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Cecilia Follin, Katarina Link, Thomas Wiebe, Christian Moëll, Jonas Björk and E M Erfurth

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.

Free access

Helene Holmer, Vera Popovic, Bertil Ekman, Cecilia Follin, Ann Britt Siversson and Eva Marie Erfurth

Context

Data on bone mineral density (BMD) are lacking in adults with childhood onset (CO)–craniopharyngioma (CP) with hypothalamic damage from the tumor. In patients with CO GH deficiency, BMD increases during GH treatment.

Objective

The aims were to evaluate BMD in adults with CO–CPs on complete hormone replacement, including long-term GH and to evaluate the impact of hypothalamic damage on these measures.

Design and participants

BMD (dual-energy X-ray absorptiometry), markers of bone turn over, physical activity and calcium intake were assessed in 39 CO–CP adults (20 women), with a median age of 28 (17–57) years, in comparison with matched population controls.

Results

Late puberty induction was recorded in both genders, but reduced androgen levels in females only. Only CP women had lower BMD (P=0.03) at L2–L4, and reduced Z-scores at femoral neck (P=0.004) and L2–L4 (P=0.004). Both genders had increased serum leptin levels (P=0.001), which significantly correlated negatively with BMD at L2–L4 (P=0.003; r=−0.5) and 45% of CP women had Z-score levels ≤−2.0 s.d. Furthermore, 75% of those with a Z-score ≤−2.0 s.d. had hypothalamic involvement by the tumor. Calcium intake (P=0.008) and physical activity (P=0.007) levels were reduced in CP men only. Levels of ostecalcin and crossLaps were increased in CP men only.

Conclusions

Despite continuous GH therapy, low BMD was recorded in CO–CP females. Insufficient estrogen and androgen supplementation during adolescence was the main cause, but hypothalamic involvement with consequent leptin resistance was also strongly associated with low BMD in both genders.