Intermittent Zoledronic Acid Prevents Bone Loss in Adults after Allogeneic Hematopoietic Cell Transplantation

Abstract

Bone mineral density (BMD) loss is common in survivors of allogeneic hematopoietic cell transplantation (alloHCT). We performed a multicenter, phase II, randomized open-label trial of intravenous zoledronic acid (ZA) to prevent BMD loss in adult recipients of alloHCT with osteopenia before HCT. The treatment group received ZA 4 mg intravenously within 28 days pre-HCT and at 3 and 6 months after HCT. Both treatment and control groups received calcium carbonate and vitamin D supplements. Of 61 patients, 32 were randomized to the ZA cohort and 29 to the control cohorts. More patients in the ZA group had an HCT comorbidity index high-risk score of ≥3 (50% versus 21%, P < .01). Baseline BMD, T-scores, serum osteocalcin, bone alkaline phosphatase, and urine N-telopeptide (UNTX) levels were similar in both cohorts. Thirty patients were evaluable for outcomes (11 from the treatment and 19 from the control group). At 12 months, subjects in the treatment group had an improvement in BMD at the femoral neck (mean change, .018 for ZA group versus -.054 for controls; P = .04) and a significant decline in levels of UNTX (-56 for ZA group versus -9 for control; P = .04) compared with baseline. ZA was well tolerated and not associated with any cases of osteonecrosis of jaw or renal impairment. Lower survival observed in the ZA cohort was likely related to baseline imbalance in HCT-CI scores. Intermittent ZA is effective in preserving long-term bone health in adult alloHCT recipients at risk for osteoporosis.

Factors influencing the late phase of recovery after bone mineral density loss in allogeneic stem cell transplantation survivors

“…25,[31][32][33] A randomized multicenter phase II trial showed intermittent Zoledronic acid preserved long-term bone health in adult SCT recipients at risk for osteoporosis. 34 We expect that the conclusive demonstration by Pundole et al 8 of increased fractures in transplant patients should promote more aggressive efforts to preserve BMD and greater involvement by the transplant team.…”

Ibandronate for the prevention of bone loss after allogeneic stem cell transplantation for hematologic malignancies: a randomized-controlled trial

“…The differences in BMD of the femoral neck and total hip between our study and the study by Grigg et al 18 may be attributable in part to the smaller number of patients, higher median age, predominance of male patients and smaller proportion of patients receiving stem cells from related donors in our study. In the study by Hari et al, 16 three doses of zoledronic acid at 3-month intervals were administered before SCT to those with osteopenia on pre-SCT DEXA scan and considered to be at high risk of post transplantation bone loss. Zoledronic acid prevented bone loss at the lumbar spine and femoral neck.…”

“…at 2 months after allo-SCT and then every 3 months until 2 years 20 (in doses higher than the usual dose in treating osteoporosis), prevented bone loss at the femoral neck. 16,19,20 Collectively, these studies suggest the need for a different bisphosphonate or dosing regimens for more durable maintenance of bone mass following transplantation. Ibandronate, in oral or i.v.…”

“…15 Similar results were observed in another study of zoledronic acid. 16 Two studies of pamidronate in allo-SCT patients showed some promise. In one study, treatment with pamidronate decreased bone loss of the lumbar spine and femoral neck; however, bone loss was not completely prevented in the hip.…”

“…form of zoledronic acid at a dose of 4 mg i.v. before allo-SCT, and at 3 and 6 months after 16 a dose of 4 mg i.v. every 28 days for 3 months 19 and at a dose of 4 mg i.v.…”