br There are several strengths to our study This
There are several strengths to our study. This is the first study to use robust measures to assess estimates of bone strength and its determi-nants at distal and proximal skeletal sites, including vBMD, bone structure, strength and cortical bone density distribution, in ADT-treated men. In addition, the inclusion of both non-ADT treated PCa men and healthy controls allowed for the effects of ADT to be compared independently of any effects of a PCa diagnosis or any non-hormonal PCa treatment. However, there are also a number of limitations that should be considered. Firstly, the cross-sectional design of the study means that causality cannot be established for the outcomes assessed. Secondly, although the sample size was relatively large compared to previous studies, this study may still have been underpowered to detect some differences in the pQCT-derived outcomes given that changes in bone geometry tend to occur more slowly over time compared to density. The sample size was further reduced for certain pQCT out-comes due to limitations in scan analysis and acquisition. Thirdly, it is possible that some hypogonadal men may have been included in the
control groups. However, the prevalence of middle-aged and older men having total Concanamycin A levels below 200 ng/dL (considered androgen deficient) is reported to be very low (~2.0%) ; this would be even lower if using the castrate threshold of 50 ng/dL typically achieved by ADT [4,54]. Additionally, factors such as ADT adherence and efficacy may influence skeletal health, however we did not collect treatment information other than ADT duration. Finally, volunteer bias due to the way in which participants were recruited may limit the generalisability of the results. ADT-treated men included in this study were involved in a larger RCT, so all volunteered to potentially be allocated to a 52-week exercise training and nutritional supplementation intervention. It is therefore possible that only ADT-treated men who were capable of completing the intervention volunteered for the study, and as a result, they may represent a healthier subsection of the broader population of ADT-treated men. Conversely, PCa and healthy control group partici-pants were recruited for a single testing session promoted as a ‘free health assessment’. It is therefore possible that men with an existing health issue or concern were more likely to volunteer, so participants in the control groups may have been less healthy than the general popu-lation.
In conclusion, ADT treatment in men with PCa was associated with lower aBMD and vBMD and reduced estimated compressive bone strength, particularly at distal trabecular skeletal sites, compared to non-ADT treated PCa and healthy controls. In contrast, there were no differences in cortical bone density, structure or bending strength at proximal sites between groups, which suggests that treatment with ADT may predominantly affect trabecular bone.
Declaration of Competing Interest
The authors thank the contributions of Deakin University School of Exercise and Nutrition Sciences Honours student Mr. Stephen J Foulkes. Gerontology Research Center is a joint effort between the University of Jyvaskyla and the University of Tampere.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Study design: PO, RD, SF. Study conduct: JDV, PO, NM. Data col-lection: JDV, PO, NM. Data analysis: JDV, PO, RD, TR. Data inter-pretation: JDV, RD, SF. Drafting manuscript: JDV. Revising manuscript content: JDV, RD, PO, NM, TR, SF. Approving final version of manu-script: JDV, RD, PO, NM, TR, SF. JDV takes responsibility for the in-tegrity of the data analysis.