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25.04.2018 | Original Article

Long-term effect of testosterone replacement therapy on bone in hypogonadal men with Klinefelter Syndrome

verfasst von: N. Tahani, L. Nieddu, G. Prossomariti, M. Spaziani, S. Granato, F. Carlomagno, A. Anzuini, A. Lenzi, A. F. Radicioni, E. Romagnoli

Erschienen in: Endocrine | Ausgabe 2/2018

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Abstract

Purpose

To assess different aspects of bone damage in untreated adult patients with Klinefelter Syndrome (KS) before and during testosterone replacement therapy (TRT).

Methods

Fifteen untreated hypogonadal men with KS and 26 control subjects (C) matched for age and BMI were recruited. Sex hormone levels were measured in all subjects. Lumbar spine (LS) and femoral (neck: FN and total hip: TH) bone mineral density (BMD), trabecular bone score (TBS), hip structure analysis (HSA) and fat measures (percentage of fat mass, android/gynoid ratio and visceral adipose tissue) were evaluated by DEXA. In KS patients, blood analysis and DEXA measurements were assessed at baseline and repeated yearly for three years during TRT.

Results

Fat measures were significantly higher in KS than C (p < 0.01). In contrast, mean LS, FN and TH BMD were significantly reduced in KS compared to C (p < 0.01), while there was no difference in TBS. HSA revealed a significantly lower cortical thickness and significantly higher buckling ratio in KS compared to C at all femoral sites (p < 0.01). In KS patients, TRT significantly increased BMD at LS only, but did not improve TBS and HSA parameters. Fat measures were inversely associated with TBS values, and TRT did not influence this relationship.

Conclusions

In untreated hypogonadal men with KS, lumbar and femoral BMD was reduced, and femoral bone quality was impaired. Adiposity seemed to have a detrimental effect on lumbar bone microarchitecture, as indirectly evaluated by TBS. However, TRT failed to remedy these negative effects on bone.

A. Bojesen, S. Juul, C.H: Gravholt, Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J. Clin. Endocrinol. Metab. 88(2), 622–626 (2003)CrossRefPubMed

H.F. Klinefelter, E.C. Reifenstein, F. Albright, Syndrome characterized by gynecomastia, aspermatogenesis without A-Leydigism, and increased excretion of follicle-stimulating hormone. J. Clin. Endocrinol. Metab. 2, 615–627 (1942)CrossRef

W.A. Hsueh, T.H. Hsu, D.D. Federman, Endocrine feature of Klinefelter’s syndrome. Medicine 57(5), 447–461 (1978)CrossRefPubMed

A. Bojesen, C. Host, C.H. Gravholt, Klinefelter’s syndrome, type 2 diabetes and the metabolic syndrome: the impact of body composition. Mol. Hum. Reprod. 16(6), 396–401 (2010)CrossRefPubMed

V. Breuil, L. Euller-Ziegler, Gonadal dysgenesis and bone metabolism. Jt. Bone Spine 68(1), 26–33 (2001)CrossRef

A. Ferlin, M. Schipilliti, A. Di Mambro, C. Vinanzi, C. Foresta, Osteoporosis in Klinefelter’s syndrome. Mol. Hum. Reprod. 16(6), 402–410 (2010)CrossRefPubMed

J.P. Van den Bergh, A.R. Hermus, A.I. Spruyt, C.G. Sweep, F.H. Corstens, A.G. Smals, Bone mineral density and quantitative ultrasound parameters in patients with Klinefelter’s syndrome after long-term testosterone substitution. Osteoporos. Int. 12(1), 55–62 (2001)CrossRefPubMed

A.M. Isidori, G. Balercia, A.E. Calogero, G. Corona, A. Ferlin, S. Francavilla, D. Santi, M. Maggi, Outcomes of androgen reolacement therapy in adult male hypogonadism: recommendations from the Italian Society of endocrinology. J. Endocrinol. Invest. 38, 103–112 (2015)CrossRefPubMed

F.H. Wong, K.K. Pun, C. Wang, Loss of bone mass in patients with Klinefelter’s syndrome despite sufficient testosterone replacement. Osteoporos. Int. 3(1), 3–7 (1993)CrossRefPubMed

10.

J.T. Seo, J.S. Lee, T.H. Oh, K.J. Joo, The clinical significance of bone mineral density and testosterone levels in Korean men with non-mosaic Klinefelter’s syndrome. BJU Int. 99(1), 141–146 (2007)CrossRefPubMed

11.

A.M. Rathbun, M. Shardell, D. Orwig, J.R. Hebel, G.E. Hicks, T.J. Beck, J. Magaziner, M.S. Hyg, M.C. Hochberg, Difference in the trajectory of change in bone geometry as measured by hip structural analysis in the narrow neck, intertrochanteric region, and femoral shaft between men and women following hip fracture. Bone 92, 124–131 (2016)CrossRefPubMedPubMedCentral

12.

E. Romagnoli, C. Cipriani, I. Nofroni, C. Castro, M. Angelozzi, A. Scarpiello, J. Pepe, D. Diacinti, S. Piemonte, V. Carnevale, S. Minisola, “Trabecular Bone Score” (TBS): an indirect measure of bone micro-architecture in postmenopausal patients with primary hyperparathyroidism. Bone 53, 154–159 (2013)CrossRefPubMed

13.

E. Romagnoli, C. Lubrano, V. Carnevale, D. Costantini, L. Nieddu, S. Morano, S. Migliaccio, L. Gnessi, A. Lenzi, Assessment of trabecular bone score (TBS) in overweight/obese men: effect of metabolic and anthropometric factors. Endocrine 54(2), 342–347 (2016)CrossRefPubMed

14.

K. Ramamurthi, O. Ahmad, K. Engelke, R.H. Taylor, K. Zhu, S. Gustafsson, R.L. Prince, K.E. Wilson, An in vivo comparison of hip structure analysis (HSA) with measurements obtained by QCT. Osteoporos. Int. 23(2), 543–551 (2012)CrossRefPubMed

15.

V. Bousson, C. Bergot, B. Sutter, P. Levitz, B. Cortet, Scientific Committee of the Group de Recherche et d’Information sur les Ostéoporoses: trabecular bone score (TBS): available knowledge, clinical relevance, and future prospects. Osteoporos. Int. 23(5), 1489–1501 (2012)CrossRefPubMed

16.

L. Pothuaud, P. Carceller, D. Hans, Correlations between grey-level variations in 2D projection images (TBS) and 3D microarchitecture: applications in the study of human trabecular bone microarchitecture. Bone 42(4), 775–787 (2008)CrossRefPubMed

17.

L. Pothuaud, C.L. Benhamou, P. Porion, E. Lespessailles, R. Harba, P. Levitz, Fractal dimension of trabecular bone projection texture is related to three-dimensional microarchitecture. J. Bone Miner. Res. 15(4), 691–699 (2000)CrossRefPubMed

18.

D. Hans, N. Barthe, S. Boutroy, L. Pathuaud, R. Winzenrieth, M.A. Krieg, Correlations between trabecular bone score, measured using anteroposterior dual energy X-ray absorptiometry acquisition, and 3-dimensional parameters of bone microarchitecture: an experimental study on human cadaver vertebrae. J. Clin. Densitom. 14(3), 302–312 (2011)CrossRefPubMed

19.

L. Pothuaud, N. Barthe, M.A. Krieg, N. Mehsen, P. Carceller, D. Hans, Evaluation of the potential use of trabecular bone score to complement bone mineral density in the diagnosis of osteoporosis: a preliminary spine BMD-matched, case-control study. J. Clin. Densitom. 12(2), 170–176 (2009)CrossRefPubMed

20.

D. Hans, E. Šteňová, O. Lamy: The Trabecular Bone Score (TBS) complements DXA and the FRAX as a fracture risk assessment tool in routine clinical practice. Curr. Osteoporos. Rep. (2017). https://doi.org/10.1007/s11914-017-0410-z.

21.

J. Cohen. Statistical Power Analysis for the Behavioral Sciences. (L. Erlbaum Associates, Hillsdale, N.J., 1988)

22.

B.C. Silva, W.D. Leslie, H. Resch, O. Lamy, O. Lesnyak, N. Binkley, E.V. McCloskey, J.A. Kanis, J.P. Bilezikian, Trabecular bone score: a noninvasive analytical method based upon the DXA image. J. Bone Miner. Res. 29(3), 518–530 (2014)CrossRefPubMed

23.

A. Bojsen, N. Birkebaek, K. Kristensen, L. Heickendorff, L. Mosekilde, J.S. Cristiansen, C.H. Gravholt, Bone mineral density in Klinefelter syndrome is reduced and primarily determined by muscle strength and resorptive markers, but not directly by testosterone. Osteoporos. Int. 22(5), 1441–1450 (2011)CrossRef

24.

J.H. Romeo, J. Ybarra, Hypogonadal hypogonadism and osteoporosis in men. Nurs. Clin. North. Am. 42(1), 87–99 (2007)CrossRefPubMed

25.

K. Dupree, A. Dobs, Osteopenia and male hypogonadism. Rev. Urol. 6(6), S30–S34 (2004)PubMedPubMedCentral

26.

P.Y. Liu, R. Kalak, Y. Lue, Y. Jia, K. Erkkila, H. Zhou, M.J. Seibel, C. Wang, R.S. Swerdloff, C.R. Dunstan, Genetic and hormonal control of bone volume, architecture, and remodeling in XXY mice. J. Bone Miner. Res. 25(10), 2148–2154 (2010)CrossRefPubMedPubMedCentral

27.

A. Ferlin, M. Schipilliti, C. Foresta, Bone density and risk of osteoporosis in Klinefelter syndrome. Acta Paediatr. 100(6), 878–884 (2011)CrossRefPubMed

28.

A. Ferlin, M. Schipilliti, C. Vinanzi, A. Garolla, A. Di Mambro, R. Selice, A. Lenzi, C. Foresta, Bone mass in subjects with Klinefelter Syndrome: role of testosterone levels and androgen receptor gene CAG polymorphism. J. Clin. Endocrinol. Metab. 96(4), 739–745 (2011)CrossRef

29.

F. Lanfranco, A. Kamischke, M. Zitzmann, E. Nieschlag, Klinefelter’s syndrome. Lancet 364(9430), 273–283 (2004)CrossRefPubMed

30.

A. Bojesen, K. Kristensen, N.H. Birkebaek, J. Fedder, L. Mosekilde, P. Bennett, P. Laurberg, J. Frystyk, A. Flyvbjerg, J.S. Christiansen, C.H. Gravholt, The metabolic syndrome is frequent in Klinefelter’s syndrome and is associated with abdominal obesity and hypogonadism. Diabetes Care 29(7), 1591–1598 (2006)CrossRefPubMed

31.

C. Høst, A. Skakkebæk, K.A. Groth, A. Bojesen, The role of hypogonadism in Klinefelter Syndrome. Asian J. Androl. 16(2), 185–191 (2014)CrossRefPubMedPubMedCentral

32.

L.E. Aguirre, G. Colleluori, K.E. Fowler, I. Zeb Jan, K. Villareal, C. Qualls, D. Robbins, D.T. Villareal, R. Armamento-Villareal, High aromatase activity in hypogonadal men is associated with higher spine bone mineral density, increased truncal fat and reduced lean mass. Eur. J. Endocrinol. 173, 167–174 (2015)CrossRefPubMedPubMedCentral

33.

L. Aksglaede, C. Molgaard, N.E. Skakkebaek, A. Juul, Normal bone mineral content but unfavourable muscle/fat ratio in Klinefelter syndrome. Arch. Dis. Child. 93(1), 30–34 (2008)CrossRefPubMed

34.

E. Leifke, H.C. Körner, T.M. Link, H.M. Behre, P.E. Peters, E. Nieschlag, Effects of testosterone replacement therapy on cortical and trabecular bone mineral density, vertebral body area and paraspinal muscle area in hypogonadal men. Eur. J. Endocrinol. 138(1), 51–58 (1998)CrossRefPubMed

35.

D.G. Jo, H.S. Lee, Y.M. Joo, J.T. Seo, Effect of testosterone replacement therapy on bone mineral density in patients with Klinefelter Syndrome. Yonsei. Med. J. 54(6), 1331–1335 (2013)CrossRefPubMedPubMedCentral

36.

V.V. Shanbhogue, S. Hansen, N.R. Jorgensen, K. Brixen, C.H. Gravholt, Bone geometry, volumetric density, microarchitecture and estimated bone strength assessed by HR-pQCT in Klinefelter Syndrome. J. Bone Miner. Res. 29(11), 2474–2482 (2014)CrossRefPubMed

37.

P. Martineau, W.D. Leslie, Trabecular bone score (TBS): method and applications. Bone 104, 66–72 (2017)CrossRefPubMed

38.

C.P. Edmondson, E.N. Schwartz, Non-BMD DXA measurements of the hip. Bone 104, 73–83 (2017)CrossRefPubMed

39.

H.R. Choi, S.K. Lim, M.S. Lee, Site-specific effect of testosterone on bone mineral density in male hypogonadism. J. Korean Med. Sci. 10(6), 431–435 (1995)CrossRefPubMedPubMedCentral

40.

S.C. Wong, D. Scott, A. Lim, S. Tandon, P.R. Ebeling, M. Zacharin, Mild deficits of cortical bone in young adults with Klinefelter Syndorme or anorchia treated with testosterone. J. Clin. Endocrinol. Metab. 100(9), 3581–3589 (2015)CrossRefPubMed

41.

F. Saad, A. Aversa, A.M. Isidori, L.J. Gooren, Testosterone as potential effective therapy in treatment of obesity in men with testosterone deficiency: a review. Curr. Diabetes Rev. 8(2), 131–143 (2012)CrossRefPubMedPubMedCentral

42.

X. Bi, S. Ho, Dual energy X- ray absorptiometry quantification of visceral adipose tissue. Int. J. Diabetes Res. 3(2), 22–26 (2014)

43.

A.M. Hill, J. LaForgia, A.M. Coates, J.D. Buckley, P.R. Howe, Estimating abdominal adipose tissue with DXA and anthropometry. Obesity 15(2), 504–510 (2007)CrossRefPubMed

44.

A. Andreoli, G. Scalzo, S. Masala, U. Tarantino, G. Guglielmi, Body composition assessment by dual-energy X-ray absorptiometry (DXA). Radiol. Med. 114(2), 286–300 (2009)CrossRefPubMed

45.

L.K. Micklesfield, J.H. Goedecke, M. Punyanitya, K.E. Wilson, T.L. Kelly, Dual energy X-ray performs as well as clinical computed tomography for the measurement of visceral fat. Obesity 20(5), 1109–1114 (2012)CrossRefPubMed

Titel: Long-term effect of testosterone replacement therapy on bone in hypogonadal men with Klinefelter Syndrome
verfasst von: N. Tahani
L. Nieddu
G. Prossomariti
M. Spaziani
S. Granato
F. Carlomagno
A. Anzuini
A. Lenzi
A. F. Radicioni
E. Romagnoli
Publikationsdatum: 25.04.2018
Verlag: Springer US
Erschienen in: Endocrine / Ausgabe 2/2018
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-018-1604-6

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Long-term effect of testosterone replacement therapy on bone in hypogonadal men with Klinefelter Syndrome