**7. Patients at high risk of bone disease. Who should be screened?**

Gold-standard therapeutic care for relapsed hormone-sensitive prostate cancer (HSPC) patients demands chemical or surgical hormonal blockade over the course of the therapeutic strategy. With the advent of prostate-specific antigen (PSA), early detection of HSPC recurrence and early hormonal blockade has become possible. In turn, this may lead to osteoporosis and bone fragility (Smith MR, 2003). Pathological fractures related to osteoporosis are very expensive (Groot MT, et al., 2003) and highly correlated with decreased survival with mortality in the first year as high as 70% (Berruti A, et al., 2000).

There are 4 robust, independent risk factors for osteoporotic fracture described: low bone mineral density (BMD), a prior fragility fracture, age ≥65 and a family history of osteoporosis (Brown JP, & Josse RG, 2002). There are also other risk factors for osteoporosis, including lifestyle and dietary factors, such as smoking, excessive intake of alcohol or caffeine, inadequeate dietary calcium intake, weight < 57 kg or loss of > 10% of weight at age 25 and diseases and treatments associated with bone loss (Brown JP, & Josse RG, 2002; Greenspan SL, 2008).

metastatic prostate cancer and for those with recurrent disease (Meng MW, et al., 2002; Sharifi N, et al., 2005). With this increased exposure to ADT, clinicians have seen the emergence of longer-term treatment complications, including osteoporosis and osteopenia. Although osteoporosis is generally less frequent in men, it is increasingly recognized as a source of substantial morbidity and even mortality in the aging male. Men suffer one third of all hip fractures. Osteoporotic vertebral fractures have a radiological prevalence of up to 50% in both sexes; they often cause chronic pain, and even clinically silent fractures are associated with increased risks of future fracture (both vertebral and hip), kyphosis, restricted lung function, impaired activities of daily living and even increased mortality (Mavrokokki A, et al., 2007). A study of Canadian prostate cancer patients who were orchiectomized found that their 5-year risks of vertebral and hip fractures were 2.2 fold higher than those of patients who had not

Fractures also independently predict diminished survival in prostate cancer patients on ADT. In one retrospective study, a history of fracture since the diagnosis of prostate cancer decreased median overall survival from 160 months to 121 months (p = 0.04)

**6. Non-invasive markers of bone turnover in normal men and in men with** 

The slow dynamics of bone turnover and the infrequency with which bone density is monitored following castration in prostate cancer cases justify the recent increasing interest

Bone loss in elderly men occurs predominantly as a result of increased bone turnover. On bone histomorphometry, trabecular plate thinning and endocortical bone resorption is evident (Clarke BL, 1996). Non-invasive serologic and urinary markers of bone turnover now can be quantitated accurately. Markers of bone formation, such as bone-specific serum alkaline phosphatase, osteocalcin, procollagen type I propeptides and bone glaprotein, are usually normal in elderly men; whereas markers of bone resorption, such as urinary deoxypyridinoline excretion rates and the NTx and CTx telopeptides of Type I collagen and

Gold-standard therapeutic care for relapsed hormone-sensitive prostate cancer (HSPC) patients demands chemical or surgical hormonal blockade over the course of the therapeutic strategy. With the advent of prostate-specific antigen (PSA), early detection of HSPC recurrence and early hormonal blockade has become possible. In turn, this may lead to osteoporosis and bone fragility (Smith MR, 2003). Pathological fractures related to osteoporosis are very expensive (Groot MT, et al., 2003) and highly correlated with decreased survival with mortality in the first year as high as 70% (Berruti A, et al., 2000). There are 4 robust, independent risk factors for osteoporotic fracture described: low bone mineral density (BMD), a prior fragility fracture, age ≥65 and a family history of osteoporosis (Brown JP, & Josse RG, 2002). There are also other risk factors for osteoporosis, including lifestyle and dietary factors, such as smoking, excessive intake of alcohol or caffeine, inadequeate dietary calcium intake, weight < 57 kg or loss of > 10% of weight at age 25 and diseases and treatments associated with bone loss (Brown JP, & Josse RG, 2002;

**prostate carcinoma treated with androgen deprivation therapy** 

in studying the effects of ADT and the pathophysiology of bone metastasis.

**7. Patients at high risk of bone disease. Who should be screened?** 

pyridinolines, often are found to be elevated (Khosla S, 1998).

been orchiectomized (p < 0.001 for both) (Body JJ, 2003).

(Oefelein MG, 2002).

Greenspan SL, 2008).

Prostate cancer itself is associated with osteoporosis, even among ADT-naïve patients without metastatic disease. In a cross-sectional study, 45.2% of such patients had osteopenia and 35.4% had osteoporosis even before starting ADT. Systematic retrospective reviews have also shown the association between ADT and increased fracture risk (Saad F, et al., 2008; Brufsky AM, 2008).

Because age and hypogonadism are both considered major risk factors for osteoporosis, all prostate cancer patients beginning ADT should be screened with DXA scans at baseline; anyone aged ≥ 65 and anyone with kyphosis, back pain, substantial height loss, or other symptoms suggesting vertebral fractures should also be screened with thoracic and lumbar spine x-rays.
