Bone mineral density and markers of bone turnover in young adult survivors of childhood lymphoblastic leukaemia.
OBJECTIVE
In order to determine if a serious disease like childhood acute lymphoblastic leukaemia (ALL) and the treatment necessary to cure the patients has long term effects on bone mass, we assessed bone mineral density (BMD) and several parameters involved in bone formation in a group of young adult survivors of ALL.


METHODS
Fourteen male and ten female survivors, treated for ALL in childhood, were cross-sectionally studied, at a mean age of 25.1 years (range 20.1-34.9). All patients, except for two, had received cranial irradiation as part of their treatment (mean radiation dose 2460 cGy).


METHODS
Height and weight were measured. Bone mineral density (BMD) was assessed using dual energy X-ray absorptiometry in the lumbar spine, femoral neck, femoral trochanter and at 1/3 distal and ultradistal in the radius. Early morning serum levels of LH, FSH, oestradiol or testosterone, IGF-1 and IGF-BP3 were determined as well as several specific markers of bone turnover.


RESULTS
Mean height, expressed as standard deviation score (SDS) was -1.12, significantly reduced. BMD in the lumbar spine, femoral neck and at 1/3 distal and ultradistal in the radius, was significantly lower compared to the reference population (P < 0.05). No correlation was found between the BMD values and the cumulative dose of administered cytotoxic drugs, the age at diagnosis of ALL or the duration of follow-up. Mean IGF-1 and IGF-BP3 SDS-scores were -1.24 and -0.78 respectively, significantly reduced. GH stimulation tests performed in a subgroup of 9 patients showed an insufficient peak GH response in at least one test in all tested patients. The values of LH, FSH oestradiol or testosterone were within the normal adult range. Serum markers of bone formation and bone resorption were in the normal range, indicating that bone turnover was normal at the time of the study.


CONCLUSIONS
Bone development in patients cured of acute lymphoblastic leukaemia is disturbed, resulting in a significantly reduced bone mineral density. Impaired growth hormone activity, as a long term effect of cranial irradiation, may be one of the underlying causes as well as the illness itself and the administered cytotoxic drugs. Since a reduced bone mineral density predispose patients to osteoporosis, intervention in order to improve bone mass should be considered.
Department of Paediatrics, Vrije Universiteit, Amsterdam, The Netherlands.
J J
JJ
Hoorweg-Nijman
G
G
Kardos
J C
JC
Roos
H J
HJ
van Dijk
C
C
Netelenbos
C
C
Popp-Snijders
C M
CM
de Ridder
H A
HA
Delemarre-van de Waal
D000328:Adult; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D015519:Bone Density; D016723:Bone Remodeling; D003430:Cross-Sectional Studies; D005260:Female; D005269:Femur; D013006:Growth Hormone / Q000097:blood; D013007:Growth Hormone-Releasing Hormone; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008159:Lumbar Vertebrae; D008297:Male; D010910:Pituitary Irradiation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000503:physiopathology* / Q000532:radiotherapy; D017741:Survivors
D015415:Biomarkers; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone