Fracture risk in patients with prostate cancer on androgen deprivation therapy

Abstract

Although a decrease in bone mass is a well-known side effect of hormone therapy for prostate carcinoma, its clinical significance is unclear, as there is only scanty information about the incidence of fractures. Therefore, the aim of this study was to determine the risk of non-metastatic fractures in patients with prostate cancer undergoing androgen deprivation therapy. We performed a retrospective cohort study that comprised 288 patients with cancer who were subjected to androgen deprivation therapy (ADT). All were given LHRH agonists, and most of them also received peripheral androgen receptor blockers. The results were compared with a control group of 300 men that were not receiving ADT. The incidence rates of peripheral and vertebral fractures in the group of men on ADT were 1.9 and 0.8 per 100 patient-years, respectively. Incidence rates in the control group were 0.5 and 0.2, respectively. In the whole study group, 35 patients had at least one fracture during follow-up (25 on ADT, ten controls). Thus, the number of patients with at least one fracture was significantly higher in the group on ADT (P = 0.001 by the log-rank test). The unadjusted risk ratio was 4.2 (CI 2.0-8.9). A similar value (risk ratio 3.6; CI 1.6-7.7, P = 0.001) was found after it was adjusted for other factors, such as age or prior fractures. Therefore, ADT is associated with a fourfold increase in the incidence rate of both peripheral and vertebral fractures. Although the absolute incidence remains relatively small, preventive measures should be considered for high-risk patients.

Fracture risk in patients with different types of cancer

“…Prostate cancer has a high likelihood of metastases to bone, and is treated with androgen deprivation therapy, which may lead to bone loss, and these two factors in combination may explain why a sustained increase in risk of fractures was seen. Furthermore, localised prostate cancer may be associated with a prolonged survival [43] and thus a sustained risk of even late metastases to the skeleton and detrimental effects of long-term androgen deprivation therapy [1,44]. Dickman et al [45] reported an early and sustained increase in the risk of hip fractures in patients who underwent bilateral orchiectomy for prostate cancer, In our study the increase was seen later in the cause of the prostate cancer and this may be due to the fact that not all patients underwent orchiectomy or received androgen deprivation therapy.…”

“…Most research has focused on prostate cancer, where a decreased bone mineral density (BMD) and an increased risk of fractures, mainly linked to the use of anti-androgen therapy (androgen deprivation therapy) has been demonstrated [1]. Other types of cancer have not been studies in detail.…”

Osteoporosis Management in Prostate Cancer Patients Treated with Androgen Deprivation Therapy

“…In prospective clinical trials, bone loss rates in ADT-treated men with prostate cancer have been reported to range from 0.6% to 9% per year. [5][6][7][8][9][10][11][12] Retrospective studies in these men report fracture rates of 2.7% per year, 13 20% at 10 years, 14 and 8 per 100 person-years at risk. 15,16 Prostate cancer patients who underwent bilateral orchiectomy had even higher fracture rates than age-matched controls during 15 years of follow-up: 40% vs 19% (P<0.001).…”

Biphosphonates in Advanced Prostate and Renal Cell Cancer – Current Status and Potential Applications

“…Overall, only 14.7% of patients (95% CI = 9.5-20.0%) were treated to maintain physiological BMD. Oral and [15,17] . HCM = Hypercalcemia of malignancy .…”

“…Androgen-deprivation therapy, either by bilateral orchiectomy or treatment with a gonadotropin-releasing hormone agonist (GnRH-A), has been found to further reduce BMD by 4-13% per year [1,[11][12][13][14] . ADT is associated with a fourfold increase in the incidence rate of both peripheral and vertebral fractures [15] . Continuous monitoring of BMD and preventive measures against bone loss are strongly recommended.…”