Effects of androgen deprivation therapy on bone health in New Zealand men with prostate cancer: Can nutrient intake modulate these effects?

Abstract

Backgrounds The use of androgen deprivation therapy (ADT) in prostate cancer (PCa) treatment is associated with significant bone loss and increased risk of fracture. The overall objective of this thesis was to examine the burden of the effect of ADT on bone health in a PCa cohort in New Zealand. This includes assessment of the importance of monitoring bone density or bone markers, or both, in this group of men. Additionally the importance of diet to modulate bone effects is also assessed. Methods Five studies were performed: 1) A systematic review examined the association between ADT and bone mineral density (BMD), rate of osteoporosis, bone turnover and fracture risk 2) Using a dataset created through linking records from the New Zealand Cancer Registry, National Minimal Dataset, Pharmaceutical Collection and Mortality collection, we examined the fracture burden of ADT in New Zealand PCa population and the subsequent mortality risk following a fracture. 3) A cross-sectional and longitudinal study examined the effect of acute and long-term ADT on BMD and change in BMD in a PCa cohort in New Zealand, and compared this to patients who discontinued ADT, as well as patients managed without ADT options. 4) A cross-sectional and longitudinal study investigated the effect of acute and long term ADT on bone markers. These effects were compared with patients who discontinued ADT as well as patients managed without ADT options. The bone markers studied included: procollagen type-I N-terminal propeptide (PINP), a bone formation marker; C-terminal telopeptide of type I collagen (CTX), a bone resorption marker; Sclerostin and Dickkopf-1 (DKK-1), two inhibitors of bone formation; and osteoprotegerin (OPG), an inhibitor of osteoclastogenesis. 5) An analysis of the relationship between the bone markers and nutrients intakes Results 1) Reviewed literature indicates that men treated with ADT are associated with a significant lower BMD, increased bone loss, higher bone turnover and higher fracture rate than men not treated with ADT. 2) ADT was significantly associated with an increased risk of any fracture and hip fracture requiring hospitalisation in the New Zealand PCa population. 3) Cross-sectional analysis showed that men receiving chronic ADT had significantly decreased total body BMD than former ADT users and men with no ADT. In the longitudinal analysis, men on acute ADT had a similar rate of bone loss to men on chronic ADT and ADT-induced bone loss appear to be reversed after discontinuation of the treatment. 4) In the cross-sectional analysis, higher levels of PINP, CTX, and sclerostin were observed in acute and chronic ADT users than former ADT users or PCa controls. Serum OPG was significantly higher in chronic ADT users and former ADT users as compared to PCa controls. BMD significantly correlated with sclerostin levels. Patients recording lower BMD accompanied by increased level of sclerostin could be suitable for osteoporosis treatment. 5) Serum sclerostin and OPG levels were inversely related to dietary intake of several nutrients including magnesium and selenium, while CTX levels were directly correlated with dietary sodium levels. This indicated the importance of modulating nutrient intake in suppressing ADT-induced bone loss. Conclusion Men receiving ADT had a detrimental effect on bone health, and may require monitoring with BMD complemented by bone markers. Diet may play a role in modulating the effect of ADT on bone health. Clinicians should inform their patients, regarding the importance of bone health monitoring, as well as the importance of a well-balanced diet for their bone health. Dietary counselling by a dietician may be beneficial, especially before initiating ADT.