Bone metabolic disorder in patients with prostate cancer receiving androgen deprivation therapy (ADT): impact of ADT on the growth hormone/insulin‐like growth factor‐1/parathyroid hormone axis

Abstract

Although androgen deprivation therapy (ADT) has been associated with bone loss in patients with prostate cancer, its mechanism remains unclear. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1)/parathyroid hormone (PTH) axis plays a critical role in bone synthesis, but its activity during ADT is also unknown. Seventy-one patients with localized prostate cancer, who received ADT, were prospectively studied based on their bone mineral density (BMD) and blood and urine samples at the baseline and after ADT for 6 months. The IGF-1 level was correlated with BMD before ADT (rs = 0.325, P = 0.007), but such a relationship disappeared after ADT (P = 0.565). Following ADT, the serum IGF-1 level increased compared with that at the baseline (22 +/- 6 nmol/L vs. 19 +/- 5 nmol/L, respectively, P < 0.001). The serum PTH level was reduced after ADT (41 +/- 33 ng/L) compared with the baseline (55 +/- 44 ng/L) (P < 0.001), but no change was observed in the serum GH level (P = 0.691). Bone resorption markers such as blood N-telopeptide (NTx), urinary NTx, calcium, and inorganic phosphorus levels increased after ADT (P < 0.001 in all). The ratio of the IGF-1 level after ADT/before ADT was associated with the ratio of the value after ADT/before ADT of alkaline phosphatase (rs = 0.266, P = 0.025) and calcium (rs = 0.242, P = 0.042). Despite the unaffected GH and upregulated bone resorption, the serum IGF-1 level was elevated by ADT. The IGF-1 level was correlated with BMD before ADT, but the relationship was disrupted after ADT. IGF-1 or its receptor in the bone may be functionally inactivated during ADT.