Endocrine Abstracts

Background: Recent data suggest a direct effect of follicle stimulating hormone (FSH) on the skeletal metabolism. Particularly, it can encourage bone resorption and also inhibit osteoblast differentiation. High FSH levels have been found to correlate with impaired bone health in females, whilst evidence in males remains somewhat poor and conflicting. Intriguingly, men with primary and central hypogonadism might represent a novel study model in this context.

Aims: To investigate the possible association of FSH excess with male osteoporosis.

Patients and Methods: 119 men, consecutively referred to Istituto Auxologico Italiano and Newcastle upon Tyne Hospitals, were enrolled in this prospective cross-sectional observational study at the time of the first diagnosis of hypogonadism. All participants had spontaneous pubertal development. Regarding those with hypergonadotropic hypogonadism (Hyper Hypo), patients with a pre-pubertal onset form (PPO) (i.e., Klinefelter syndrome) were distinguished from the ones with an adult-onset form (AO) based on the onset of FSH elevation. Bone mineral density (BMD) at both lumbar spine (LS) and femoral neck (FN) was measured using dual-energy X-ray absorptiometry. The prevalence of morphometric vertebral fractures (VFx) was evaluated by performing spinal radiographs.

Results: Across the whole cohort, LS and FN BMD were directly associated with age at diagnosis and body mass index (BMI), respectively. After adjusting for potential confounders (age at diagnosis, BMI, smoking habits, calculated free testosterone (cfT) and 25OH vitamin D levels) by means of General Linear Model analysis, AO-Hyper Hypo patients showed significantly lower LS BMD and tended to show lower FN BMD values, as compared to those with hypogonadotropic hypogonadism (Hypo Hypo). In men with PPO-Hyper Hypo LS BMD was significantly lower than in AO-Hyper Hypo ones. No significant differences in the prevalence of VFx were found between the groups.

Conclusions: This is the first prospective study comparing men with primary and central hypogonadism in order to better delineate the putative role of FSH on the male bone health. These findings indicate a potential negative effect of FSH excess on the male bone mass, especially at spine. The duration of high FSH levels may also play a part in this setting. Longitudinal studies, involving hypogonadal men on testosterone replacement therapy, are required. Indeed, it would be crucial to identify new risk factors and mediators of male bone fragility, with a view to ultimately reducing the huge public health burden related to fractures.