Effect of Androgen-Deprivation Therapy on Bone Mineral Density in Patients with Prostate Cancer: A Systematic Review and Meta-Analysis

We aimed to evaluate the change in bone mineral density (BMD) in patients with prostate cancer (PCa) receiving androgen deprivation therapy (ADT) compared to those with PCa or other urologic conditions not receiving ADT. Literature searches were conducted throughout October 2018. The eligibility of each study was assessed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the Participant, Intervention, Comparator, Outcome, and Study design method. The outcomes analyzed were the mean difference (MD) of percent changes in BMD of lumbar spine, femur neck, and total hip. Five prospective cohort studies with a total of 533 patients were included in the present study. Statistically significant decreases of BMD change relative to the control group were observed in the ADT treatment group in the lumbar spine (MD −3.60, 95% CI −6.72 to −0.47, P = 0.02), femoral neck (MD −3.11, 95% CI −4.73 to −1.48, P = 0.0002), and total hip (MD −1.59, 95% CI −2.99 to −0.19, P = 0.03). There is a significant relationship between ADT and BMD reduction in patients with PCa. Regular BMD testing and the optimal treatment for BMD loss should, therefore, be considered in patients with PCa undergoing ADT.

2 Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.

2,3
Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.
2 Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.
2 Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).

2,3
Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

3
Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

Risk of bias in individual studies
12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.

3
Summary measures 13 State the principal summary measures (e.g., risk ratio, difference in means).

Synthesis of results
14 Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I 2 ) for each meta-analysis.

# Checklist item Reported on page #
Risk of bias across studies 15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).

3
Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.

Study selection
17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.
3, figure 1 Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

3, table 1
Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12). Table 2 Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.  Table 2 Additional analysis 23 Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16]).

DISCUSSION
Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).

8,9
Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).

10
Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research.

FUNDING
Funding 27 Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.