How to optimize bone health in men receiving androgen deprivation therapy

Advances in prostate cancer treatment have resulted in longer life expectancy and the need for greater focus on cancer treatment-induced bone loss. Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone agonists and antagonists, or orchiectomy, decreases bone mineral density (BMD) and increases the risk of fracture. Men with prostate cancer often have other risk factors for low BMD, including advanced age, smoking, low protein intake, family history of osteoporosis, glucocorticoid use, and a prior history of fall or fracture. Men on ADT often have low rates of osteoporosis screening and infrequently receive interventions to reduce bone loss. Read: Dual or single immunotherapy with chemotherapy improves esophagus cancer survival To help optimize bone health in men with prostate cancer receiving ADT, the Canadian Urological Association (CUA) has issued recommendations for the assessment and management of cancer treatment-induced bone loss. The document reviews the mechanisms whereby androgens lead to improved bone density, and how decreased androgen levels (in patients on ADT) reduce bone density through down-regulation of osteoblasts and up-regulation of osteoclasts. BMD decreases at an accelerated rate in men on ADT, compared to healthy controls, with the most significant changes occurring in the first year of therapy. Loss of BMD is progressive, with up to 85% of men developing osteoporosis after 10 years of ADT, and up to 20% experiencing a fracture within the first five years. Other cancer therapies used in conjunction with ADT may also be associated with an increased risk of osteoporotic fracture. These include glucocorticoids and androgen receptor axis-targeted therapies (e.g., abiraterone, enzalutamide, apalutamide, darolutamide). Read: Active surveillance reduces unnecessary treatment in prostate cancer Key CUA recommendations Men on ADT should be evaluated for fracture risk. It can be estimated using the FRAX or CAROC risk assessment tools and/or BMD assessment with a dual energy X-ray absorptiometry (DXA) scan. Treatment to prevent bone loss should be started in patients on ADT with: osteoporosis (T-score ≤ -2.5), or a prior fragility fracture, or a 10-year major osteoporotic fracture risk of > 20%. Patients starting ADT should receive education regarding cancer treatment-induced bone loss, its consequences and prevention strategies. Patients starting ADT should be educated on smoking cessation, moderation of alcohol consumption, weight-bearing and balance exercises, and fall prevention strategies where appropriate. Patients on ADT should target a calcium intake of 1200 mg/day and consider calcium supplementation if dietary calcium is inadequate. Patients on ADT should target a vitamin D intake of 800–2000 IU daily. Men with castrate-sensitive prostate cancer (CSPC) and non-metastatic castrate-resistant prostate cancer (CRPC) should not receive bone-targeted therapies for the prevention of skeletal-related events. Treatment for the prevention of bone loss should be considered in all men on ADT as per Recommendation 2. Men with CRPC and bone metastases should receive denosumab 120 mg SC every four weeks (preferred) or zoledronic acid 4 mg IV every four weeks to prevent skeletal-related events. Patients receiving bone-targeted therapies, including zoledronic acid and denosumab, should be counselled regarding osteonecrosis of the jaw and should receive a baseline dental exam prior to initiating therapy. Baseline renal function and serum calcium should be assessed. Combining radium-223 and androgen receptor axis-targeted therapies should be avoided due to increased fracture risk, until further data are available. All of these recommendations are discussed in further detail in the CUA guidance document. The document also includes an algorithm summarizing the assessment and management of bone health in men on ADT, as well as a table detailing risk factors for osteoporotic-related fracture. Reference 1. Lavallée LT, McLarty R, Tran C, et al. Canadian Urological Association best practice report: bone health in prostate cancer. Can Urol Assoc J 2021;15:375-82.(accessed December 16, 2021).

How to optimize bone health in men receiving androgen deprivation therapy

Register for free access or login.

Related Topics