br Introduction br Prostate cancer PCa is
Prostate cancer (PCa) is the most commonly diagnosed male cancer in the developed world, but with improving detection and treatment, the survival rate of PCa is among the highest of all cancers [1–3]. An-drogen deprivation therapy (ADT) is a mainstay in the treatment of locally advanced and metastatic prostate cancer, with evident benefit in controlling PCa progression and improving overall survival when pre-scribed appropriately . However, hypogonadism induced by ADT is associated with a range of adverse effects on cardiovascular and me-tabolic health, sexual function and musculoskeletal health [5–8]. Re-garding skeletal health, most cross-sectional studies have reported lower dual-energy x-ray absorptiometry (DXA) areal bone mineral
density (aBMD) at various skeletal sites in ADT-treated men compared to PCa patients not treated with ADT and to healthy older adults [9–12], while others have reported no differences [13,14]. Long-itudinally, ADT-treated men have been shown to have up to a five-fold greater rate of decline in aBMD compared to normal age-related losses [8,15–17]. However, little research has investigated the effects of ADT on other key determinants of bone strength beyond aBMD, such as cortical volumetric BMD (vBMD) and its distribution which provides an indication of whole bone and regional bone material properties (mi-neralization and/or porosity), cortical bone structure and mass dis-tribution or trabecular bone properties. This is important because changes in whole bone strength can occur without a measurable change in aBMD, justifying their independent assessment when evaluating
Corresponding author at: Deakin University, Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, 221 Burwood Highway, Burwood, Victoria 3125, Australia. E-mail address: [email protected] (J. Dalla Via).
skeletal health [18–20]. The assessment of cortical bone mass and density distribution is also important given that cortical bone vBMD is not uniform throughout the cortex, and that cortical bone distribution changes with age leading to regional variations in the porosity, degree of mineralization and osteon Quizartinib (AC220) density [21–26]. Indeed, it has been reported that around 70% of the age-related loss in cortical vBMD is due to increased porosity, particularly on the inner endosteal surface [23,27]. Whether ADT leads to a preferential loss or change in cortical bone mass or density distribution has not been examined.
Peripheral quantitative computed tomography (pQCT) is an estab-lished technique that is able to assess bone geometric properties such as bone size and shape at peripheral skeletal sites, distinguish cortical and trabecular components, provide an estimate of bone strength as well as measure region-specific changes in the distribution of cortical bone within a given cross-section [18–20]. Longitudinally, one study using high-resolution pQCT (HR-pQCT) reported marked declines (1.5–12.5%) in cortical and trabecular vBMD as well as in cortical area at both the distal tibia and radius during the first 12-months of ADT . This is an important study as it was the first to report deleterious effects of ADT on bone microarchitecture . These results are sup-ported by a longitudinal study in older men that reported more rapid declines in HR-pQCT assessed cortical bone outcomes of the distal tibia and radius among a subsample of men treated with ADT (N = 16), compared to those not treated with ADT (N = 779) . The current study adds to this previous research by comparing ADT-treated men to both non-ADT men with prostate cancer and healthy controls and by assessing proximal sites of the tibia and radius that are predominantly comprised of cortical bone, as well as cortical bone distribution, which has not been previously investigated in this population. Therefore, the aim of this study was to investigate DXA areal BMD and pQCT cortical and trabecular vBMD, cortical bone structure, distribution and esti-mates of whole bone strength in PCa survivors treated with ADT compared to PCa survivors not treated with ADT and to healthy older men.
2. Materials and methods
This was a cross-sectional study that included 70 men treated with ADT for PCa, 52 men treated with non-hormonal therapies (including active surveillance) for PCa (PCa controls) and 70 men not diagnosed with PCa (healthy controls). Men treated with ADT in this analysis were involved in a larger randomised controlled trial involving exercise training and nutritional supplementation . This cross sectional study includes the baseline data from these ADT-treated men. Eligible participants were men aged 50–85 years. Participants were excluded if they did not have the ability to complete surveys in the English lan-guage, had any disorder(s) known to affect bone, calcium or vitamin D metabolism (other than hypogonadism), were currently receiving pharmacological intervention known to affect bone metabolism (other than ADT), had supplemented with protein, calcium (> 600 mg/day) or vitamin D (> 1000 IU/day) in the past three months, had undertaken progressive resistance training (> 1 session/week) or regular weight bearing impact exercise (> 150 min/week) in the past three months, were current smokers, had a weight > 159 kg or had any absolute contraindications to exercise testing according to the American College of Sports Medicine guidelines . Specific to ADT-treated men, treatment must have been pharmacological (surgical orchiectomy ex-cluded) and administered for > 12 weeks at enrolment.