**3. Bone health in prostate cancer**

316 Prostate Cancer – Diagnostic and Therapeutic Advances

preexisting osteoporosis, subclinical vitamin D deficiency, or any of a multitude of medical

Bone mineral density (BMD) is considered to be the gold standard for diagnosing and assessing the severity of osteoporosis and fracture risk in women. The role of BMD in men is less clear. BMD is measured most commonly by dual-energy X-ray absorptiometry (DXA), but quantitative computed tomography (QCT) of the lumbar spine also is used, particularly

BMD of the wrist and hip, after adjusting for age, is a strong predictor of fracture risk (Melton L et al., 1998). Although the BMD criteria for diagnosing osteoporosis in men remain controversial (Binkley NC et al., 2002), a definition based on World Health

According to definition, osteoporosis exists when the BMD value is > 2.5 standard deviations (SD) below the peak young normal mean reference range (T-score < 2.5). Accurate T-score calculations in individual men can be obtained from bone densitometers using standardized software derived from reference databases for 'healthy' Caucasian men ages 20–40 years. In elderly men, it has been reported that advanced spondyloarthropathy, facet joint disease, and aortic calcification elevate spinal BMD falsely, as assessed by DXA (Zmuda JM et al., 2000)). Spinal BMD of the second through fourth lumbar vertebrae should be measured routinely to diagnose osteoporosis. Interpretation of the results often requires the addition of spinal radiographs to improve diagnostic accuracy. QCT of the lumbar spine, using the new three-dimensional multislice scanners, may overcome this problem, but it is not available at many centers; this technique has the ability to accurately define a region of interest unconfounded by extravertebral calcification (Faulkner KG et al., 1998; Weigert JM & Cann CE, 1988). Femoral neck DXA in elderly men, for practical purposes, is used routinely for the diagnosis of osteoporosis, especially if spinal BMD is pseudoelevated. Both spinal BMD and total hip BMD are the preferred sites for monitoring changes in BMD in response to therapies (Kaufman JM et al., 2000; Lenchik L et al., 2002). In a recent study, the relative risk of hip fracture in men was 3.0 (range, 1.7–5.4) for each SD decrease in femoral neck BMD (Delaet C et al., 1998). Longitudinal studies suggest that the rate of lumbar spine bone loss in elderly men is approximately 5–10% per decade, with acceleration after age 75 years. Femoral neck bone loss in normal elderly men is estimated at approximately 0.7% per year (Jones G et al., 2004). A number of factors may increase the bone loss normally associated with aging. These include physical immobility, poor nutrition, reduced calcium dietary intake and intestinal absorption, vitamin D deficiency, increased cytokines, reduced growth factors and osteoblastic activity, and a gradual decline in gonadal androgen production (Kaufman JM et al., 2000). Accelerated bone loss similar to that seen in women undergoing bilateral oophorectomy has been demonstrated in men with hypogonadism who undergo gonadectomy (Daniell HW, 1997) or who receive ADT (Bruder JM & Welch MD, 2002; Yaturu S et al., 2002). In male sex offenders who underwent surgical castration, spinal bone loss occurred at a rate of 4% per year (Stepan JJ et al., 1999). Because these rates of loss are higher compared with the rates of loss observed in otherwise healthy elderly men, the abrupt loss of sex steroids appears to

problems, the risk of skeletal deterioration is increased (Elliot ME et al., 2002).

**2. Diagnosis of osteoporosis in men** 

in research studies (Faulkner KG et al., 1998).

initiate a period of rapid bone loss.

Organization recommendations is accepted currently.

In advanced prostate cancer, 65–75% of patients may eventually develop bone metastases. It is also important to note that approximately 10% of men with prostate cancer have bone metastases at initial presentation. Almost all patients who die of prostate cancer have bone involvement (Greenspan SL, 2008).

Men with prostate carcinoma who are treated with ADT are elderly and are at risk for a wide variety of metabolic bone problems. In a recent retrospective study of 125 men with a mean age of 77 years who were treated with ADT, Bruder and Welch reported a 27% prevalence of osteoporosis and a 51% prevalence of osteopenia (lumbar spine or femoral neck BMD T-score, -2.5 to -1.0) (Bruder JM & Welch MD, 2002); furthermore, 44% of the cohort had biochemical evidence of vitamin D insufficiency and secondary hyperparathyroidism.

Osteoporosis has become an increasingly important problem in men's health, accounting for significant morbidity in the aging male population. Patients with prostate cancer treated with ADT are at a high risk of osteoporosis. These patients may have additional morbidity from decreased bone mineralization, such as skeletal fractures. Moreover, a direct association has been noted between fractures and a decreased quality of life and increased mortality (Gilbert SM & Mckiernan JM, 2005).

The prevalence of osteoporosis is lower in men than in women for several physiologic reasons, including a greater accumulation of skeletal mass during growth, greater bone size, absence of midlife menopause, a slower rate of bone loss, and a shorter male life expectancy (Amin S & Felson DT, 2001). The rates of annual bone mass loss in aging men range from 0.5% to 1% compared with 1% to 2% in women (Gilbert SM & Mckiernan JM, 2005; Smith MR, et al., 2001). The prevalence of osteoporosis increases progressively during ADT, reaching almost 50% after 4 years of ADT and more than 80% after 10 years. In contrast, it affects 35.4% of hormone-naive patients with prostate cancer (Morote J, et al., 2007).
