Reduced Bone Mineral Density in Middle-Aged Male Patients with Adult Growth Hormone Deficiency

Abstract

The aim of the work was to investigate the bone mineral density (BMD) in middle-aged male patients with both childhood-onset (CO) and adulthood-onset (AO) adult growth hormone deficiency (AGHD). In this retrospective cross-sectional study in a major medical center in China, dual X-ray absorptiometry was performed in 50 male AGHD patients (average age was 35.2±9.8 years) and 50 age- and BMI-matched non-athletic healthy men. BMD was compared between AGHD patients and controls. Compared with healthy controls, AGHD group had significantly decreased IGF-1 (p1<0.001) and IGF-1 SDS (p1<0.001). Serum testosterone levels were significantly lower in AGHD patients (p1<0.001), mainly in AO AGHD patients (p3<0.001). The BMD of the femoral neck, trochanter, femoral shaft, total hip, and lumbar spine were significantly lower in all AGHD patients compared with healthy controls (all p1<0.05), especially in CO AGHD patients (all p2<0.05). Multiple stepwise linear regression indicated AGHD was negatively correlated with BMD at each site (β<0, p<0.05). Additionally, serum testosterone level was an independent influencing factor of BMD of the femoral neck (β=0.256, p=0.018) and lumbar spine (β=0.219, p=0.040). BMD was significantly reduced in AGHD patients, especially in CO AGHD patients. Our data suggested that the status of growth hormone deficiency and testosterone level were important for maintaining of bone mineral density in middle-aged male patients with AGHD.

Key words

childhood-onset - adulthood-onset - IGF-1 SDS - serum testosterone - bone mass

Publikationsverlauf

Eingereicht: 09. März 2022

Angenommen nach Revision: 12. Mai 2022

Accepted Manuscript online:
12. Mai 2022

Artikel online veröffentlicht:
14. Juli 2022

• References

• 1 Yuen KCJ, Biller BMK, Radovick S. et al. American association of clinical endocrinologists and American college of endocrinology guidelines for management of growth hormone deficiency in adults and patients transitioning from pediatric to adult care. Endocr Pract 2019; 25: 1191-1232
• 2 Stochholm K, Gravholt CH, Laursen T. et al. Incidence of GH deficiency - a nationwide study. Eur J Endocrinol 2006; 155: 61-71
• 3 Melmed S. Pathogenesis and diagnosis of growth hormone deficiency in adults. N Engl J Med 2019; 380: 2551-2562
• 4 Tritos NA, Biller BMK. Current concepts of the diagnosis of adult growth hormone deficiency. Rev Endocr Metab Disorders 2021; 22: 109-116
• 5 Allo Miguel G, Serraclara Plá A, Partida Muñoz ML. et al. Seven years of follow up of trabecular bone score, bone mineral density, body composition and quality of life in adults with growth hormone deficiency treated with rhGH replacement in a single center. Therap Adv Endocrinol Metab 2016; 7: 93-100
• 6 Underwood LE, Attie KM, Baptista J. Growth hormone (GH) dose-response in young adults with childhood-onset GH deficiency: a two-year, multicenter, multiple-dose, placebo-controlled study. J Clin Endocrinol Metab 2003; 88: 5273-5280
• 7 Monson JJ. Long-term experience with GH replacement therapy: efficacy and safety. Eur J Endocrinol 2003; 148: S9-S14
• 8 Giustina A, Mazziotti G. Canalis. Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev 2008; 29: 535-559
• 9 Kaufman J, Taelman P, Vermeulen A. et al. Bone mineral status in growth hormone-deficient males with isolated and multiple pituitary deficiencies of childhood onset. J Clin Endocrinol Metab 1992; 74: 118-123
• 10 Holmes SJ, Economou G, Whitehouse RW. et al. Reduced bone mineral density in patients with adult onset growth hormone deficiency. J Clin Endocrinol Metab 1994; 78: 669-674
• 11 Murray RD, Columb B, Adams JE. et al. Low bone mass is an infrequent feature of the adult growth hormone deficiency syndrome in middle-age adults and the elderly. J Clin Endocrinol Metab 2004; 89: 1124-1130
• 12 Baroncelli GI, Bertelloni S, Sodini F. et al. Longitudinal changes of lumbar bone mineral density (BMD) in patients with GH deficiency after discontinuation of treatment at final height; timing and peak values for lumbar BMD. Clin Endocrinol (Oxf) 2004; 60: 175-184
• 13 Fernholm R, Bramnert M, Hägg E. et al. Growth hormone replacement therapy improves body composition and increases bone metabolism in elderly patients with pituitary disease. J Clin Endocrinol Metab 2000; 85: 4104-4112
• 14 Colao A, Di Somma C, Pivonello R. et al. Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism. J Clin Endocrinol Metab 1999; 84: 1919-1924
• 15 Janssen YJ, Hamdy NA, Frölich M. et al. Skeletal effects of two years of treatment with low physiological doses of recombinant human growth hormone (GH) in patients with adult-onset GH deficiency. J Clin Endocrinol Metab 1998; 83: 2143-2148
• 16 Brabant G, Poll EM, Jönsson P. et al. Etiology, baseline characteristics, and biochemical diagnosis of GH deficiency in the adult: are there regional variations?. Eur J Endocrinol 2009; 161: S25-S31
• 17 Yang H, Zhu H, Yan K. et al. Childhood-onset adult growth hormone deficiency: clinical, hormonal, and radiological assessment in a single center in China. Horm Res Paediatr 2017; 88: 155-159
• 18 Yang H, Yan K, Yuping X. et al. Bone microarchitecture and volumetric bone density impairment in young male adults with childhood-onset growth hormone deficiency. Eur J Endocrinol 2019; 180: 145-153
• 19 Lissett CA, Murray RD, Shalet SM. Timing of onset of growth hormone deficiency is a major influence on insulin-like growth factor I status in adult life. Clin Endocrinol (Oxf) 2002; 57: 35-40
• 20 Molitch ME, Clemmons DR, Malozowski S. et al. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96: 1587-1609
• 21 Group CMAEBO. Chinese experts consensus on prevention and treatment of obesity. Chin J Endocrinol Metab 2011; 27: 711-717
• 22 Zeng Q, Li N, Wang Q. et al. The prevalence of osteoporosis in China, a nationwide, multicenter DXA survey. J Bone Mineral Res 2019; 34: 1789-1797
• 23 Lewiecki E, Gordon C, Baim S. et al. International society for clinical densitometry 2007 adult and pediatric official positions. Bone 2008; 43: 1115-1121
• 24 de Boer H, Blok GJ, van Lingen A. et al. Consequences of childhood-onset growth hormone deficiency for adult bone mass. J Bone Mineral Res 1994; 9: 1319-1326
• 25 Degerblad M, Bengtsson BA, Bramnert M. et al. Reduced bone mineral density in adults with growth hormone (GH) deficiency: increased bone turnover during 12 months of GH substitution therapy. Eur J Endocrinol 1995; 133: 180-188
• 26 Gracia-Marco L, Vicente-Rodríguez G, Valtueña J. et al. Bone mass and bone metabolism markers during adolescence: The HELENA Study. Horm Res Paediatr 2010; 74: 339-350
• 27 Carroll PV, Christ ER, Bengtsson BA. et al. Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. Growth hormone research society scientific committee. J Clin Endocrinol Metab 1998; 83: 382-395
• 28 Kosowicz J, El Ali Z, Ziemnicka K. et al. Abnormalities in bone mineral density distribution and bone scintigraphy in patients with childhood onset hypopituitarism. J Clin Densitom 2007; 10: 332-339
• 29 Yang H, Yan K, Xu Y. et al. Effects of 24 weeks of growth hormone treatment on bone microstructure and volumetric bone density in patients with childhood-onset adult GH deficiency. Int J Endocrinol 2020; 1-9
• 30 Holmes SJ, Shalet SM. Adult growth hormone deficiency and bone mass. Horm Res 1996; 45: 69-71
• 31 Kuzma M, Homerova Z, Dlesk A. et al. Effect of growth hormone on bone status in growth hormone-deficient adults. Bratislavske Lekarske Listy 2013; 114: 689-695
• 32 Hyer SL, Rodin DA, Tobias JH. et al. Growth hormone deficiency during puberty reduces adult bone mineral density. Archiv Disease Childhood 1992; 67: 1472-1474
• 33 Elbornsson M, Götherström G, Bosæus I. et al. Fifteen years of GH replacement increases bone mineral density in hypopituitary patients with adult-onset GH deficiency. Eur J Endocrinol 2012; 166: 787-795
• 34 Thilmany S, McHirgui L, Brunelle C. et al. Correlation between the responses to growth hormone (GH) treatment during childhood and Adulthood in a monocentric cohort of GH-deficient patients. Horm Metab Res 2018; 50: 462-468
• 35 Davidson P, Milne R, Chase D. et al. Growth hormone replacement in adults and bone mineral density: a systematic review and meta-analysis. Clin Endocrinol (Oxf) 2004; 60: 92-98
• 36 Barake M, Klibanski A, Tritos NA. Effects of recombinant human growth hormone therapy on bone mineral density in adults with growth hormone deficiency: a meta-analysis. J Clin Endocrinol Metab 2014; 99: 852-860