Denosumab is really effective in the treatment of osteoporosis secondary to hypogonadism in prostate carcinoma patients? A prospective randomized multicenter international study

Abstract

SummaryIntroduction. Osteoporosis is a complication of androgen deprivation therapy (ADT) in men with prostate carcinoma. The best defense against osteoporosis in prostate cancer is to identify patients with a high risk for fracture during the first clinical visit, select an effective anti-osteoporosis agent, and advise the patient to change his lifestyle and diet to prevent further bone loss. New agents include denosumab, a human monoclonal antibody that inhibits the RANK ligand (RANKL). RANKL promotes the formation, activity, and survival of osteoclasts and, thus, supports the breakdown of bone. Purpose. This is a multicenter, randomized, double-blind prospective study on use of denosumab versus alendronate in the therapy of secondary osteoporosis related to ADT in prostate cancer patients in three European countries (Italy, France, Switzerland). Patients and methods. In this 24-month observation study we enrolled 234 patients with diagnosis of osteoporosis underwent ADT for prostate cancer. All patients aged ≥55 years and had a dual-energy X-ray absorptiometry (DEXA) T-score <-1.0 (hip or spine, measured within last 2 years) and ≥ 1 fragility fracture. Patients were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months or alendronate (70 mg weekly) for 2 years. All patient received supplemental vitamin D (600 IU per day) and supplemental calcium to maintain a calcium intake of 1200 mg per day. Effectiveness of therapy in both groups (denosumab group and alendronate group) was assessed by changes in bone turnover markers (BTMs), Bone Mineral Density (BMD), fracture incidence, Visual Analogue Scale (VAS) score for back pain, and Short Form-8 (SF-8TM) health survey score for healthrelated quality of life (HRQoL). Percent changes from baseline in BTMs and BMD were assessed using the paired t test; a P-value 0.05). Mean changes in BMD at final follow-up differed significantly between two groups. BMD changes at the lumbar spine at 24 months were 5.6% with denosumab vs -1.1% with alendronate (P<0.001). New vertebral fractures developed in fewer patients in the denosumab group than in the alendronate group during the 24-month period, although this difference was not significant (P=0.10). Back pain significantly (P<0.001) improved from baseline at all time points during the study in both study groups. SF-8 health survey scores significantly improved following treatment with both drugs. Incidence of adverse drug reactions were similar in both groups. Conclusion. In our study denosumab and alendronate showed similar clinical efficacy in the therapy of ADT-related osteoporosis in men with prostate carcinoma; both drugs provided significant improvements in back pain and general health conditions. Denosumab showed significant increase of BTMs and BMD than alendronate with lower rate of new vertebral fractures.

Thyroid Hormone Diseases and Osteoporosis

“…The peak bone mass achieved at maturity and the age of menopause are strong predictors of an increased risk for fracture. Bisphosphonates are the cornerstone for the treatment of osteoporosis [5] and are commonly prescribed for its treatment, both in women and men [6]. More recently, other drugs (i.e., teriparatide and denosumab) are often prescribed and showed a safety profile [7], even when prescribed for therapy of non-unions [8].…”

Comparing the Efficacy and Safety of Denosumab with Bisphosphonates in Increasing Bone Mineral Density in Patients with Prostate Cancer and Breast Cancer on Antihormonal Treatment

“…Of the 18 selected research papers, there were seven RCTs using denosumab in breast cancer and prostate cancer [9,[15][16][17][18][19][20]. Three of these RCTs evaluated the role of denosumab in breast cancer [16,17,18], while one evaluated the role of denosumab in prostate cancer [15]. There were two systematic reviews and meta-analyses that compared the role of denosumab with bisphosphonates in both prostate cancer and breast cancer [9,20].…”

“…Normally, estrogen has a key role in maintaining bone density in healthy postmenopausal women; estrogen acts on both osteoblasts and osteoclasts to decrease bone turnover by suppressing bone remodeling action [26]. Antihormonal therapy, whether it is ADT or AI therapy, ultimately decreases estrogen activity [15,27]. Figure 2 illustrates the mechanism of action of denosumab and bisphosphonates.…”

“…A prospective 24-month observational study by Doria et al compared the effect of denosumab 60 mg subcutaneously with alendronate 70 mg once weekly in prostate cancer patients on ADT [15]. Both denosumab and alendronate improved BMD, but denosumab showed significantly better results (p = <0.001) [15]. Denosumab demonstrated an increase in BMD up to 5.6% at the lumbar spine after 24 months, while alendronate increased BMD by up to 1.1%.…”

Bone Health in Men with Prostate Cancer: Review Article

“…A comparison of the effects of denosumab and alendronate on BMD and fracture risk was performed in a randomized study of 234 prostate cancer patients on ADT. The authors found that denosumab was associated with a significant increase in BMD (measured at the lumbar spine) at 24 months compared to alendronate (5.6% vs 1.1%, p < 0.001) with a concomitant lower incidence of vertebral fractures, which was not statistically significant [92]. Denosumab is currently the only agent that has regulatory approval for the treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures.…”