Bone mineral density and markers of bone turnover in young adult survivorsof childhood lymphoblastic leukaemia

OBJECTIVE In order to determine if a serious disease like childhood acute l ymphoblastic leukaemia (ALL) and the treatment necessary to cure the patien ts has long term effects on bone mass, we assessed bone mineral density (BM D) and several parameters involved in bone formation in a group of young ad ult survivors of ALL. DESIGN AND PATIENTS 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 irrad iation as part of their treatment (mean radiation dose 2460 cGy). MEASUREMENTS Height and weight were measured. Bone mineral density (BMD) wa s assessed using dual energy X-ray absorptiometry in the lumbar spine, femo ral neck, femoral trochanter and at 1/3 distal and ultradistal in the radiu s. Early morning serum levels of LH, FSH, oestradiol or testosterone, IGF-1 and IGF-BPS were determined as well as several specific markers of bone tu rnover. 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 di stal 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-s cores were -1.24 and -0.78 respectively, significantly reduced. GH stimulat ion 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 m arkers of bone formation and bone resorption were in the normal range, indi cating that bone turnover was normal at the time of the study. CONCLUSIONS Bone development in patients cured of acute lymphoblastic leuka emia is disturbed, resulting in a significantly reduced bone mineral densit y. Impaired growth hormone activity, as a long term effect of cranial irrad iation, may be one of the underlying causes as well as the illness itself a nd the administered cytotoxic drugs. Since a reduced bone mineral density p redispose patients to osteoporosis, intervention in order to improve bone m ass should be considered.