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13.02.2022 | Original Research

Klinefelter Bone Microarchitecture Evolution with Testosterone Replacement Therapy

verfasst von: A. Piot, I. Plotton, S. Boutroy, J. Bacchetta, S. Ailloud, H. Lejeune, R. D. Chapurlat, P. Szulc, C. B. Confavreux

Erschienen in: Calcified Tissue International | Ausgabe 1/2022

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Abstract

Klinefelter Syndrome (KS) patients, defined by a 47 XXY karyotype, have increased risk of fragility fractures. We have assessed bone microarchitecture by high resolution peripheral quantitative CT (HR-pQCT) at the radius and tibia in young KS patients, naïve from testosterone replacement therapy (TRT). Areal bone mineral density (BMD) and body composition were assessed by dual X-ray absorptiometry (DXA). Total testosterone (tT) was measured at baseline. Bone measurements have been repeated after 30 months of TRT. We enrolled 24 KS patients and 72 age-matched controls. KS patients were (mean ± SD) 23.7 ± 7.8 year-old. KS patients had significantly lower relative appendicular lean mass index (RALM) and lower aBMD at spine and hip than controls. Ten patients (42%) had low tT level (≤ 10.4 nmol/L). At baseline, we observed at radius a marked cortical (Ct) impairment reflected by lower Ct.area, Ct.perimeter, and Ct.vBMD than controls. At tibia, in addition to cortical fragility, we also found significant alterations of trabecular (Tb) compartment with lower trabecular bone volume (BV/TV) and Tb.vBMD as compared to controls. After 30 months of TRT, 18 (75%) KS patients were reassessed. Spine aBMD and RALM significantly increased. At radius, both cortical (Ct.Pm, Ct.Ar, Ct.vBMD, Ct.Th) and trabecular (Tb.vBMD) parameters significantly improved. At tibia, the improvement was found only in the cortical compartment. Young TRT naïve KS patients have inadequate bone microarchitecture at both the radius and tibia, which can improve on TRT.

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Forti G, Corona G, Vignozzi L, Krausz C, Maggi M (2010) Klinefelter’s syndrome: a clinical and therapeutical update. Sex Dev 4(4–5):249–258PubMedCrossRef

Groth KA, Skakkebæk A, Høst C, Gravholt CH, Bojesen A (2013) Clinical review: Klinefelter syndrome—a clinical update. J Clin Endocrinol Metab 98(1):20–30PubMedCrossRef

Swerdlow AJ, Higgins CD, Schoemaker MJ, Wright AF, Jacobs PA (2005) United Kingdom Clinical Cytogenetics Group. Mortality in patients with Klinefelter syndrome in Britain: a cohort study. J Clin Endocrinol Metab 90(12):6516–6522PubMedCrossRef

Bojesen A, Juul S, Birkebæk N, Gravholt CH (2004) Increased mortality in Klinefelter Syndrome. J Clin Endocrinol Metab 89(8):3830–3834PubMedCrossRef

Pizzocaro A, Vena W, Condorelli R, Radicioni A, Rastrelli G, Pasquali D, Selice R, Ferlin A, Foresta C, Jannini EA et al (2020) Testosterone treatment in male patients with Klinefelter syndrome: a systematic review and meta-analysis. J Endocrinol Investig 43(12):1675–1687CrossRef

Stepan JJ, Burckhardt P, Hána V (2003) The effects of three-month intravenous ibandronate on bone mineral density and bone remodeling in Klinefelter’s syndrome: the influence of vitamin D deficiency and hormonal status. Bone 33(4):589–596PubMedCrossRef

van den Bergh JP, Hermus AR, Spruyt AI, Sweep CG, Corstens FH, Smals AG (2001) Bone mineral density and quantitative ultrasound parameters in patients with Klinefelter’s Syndrome after long-term testosterone substitution. Osteoporos Int 12(1):55–62PubMedCrossRef

Behre HM, Kliesch S, Leifke E, Link TM, Nieschlag E (1997) Long-term effect of testosterone therapy on bone mineral density in hypogonadal men. J Clin Endocrinol Metab 82(8):2386–2390PubMedCrossRef

Horowitz M, Wishart JM, O’Loughlin PD, Morris HA, Need AG, Nordin BE (1992) Osteoporosis and Klinefelter’s syndrome. Clin Endocrinol 36(1):113–118CrossRef

10.

Choi HR, Lim SK, Lee MS (1995) Site-specific effect of testosterone on bone mineral density in male hypogonadism. J Korean Med Sci 10(6):431–435PubMedPubMedCentralCrossRef

11.

Foresta C, Ruzza G, Mioni R, Meneghello A, Baccichetti C (1983) Testosterone and bone loss in Klinefelter syndrome. Horm Metab Res 15(1):56–57PubMedCrossRef

12.

Hiéronimus S, Lussiez V, Le Duff F, Ferrari P, Bständig B, Fénichel P (2011) Klinefelter’s syndrome and bone mineral density: is osteoporosis a constant feature? Ann Endocrinol 72(1):14–18CrossRef

13.

Kübler A, Schulz G, Cordes U, Beyer J, Krause U (1992) The influence of testosterone substitution on bone mineral density in patients with Klinefelter’s syndrome. Exp Clin Endocrinol Diabetes 100(3):129–132

14.

Stagi S, Cavalli L, Cavalli T, de Martino M, Brandi ML (2016) Peripheral quantitative computed tomography (pQCT) for the assessment of bone strength in most of bone affecting conditions in developmental age: a review. Ital J Pediatr. https://doi.org/10.1186/s13052-016-0297-9CrossRefPubMedPubMedCentral

15.

Devogelaer JP, De Cooman S, de Deuxchaisnes CN (1992) Low bone mass in hypogonadal males. Effect of testosterone substitution therapy, a densitometric study. Maturitas 15(1):17–23PubMedCrossRef

16.

Smith DA, Walker MS (1977) Changes in plasma steroids and bone density in Klinefelter’s Syndrome. Calcif Tissue Res 22:225–228PubMedCrossRef

17.

Ferlin A, Schipilliti M, Vinanzi C, Garolla A, Di Mambro A, Selice R, Lenzi A, Foresta C (2011) Bone mass in subjects with Klinefelter Syndrome: role of testosterone levels and androgen receptor gene CAG polymorphism. J Clin Endocrinol Metab 96(4):E739–E745PubMedCrossRef

18.

Luisetto G, Mastrogiacomo I, Bonanni G, Pozzan G, Botteon S, Tizian L, Galuppo P (1995) Bone mass and mineral metabolism in Klinefelter’s syndrome. Osteoporos Int 5(6):455–461PubMedCrossRef

19.

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

20.

Vena W, Pizzocaro A, Indirli R, Amer M, Maffezzoni F, Delbarba A, Leonardi L, Balzarini L, Ulivieri FM, Ferlin A et al (2020) Prevalence and determinants of radiological vertebral fractures in patients with Klinefelter Syndrome. Andrology 8(6):1699–1704PubMedCrossRef

21.

Delmas P, Meunier PJ (1981) Osteoporosis in Klinefelter’s syndrome Quantitative bone histological data in 5 cases and relationship with hormonal deficiency (author’s transl). Nouv Presse Med 10(9):687–690PubMed

22.

Liu PY, Kalak R, Lue Y, Jia Y, Erkkila K, Zhou H, Markus JS, Wang C, Swerdloff RS, Dunstan CR (2010) Genetic and hormonal control of bone volume, architecture, and remodeling in XXY mice. J Bone Miner Res 25(10):2148–2154PubMedPubMedCentralCrossRef

23.

Shanbhogue VV, Hansen S, Jørgensen NR, Brixen K, Gravholt CH (2014) Bone geometry, volumetric density, microarchitecture, and estimated bone strength assessed by HR-pQCT in Klinefelter Syndrome. J Bone Miner Res 29(11):2474–2482PubMedCrossRef

24.

Tournaye H, Liu J, Nagy Z, Verheyen G, Van Steirteghem A, Devroey P (1996) The use of testicular sperm for intracytoplasmic sperm injection in patients with necrozoospermia. Fertil Steril 66(2):331–334PubMedCrossRef

25.

Chaitou A, Boutroy S, Vilayphiou N, Munoz F, Delmas PD, Chapurlat R, Szulc P (2010) Association between bone turnover rate and bone microarchitecture in men: the STRAMBO study. J Bone Miner Res 25(11):2313–2323PubMedCrossRef

26.

Bacchetta J, Ginhoux T, Bernoux D, Dubourg L, Ranchin B, Roger C (2019) Assessment of mineral and bone biomarkers highlights a high frequency of hypercalciuria in asymptomatic healthy teenagers. Acta Paediatr 108(12):2253–2260PubMedCrossRef

27.

Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, Snyder PJ, Swerdloff RS, Wu FC, Yialamas MA (2018) Testosterone therapy in men with hypogonadism: an endocrine society* clinical practice guideline. J Clin Endocrinol Metab 103(5):1715–1744PubMedCrossRef

28.

Boutroy S, Bouxsein ML, Munoz F, Delmas PD (2005) In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab 90(12):6508–6515PubMedCrossRef

29.

Szulc P, Boutroy S, Chapurlat R (2018) Prediction of fractures in men using bone microarchitectural parameters assessed by high-resolution peripheral quantitative computed tomography—the prospective STRAMBO study. J Bone Miner Res 33(8):1470–1479PubMedCrossRef

30.

Haider A, Meergans U, Traish A, Saad F, Doros G, Lips P, Gooren L (2014) Progressive improvement of T-scores in men with osteoporosis and subnormal serum testosterone levels upon treatment with testosterone over six years. Int J Endocrinol 2014:496948PubMedPubMedCentral

31.

Wong FH, Pun KK, Wang C (1993) Loss of bone mass in patients with Klinefelter’s Syndrome despite sufficient testosterone replacement. Osteoporos Int 3(1):3–7PubMedCrossRef

32.

Zitzmann M, Aksglaede L, Corona G, Isidori AM, Juul A, T’Sjoen G, Kliesch S, D’Hauwers K, Toppari J, Słowikowska-Hilczer J (2021) European academy of andrology guidelines on Klinefelter Syndrome endorsing organization: European Society of Endocrinology. Andrology 9(1):145–167PubMedCrossRef

33.

Lee YS, Cheng AWF, Ahmed SF, Shaw NJ, Hughes IA (2007) Genital anomalies in Klinefelter’s syndrome. Hormone Res Paediatr 68(3):150–155CrossRef

34.

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

35.

Seo JT, Lee JS, Oh TH, Joo KJ (2007) The clinical significance of bone mineral density and testosterone levels in Korean men with non-mosaic Klinefelter’s Syndrome. BJU Int 99(1):141–146PubMedCrossRef

36.

Bojesen A, Birkebæk N, Kristensen K, Heickendorff L, Mosekilde L, Christiansen JS, Gravholt CH (2011) 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):1441–1450PubMedCrossRef

37.

Wong SC, Scott D, Lim A, Tandon S, Ebeling PR, Zacharin M (2015) Mild deficits of cortical bone in young adults with Klinefelter Syndrome or anorchia treated with testosterone. J Clin Endocrinol Metab 100(9):3581–3589PubMedCrossRef

38.

Eulry F, Bauduceau B, Lechevalier D, Magnin J, Flageat J, Gautier D (1993) Early spinal bone loss in Klinefelter syndrome. X-ray computed tomographic evaluation in 16 cases. Rev du Rhumat Ed Française 60(4):287–291

39.

Bojesen A, Kristensen K, Birkebaek NH, Fedder J, Mosekilde L, Bennett P, Laurberg P, Frystyk J, Flyvbjerg A, Flyvbjerg A (2006) The metabolic syndrome is frequent in Klinefelter’s Syndrome and is associated with abdominal obesity and hypogonadism. Diabetes Care 29(7):1591–1598PubMedCrossRef

40.

Kanakis GA, Nieschlag E (2018) Klinefelter Syndrome: more than hypogonadism. Metabolism 86:135PubMedCrossRef

41.

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

42.

Gennari L, Nuti R, Bilezikian JP (2004) Aromatase activity and bone homeostasis in men. J Clin Endocrinol Metab 89(12):5898–5907PubMedCrossRef

43.

Srinivas-Shankar U, Roberts SA, Connolly MJ, O’Connell MDL, Adams JE, Oldham JA, Wu FC (2010) Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 95(2):639–650PubMedCrossRef

44.

Beilin J, Ball EM, Favaloro JM, Zajac JD (2000) Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines. J Mol Endocrinol 25(1):85–96PubMedCrossRef

45.

Zitzmann M, Depenbusch M, Gromoll J, Nieschlag E (2004) X-chromosome inactivation patterns and androgen receptor functionality influence phenotype and social characteristics as well as pharmacogenetics of testosterone therapy in Klinefelter patients. J Clin Endocrinol Metab 89(12):6208–6217PubMedCrossRef

46.

Bojesen A, Hertz JM, Gravholt CH (2011) Genotype and phenotype in Klinefelter syndrome—impact of androgen receptor polymorphism and skewed X inactivation. Int J Androl 34(6 Pt 2):e642–e648PubMedCrossRef

Titel: Klinefelter Bone Microarchitecture Evolution with Testosterone Replacement Therapy
verfasst von: A. Piot
I. Plotton
S. Boutroy
J. Bacchetta
S. Ailloud
H. Lejeune
R. D. Chapurlat
P. Szulc
C. B. Confavreux
Publikationsdatum: 13.02.2022
Verlag: Springer US
Erschienen in: Calcified Tissue International / Ausgabe 1/2022
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-022-00956-2

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