Bone loss after childhood acute lymphoblastic leukaemia: an observational study with and without GH therapy

Objective: Bone mineral density (BMD) in survivors of acute lymphoblastic leukaemia (ALL) seems to vary with time, type of treatments and GH status. We aimed to evaluate BMD in ALL patients with GH deficiency (GHD), with and without GH therapy. Design: Case-control study. Methods: We examined 44 (21 women) GHD patients (median 25 years) treated with cranial radiotherapy (18-24 Gy) and chemotherapy and matched population controls for BMD with dual-energy X-ray absorptiometry. For 5 and 8 years, two subgroups with (0.5 mg/day) (n=16) and without GH therapy (n = 13) and matched controls were followed respectively. Results: At baseline, no significant differences in BMD or Z-scores at femoral neck and L2-L4 were recorded (all P > 0.3). After another 8 years with GHD, the Z-scores at femoral neck had significantly decreased compared with baseline (0.0 to -0.5; P < 0.03) and became lower at the femoral neck (P=0.05), and at L2-L4 (P < 0.03), compared with controls. After 5 years of GH therapy, only female ALL patients had a significantly lower femoral neck Z-scores (P=0.03). The female ALL patients reached an IGF1 level of -0.7 S. D. and male patients reached the level of +0.05 S. D. Conclusions: On average, 25 years after diagnosis, GH-deficient ALL patients experienced a significant decrease in Z-scores at femoral neck, and if Z-scores continue to decrease, there could be a premature risk for osteoporosis. GH therapy was not shown to have a clear beneficial effect on BMD. Whether higher GH doses, particularly in women, will improve Z-scores needs further investigation.