Hypogonadism, Type-2 Diabetes Mellitus, and Bone Health: A Narrative Review

Abstract

One of the complications from chronic hyperglycemia and insulin resistance due to type 2 diabetes mellitus (T2DM) on the hypothalamic-pituitary-gonadal axis in men is the high prevalence of hypogonadotropic hypogonadism (HH). Both T2DM and hypogonadism are associated with impaired bone health and increased fracture risk but whether the combination results in even worse bone disease than either one alone is not well-studied. It is possible that having both conditions predisposes men to an even greater risk for fracture than either one alone. Given the common occurrence of HH or hypogonadism in general in T2DM, a significant number of men could be at risk. To date, there is very little information on the bone health men with both hypogonadism and T2DM. Insulin resistance, which is the primary defect in T2DM, is associated with low testosterone (T) levels in men and may play a role in the bidirectional relationship between these two conditions, which together may portend a worse outcome for bone. The present manuscript aims to review the available evidences on the effect of the combination of hypogonadism and T2DM on bone health and metabolic profile, highlights the possible metabolic role of the skeleton, and examines the pathways involved in the interplay between bone, insulin resistance, and gonadal steroids.

Strontium-incorporated bioceramic scaffolds for enhanced osteoporosis bone regeneration

“…Osteoporosis reduces bone mass, increases bone brittleness, and particularly weakens the regeneration ability of damaged bone. Hence, it has high morbidity, mortality, and disability rates 16 , 17 . The restoration of bone tissue in osteoporosis-affected patients remains a significant problem.…”

The associations of total testosterone with probable nonalcoholic steatohepatitis and nonalcoholic fatty liver disease fibrotic progression in men with type 2 diabetes: a cross-sectional study

“…Testosterone may account for this gender difference. Testosterone, usually considered as the main sex steroids in male, has gender-dimorphic impact on the development of metabolic disease, such as type 2 diabetes mellitus [11,12], and in turn, men with T2DM are particularly susceptible to sex hormone disturbance or hypogonadism [13,14]. What is more, preclinical studies demonstrated that testosterone can influence hepatic insulin sensitivity and lipid metabolism [15][16][17].…”

The occurrence of hypogonadotropic hypogonadism in Chinese men with type 2 diabetes

“…Hypogonadism is a clinical syndrome in men characterized by the presence of testosterone deficiency and decreased circulating testosterone levels 15,16 . It is associated with symptoms of sexual dysfunction, cardiovascular disease, IR, anaemia and osteoporosis 17,18 . Physically, about 44% of total testosterone (TT) is tightly bound to sex hormone‐binding globulin (SHBG) and 54% is connected with albumin with lower affinity.…”

“…15,16 It is associated with symptoms of sexual dysfunction, cardiovascular disease, IR, anaemia and osteoporosis. 17,18 Physically, about 44% of total testosterone (TT) is tightly bound to sex hormone-binding globulin (SHBG) and 54% is connected with albumin with lower affinity. Only 2% of TT is unbound testosterone, which is called free testosterone (FT).…”