Osteoporosis in men with prostate carcinoma receiving androgen‐deprivation therapy

Abstract

BACKGROUNDAndrogen‐deprivation therapy (ADT) is prescribed with increasing frequency for men with prostate carcinoma. There is growing concern about the effects of such therapy on the skeleton. In the current review, the authors addressed the current research, diagnostic methods, and treatment recommendations for bone loss and osteoporosis in men with prostate carcinoma who received ADT.METHODSData were obtained from electronic literature searches (for the years 1986 through 2002) and from abstracts and meeting proceedings. All randomized and nonrandomized clinical trials, retrospective studies, and cross‐sectional studies of osteoporosis in men with prostate carcinoma who received ADT with or without other therapies were reviewed.RESULTSThe findings confirmed that ADT resulted in significant bone loss in men with prostate carcinoma. Bone mineral density (BMD) of the hip, as measured by dual‐energy X‐ray absorptiometry (DXA), is considered the preferred site of assessment in older men. Spinal BMD is equally important, although careful interpretation of spinal DXA values is required, because of coexisting facet joint disease and extravertebral calcification. Osteoporosis is diagnosed when BMD is > 2.5 standard deviations below a reference mean. Men with prostate carcinoma who were treated with ADT had average BMD measurements below those of eugonadal men. Rates of bone loss ranged from 2% to 8% in the lumbar spine and from 1.8% to 6.5% in the femoral neck during the initial 12 months of continuous ADT. Retrospective data indicated an increased risk of fracture in men with prostate carcinoma who were treated with ADT.CONCLUSIONSFor men with prostate carcinoma who are at high risk for osteoporosis and fractures, clinical management should be dictated by the results of radiographic and DXA skeletal assessment. Cancer 2004;100:892–9. © 2004 American Cancer Society.

Estradiol for the mitigation of adverse effects of androgen deprivation therapy

“…Areal BMD measured by dual-energy X-ray absorptiometry (DXA) underestimates the degree of cortical BMD loss and microarchitectural deterioration in cortical and trabecular compartments (Hamilton et al 2010). There is a lack of prospective studies reporting fracture rates in men undergoing ADT (Diamond et al 2004). Large retrospective studies report higher fracture rates in these men (Shahinian et al 2005, Shao et al 2013) and fracture post ADT was associated with a 10% 12-month mortality (Shao et al 2013).…”

“…Subsequent epidemiologic, basic and clinical studies have demonstrated the role of estrogens in PCa to be highly complex (Di Zazzo et al 2016, Rahman et al 2016. The ageassociated rise in PCa incidence coincides with a decrease in circulating free testosterone/E 2 ratio due to declines in hypothalamic-pituitary-testicular axis function and increases in sex hormone binding globulin (SHBG) (Rahman et al 2016, Cooke et al 2017.…”

“…The net effect of estrogens or the androgen/estrogen ratio on PCa development and progression has not been established, and is unlikely to be simply defined (reviewed in Rahman et al 2016 andDi Zazzo et al 2016). Overall experience with the therapeutic use of estrogens in PCa does not suggest a clinically important pro-carcinogenic effect.…”

The 2014 CUA-CUOG Guidelines for the Management of Castration Resistant Prostate Cancer (CRPC)

“…[18][19][20][21][22] Moreover, about 90% of patients with mCRPC will develop bone metastases, which cause local decreases in bone integrity. Patients are at significant risk of SREs that include pathological fractures, debilitating bone pain requiring palliative radiation therapy and spinal cord compression.…”

CUA-CUOG Guidelines for the Management of Castration Resistant Prostate Cancer (CRPC): 2013 Update

“…20,21 Bone-targeted therapy Bone loss associated with ADT has been shown to increase the risk of fracture. [22][23][24][25][26] Moreover, about 90% of patients with metastatic CRPC will develop bone metastases, which cause local decreases in bone integrity. Patients are at significant risk of SREs that include pathological fractures, debilitating bone pain requiring palliative radiation therapy and spinal cord compression.…”