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

Abstract

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 dualenergy X-ray absorptiometry. For 5 and 8 years, two subgroups with (0.5 mg/day) (nZ16) and without GH therapy (nZ13) 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 PO0.3). After another 8 years with GHD, the Z-scores at femoral neck had significantly decreased compared with baseline (0.0 to K0.5; P!0.03) and became lower at the femoral neck (PZ0.05), 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 (PZ0.03). The female ALL patients reached an IGF1 level of K0.7 S.D. and male patients reached the level of C0.05 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.

Are Survivors of Childhood Acute Lymphoblastic Leukemia at Increased Risk for Low Bone Mass?

“…Therapy with methotrexate and particularly with corticosteroids is one of the most important factors which can interfere with bone metabolism. Other factors include irradiation and other hormonal deficiencies, especially of Growth Hormone (GH) and gonadotropins [11,21,[39][40][41][42].…”

“…Cranial radiation therapy (CRT) at or above 24 Gy, craniospinal irradiation and total body irradiation (TBI) are some of the primary predictors of suboptimal BMD in ALL survivors [11,[39][40][41]. Low lumbar spine BMD was also associated with male or female gender, white race, lower BMI, and cumulative doses of glucocorticoid of at or above 5,000 mg [41,42].…”

“…Low lumbar spine BMD was also associated with male or female gender, white race, lower BMI, and cumulative doses of glucocorticoid of at or above 5,000 mg [41,42]. GH deficiency, mostly after CRT, may lead to several negative effects on bone mass, so that 25 years after diagnosis, GH-deficient ALL patients may experience a decrease in Z scores at femoral neck [41,42].…”

“…In summary, ALL patients may show a deficit in both trabecular and cortical bone deposition related to host profile (chronological age, sex and genetic predisposition), disease characteristics (risk for recurrence of the disease), direct effects of chemotherapy (methotrexate and glucocorticoids) and/or CRT, in addition to possible hormone deficiencies (gonadal failure or GH insufficiency) [10][11][12][13][14][15][16][17][18][39][40][41][42][43][44][45].…”

Long-term skeletal consequences of childhood acute lymphoblastic leukemia in adult males: a cohort study

“…Previous studies have shown that among adult ALL survivors, hormonal deficiencies, hypogonadism, insulin resistance, and dyslipidemia are prevalent (3,4,5,6). Low bone mineral density (BMD) and osteoporosis are also recognized complications of ALL, and according to some studies, adverse skeletal effects may persist until adulthood (7,8,9,10,11,12).…”