Fracture prevention and osteoporosis treatment
For all patients on ADT, a daily 30-minute weight-bearing exercise program should be recommended. Walking is an ideal and simple weight-bearing exercise. Likewise, strength training and balance exercises will also reduce fall risk. Gralow et al suggest that Tai Chi and dancing are examples of activities to improve balance and strength to potentially lower fracture risk.22
Modifiable risk factors for osteoporosis should be addressed; patients who smoke should be counseled to quit tobacco and men with excessive alcohol intake should be counseled as well. Given that the majority of men over 50 have inadequate calcium and vitamin D intake, it is reasonable in all patients to follow the NOF Guidelines and recommend 1,200 mg of calcium (from food and supplements) daily and 800 to 1,000 units of vitamin D (cholecalciferol).21
The least expensive calcium supplement is calcium carbonate and this is best absorbed in an acidic environment. Therefore, it should be taken with meals. Patients should be counseled about the risk of constipation with calcium carbonate, and if not well tolerated (or the patient is on a proton pump inhibitor) then calcium citrate is recommended. Non-prescription preparations of vitamin D are widely available and inexpensive and can be taken daily.
For patients at a high risk for fracture, consider obtaining a serum 25-hydroxyvitamin D level. If the value is below the lower limit of normal, we suggest consulting the patient’s primary care physician for appropriate vitamin D supplementation.
Men with a >3% 10-year risk for hip fracture and a >20% 10-year risk for major osteoporotic fractures as measured by the FRAX calculator, and/or with osteoporosis by DEXA scan should be strongly considered for pharmacologic therapy. Alternatively, the practitioner can assess fracture risk based on the history, physical, and BMD results. In addition, pharmacologic therapy should be considered in men with severe osteopenia (T-score approaching -2), especially given that these patients are on ADT and are at risk for further loss in BMD. As per NCCN guidelines, therapy options include alendronate, zoledronic acid, and denosumab.
Bisphosphonates act as pyrophosphate analogues, adhere to the bone matrix, and are internalized by osteoclasts during active bone resorption. This results in inhibition of osteoclast activity and survival.23 The oral bisphosphonate alendronate is FDA approved for the treatment of osteoporosis in men. In a randomized, placebo controlled trial of men with osteoporosis (not ADT-induced osteoporosis), the alendronate group had an increase in BMD, a decrease in loss of height, and a decrease in the incidence of vertebral fractures.24
In a randomized, placebo-controlled trial that enrolled men with osteoporosis (not ADT-induced), those receiving 5 mg of zoledronic acid (a more potent bisphosphonate than alendronate) at baseline and at 12 months had a 67% risk reduction of incurring a new vertebral fracture.25 Zoledronic acid is administered as a once yearly intravenous infusion of 5 mg, making its use appealing for compliance reasons.
Denosumab, a human monoclonal antibody against receptor activator of nuclear factor-κB ligand, was tested in a randomized, placebo-controlled trial of 1,468 men receiving ADT for nonmetastatic PCa. Denosumab increased bone density in the spine, hip, and forearm, reduced markers of bone turnover, and reduced the number of new vertebral fractures.15 Denosumab (60 mg subQ every six months) was FDA approved in 2010 as a treatment to increase bone mass in patients who are at high risk for fracture, including those receiving ADT for nonmetastatic PCa.
Once patients initiate pharmacologic therapy, bone densitometry should be performed at one year and every two to three years thereafter. If bone density continues to decline, then referral should be made to an endocrinologist or osteoporosis specialist.