Introduction:
The discovery of androgen activities began in the nineteenth century with Dr. Charles Brown-Sequard's concept of self-injection. It was previously understood that androgen receptors regulate the development and maintenance of men where the androgens attach to the androgen receptor (AR) in the cytoplasm; this then moves to the nucleus and binds to DNA to operate as a transcription factor that influences the human skeleton in both males and females. While androgen is employed to sustain the amount of bony patterns (trabeculae), testosterone also helps maintain cortical thickness, volumetric density, and mechanical strength by converting them into T and DTH. This also helps manipulate the growth hormone according to the body's needs.
What Is Androgen?
Androgens are sex hormones found in both males and females that are responsible for people's attainment of puberty and maturity. While both genders make these hormones, men especially are shown to have a higher androgen rate. Some examples of androgen hormones are testosterone, androstenedione, DHEA-S (DHEA sulfate), Dehydroepiandrosterone (DHEA), and dihydrotestosterone.
What Are the Functions of Androgen in Bone Growth?
When it comes to improving bone health and bone density, androgens play a very important part, and their functions are as follows:
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The Impact of Androgen and Its Receptors on Bone Growth: Androgen is a hormone known to increase the density of the cortical bone both lengthwise and sideways. The growth pattern in the longitudinal direction involves the endochondral bones like the ribs or vertebrae and the epiphyseal growth plate at the end of long bones. Here, the androgenic growth hormones also impact the cartilage cells for their proliferation, maturation, and differentiation, and they are the most common hormones involved in chondrocytes.
The other adjacent factors that drive bone formation include bone growth factor (GH), TGF-beta (the transforming growth factor), IGF - 1 (Insulin-like growth factor), and metabolites of vitamin D. All these influences of the sex hormones on bone growth begin since puberty showing a biphasic effect on the body. The estrogen hormones predominantly create the biphasic effect, affecting epiphyseal bone growth. Also, the changes in the cortical plate with an increase in thickness and diameter is a typical feature of puberty in men.
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Role of Androgen in Bone Hemostasis: When androgen is influenced in the bone, the bone's trabecular (honeycomb) structure must be maintained. The factors that maintain this pattern are done by osteocytes directly or indirectly blocking the formation of osteoclasts (cells that break down the bone structure). Here, the role of androgen is inactivated to prevent it from activating the osteoclast and osteoblastic cells, thus limiting bone resorption. This applies to both genders and all age groups.
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Regulating Bone Cell Turnover Predominantly in Men: The activity of bone cell turnover In humans is carried out by makers that are essential for bone matrix, or cellular remodeling are called C or N terminal telopeptides present in type 1 collagen and Pyridinoline where these are classified as catabolic markers. In contrast, the anabolic markers include type 1 procollagen or osteoclasts. Here, the function of these androgenic markers is associated with men in the second and third decades of their age, which shows an increase in bone remodeling and bone cell turnover. However, there is a decline in bone turnover after the fourth decade of life.
What Are the Factors Affecting Androgen Function?
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Age: Bone health in men is originally regulated by an androgenic hormone called the circulating T, where the androgenic sex hormone helps control T cell circulation. However, as age progresses, there is a decline in the levels of these T cells and their bioavailability in the body. Because of this, the body has various impacts, such as altered sexual symptoms, decreased physical activity, and the body’s metabolism. The reason for the decline in T Cells is a continuous reduction in the function of the gonads in the pituitary gland called HPG.
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Deficiency in Androgen Hormone: Androgen deficiency was characterized by a delay in sexual development, decreased testicular volume, axillary and pubic hair loss, gynecomastia, erectile dysfunction, decreased libido, low sperm count, and skeletal disorders such as height loss, low traumatic fracture, or decreased bone marrow density. Bone mineral density (BMD) is much reduced in hypogonadal males (men with less androgen hormones), particularly in the spine.
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Increase in Androgen Levels: An increase in androgen levels again increases bone density and T cells, especially in women with PCOS, leading to an increase in bone fractures post menopause.
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Klinefelter’s Syndrome: Klinefelter's syndrome is the presence of an extra X chromosome in a male gene pattern. The patients exhibit characteristics such as tall stature, very small testes, spermatogenesis, gynecomastia, reduced body hair, and other symptoms of androgen insufficiency. It is clinically identified as a kind of hypogonadotropic hypogonadism, which causes functional and anatomical testicular insufficiency during puberty. Impaired bone metabolism develops early in life, and children and adolescents with this syndrome may have abnormal bone structure. Long-term patients have revealed decreasing bone marrow density despite T Cell therapy, failing to improve the honeycomb pattern of long bones.
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Isolated Hypogonadotropic Hypogonadism (IHH): This is a genetic condition caused by improper secretion or production of the gonadotropin hormone, which is involved in producing androgens. The main reason for this condition is disorientation in the hypothalamus.
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Insensitivity of the Body to Androgens: This term means the androgen production and supply are adequate, but the body fails to recognize it and work along with the androgen resource found, leading to various complications, including bone fractures
Conclusion:
The activities and impacts of androgens on bone were mostly unclear in the earlier days, and to overcome this, many medical studies were conducted. Knowing the causes of fractures in men and women associated with androgenic hormones, as well as how to treat them, such as hormonal replacement treatment or preventive physiotherapy, can help prevent them. However, there has been significant progress in understanding the effects of estrogen on bone over the years, resulting in improved osteoporosis treatment.
