A Comprehensive Bone-Health Management Approach for Men with Prostate Cancer Receiving Androgen Deprivation Therapy

Lee, C.E.; Leslie, William D.; Czaykowski, Piotr; Gingerich, Joel Roger; Geirnaert, Marc; Lau, Yiu-Keung

doi:10.3747/co.v18i4.746

Cited by 32 publications

(47 citation statements)

References 81 publications

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“…There is emerging evidence that lifestyle interventions, such as exercise training and to a lesser extent nutritional supplementation, may improve or maintain muscle, fat and performance outcomes in men treated with ADT, which may in turn reduce the likelihood of further clinical complications [14,[56][57][58][59] . To date, previously evaluated interventions have been limited to singular modalities (e.g.…”

Section: List Of Tables Chaptermentioning

confidence: 99%

“…However, ADT use in general has been associated with an increased risk of falls [201] and subsequent fractures [202][203][204] . Similarly, ADT has been associated with increased cardiometabolic risk via compromised blood lipid profiles, decreased insulin sensitivity and increased arterial stiffness [59,205,206] ; however, this elevated risk appears to be associated with cardiometabolic morbidity [207] , but not mortality within these men [208] . ADT is also associated with increased fatigue, depressive symptoms and sexual dysfunction may in part explain the lower health-related quality of life commonly reported in men treated with ADT [209] , which is of further concern given the susceptibility to suicide among these men [187] .…”

Section: The Clinical Implications Of Androgen Deprivation Therapy-rementioning

confidence: 99%

“…Current guidelines for managing the myriad of ADT-induced adverse effects generally involve monitoring known risk factors, pharmacotherapy and/or lifestyle interventions; however guidelines appear to vary by country, organisation and expert opinion [14,[56][57][58][59] . Moreover, these guidelines tend to focus on addressing decrements in bone health, rather than the adverse effects associated with ADT on muscle, fat and performance.…”

Section: Potential Interventions To Improve Muscle Fat and Performanmentioning

confidence: 99%

“…Moreover, these guidelines tend to focus on addressing decrements in bone health, rather than the adverse effects associated with ADT on muscle, fat and performance. The limited number of guidelines that address changes in body composition associated with ADT tend to have placed greater emphasis on weight management, and do not specifically focus on monitoring fat or lean mass and size via robust measures, such as DXA or pQCT [56,59] . Whilst guidelines for managing resistance, they did not recommend any interventions specifically intended to preserve or improve lean mass or muscle CSA [14,56,57,59] .…”

Section: Potential Interventions To Improve Muscle Fat and Performanmentioning

confidence: 99%

“…The limited number of guidelines that address changes in body composition associated with ADT tend to have placed greater emphasis on weight management, and do not specifically focus on monitoring fat or lean mass and size via robust measures, such as DXA or pQCT [56,59] . Whilst guidelines for managing resistance, they did not recommend any interventions specifically intended to preserve or improve lean mass or muscle CSA [14,56,57,59] . However, regular exercise training and/or physical activity are recommended, but greater emphasis is placed on weight management as an outcome, rather than lean mass or muscle CSA [14,56,57,59] .…”

Section: Potential Interventions To Improve Muscle Fat and Performanmentioning

confidence: 99%

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Muscle, fat and performance during androgen deprivation for prostate cancer

Owen¹

2018

Preprint

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Introduction: Prostate cancer (PCa) is one of the most frequently diagnosed male cancers worldwide. One treatment, androgen deprivation therapy (ADT), is often accompanied with a myriad of adverse effects, including those that negatively impact muscle, fat and performance outcomes. Therefore, ADT-treated men may be living longer, but are at risk of both age- and treatment-related complications. The overall aim of this thesis was to quantify outcomes of muscle, fat and performance in men treated with ADT when compared to PCa (men diagnosed with PCa, not treated with ADT) and healthy controls (men not diagnosed with PCa), and assess the feasibility of implementing a multi-component exercise program combined with protein, calcium and vitamin D supplementation (Ex+ProCaD) compared to usual care in ADT-treated men. Methods: This thesis presents two studies that form part of a larger 52-week randomised controlled trial (RCT), which examined the efficacy of Ex+ProCaD compared to usual care in men treated with ADT for PCa. The first study presented was a nested cross-sectional study performed parallel to the baseline assessment of the RCT and examined differences in muscle, fat and performance outcomes between men treated with ADT when compared to PCa and healthy controls. The second study presented examined the feasibility of implementing the first 26 weeks of the RCT. Results: The cross-sectional study showed that height, weight, body mass index and diet were similar between the three groups, but ADT-treated men were four years older and tended to be less physically active (23-30%; P=0.054). After adjusting for age and physical activity, total body fat mass was 3.3-5.0 kg (P < 0.05) greater in men treated with ADT compared to PCa controls, but there was no difference in total body and regional lean mass. When adiposity was considered, ADT-treated men had 10-12% (P < 0.05) lower appendicular lean mass adjusted for body mass index and 5.6-6.4% (P < 0.05) lower forearm percent muscle cross-sectional area compared to controls. Absolute muscle strength was similar between groups, but when expressed relative to body weight, men treated with ADT had 13-21% (P < 0.05) lower muscle strength compared to controls. Whilst only two ADT-treated men had sarcopenia, these men had a higher proportion (P < 0.001) of pre-sarcopenia when appendicular lean mass was adjusted for body mass index (42%) compared to PCa (15%) and healthy (7%) controls. Men treated with ADT had 15-36% (P < 0.05) greater storage of fat within subcutaneous depots when compared to controls, whereas visceral and intermuscular fat was similar. The majority of subcutaneous fat depots (excluding android region) were shown to be positively associated with ADT duration (P < 0.05). Forearm muscle density was shown to negatively correlate with ADT duration (P < 0.05). The RCT had a high participant retention rate (96%). Adherence was high for the supplement (mean, 92-93%) and modest for the exercise program (mean, 60%). A relatively high proportion (81%) of men in the intervention group reported an adverse event, although only 16% were confirmed to be related to the intervention and the vast majority (97%) were determined to be mild or moderate in terms of severity. Across the ten separate recruitment pathways considered, clinician referral (43%) and PCa support groups (29%) yielded the greatest proportion of enrolled participants. A total of 149 potential participants were screened, which resulted in 42 participants at the time of write up for this thesis. Among the first 28 participants to complete the 26-week intervention, 21-50% were unable to complete at least one measure of muscle strength due to pre-existing comorbidities. Data from the initial 28 participants tended to show that when compared to usual care, Ex+ProCaD led to net improvements in lean mass (0.2-1.4 kg), fat mass (-0.1 to -0.9 kg), muscle strength (8.0-19%), functional muscle power (8.6%) and functional capacity (12-14%). Conclusions: The following key themes emerged from this thesis and may be used to guide clinical practice guidelines and future research: 1) Men treated with ADT for PCa had greater amounts of fat when compared to non-ADT counterparts, 2) Current definitions of sarcopenia and sarcopenic obesity were limited in men treated with ADT for PCa, 3) The greater amounts of fat observed in men treated with ADT for PCa tended to be stored in subcutaneous depots and supersede age-related plateaus/losses, 4) The recruitment of men treated with ADT for PCa into a lifestyle intervention was challenging, and 5) Men treated with ADT for PCa tended to respond positively to a multi-modal exercise training combined with multi-nutrient supplementation.

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