With Supplements, ADT in Prostate Cancer of Little Threat to Bone Density

Despite a slight decline in bone mineral density (BMD) in patients with localized high-risk prostate cancer on long-term androgen deprivation therapy (ADT), there was little change in clinical BMD status, according to an analysis of men enrolled in a phase III trial.

After 30 months of follow-up, no patient converted from normal BMD at baseline to osteoporosis, and none suffered fragility fractures, reported Tamim Niazi, MDCN, of Jewish General Hospital in Montreal, and colleagues.

“Consequently, calcium and vitamin D supplementation alone may suffice for most localized prostate cancer patients on long-term androgen deprivation therapy,” they wrote in the Journal of Urology.

Long-term ADT in combination with radiotherapy has been shown to improve progression-free, disease-free, and overall survival in patients with localized high-risk prostate cancer. However, ADT is also associated with a decrease in BMD that goes beyond that seen with normal aging, leading to an increased risk of osteoporosis and fracture. Therefore, calcium and vitamin D supplements are recommended for patients on long-term ADT, with or without bone-modifying agents.

Niazi and his colleagues pointed out that numerous trials have compared calcium/vitamin D supplementation with or without bone-modifying agents. And while these have shown that supplements in combination with bone-modifying agents lessen BMD loss, only a few studies have shown decreases in fracture rates.

“A change in BMD would be clinically meaningful only if it resulted in osteoporosis and an increase in clinical fractures,” the authors wrote. In this study their objective was to quantify changes in BMD based on data extracted from the Prostate Cancer Study 5 (PCS-V), which was designed to compare conventional and hypofractionated radiation therapy.

A total of 329 patients were enrolled in PCS-V. Only those who underwent dual energy x-ray absorptiometry scans to assess BMD were included in this study, with lumbar spine, femoral neck, and total femoral BMD measured for 226, 231, and 173 patients, respectively. Patients received 28 months of luteinizing hormone-releasing hormone agonist with calcium and vitamin D supplementation.

At follow-up, the mean percent change in BMD was -2.65% for the lumbar spine, -2.76% for the femoral neck, and -4.27% for total femoral BMD. According to Niazi and his colleagues, most changes were not clinically meaningful, with 79% of men remaining within the normal BMD category.

Noting that proximal femur BMD measurements are the best predictors of fracture risk, the authors found that there was no clinical change in BMD status from normal to osteoporosis after ADT and that 83% of patients maintained a normal proximal femur BMD. Changes from normal to osteopenic and osteopenic to osteoporotic were seen in 11% and 5% of patients, respectively.

Just two patients suffered fractures, both traumatic in nature — one lumbar fracture caused by a garage door closing on a patient 16 months after the start of hormone therapy, and the other a traumatic rib fracture 14 months after the initiation of ADT. Both of these patients had baseline osteopenia and remained in that category after ADT.

Niazi and his colleagues suggested that the “lack of meaningful change” in BMD and fracture risk challenges the added value of bone-modifying agents in patients with localized high-risk prostate cancer who are on ADT and receiving calcium and vitamin D supplementation.

“Denosumab [Xgeva] may reduce radiological vertebral fractures by 2%, but this has to be balanced with cost-effectiveness,” they wrote, adding that potential toxicities of bone-modifying agents such as renal failure, mandibular osteonecrosis, hypophosphatemia, and hypocalcemia should also be considered.

Further studies are needed to determine which patients benefit the most from bone-modifying agents in addition to calcium and vitamin D, the researchers suggested.