Online First

Original Article
Randomized controlled trial of pre-transplant zoledronate versus observation for prevention of bone loss in allogeneic hematopoietic cell transplantation
Niranjan Khaire1,2, Urmimala Bhattacharjee1,3, Arjun Dinesan1, Anindita Sinha4, Sanjay Bhadada5, Andrew Pardeep1, Prashant Chhabra1, Ritika Sharma1, Renaissa De1, Shaweta Kaundal1, Kripa Shanker Kasudhan1, Lekshmon KS1, Charanpreet Singh1, Aditya Jandial1, Arihant Jain1, Gaurav Prakash1, Alka Khadwal1, Amol Patil6, Pankaj Malhotra1, Deepesh Lad1,7

1Department of Clinical Hematology & Medical Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

2Hans Messner Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, Toronto, Canada

3Department of Haematology, Barts Health NHS Trust, London, UK

4Department of Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, India

5Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

6Department of Clinical Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

7Leukemia/BMT Program of BC, Division of Hematology, Department of Medicine, University of British Columbia, Vancouver, Canada

RCT, zoledronate, prophylaxis, bone loss, HCT
Submitted:January 21, 2024
Accepted:March 13, 2024
Published online:July 5, 2024


Background: Approximately half of allogeneic hematopoietic cell transplantation (HCT) recipients experience significant bone loss in the early post-HCT period. Only recently have international guidelines started recommending early screening. However, the guidance for intervention remains conservative. In this study, we sought to evaluate the efficacy of pre-transplant prophylactic zoledronate in preventing early bone loss in allogeneic HCT recipients.

Methods: This was an open-label, investigator-initiated, phase 2 randomized controlled trial (RCT) of prophylactic zoledronate versus observation to prevent bone loss in allogeneic HCT recipients. Recipients aged ≥ 18 years of age were included after informed consent and randomized to prophylactic zoledronate 4 mg pre-HCT or observation in a 1:1 ratio. The primary outcome of the study was bone mineral density (BMD) loss at the femoral neck (FN), total hip (TH), and lumbar spine (LS), as assessed using dual-energy X-ray absorptiometry (DXA) on day+100 post-HCT. The secondary outcomes included BMD loss on day+365 and Z scores on day+100 and day+365 at the FN, TH, and LS sites.

Results: The trial was terminated because the interim analysis showed a significant benefit in the intervention arm, with 50% planned recruitment. A total of 40 patients were randomized to the zoledronate and control arms. Both arms were matched for age, sex, diagnosis, pre-HCT steroid exposure, body mass index, human leukocyte antigen (HLA) match, and conditioning intensity. The grade 2-4 acute graft versus host disease (GVHD) incidences were comparable. The primary endpoint of BMD loss at FN and TH at day+100 was significant (5.62% vs. -6.78%, p = 0.009, -1.59 vs. -3.98, p = 0.016, respectively). There was no difference in the secondary endpoint of BMD loss on day+365 compared to that on day+100 or baseline at any BMD site. There was no difference in the Z-scores at any site on day+100 or day+365.

Conclusions: Prophylactic zoledronate prevented early bone loss on day+100. The indicated preemptive zoledronate beyond day+100 in recipients prevented further bone loss. Patients receiving prophylactic zoledronate may benefit from a supplementary dose of the indicated preemptive zoledronate.


Online ISSN:2432-7026