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Review Article

The Role of Growth Hormone Receptor Isoforms and Their Effects in Bone Metabolism and Skeletal Fragility

Author(s): Sabrina Chiloiro*, Federica Mirra, Donfrancesco Federico, Antonella Giampietro, Felicia Visconti, Laura Rossi, Alfredo Pontecorvi, Laura De Marinis and Antonio Bianchi

Volume 27, Issue 12, 2020

Page: [1260 - 1267] Pages: 8

DOI: 10.2174/0929866527666200616151105

Price: $65

Abstract

Acromegaly and Growth Hormone Deficiency (GHD) are associated with skeletal fragility and with an increased prevalence of Vertebral Fractures (VFs). In the most recent years, several authors tried to investigate surrogate markers that may predict the risk of bone fragility in these endocrine disorders. The aim of this review is to evaluate the role of GH receptor polymorphisms in skeletal fragility in patients affected by GHD and acromegaly. In fact, until now, two different isoforms of the GH Receptor (GHR) were described, that differ for the presence or the absence of transcription of the exon 3 of the GHR gene. Both the isoforms produce a functioning receptor, but the exon 3-deleted isoforms (d3-GHR) has a higher sensitivity to endogenous and recombinant GH as compared to the full-length isoform (fl-GHR).

Keywords: Fracture, acromegaly, growth hormone, growth hormone deficiency, vertebral fractures, isoforms.

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[1]
Giustina, A.; Mazziotti, G.; Canalis, E. Growth hormone, insulin-like growth factors, and the skeleton. Endocr. Rev., 2008, 29(5), 535-559.
[http://dx.doi.org/10.1210/er.2007-0036] [PMID: 18436706]
[2]
Killinger, Z.; Kužma, M.; Sterančáková, L.; Payer, J. Osteoarticular changes in acromegaly. Int. J. Endocrinol., 2012, 2012, 839282.
[http://dx.doi.org/10.1155/2012/839282] [PMID: 23008710]
[3]
Hubina, E.; Lakatos, P.; Kovács, L.; Szabolcs, I.; Rácz, K.; Tóth, M.; Szucs, N.; Góth, M.I. Effects of 24 months of Growth Hormone (GH) treatment on serum carboxylated and undercarboxylated osteocalcin levels in GH-deficient adults. Calcif. Tissue Int., 2004, 74(1), 55-59.
[http://dx.doi.org/10.1007/s00223-002-2149-4] [PMID: 14508626]
[4]
Sugiyama, T.; Kawai, S. Carboxylation of osteocalcin may be related to bone quality: A possible mechanism of bone fracture prevention by vitamin K. J. Bone Miner. Metab., 2001, 19(3), 146-149.
[http://dx.doi.org/10.1007/s007740170034] [PMID: 11368299]
[5]
Lancer, S.R.; Bowser, E.N.; Hargis, G.K. The effect of growth hormone on parathyroid function in rats. Endocrinology, 1976, 98(5), 1289-1293.
[http://dx.doi.org/10.1210/endo-98-5-1289] [PMID: 1261522]
[6]
Daughaday, W.H.; Hall, K.; Raben, M.S.; Salmon, W.D., Jr; van den Brande, J.L.; van Wyk, J.J. Somatomedin: Proposed designation for sulphation factor. Nature, 1972, 235(5333), 107.
[http://dx.doi.org/10.1038/235107a0] [PMID: 4550398]
[7]
Green, H.; Morikawa, M.; Nixon, T. A dual effector theory of growth-hormone action. Differentiation, 1985, 29(3), 195-198.
[http://dx.doi.org/10.1111/j.1432-0436.1985.tb00316.x] [PMID: 3908201]
[8]
Zezulak, K.M.; Green, H. The generation of insulin-like growth factor-1--sensitive cells by growth hormone action. Science, 1986, 233(4763), 551-553.
[http://dx.doi.org/10.1126/science.3726546] [PMID: 3726546]
[9]
Ohlsson, C.; Nilsson, A.; Isaksson, O.; Lindahl, A. Growth hormone induces multiplication of the slowly cycling germinal cells of the rat tibial growth plate. Proc. Natl. Acad. Sci. USA, 1992, 89(20), 9826-9830.
[http://dx.doi.org/10.1073/pnas.89.20.9826] [PMID: 1409707]
[10]
McCarthy, T.L.; Centrella, M.; Canalis, E. Cyclic AMP induces insulin-like growth factor I synthesis in osteoblast-enriched cultures. J. Biol. Chem., 1990, 265(26), 15353-15356.
[PMID: 1697590]
[11]
Canalis, E.; Rydziel, S.; Delany, A.M.; Varghese, S.; Jeffrey, J.J. Insulin-like growth factors inhibit interstitial collagenase synthesis in bone cell cultures. Endocrinology, 1995, 136(4), 1348-1354.
[http://dx.doi.org/10.1210/endo.136.4.7895645] [PMID: 7895645]
[12]
Playford, M.P.; Bicknell, D.; Bodmer, W.F.; Macaulay, V.M. Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of β-catenin. Proc. Natl. Acad. Sci. USA, 2000, 97(22), 12103-12108.
[http://dx.doi.org/10.1073/pnas.210394297] [PMID: 11035789]
[13]
Krishnan, V.; Bryant, H.U.; Macdougald, O.A. Regulation of bone mass by Wnt signaling. J. Clin. Invest., 2006, 116(5), 1202-1209.
[http://dx.doi.org/10.1172/JCI28551] [PMID: 16670761]
[14]
Birnbaum, R.S.; Wiren, K.M. Changes in insulin-like growth factor-binding protein expression and secretion during the proliferation, differentiation, and mineralization of primary cultures of rat osteoblasts. Endocrinology, 1994, 135(1), 223-230.
[http://dx.doi.org/10.1210/endo.135.1.8013356] [PMID: 8013356]
[15]
Ahmad, A.M.; Hopkins, M.T.; Fraser, W.D.; Ooi, C.G.; Durham, B.H.; Vora, J.P. Parathyroid hormone secretory pattern, circulating activity, and effect on bone turnover in adult growth hormone deficiency. Bone, 2003, 32(2), 170-179.
[http://dx.doi.org/10.1016/S8756-3282(02)00952-3] [PMID: 12633789]
[16]
Ahmad, A.M.; Hopkins, M.T.; Thomas, J.; Durham, B.H.; Fraser, W.D.; Vora, J.P. Parathyroid responsiveness to hypocalcemic and hypercalcemic stimuli in adult growth hormone deficiency after growth hormone replacement. Am. J. Physiol. Endocrinol. Metab., 2004, 286(6), E986-E993.
[http://dx.doi.org/10.1152/ajpendo.00325.2003] [PMID: 15140756]
[17]
Murray, RD.; Adams, JE.; Shalet, SM. A densitometric and morphometric analysis of the skeleton in adults with varying degrees of growth hormone deficiency. J. Clin. Endocrinol. Metab., 2006, 91, 432-438.
[18]
Kosowicz, J.; El Ali, Z.; Ziemnicka, K.; Sowinski, J. Abnormalities in bone mineral density distribution and bone scintigraphy in patients with childhood onset hypopituitarism. J. Clin. Densitom., 2007, 10(3), 332-339.
[http://dx.doi.org/10.1016/j.jocd.2007.03.098] [PMID: 17470407]
[19]
Colao, A.; Di Somma, C.; Pivonello, R.; Loche, S.; Aimaretti, G.; Cerbone, G.; Faggiano, A.; Corneli, G.; Ghigo, E.; Lombardi, G. Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism. J. Clin. Endocrinol. Metab., 1999, 84(6), 1919-1924.
[http://dx.doi.org/10.1210/jc.84.6.1919] [PMID: 10372687]
[20]
White, H.D.; Ahmad, A.M.; Durham, B.H.; Patwala, A.; Whittingham, P.; Fraser, W.D.; Vora, J.P. Growth hormone replacement is important for the restoration of parathyroid hormone sensitivity and improvement in bone metabolism in older adult growth hormone-deficient patients. J. Clin. Endocrinol. Metab., 2005, 90(6), 3371-3380.
[http://dx.doi.org/10.1210/jc.2004-1650] [PMID: 15741264]
[21]
Janssen, Y.J.; Hamdy, N.A.; Frölich, M.; Roelfsema, F. 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(6), 2143-2148.
[PMID: 9626153]
[22]
Lissett, C.A.; Shalet, S.M. Effects of growth hormone on bone and muscle. Growth Horm. IGF Res., 2000, 10(Suppl. B), S95-S101.
[http://dx.doi.org/10.1016/S1096-6374(00)80018-0] [PMID: 10984262]
[23]
Mazziotti, G.; Bianchi, A.; Cimino, V.; Bonadonna, S.; Martini, P.; Fusco, A.; De Marinis, L.; Giustina, A. Effect of gonadal status on bone mineral density and radiological spinal deformities in adult patients with growth hormone deficiency. Pituitary, 2008, 11(1), 55-61.
[http://dx.doi.org/10.1007/s11102-007-0069-z] [PMID: 17965964]
[24]
Stall, G.M.; Harris, S.; Sokoll, L.J.; Dawson-Hughes, B. Accelerated bone loss in hypothyroid patients overtreated with L-thyroxine. Ann. Intern. Med., 1990, 113(4), 265-269.
[http://dx.doi.org/10.7326/0003-4819-113-4-265] [PMID: 2375563]
[25]
Mazziotti, G.; Angeli, A.; Bilezikian, J.P.; Canalis, E.; Giustina, A. Glucocorticoid-induced osteoporosis: An update. Trends Endocrinol. Metab., 2006, 17(4), 144-149.
[http://dx.doi.org/10.1016/j.tem.2006.03.009] [PMID: 16678739]
[26]
Wüster, C.; Abs, R.; Bengtsson, B.A.; Bennmarker, H.; Feldt-Rasmussen, U.; Hernberg-Ståhl, E.; Monson, J.P.; Westberg, B.; Wilton, P. KIMS Study Group and the KIMS International Board. Pharmacia & Upjohn International Metabolic Database. The influence of growth hormone deficiency, growth hormone replacement therapy, and other aspects of hypopituitarism on fracture rate and bone mineral density. J. Bone Miner. Res., 2001, 16(2), 398-405.
[http://dx.doi.org/10.1359/jbmr.2001.16.2.398] [PMID: 11204440]
[27]
Rosen, T.; Wilhelmsen, L.; Landin-Wilhelmsen, K.; Lappas, G.; Bengtsson, BA. Increased fracture frequency in adult patients with hypopituitarism and GH deficiency. Eur. J. Endocrinol., 1997, 137(3), 240–245.
[http://dx.doi.org/10.1530/eje.0.1370240]
[28]
Bouillon, R.; Koledova, E.; Bezlepkina, O.; Nijs, J.; Shavrikhova, E.; Nagaeva, E.; Chikulaeva, O.; Peterkova, V.; Dedov, I.; Bakulin, A.; Oganov, V.; Attanasio, A.F. Bone status and fracture prevalence in Russian adults with childhood-onset growth hormone deficiency. J. Clin. Endocrinol. Metab., 2004, 89(10), 4993-4998.
[http://dx.doi.org/10.1210/jc.2004-0054] [PMID: 15472196]
[29]
Vestergaard, P.; Jørgensen, J.O.; Hagen, C.; Hoeck, H.C.; Laurberg, P.; Rejnmark, L.; Brixen, K.; Weeke, J.; Andersen, M.; Conceicao, F.L.; Nielsen, T.L.; Mosekilde, L. Fracture risk is increased in patients with GH deficiency or untreated prolactinomas--a case-control study. Clin. Endocrinol. (Oxf.), 2002, 56(2), 159-167.
[http://dx.doi.org/10.1046/j.0300-0664.2001.01464.x] [PMID: 11874406]
[30]
Mazziotti, G.; Bianchi, A.; Bonadonna, S.; Nuzzo, M.; Cimino, V.; Fusco, A.; De Marinis, L.; Giustina, A. Increased prevalence of radiological spinal deformities in active acromegaly: A cross-sectional study in postmenopausal women. J. Bone. Miner. Res., 2006, 20, 1837-1844.
[31]
Bonadonna, S.; Mazziotti, G.; Nuzzo, M.; Bianchi, A.; Fusco, A.; De Marinis, L.; Giustina, A. Increased prevalence of radiological spinal deformities in active acromegaly: a cross-sectional study in postmenopausal women. J. Bone Miner. Res., 2005, 20(10), 1837-1844.
[http://dx.doi.org/10.1359/JBMR.050603] [PMID: 16160741]
[32]
Vestergaard, P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a metaanalysis. Osteoporos. Int., 2007, 18(4), 427–444 278.
[33]
Canalis, E.; Mazziotti, G.; Giustina, A.; Bilezikian, J.P. Glucocorticoid-induced osteoporosis: Pathophysiology and therapy. Osteoporos. Int., 2007, 18(10), 1319-1328.
[http://dx.doi.org/10.1007/s00198-007-0394-0] [PMID: 17566815]
[34]
Mazziotti, G.; Frara, S.; Giustina, A. Pituitary diseases and bone. Endocr. Rev., 2018, 39(4), 440-488.
[http://dx.doi.org/10.1210/er.2018-00005] [PMID: 29684108]
[35]
Parkinson, C.; Kassem, M.; Heickendorff, L.; Flyvbjerg, A.; Trainer, P.J. Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal. J. Clin. Endocrinol. Metab., 2003, 88(12), 5650-5655.
[http://dx.doi.org/10.1210/jc.2003-030772] [PMID: 14671148]
[36]
Chiloiro, S.; Giampietro, A.; Frara, S.; Bima, C.; Donfrancesco, F.; Fleseriu, C.M.; Pontecorvi, A.; Giustina, A.; Fleseriu, M.; De Marinis, L.; Bianchi, A. Effects of pegvisomant and pasireotide LAR on vertebral Fractures in acromegaly resistant to first-generation SRLs. J. Clin. Endocrinol. Metab., 2020, 105(3), 1-8.
[http://dx.doi.org/10.1210/clinem/dgz054] [PMID: 31613969]
[37]
Kamenický, P.; Mazziotti, G.; Lombès, M.; Giustina, A.; Chanson, P. Growth hormone, insulin-like growth factor-1, and the kidney: Pathophysiological and clinical implications. Endocr. Rev., 2014, 35(2), 234-281.
[http://dx.doi.org/10.1210/er.2013-1071] [PMID: 24423979]
[38]
Mormando, Chiloiro S; Piacenti , S Metabolismo osseo e rischio di frattura nel paziente acromegalico. Pituitary Focus. Anno I , 2012, 1 (3).
[39]
Romijn, J.A. Acromegalic arthropathy: current perspectives. Endocrine, 2013, 43(2), 245-246.
[http://dx.doi.org/10.1007/s12020-012-9781-1] [PMID: 22941465]
[40]
Mazziotti, G.; Porcelli, T.; Mormando, M.; De Menis, E.; Bianchi, A.; Mejia, C.; Mancini, T.; De Marinis, L.; Giustina, A. Vertebral fractures in males with prolactinoma. Endocrine, 2011, 39(3), 288-293.
[http://dx.doi.org/10.1007/s12020-011-9462-5] [PMID: 21479837]
[41]
Mazziotti, G.; Bianchi, A.; Bonadonna, S.; Cimino, V.; Patelli, I.; Fusco, A.; Pontecorvi, A.; De Marinis, L.; Giustina, A. Prevalence of vertebral fractures in men with acromegaly. J. Clin. Endocrinol. Metab., 2008, 93(12), 4649-4655.
[http://dx.doi.org/10.1210/jc.2008-0791] [PMID: 18827004]
[42]
Kelly, P.A.; Djiane, J.; Postel-Vinay, M.C.; Edery, M. The prolactin/growth hormone receptor family. Endocr. Rev., 1991, 12(3), 235-251.
[http://dx.doi.org/10.1210/edrv-12-3-235] [PMID: 1935820]
[43]
Bazan, J.F. Structural design and molecular evolution of a cytokine receptor superfamily. Proc. Natl. Acad. Sci. USA, 1990, 87(18), 6934-6938.
[http://dx.doi.org/10.1073/pnas.87.18.6934] [PMID: 2169613]
[44]
Leung, D.W.; Spencer, S.A.; Cachianes, G.; Hammonds, R.G.; Collins, C.; Henzel, W.J.; Barnard, R.; Waters, M.J.; Wood, W.I. Growth hormone receptor and serum binding protein: Purification, cloning and expression. Nature, 1987, 330, 537-543.
[http://dx.doi.org/10.1038/330537a0]
[45]
Godowski, P.J.; Leung, D.W.; Meacham, L.R.; Galgani, J.P.; Hellmiss, R.; Keret, R.; Rotwein, P.S.; Parks, J.S.; Laron, Z.; Wood, W.I. Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism. Proc. Natl. Acad. Sci. USA, 1989, 86(20), 8083-8087.
[http://dx.doi.org/10.1073/pnas.86.20.8083] [PMID: 2813379]
[46]
Pekhletsky, R.I.; Chernov, B.K.; Rubtsov, P.M. Variants of the 5′-untranslated sequence of human growth hormone receptor mRNA. Mol. Cell. Endocrinol., 1992, 90(1), 103-109.
[http://dx.doi.org/10.1016/0303-7207(92)90107-H] [PMID: 1301391]
[47]
Urbanek, M; MacLeod, JN; Cooke, NE; Liebhaber, SA Expression of a human growth hormone (hGH) receptor isoform is predicted by tissue-specific alternative splicing of exon 3 of the hGHreceptor gene transcript. Mol Endocrinol, 1992, 6(2), 279-287.
[48]
Wickelgren, R.B.; Landin, K.L.; Ohlsson, C.; Carlsson, L.M. Expression of exon 3-retaining and exon 3-excluding isoforms of the human growth hormone-receptor is regulated in an interindividual, rather than a tissue-specific, manner. J. Clin. Endocrinol. Metab., 1995, 80(7), 2154-2157.
[PMID: 7608270]
[49]
Dos Santos, C.; Essioux, L.; Teinturier, C.; Tauber, M.; Goffin, V.; Bougnères, P. A common polymorphism of the growth hormone receptor is associated with increased responsiveness to growth hormone. Nat. Genet., 2004, 36(7), 720-724.
[http://dx.doi.org/10.1038/ng1379] [PMID: 15208626]
[50]
Sobrier, M.L.; Duquesnoy, P.; Duriez, B.; Amselem, S.; Goossens, M. Expression and binding properties of two isoforms of the human growth hormone receptor. FEBS Lett., 1993, 319(1-2), 16-20.
[http://dx.doi.org/10.1016/0014-5793(93)80028-S] [PMID: 8454051]
[51]
Binder, G.; Baur, F.; Schweizer, R.; Ranke, M.B. The d3-growth hormone (GH) receptor polymorphism is associated with increased responsiveness to GH in Turner syndrome and short small-for-gestational-age children. J. Clin. Endocrinol. Metab., 2006, 91(2), 659-664.
[http://dx.doi.org/10.1210/jc.2005-1581] [PMID: 16291706]
[52]
Jorge, A.A.; Marchisotti, F.G.; Montenegro, L.R.; Carvalho, L.R.; Mendonca, B.B.; Arnhold, I.J. Growth hormone (GH) pharmacogenetics: Influence of GH receptor exon 3 retention or deletion on first-year growth response and final height in patients with severe GH deficiency. J. Clin. Endocrinol. Metab., 2006, 91(3), 1076-1080.
[http://dx.doi.org/10.1210/jc.2005-2005] [PMID: 16291702]
[53]
Bianchi, A.; Giampietro, A.; Tartaglione, L.; Chiloiro, S.; Gentilella, R.; Bima, C.; Anile, C.; Olivi, A.; Pontecorvi, A.; De Marinis, L. Short- and long-term responsiveness to low dose growth hormone (GH) in adult GH deficiency: Role of GH receptor polymorphism. J. Neuroendocrinol., 2019, 31(4), e12692.
[http://dx.doi.org/10.1111/jne.12692] [PMID: 30712287]
[54]
Glad, C.A.; Carlsson, L.M.; Melander, O.; Almgren, P.; Sjöström, L.; Nilsson, S.; Larsson, I.; Svensson, P.A.; Johannsson, G. The GH receptor exon 3 deleted/full-length polymorphism is associated with central adiposity in the general population. Eur. J. Endocrinol., 2015, 172(2), 123-128.
[http://dx.doi.org/10.1530/EJE-14-0723] [PMID: 25391539]
[55]
Filopanti, M.; Giavoli, C.; Grottoli, S.; Bianchi, A.; De Marinis, L.; Ghigo, E.; Spada, A. The exon 3-deleted growth hormone receptor: molecular and functional characterization and impact on GH/IGF-I axis in physiological and pathological conditions. J. Endocrinol. Invest., 2011, 34(11), 861-868.
[http://dx.doi.org/10.1007/BF03346731] [PMID: 22322534]
[56]
Moyes, V.J.; Walker, D.M.; Owusu-Antwi, S.; Maher, K.T.; Metherell, L.; Akker, S.A.; Monson, J.P.; Clark, A.J.L.; Drake, W.M. d3-GHR genotype does not explain heterogeneity in GH responsiveness in hypopituitary adults. Clin. Endocrinol. (Oxf.), 2010, 72(6), 807-813.
[http://dx.doi.org/10.1111/j.1365-2265.2009.03768.x] [PMID: 20039885]
[57]
Mormando, M.; Chiloiro, S.; Bianchi, A.; Giampietro, A.; Angelini, F.; Tartaglione, L.; Nasto, L.; Milardi, D.; Formenti, A.M.; Giustina, A.; De Marinis, L. Growth hormone receptor isoforms and fracture risk in adult-onset growth hormone-deficient patients. Clin. Endocrinol. (Oxf.), 2016, 85(5), 717-724.
[http://dx.doi.org/10.1111/cen.13161] [PMID: 27437620]
[58]
Mormando, M.; Nasto, L.A.; Bianchi, A.; Mazziotti, G.; Giampietro, A.; Pola, E.; Pontecorvi, A.; Giustina, A.; De Marinis, L. GH receptor isoforms and skeletal fragility in acromegaly. Eur. J. Endocrinol., 2014, 171(2), 237-245.
[http://dx.doi.org/10.1530/EJE-14-0205] [PMID: 24866575]
[59]
Turgut, S.; Akın, F.; Ayada, C.; Topsakal, S.; Yerlikaya, E.; Turgut, G. The growth hormone receptor polymorphism in patients with acromegaly: Relationship to BMI and glucose metabolism. Pituitary, 2012, 15(3), 374-379.
[http://dx.doi.org/10.1007/s11102-011-0329-9] [PMID: 21744231]
[60]
Wassenaar, M.J.; Biermasz, N.R.; Pereira, A.M.; van der Klaauw, A.A.; Smit, J.W.; Roelfsema, F.; van der Straaten, T.; Cazemier, M.; Hommes, D.W.; Kroon, H.M.; Kloppenburg, M.; Guchelaar, H.J.; Romijn, J.A. The exon-3 deleted growth hormone receptor polymorphism predisposes to long-term complications of acromegaly. J. Clin. Endocrinol. Metab., 2009, 94(12), 4671-4678.
[http://dx.doi.org/10.1210/jc.2009-1172] [PMID: 19864451]
[61]
Diamond, T.; Nery, L.; Posen, S. Spinal and peripheral bone mineral densities in acromegaly: The effects of excess growth hormone and hypogonadism. Ann. Intern. Med., 1989, 111(7), 567-573.
[http://dx.doi.org/10.7326/0003-4819-111-7-567] [PMID: 2774387]
[62]
Wassenaar, M.J.; Biermasz, N.R.; Hamdy, N.A.; Zillikens, M.C.; van Meurs, J.B.; Rivadeneira, F.; Hofman, A.; Uitterlinden, A.G.; Stokkel, M.P.; Roelfsema, F.; Kloppenburg, M.; Kroon, H.M.; Romijn, J.A.; Pereira, A.M. 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.
[http://dx.doi.org/10.1530/EJE-10-1005] [PMID: 21257726]
[63]
Battista, C.; Chiodini, I.; Muscarella, S.; Guglielmi, G.; Mascia, M.L.; Carnevale, V.; Scillitani, A. Spinal volumetric trabecular bone mass in acromegalic patients: A longitudinal study. Clin. Endocrinol. (Oxf.), 2009, 70(3), 378-382.
[http://dx.doi.org/10.1111/j.1365-2265.2008.03322.x] [PMID: 18616713]
[64]
Madeira, M; Neto, LV; de Lima, GA; Moreira, RO; de Mendonc¸a, LM; Gadelha, MR; Farias, ML Effects of GH–IGF-I excess and gonadal status on bone mineral density and body composition in patients with acromegaly. Osteoporosis International , 2010, 21, 2019–2025.
[http://dx.doi.org/10.1007/s00198-009-1165-x]
[65]
Mazziotti, G.; Bianchi, A.; Porcelli, T.; Mormando, M.; Maffezzoni, F.; Cristiano, A.; Giampietro, A.; De Marinis, L.; Giustina, A. Vertebral fractures in patients with acromegaly: A 3-year prospective study. J. Clin. Endocrinol. Metab., 2013, 98(8), 3402-3410.
[http://dx.doi.org/10.1210/jc.2013-1460] [PMID: 23771918]
[66]
Chiloiro, S.; Mormando, M.; Bianchi, A.; Giampietro, A.; Milardi, D.; Bima, C.; Grande, G.; Formenti, A.M.; Mazziotti, G.; Pontecorvi, A.; Giustina, A.; De Marinis, L. Prevalence of morphometric vertebral fractures in “difficult” patients with acromegaly with different biochemical outcomes after multimodal treatment. Endocrine, 2018, 59(2), 449-453.
[http://dx.doi.org/10.1007/s12020-017-1391-5] [PMID: 28836162]
[67]
Bianchi, A.; Giustina, A.; Cimino, V.; Pola, R.; Angelini, F.; Pontecorvi, A.; De Marinis, L. Influence of growth hormone receptor d3 and full-length isoforms on biochemical treatment outcomes in acromegaly. J. Clin. Endocrinol. Metab., 2009, 94(6), 2015-2022.
[http://dx.doi.org/10.1210/jc.2008-1337] [PMID: 19336510]
[68]
Bianchi, A.; Mazziotti, G.; Tilaro, L.; Cimino, V.; Veltri, F.; Gaetani, E.; Pecorini, G.; Pontecorvi, A.; Giustina, A.; De Marinis, L. Growth hormone receptor polymorphism and the effects of pegvisomant in acromegaly. Pituitary, 2009, 12(3), 196-199.
[http://dx.doi.org/10.1007/s11102-008-0157-8] [PMID: 19089622]

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