Early bone loss in Indian patients undergoing allogeneic hematopoietic cell transplantation

BACKGROUND : There is a lack of prospective studies to address the issue of timing of bone mineral density (BMD) measurement and anti-resorptive therapy before and after allogeneic hematopoietic cell transplantation (allo-HCT), specifically in the younger population (age < 40 years). This study evaluated the incidence and risk factors of poor BMD in young Indian patients undergoing allogeneic hematopoietic cell transplant and the effect of anti-resorptive therapy in allogeneic transplant recipients who are at high risk for severe bone loss. METHODS : This was a single-center, prospective study conducted from 2016 to 2019. All patients aged ≥ 12 years undergoing allo-HCT were included in the study. Data regarding the risk factors for osteoporosis, underlying diagnoses, and HCT characteristics were recorded. BMD was measured by dual-energy X-ray absorptiometry (DXA) (HOLOGIC Discovery A) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) at pre-HCT, day+100, and day+365 post-HCT. Patients with Z-score ≤ -2 at day+100 were given one dose (4 mg) of intravenous zoledronate. Patients with moderate to severe chronic graft-versus-host disease (GVHD) also received a dose of zoledronate if they had not received it earlier. RESULTS : The median age of our cohort was 24 years (IQR 18.5 – 39.5). Day+100 DXA was available for 25 (54.3%) patients, a paired day+100, and day+365 DXA was available for 15 patients. For pre-HCT, a Z-score ≤ -2 was seen in 30% of patients. For day+100 post-HCT, a Z-score ≤ -2 was seen in 44% of patients. Low body mass index was associated with a Z-score ≤ -2 (median 18 vs. 23 kg/m(2), P = 0.04). Despite a single dose of zoledronate in this cohort, the median Δ BMD (day+365 - day+100) loss at FN and LS was -0.8% to -3.7%, respectively. Seven (64%) of these patients also had moderate-severe chronic GVHD. CONCLUSIONS : BMD below the expected range for age (Z-score ≤ -2) was present in one-third of young Indian patients undergoing allo-HCT in this single center study. Without intervention, up to half of the patients had a Z-score ≤ -2 at day+100 post-HCT. BMD loss at day+100 persisted at day+365 despite anti-resorptive therapy.