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Klinefelter Bone Microarchitecture Evolution with Testosterone Replacement Therapy

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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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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors thank Y Bourgin, C Coutisson, B Dancer, D Foesser, N Paquin, C Planckaert, N Trehet-Mendel and V Ripoll for their help to conduct the study. The authors thank François Duboeuf (INSERM UMR 1033) for extracting data on body composition. The authors thank Dr M. Proriol for her advice on growth plate aspect. The authors thank P Robinson (Hospices Civils de Lyon) for editing corrections. This study was supported by a non restricted Research Grant from Roche-Chugai to CC.

Funding

This study was supported by a non restricted Research Grant from Roche-Chugai Pharmaceutical (CC). An institutional funding for the VITADOS cohort was provided by the Programme Hospitalier de Recherche Clinique Inter-régional (PHRCi AURA) (J Bacchetta, 2011).

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Author notes

  1. A. Piot and I. Plotton have contributed equally to this work.

Authors and Affiliations

  1. Département de Rhumatologie, Hospices Civils de Lyon, Lyon, France

    A. Piot, S. Ailloud, R. D. Chapurlat & C. B. Confavreux

  2. INSERM UMR 1033, Université de Lyon, Lyon, France

    A. Piot, S. Boutroy, J. Bacchetta, R. D. Chapurlat, P. Szulc & C. B. Confavreux

  3. Hormonologie et Endocrinologie Moleculaire et Maladies Rares, Hospices Civils de Lyon, Lyon, France

    I. Plotton

  4. Service de Néphrologie Rhumatologie et Dermatologie Pédiatriques, Hospices Civils de Lyon, Lyon, France

    J. Bacchetta

  5. Départment de Médecine de la Reproduction, Hospices Civils de Lyon, Lyon, France

    I. Plotton & H. Lejeune

  6. INSERM UMR 1208, Université de Lyon, Lyon, France

    I. Plotton & H. Lejeune

  7. Service de Rhumatologie Sud, Centre Hospitalier Lyon Sud, 165, Chemin du Grand Revoyet, 69310, Pierre Bénite, France

    C. B. Confavreux

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  1. A. Piot
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Contributions

Study design: IP, SB and CC. Study conduct: IP and CC. Data collection: IP, SA, SB, JB, HL and CC. Data analysis: AP, CC, MP, PS. Data interpretation: AP, CC, PS. Drafting manuscript: AP, CC, PS. Revising manuscript content: IP, SA, SB, JB, HL and RC. Approving final version of manuscript: AP, PS, IP, SA, SB, JB, HL, RC and CC. AP and CC take responsibility for the integrity of the data analysis.

Corresponding author

Correspondence to C. B. Confavreux.

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Conflict of interest

A. Piot, I. Plotton, S. Boutroy, J. Bacchetta, S. Ailloud, H. Lejeune, R. D. Chapurlat, P. Szulc and C. B. Confavreux declare that they have no conflict of interest concerning this study.

Ethical Approval

It has been approved by the local ethics committee “Comité de Protection des Personnes Lyon Sud-Est II—CHU de Lyon, France” (study number 2010-017-2 on June 17th 2010 with amendments on September 9th 2015 and October 10th 2017). The study has been performed in agreement with the Helsinki Declarations of 1975 and 1983.

Informed Consent

All patients, and parents in case of minors, provided written consent for the study.

Human and Animal Rights statement

The authors certify that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

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Piot, A., Plotton, I., Boutroy, S. et al. Klinefelter Bone Microarchitecture Evolution with Testosterone Replacement Therapy. Calcif Tissue Int 111, 35–46 (2022). https://doi.org/10.1007/s00223-022-00956-2

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