following autologous and allogeneic HCT. BMD change persists in autologous and allogeneic (myeloablative and non-myeloablative) HCT patients, at least to 1 year and 2 years, respectively. In the short follow-up presented here, bisphosphonates show mixed results at reversing HCT associated BMD loss. High dose vitamin D replacement therapy (>2000 IU/day) shows no significant effect on BMD change post-HCT.