Compromised Volumetric Bone Density and Microarchitecture in men with Congenital Hypogonadotropic Hypogonadism.

Context Men with Congenital Hypogonadotropic Hypogonadism (CHH) and Kallmann syndrome (KS) have both low circulating testosterone and estradiol levels. Whether bone structure is affected remains unknown. Objective To characterize bone geometry, volumetric density and microarchitecture in CHH/KS. Design Cross-sectional study. Setting One tertiary academic French center. Patients and controls 51 genotyped CHH/KS patients and 40 healthy volunteers were included. Ninety-eight percent of CHH/KS men had received testosterone and/or combined gonadotropins. Intervention(s) High-resolution Peripheral Quantitative Computed Tomography (HR-pQCT), Dual X-ray absorptiometry (DXA) and measurement of serum bone markers. Main outcome Volumetric bone mineral density (vBMD), cortical and trabecular microarchitecture. Results CHH and controls did not differ for age, BMI, vitamin D and PTH levels. Despite long-term hormonal treatment (10.8 ± 6.8 years), DXA showed lower areal BMD in CHH/KS at lumbar spine, total hip, femoral neck and distal radius. Consistent with persistently higher serum bone markers, HR-pQCT revealed lower cortical and trabecular vBMD as well as cortical thickness at the tibia and the radius. CHH/KS men had altered trabecular microarchitecture with a predominant decrease of trabecular thickness. Moreover, CHH/KS men exhibited lower cortical bone area, whereas total and trabecular areas were higher only at the tibia. Earlier treatment onset (before the age of 19 years) conferred a significant advantage for trabecular bone volume/tissue volume and trabecular vBMD at the tibia. Conclusion Both vBMD and bone microarchitecture remain impaired in CHH/KS men despite long-term hormonal treatment. Treatment initiation during adolescence is associated with enhanced trabecular outcomes, highlighting the importance of early diagnosis.