Volumetric Bone Mineral Density in Patients with Childhood Craniopharyngioma[*]

Abstract

As the overall survival rate is high in patients with craniopharyngioma, the prognosis in survivors depends mainly on late effects. Late effects such as hypogonadism, growth hormone deficiency, glucocorticoid overreplacement and obesity have a strong impact on volumetric bone mineral density (vBMD). We analyzed vBMD and possible risk factors for reduced vBMD in 61 patients with childhood craniopharyngioma (29 f; 32 m) and in 14 weight, age, and sex-matched controls. VBMD was quantified by peripheral quantitative computed tomography (pQCT). Endocrine status, hormonal substitution therapy and calcium phosphate metabolism were evaluated.

VBMD was in the lower normal range in 61 craniopharyngioma patients (total radial z-scores: median - 1.5; range - 3.1 to 1.4; trabecular z-scores: median - 0.4; - 2.4 to 2.3). 23 severely obese patients (body mass index [BMI] > 4 SD) had a higher total radial (p < 0.05) and trabecular (p < 0.05) vBMD when compared with 38 non-severely obese patients and 7 weight-matched controls. Although there was no gender difference in terms of obesity, endocrine substitution therapy or calcium phosphate metabolism, male patients had lower total radial (p < 0.01) and trabecular (p < 0.05) vBMD. Only in male patients' vBMD z-scores showed a positive correlation with BMI standard deviation score (SDS) (total radial z-score: Spearman r = 0.38, p = 0.03; trabecular z-score: Spearman r = 0.35, p = 0.04).

We conclude that obesity has a major impact on vBMD in patients with craniopharyngioma. Lean male patients are at special risk for a lower vBMD, whereas female gender and severe obesity seem to have a protective effect regarding vBMD.

Key words

Bone - bone mineral density - craniopharyngioma - obesity - endocrine dysfunction

1 This work was supported by the Deutsche Kinderkrebsstiftung, Bonn, Germany, (www.kinderkrebsstiftung.de). In part presented at the 6th Joint Meeting LWPES/ESPE 2001, Montreal, Quebec, Canada.

References

• 1 Becker G, Kortmann R D, Skalej M, Bamberg M. The role of radiotherapy in the treatment of craniopharyngeoma - indications, results, side effects. Wiegel T, Hinkelbein T, Brock M, Hoell T Controversies in Neuro-Oncology. Front Radiat Ther Oncol. Basel: Karger, Vol. 33. Basel; Karger 1999: 100-113
• 2 Braun M J, Meta M D, Schneider P, Reiners Chr. Clinical evaluation of a high-resolution new peripheral quantitative computerized tomography (pQCT) scanner for the bone density at the lower limbs.  Phys Med Biol. 1998;  43 2279-2294
• 3 Burman P, Johansson A G, Siegbahn A, Vessby B, Karlsson F A. Growth hormone (GH)-deficient men are more responsive to GH replacement therapy than women.  J Clin Endocrinol Metab. 1997;  82 550-555
• 4 Einhaus S L, Sanford R A. Craniopharyngiomas. Albright AL, Pollack IF, Adelson PD Principles and Practice of Pediatric Neurosurgery. New York; Thieme 1999: 545-562
• 5 Fisher P G, Jenab J, Goldthwaite P T, Tihan T, Wharam M D, Foer D R, Burger P C. Outcomes and failure patterns in childhood craniopharyngiomas.  Child's Nerv Syst. 1998;  14 558-563
• 6 Frost H M. The Utah paradigm of skeletal physiology: an overview of its insights for bone, cartilage and collagenous tissue organs.  J Bone Miner Metab. 2000;  18 305-316
• 7 Greulich W W, Pyle S I. Radiographic atlas of skeletal development of the hand and wrist. Stanford; Stanford University Press 1959
• 8 Hayes F J, Fiad T M, McKenna T J. Gender difference in the response of growth hormone (GH)-deficient adults to GH therapy.  Metabolism. 1999;  48 308-313
• 9 Hsieh Y F, Robling A G, Ambrosius W T, Burr D B, Turner C H. Mechanical loading of diaphyseal bone in vivo: the strain threshold for an osteogenic response varies with location.  J Bone Miner Res. 2001;  16 2291-2298
• 10 Johansson A G, Engström B E, Ljunghall S, Karlsson F A, Burman P. Gender difference in the effect of long term growth hormone (GH) treatment on bone in adults with GH deficiency.  J Clin Endocrinol Metab. 1999;  84 2002-2007
• 11 Karsenty G. Leptin controls bone formation through a hypothalamic relay.  Recent Prog Horm Res. 2001;  56 401-415
• 12 Khosla S, Atkinson E J, Riggs B L, Melton III L J. Relationship between body composition and bone mass in women.  J Bone Miner Res. 1996;  11 857-863
• 13 Kruse K, Kracht U, Göpfert G. Renal threshold phosphate concentration (TmPO₄/GFR).  Arch Dis Child. 1982;  57 217-223
• 14 Lehrnbecher T, Müller-Scholden J, Danhauser-Leistner I, Sörensen N, von Stockhausen H B. Perioperative fluid and electrolyte management in children undergoing surgery for craniopharyngioma - A 10-year experience in a single institution.  Child's Nerv Syst. 1998;  14 276-279
• 15 Müller H L, Handwerker G, Wollny B, Faldum A, Sörensen N. Melatonin secretion and increased sleepiness in childhood craniopharyngioma.  J Clin Endocrinol Metab. 2002;  87 4005-4008
• 16 Müller H L, Sörensen N. Kraniopharyngeom 2000 - Multizentrische, prospektive Beobachtungsstudie von Kindern und Jugendlichen mit Kraniopharyngeom. 1st ed. Oldenburg; Verlag Isensee 2001
• 17 Müller H L, Sörensen N. Kraniopharyngeom im Kindes- und Jugendalter. Schmitt-Thomas B, Deutsche Krebsgesellschaft e. V. Kurzgefasste interdisziplinäre Leitlinien 2002. 3rd ed. Munich; W. Zuckschwerdt Verlag 2002: 515-521
• 18 Müller H L, Bueb K, Bartels U, Roth C, Harz K, Graf N, Korinthenberg R, Bettendorf M, Kühl J, Gutjahr P, Sörensen N, Calaminus G. Obesity after childhood craniopharyngioma - German multicenter study on pre-operative risk factors and quality of life.  Klin Pädiatr. 2001;  213 244-249
• 19 Müller-Scholden J, Lehrnbecher T, Müller H L, Bensch J, Hengen R H, Sörensen N, von Stockhausen H B. Radical Surgery in a neonate with craniopharyngioma. Report of a case.  Pediatr Neurosurg. 2000;  33 265-269
• 20 Prader A, Largo R H, Molinari L, Issler C. Physical growth of Swiss children from birth to 20 years of age: First Zürich longitudinal study of growth and development.  Helv Paediatr Acta Suppl. 1988;  52 1-125
• 21 Rauch F, Schoenau E. Changes in bone density during childhood and adolescence: An approach based on bone's biological organization.  J Bone Miner Res. 2001;  16 597-604
• 22 Rolland-Cachera M F, Cole T J, Sempé, Tichet J, Rossignol C, Charraud A. Body mass index variations: centiles from birth to 87 years.  Eur J Clin Nutrition. 1991;  45 13-21
• 23 Roth C, Lakomek M, Müller H L, Harz K J. Obesity in children. Etiology and treatment.  Monatsschr Kinderheilkd. 2002;  150 329-336
• 24 Roth C, Wilken B, Hanefeld F, Schröter W, Leonhardt U. Hyperphagia in children with craniopharyngioma is associated with hyperleptinemia and a failure in the downregulation of appetite.  Eur J Endocrinology. 1998;  138 89-91
• 25 Sambrook P, Lane N E. Corticosteroid osteoporosis.  Best Pract Res Clin Rheumatol. 2001;  15 401-413
• 26 Skaggs D L, Loro M L, Pitukcheewanont P, Tolo V, Gilsanz V. Increased body weight and decreased radial cross-sectional dimensions in girls with forearm fractures.  J Bone Miner Res. 2001;  16 1337-1342
• 27 Taffe D R, Cauley J A, Danielson M, Nevitt M C, Lang T F, Bauer D C, Harris T B. Race and sex effects on the association between muscle strength, soft tissue, and bone mineral density in healthy elders: the health aging, and body composition study.  J Bone Miner Res. 2001;  16 1343-1352
• 28 Tanner J M. Growth and adolescence. Oxford; Blackwell Scientific Publication 1955
• 29 Walton R J, Bijvoet O LM. Nomogram for derivation of renal threshold phosphate concentration.  Lancet. 1975;  ii 309-310
• 30 Webster J. Clinical management of prolactinomas.  Baillieres Best Pract Res Clin Endocrinol Metab. 1999;  13 395-408

1 This work was supported by the Deutsche Kinderkrebsstiftung, Bonn, Germany, (www.kinderkrebsstiftung.de). In part presented at the 6th Joint Meeting LWPES/ESPE 2001, Montreal, Quebec, Canada.