Yearly Long-Acting Zoledronic Acid (Reclast) Is Safe and Effective for Treatment of Bone Loss after Hematopoietic Stem Cell Transplantation
Authors: Li Zhuoyan , Rubinstein Samuel M , Clifton Carey , Vaughan Leigh Ann , Logue Melissa , Byrne Michael T. , Kassim Adetola A. , Engelhardt Brian G , Chinratanalab Wichai , Sengsayadeth Salyka , Brandt Stephen J. , Goodman Stacey A. , Greer John P. , Jagasia Madan , Savani Bipin N. 
Published: October 2019

Abstract
Background:
With growing numbers of hematopoietic stem cell transplantation (HSCT) survivors due to more widespread use and better long-term outcomes, recognition and treatment of long-term complications of HSCT is important. Bone demineralization with resultant osteopenia and osteoporosis is one such common long-term complication with reported incidence of up to 50% of allogeneic HSCT survivors. Known risk factors include large cumulative doses of glucocorticoids, total body irradiation, calcineurin inhibitors and graft versus host disease, placing them at higher risk of developing bone demineralization compared to the general population. Zoledronic acid (ZA) is a long acting bisphosphonate which has not been well studied in the HSCT population for the treatment of bone loss. We hypothesize that the use of ZA in the post-HSCT setting is safe and effective in preserving bone density.
Methods:
We performed a retrospective IRB approved study evaluating patients after allogeneic HSCT at Vanderbilt University Medical Center (VUMC) from January 1, 2000 to December 31, 2015 who had evidence of bone demineralization and were treated with ZA. The patients who survived more than a year and who had surveillance dual-energy X-ray absorptiometry (DXA) scans following HSCT were selected for analysis. ZA (Reclast, 5 mg intravenous, Norvatis Pharmaceuticals Corp., Basel, Switzerland) was administered once yearly when the BMD from the DXA scan showed evidence of osteopenia (T-score -1 to -2.5) or osteoporosis (T-score < -2.5). BMD measurements, Z-scores, and T-scores were obtained for the lumbar spine and femur neck within 1 year after transplant and then every 2 to 3 years thereafter for surveillance. Stabilization was determined to be minimal change in the bone mineral density pre and post ZA ± 0.010.
Results:
A total of 564 patients were analyzed with 132 patients receiving ZA in the designated time frame. Of those patients, 56 patients had received surveillance DXA monitoring pre and post administration of ZA. Patients received between one to six doses of ZA with median three doses. In this patient population, 27 (48.2%) patients had improvement in BMD over the course of surveillance. 22 (39.3%) patients had stabilization in BMD and only 7 (12.5%) had had progressive bone loss despite being on ZA at a median of two years after starting ZA. All patients with progressive bone loss have been on two or more immunosuppressive therapy regimens including daily steroids for chronic GVHD. The average BMD of the lumbar spine prior to ZA was 1.036 ± 0.119 (Z-score -1.11 ± 1.07, T-score -1.46 ± 0.89) and after was 1.094 ± 0.114 (Z-score -0.46 ± 1.14; p = 0.01, T-score -0.94 ± 0.91; p = 0.02). The average BMD of the femur prior to ZA was 0.795 ± 0.106 (Z-score -1.10 ± 0.97, T-score -1.93 ± 0.89) and after was 0.791 ± 0.116 (Z-score -0.5 ± 1.11; p = 0.06, T-score -0.97 ± 0.90; p = 0.05). This shows that there was on average an improvement of BMD in the lumbar spine and stabilization of the femur hip BMD. ZA was generally well tolerated with one (0.8%) patient developing dyspepsia, one (0.8%) developing jaw pain without evidence of osteonecrosis of the jaw, and one (0.8%) patient developing bone pain after ZA administration. No patients developed renal dysfunction or osteonecrosis of the jaw as a result of ZA. Two patients did develop asymptomatic compression fractures while on treatment with ZA that were monitored and did not require surgical management.
Conclusions:
Yearly administration of a single dose of ZA is a safe and convenient intervention for the treatment of bone loss after HSCT. The majority of patients experienced either improvement or stabilization of their bone loss after receiving ZA. Prospective large-scale studies are needed to evaluate the efficacy of ZA for the prevention and treatment of bone loss in the HSCT population.
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Disclosures
No relevant conflicts of interest to declare.