open access

Ahead of print
Original paper
Published online: 2021-03-22
Submitted: 2021-01-14
Accepted: 2021-03-01
Get Citation

New insights into the metabolic-bone crosstalk in active acromegaly

Stefana Catalina Bilha, Anca Matei, Daniela Constantinescu, Mariana Pavel Tanasa, Raluca Mogos-Cioncu, Petru Cianga, Cristina Preda, Dumitru D. Branisteanu
DOI: 10.5603/EP.a2021.0028
·
Pubmed: 33749810

open access

Ahead of print
Original Paper
Published online: 2021-03-22
Submitted: 2021-01-14
Accepted: 2021-03-01

Abstract

Introduction: Body composition (BC) and adipokines share bone active properties and display an altered profile in acromegaly. The fibroblast growth factor 23 (FGF23)/α-Klotho system, also involved in bone metabolism, is upregulated in growth hormone (GH) excess states. Hence, we aimed to investigate their impact on bone in active acromegaly, compared to controls.

Material and methods: BC, bone mineral density (BMD) (via dual X-ray absorptiometry), serum adipokines (leptin, adiponectin, resistin), parathyroid hormone (PTH), FGF23, α-Klotho, and osteocalcin were assessed in a cross-sectional study enrolling 35 patients with active acromegaly (Acro), compared to 35 sex, age, and body mass index (BMI) one-to-one matched healthy controls (CTL).

Results: The Acro group had higher bone density scores (p< 0.05), lower visceral fat depots (p = 0.011), and lower serum leptin (p < 0.001) but elevated adiponectin (p < 0.001) and resistin (p = 0.001) concentrations when compared to the CTL group. α-Klotho was not related to the GH/IGF1 axis in the Acro group. Resistin was higher in both diabetic and non-diabetic Acro compared to CTL (p < 0.05). Age and BC were the main independent BMD predictors in regression analysis in both groups, while IGF1 was a positive predictor of osteocalcin levels in the Acro (β= 0.48, p = 0.006). The correlations between adipokines, the FGF23/α-Klotho system, and bone parameters, respectively, were lost after adjusting for age and BC.

Conclusions: Age and BC were the main independent BMD predictors in the acromegalic patients with active disease, while IGF1 was independently associated with serum osteocalcin concentrations. The role of α-Klotho in evaluating acromegaly and the associated osteopathy in the long-term appears to be limited. Our study is among the first to report significant serum resistin changes in patients with active acromegaly, opening new insights in the GH-mediated insulin resistance. The GH-resistin relationship merits further investigations.

Abstract

Introduction: Body composition (BC) and adipokines share bone active properties and display an altered profile in acromegaly. The fibroblast growth factor 23 (FGF23)/α-Klotho system, also involved in bone metabolism, is upregulated in growth hormone (GH) excess states. Hence, we aimed to investigate their impact on bone in active acromegaly, compared to controls.

Material and methods: BC, bone mineral density (BMD) (via dual X-ray absorptiometry), serum adipokines (leptin, adiponectin, resistin), parathyroid hormone (PTH), FGF23, α-Klotho, and osteocalcin were assessed in a cross-sectional study enrolling 35 patients with active acromegaly (Acro), compared to 35 sex, age, and body mass index (BMI) one-to-one matched healthy controls (CTL).

Results: The Acro group had higher bone density scores (p< 0.05), lower visceral fat depots (p = 0.011), and lower serum leptin (p < 0.001) but elevated adiponectin (p < 0.001) and resistin (p = 0.001) concentrations when compared to the CTL group. α-Klotho was not related to the GH/IGF1 axis in the Acro group. Resistin was higher in both diabetic and non-diabetic Acro compared to CTL (p < 0.05). Age and BC were the main independent BMD predictors in regression analysis in both groups, while IGF1 was a positive predictor of osteocalcin levels in the Acro (β= 0.48, p = 0.006). The correlations between adipokines, the FGF23/α-Klotho system, and bone parameters, respectively, were lost after adjusting for age and BC.

Conclusions: Age and BC were the main independent BMD predictors in the acromegalic patients with active disease, while IGF1 was independently associated with serum osteocalcin concentrations. The role of α-Klotho in evaluating acromegaly and the associated osteopathy in the long-term appears to be limited. Our study is among the first to report significant serum resistin changes in patients with active acromegaly, opening new insights in the GH-mediated insulin resistance. The GH-resistin relationship merits further investigations.

Get Citation

Keywords

active acromegaly; body composition; adipokines; bone

Supp./Additional Files (1)
Title page
Download
14KB
About this article
Title

New insights into the metabolic-bone crosstalk in active acromegaly

Journal

Endokrynologia Polska

Issue

Ahead of print

Article type

Original paper

Published online

2021-03-22

DOI

10.5603/EP.a2021.0028

Pubmed

33749810

Keywords

active acromegaly
body composition
adipokines
bone

Authors

Stefana Catalina Bilha
Anca Matei
Daniela Constantinescu
Mariana Pavel Tanasa
Raluca Mogos-Cioncu
Petru Cianga
Cristina Preda
Dumitru D. Branisteanu

References (40)
  1. Mazziotti G, Lania AGA, Canalis E. Management of endocrine disease: Bone disorders associated with acromegaly: mechanisms and treatment. Eur J Endocrinol. 2019; 181(2): R45–R56.
  2. Godang K, Olarescu NC, Bollerslev J, et al. Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study. Eur J Endocrinol. 2016; 175(2): 155–164.
  3. Mazziotti G, Maffezzoni F, Frara S, et al. Acromegalic osteopathy. Pituitary. 2016; 20(1): 63–69.
  4. Katznelson L. Alterations in body composition in acromegaly. Pituitary. 2009; 12(2): 136–142.
  5. Olarescu NC, Ueland T, Godang K, et al. Inflammatory adipokines contribute to insulin resistance in active acromegaly and respond differently to different treatment modalities. Eur J Endocrinol. 2014; 170(1): 39–48.
  6. Schmid C, Neidert MC, Tschopp O, et al. Growth hormone and Klotho. J Endocrinol. 2013; 219(2): R37–R57.
  7. Olarescu N, Bollerslev J. The Impact of Adipose Tissue on Insulin Resistance in Acromegaly. Trends Endocrinol Metab. 2016; 27(4): 226–237.
  8. Damjanović SS, Petakov MS, Raicević S, et al. Serum leptin levels in patients with acromegaly before and after correction of hypersomatotropism by trans-sphenoidal surgery. J Clin Endocrinol Metab. 2000; 85(1): 147–154.
  9. Oh KiW, Lee WY, Rhee EJ, et al. The relationship between serum resistin, leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men. Clin Endocrinol (Oxf). 2005; 63(2): 131–138.
  10. Sucunza N, Barahona MJ, Resmini E, et al. A link between bone mineral density and serum adiponectin and visfatin levels in acromegaly. J Clin Endocrinol Metab. 2009; 94(10): 3889–3896.
  11. Madeira M, Neto LV, de Lima GAB, et al. Effects of GH-IGF-I excess and gonadal status on bone mineral density and body composition in patients with acromegaly. Osteoporos Int. 2010; 21(12): 2019–2025.
  12. Komaba H, Kaludjerovic J, Hu DZ, et al. Klotho expression in osteocytes regulates bone metabolism and controls bone formation. Kidney Int. 2017; 92(3): 599–611.
  13. Jawiarczyk-Przybyłowska A, Halupczok-Żyła J, Bolanowski M. Soluble α-Klotho - a new marker of acromegaly? Endokrynol Pol. 2016; 67(4): 390–396.
  14. Katznelson L, Laws ER, Melmed S, et al. Endocrine Society. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014; 99(11): 3933–3951.
  15. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001; 285(6): 785–795.
  16. Wassenaar MJE, Biermasz NR, Hamdy NAT, et al. High prevalence of vertebral fractures despite normal bone mineral density in patients with long-term controlled acromegaly. Eur J Endocrinol. 2011; 164(4): 475–483.
  17. Mazziotti G, Biagioli E, Maffezzoni F, et al. Bone turnover, bone mineral density, and fracture risk in acromegaly: a meta-analysis. J Clin Endocrinol Metab. 2015; 100(2): 384–394.
  18. Almeida M, Laurent MR, Dubois V, et al. Estrogens and Androgens in Skeletal Physiology and Pathophysiology. Physiol Rev. 2017; 97(1): 135–187.
  19. Sneve M, Emaus N, Joakimsen RM, et al. The association between serum parathyroid hormone and bone mineral density, and the impact of smoking: the Tromso Study. Eur J Endocrinol. 2008; 158(3): 401–409.
  20. Kota S, Jammula S, Kota S, et al. Correlation of vitamin D, bone mineral density and parathyroid hormone levels in adults with low bone density. Indian J Orthop. 2013; 47(4): 402–407.
  21. West DWD, Phillips SM. Anabolic processes in human skeletal muscle: restoring the identities of growth hormone and testosterone. Phys Sportsmed. 2010; 38(3): 97–104.
  22. Edwards MH, Ward KA, Ntani G, et al. Lean mass and fat mass have differing associations with bone microarchitecture assessed by high resolution peripheral quantitative computed tomography in men and women from the Hertfordshire Cohort Study. Bone. 2015; 81: 145–151.
  23. Olarescu NC, Heck A, Godang K, et al. The Metabolic Risk in Patients Newly Diagnosed with Acromegaly Is Related to Fat Distribution and Circulating Adipokines and Improves after Treatment. Neuroendocrinology. 2016; 103(3-4): 197–206.
  24. Freda PU, Shen W, Heymsfield SB, et al. Lower visceral and subcutaneous but higher intermuscular adipose tissue depots in patients with growth hormone and insulin-like growth factor I excess due to acromegaly. J Clin Endocrinol Metab. 2008; 93(6): 2334–2343.
  25. Sucunza N, Barahona MJ, Resmini E, et al. Gender dimorphism in body composition abnormalities in acromegaly: males are more affected than females. Eur J Endocrinol. 2008; 159(6): 773–779.
  26. Bilha SC, Branisteanu D, Buzduga C, et al. Modifications in the spectrum of bone mass predictive factors with menopausal status. Endocr Res. 2018; 43(3): 176–185.
  27. Kim JH, Choi HJ, Ku EJ, et al. Regional body fat depots differently affect bone microarchitecture in postmenopausal Korean women. Osteoporos Int. 2016; 27(3): 1161–1168.
  28. Roemmler J, Otto B, Arafat AM, et al. Influence of pegvisomant on serum ghrelin and leptin levels in acromegalic patients. Eur J Endocrinol. 2010; 163(5): 727–734.
  29. Bolanowski M, Milewicz A, Bidzińska B, et al. Serum leptin levels in acromegaly — a significant role for adipose tissue and fasting insulin/glucose ratio. Med Sci Monit. 2002; 8(10): CR685–R689.
  30. Sirbu AE, Buburuzan L, Kevorkian S, et al. Adiponectin expression in visceral adiposity is an important determinant of insulin resistance in morbid obesity. Endokrynol Pol. 2018; 69(3): 252–258.
  31. Gurbulak S, Akin F, Yerlikaya E, et al. Adiponectin and Cardiac Hypertrophy in Acromegaly. Adv Clin Exp Med. 2016; 25(3): 449–455.
  32. Ronchi CL, Corbetta S, Cappiello V, et al. Circulating adiponectin levels and cardiovascular risk factors in acromegalic patients. Eur J Endocrinol. 2004; 150(5): 663–669.
  33. Menzaghi C, Trischitta V. The Adiponectin Paradox for All-Cause and Cardiovascular Mortality. Diabetes. 2018; 67(1): 12–22.
  34. Silha JV, Krsek M, Hana V, et al. Perturbations in adiponectin, leptin and resistin levels in acromegaly: lack of correlation with insulin resistance. Clin Endocrinol (Oxf). 2003; 58(6): 736–742.
  35. Sarmento-Cabral A, Peinado JR, Halliday LC, et al. Adipokines (Leptin, Adiponectin, Resistin) Differentially Regulate All Hormonal Cell Types in Primary Anterior Pituitary Cell Cultures from Two Primate Species. Sci Rep. 2017; 7: 43537.
  36. Delhanty PJD, Mesotten D, McDougall F, et al. Growth hormone rapidly induces resistin gene expression in white adipose tissue of spontaneous dwarf (SDR) rats. Endocrinology. 2002; 143(6): 2445–2448.
  37. Dąbrowska AM, Tarach JS. Soluble Klotho protein as a novel serum biomarker in patients with acromegaly. Arch Med Sci. 2016; 12(1): 222–226.
  38. Varewijck AJ, van der Lely AJ, Neggers SJ, et al. In active acromegaly, IGF1 bioactivity is related to soluble Klotho levels and quality of life. Endocr Connect. 2014; 3(2): 85–92.
  39. Janssen JA. Mechanisms of putative IGF-I receptor resistance in active acromegaly. Growth Horm IGF Res. 2020; 52: 101319.
  40. Kohler S, Tschopp O, Sze L, et al. Monitoring for potential residual disease activity by serum insulin-like growth factor 1 and soluble Klotho in patients with acromegaly after pituitary surgery: is there an impact of the genomic deletion of exon 3 in the growth hormone receptor (d3-GHR) gene on "safe" GH cut-off values? Gen Comp Endocrinol. 2013; 188: 282–287.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Via MedicaWydawcą serwisu jest  "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl