Hypothalamic involvement and insufficient sex steroid supplementation are associated with low bone mineral density in women with childhood onset craniopharyngioma

Eur J Endocrinol. 2011 Jul;165(1):25-31. doi: 10.1530/EJE-11-0229. Epub 2011 Apr 18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Adolescent
  • Adult
  • Bone Density*
  • Calcium, Dietary / administration & dosage
  • Cohort Studies
  • Craniopharyngioma / drug therapy
  • Craniopharyngioma / physiopathology*
  • Craniopharyngioma / surgery
  • Female
  • Gonadal Steroid Hormones / administration & dosage*
  • Hormone Replacement Therapy
  • Human Growth Hormone / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Motor Activity
  • Osteocalcin / blood
  • Pituitary Neoplasms
  • Puberty, Delayed / etiology
  • Sex Factors
  • Testosterone / blood

Substances

  • Calcium, Dietary
  • Gonadal Steroid Hormones
  • Osteocalcin
  • Human Growth Hormone
  • Testosterone