**5. Bone loss and osteoporosis**

As shown above, androgens are important for maintenance of bone tissue. Although ADT is used in medical practice for more than 60 years, it's only few years that the clinicians became aware of serious and potentially catastrophic consequences resulting form longterm ADT.

Bone density is determined both by peak bone mass achieved during skeletal development and the subsequent amount of maintenance and resorption of bone tissue. Androgens affect both processes and thus are a pivotal determinant of bone mass in men.

#### **5.1 Osteoporosis**

Osteoporosis is defined as a systemic metabolic bone disease characterized by low bone mass density (BMD) and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture (38). Diagnosis of osteoporosis based on WHO definitions is developed for women originally (39). When based on male cutoffs, 1- 2 million (3 - 6%) of men have osteoporosis and 8 -13 million (28 - 47%) have osteopenia; when based on female cutoffs, 280,000 - 1 million (1 - 4%) have osteoporosis and 4 - 9 million (15 - 33%) have osteopenia (40, 41). While this numbers may seem disturbing, it is believed that osteoporosis in men is substantially underdiagnosed and undertreated in the United States (42).

Female osteoporosis has been studied extensively and characterized due to its high prevalence (43) whereas male osteoporosis, especially that associated with ADT has gained focus only recently.

osteoclasts (33), and osteocytes (34). Human males with mutations of ER or aromatase genes do not achieve normal bone density, despite normal or increased levels of serum TST (35).

ADT is increasingly attained through the use of luteinizing hormone-releasing hormone (LHRH) agonists, which down-regulate anterior pituitary receptors and lead to therapeutic hypogonadism, or directly by inhibiting pituary receptors by LHRH antagonists. The standard castration level is < 50 ng/dL. Prostate cells are physiologically dependent on androgens which stimulate its growth, function and proferation. TST, although not

Prostate cancer (PCa) displays a range of clinical behavior, from slow-growing tumors of no clinical significance to aggressively metastatic and lethal disease. Most PCa cases diagnosed with present diagnostic techniques fall into the moderately differentiated group (grade 2, Gleason 6), of which the cancer-specific 10–15-year mortality is 18–30%. This is even lower in the group of PCa diagnosed with grade 1 and 2 or Gleason 4–6, and there are subgroups of patients who are not at risk of dying from PCa even within 15years. Overall mortality is then determined by comorbidity (37). While both short- and long-term ADT are effective for treating PCa, it can often have significant side-effects. It is important that these complications are recognized and managed appropriately so that adverse effects on the patient's quality of life (QoL) are minimized. There has been an increase in the use of ADT at all stages of PCa in recent years. The extensive use of ADT is raising concerns about adverse

As shown above, androgens are important for maintenance of bone tissue. Although ADT is used in medical practice for more than 60 years, it's only few years that the clinicians became aware of serious and potentially catastrophic consequences resulting form long-

Bone density is determined both by peak bone mass achieved during skeletal development and the subsequent amount of maintenance and resorption of bone tissue. Androgens affect

Osteoporosis is defined as a systemic metabolic bone disease characterized by low bone mass density (BMD) and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture (38). Diagnosis of osteoporosis based on WHO definitions is developed for women originally (39). When based on male cutoffs, 1- 2 million (3 - 6%) of men have osteoporosis and 8 -13 million (28 - 47%) have osteopenia; when based on female cutoffs, 280,000 - 1 million (1 - 4%) have osteoporosis and 4 - 9 million (15 - 33%) have osteopenia (40, 41). While this numbers may seem disturbing, it is believed that osteoporosis in men is substantially underdiagnosed and undertreated in the United

Female osteoporosis has been studied extensively and characterized due to its high prevalence (43) whereas male osteoporosis, especially that associated with ADT has gained

both processes and thus are a pivotal determinant of bone mass in men.

**4. Androgen deprivation therapy (ADT) and its side effects** 

tumorigenic, is essential for the growth and perpetuation of tumor cells (36).

effects – loss of BMD being the most prominent.

**5. Bone loss and osteoporosis** 

term ADT.

States (42).

focus only recently.

**5.1 Osteoporosis** 

In men, osteoporosis occurs later than in women (44), but the prevalence of osteopenia does not differ significantly between men and women aged more than 50 years. Conversely, the prevalence of osteoporosis in men is lower than in women (40). Even though it may be underestimated when standard female BMD parameters are considered suitable for normal mineralization in men (45). Men generally have a higher BMD than women at the same age (46). Accordingly, the prevalence of male osteoporosis is greater when male-specific ranges are used in men above fifties: ranging from 1% to 4% of elderly men when the diagnosis is based on female cut-off points vs. 3% to 6% when based on male cut-off points (40).

Men are estimated to lose bone mineral density (BMD) at a rate of up to 1% per year with advancing age (47, 48), and one in eight men over age 50 years will experience an osteoporosis-related fracture in their lifetime (49). Of all osteoporotic fractures, hip fractures contribute to the greatest morbidity as well as mortality, both of which are much greater in men than in women (50-52).
