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

Vittoria Russo, Rui Chen, Reina Armamento-Villareal, Vittoria Russo, Rui Chen, Reina Armamento-Villareal

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.

Keywords: hypogonadotropic hypogonadism; hypothalamic-pituitary-gonadal axis; insulin resistance; osteoporosis; type 2 diabetes mellitus.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Russo, Chen and Armamento-Villareal.

Figures

Figure 1
Figure 1
The pancreas-bone-gonads axis. Pancreas, bone, and testis communicates in a feedforward loop in which osteocalcin (OCN), a bone-derived hormone secreted by osteoblasts regulates glucose metabolism by stimulating pancreatic β-cell proliferation, insulin expression, and production, and improving insulin sensitivity in peripheral tissues, such as liver, muscle, and adipose tissue. Moreover, OCN regulates male reproductive function by increasing T production in Leydig cells. Insulin and T in turn, act on bone by enhancing osteoblasts proliferation and differentiation, and consequently favor OCN production from osteoblasts. Insulin and T are engaged in a bidirectional relationship in which T may improve insulin sensitivity, while circulating T levels may be influenced by insulin.

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