Introduction

Prostate cancer is the second most commonly diagnosed cancer in men worldwide and a leading cause of cancer-related deaths among men1. Androgen deprivation therapy (ADT) is a cornerstone of treatment for advanced and metastatic prostate cancer, effectively suppressing androgens to inhibit tumor growth2,3. However, ADT disrupts the balance of bone remodeling by suppressing testosterone levels, leading to accelerated bone loss and an increased risk of osteoporosis4.

Osteoporosis, characterized by low bone mineral density (BMD) and microarchitectural deterioration of bone tissue, is a common consequence of long-term ADT use in prostate cancer patients5. The imbalance between bone formation and resorption induced by ADT results in decreased BMD, making bones more susceptible to fractures and skeletal complications. Dual-energy x-ray absorptiometry (DXA) examination is the major method to define BMD, allowing for the identification of osteoporosis and assessment of fracture risk6. Consequently, osteoporosis significantly impacts the quality of life and overall prognosis of prostate cancer patients7,8.

Given the detrimental effects of ADT on bone health, the importance of BMD screening cannot be overstated. BMD screening plays a crucial role in identifying individuals at risk of osteoporosis and fractures, allowing for early intervention and preventive measures. Consequently, guidelines from organizations such as NCCN and ESMO recommend routine BMD screening and the use of the Fracture Risk Assessment Tool (FRAX) to assess fracture risk in patients undergoing ADT9,10.

Despite the significance of BMD screening, it remains underutilized in clinical practice, particularly among prostate cancer patients undergoing ADT. Studies, such as those utilizing the Quebec public health care insurance database and the SEER-Medicare database, have reported alarmingly low rates of DXA testing in this population11,12. For instance, the Quebec study observed a modest increase in DXA testing rates from 4.1% in 2000 to 23.4% in 201511, while the SEER-Medicare database revealed only a slight rise from 6.8% in 2005 to 8.4% in 201512. These findings underscore the persistent challenges in ensuring adequate BMD screening among prostate cancer patients on ADT and highlight the urgent need for enhanced awareness and proactive management of bone health in this population.

To amplify screening rates and enhance patient willingness, we streamlined the screening process by developing an auto-recruit path within the outpatient system. This initiative aimed to improve surveillance rates by making the process more accessible and efficient. We also reviewed historical BMD screening rates over the past decades to evaluate improvements following the implementation of this electronic system. Furthermore, we analyzed factors influencing patients’ willingness to undergo screening and pursue subsequent related treatments, aiming to identify and address potential barriers.

Results

Impact of the auto-recruit system on bone health screening rates

From 2000 to 2018, a retrospective analysis of 3,019 patients found that only 286 (9.5%) underwent DXA screening, with just 51 (1.9%) having follow-up DXA exams before and after starting ADT. After implementing the auto-recruit system from March 2021 to February 2022, 747 patients met the inclusion criteria, with 251 (33.6%) undergoing bone health screening, significantly increasing the screening rate (p < 0.001).

Baseline characteristics of study participants and non-participants

Table 1 presents the baseline characteristics of participants and non-participants in the Auto-Recruit Outpatient System. A total of 747 patients were included in the study, with 251 participants and 496 non-participants. Participants were younger, with a median age of 73.0 years compared to 77.0 years for non-participants (p < 0.001). Participants were also significantly taller and heavier. The median BMI was higher in participants at 25.5 compared to 24.8 in non-participants (p = 0.028). The duration of ADT use was significantly shorter among participants, with a median of 0.8 years compared to 2.1 years in non-participants (p < 0.001). There was no significant difference in the proportion of patients diagnosed with CRPC between participants (32.3%) and non-participants (33.5%) (p = 0.743). However, the usage of BMAs was significantly lower among participants (7.2%) compared to non-participants (20.4%) (p < 0.001).

Table 1 Baseline characteristics of participants and non-participants in the Auto-Recruit Outpatient System.
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Analysis of participants by duration of ADT usage

We further analyzed the impact of ADT duration on bone health by dividing participants into two groups: ADT usage ≤ 1 year (138 participants) and > 1 year (113 participants) (Table 2). There were no significant differences in age, height, weight, or BMI between the groups. However, the minimal T-score was significantly lower in the group with ADT usage > 1 year (-2.1 vs. -1.7, p = 0.009), and a higher proportion met the osteoporosis criteria (T-scores ≤ -2.5) (34.5% vs. 23.2%, p = 0.039). The FRAX scores for major and hip fractures, as well as the percentage of participants with a history of fractures, did not differ significantly between the groups. Calcium supplement use before screening was similar between the groups. However, the use of BMAs before screening was significantly higher in the group with ADT usage > 1 year (14.2% vs. 1.4%, p < 0.001).

Table 2 Demographics of participants in the Auto-Recruit Outpatient System by ADT usage (≤ 1 year vs. >1 year).
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Impact of screening protocol on calcium supplement and bone health agent use

Table 3 illustrates the changes in calcium supplement and bone health agent use before and after bone health screening, categorized by ADT usage duration (≤ 1 year vs. >1 year). Overall, calcium supplement use increased significantly from 16.3 to 44.2% post-screening (p < 0.001), and bone-protective agent use rose from 7.2 to 25.5% (p < 0.001). Subgroup analysis showed that the duration of ADT usage did not alter this trend, with both groups exhibiting significant increases in calcium supplement and bone-protective agent use after screening.

Table 3 Changes in Calcium supplement and Bone Health Agent Use before and after Bone Health Screening, divided by duration of ADT (≤ 1 year vs. >1 year).
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Discussion

Addressing the unmet need for BMD screening in prostate cancer patients undergoing ADT requires a multifaceted approach13. Healthcare providers must prioritize bone health assessments and integrate BMD screening into routine clinical practice. This project, utilizing the Auto-recruit path for bone health screening in the outpatient management system, effectively increased the overall screening rate from 9.5% between 2000 and 2018 to 33.6% in 2021–2022. Additionally, patients’ willingness to accept osteoporosis-related prevention and treatment significantly improved after undergoing the screening process. To our knowledge, this study is the first to demonstrate a significant increase in prostate cancer osteoporosis screening rates through a simple program setup, proving that electronic system support can effectively enhance healthcare efficiency.

Despite a significant improvement in the screening rate, the actual rate of 33.6% remains below expectations. Several factors may explain this outcome. First, the system’s mandatory pop-up reminder is designed to comprehensively ensure that all eligible patients are considered. However, the inclusion criteria did not account for factors such as age, race, comorbidities, performance status, or life expectancy, which may make patients unsuitable for screening. These factors could potentially impact the final enrollment results and the overall screening rate. Second, some physicians may have considered BMD screening unnecessary for specific patients, as indicated by the higher age and longer ADT duration among non-participants, which could correlate with a poorer prognosis. Third, 20.4% of non-participants were already receiving BMAs without prior DXA screening, likely impacting the physicians’ decision to forgo additional screening. Furthermore, some non-participants may have undergone DXA screening over 12 months prior, or had bone metastases, where BMAs were prescribed to prevent skeletal-related events rather than to address low BMD.

Bone-modifying agents (BMAs) are effective in preventing fractures and reducing skeletal-related events (SREs) in patients with CRPC with bone metastasis14. In contrast, previous clinical trials have shown that there is no significant survival benefit from using BMAs in patients with metastatic castration-sensitive prostate cancer (mCSPC), which is why routine use of BMAs is not recommended in this population15,16. However, in recent years, this recommendation against BMA use has often been interpreted more broadly as an indication of “unnecessary use.”17 Nonetheless, providing BMAs selectively to patients who truly need it can still yield substantial benefits, as supported by the post hoc analysis of the LATITUDE trial18. A crucial component of this approach is BMD screening and the prevention of osteoporotic complications. Thus, implementing comprehensive BMD screenings for prostate cancer patients on ADT could help identify those at high risk for fractures. These high-risk patients could then receive BMAs, effectively preventing fractures while avoiding unnecessary side effects and reducing medical waste19,20.

ADT can accelerate bone loss, leading to osteoporosis and an increased risk of fractures. A 24-month prospective observational study of prostate cancer patients undergoing ADT found that the prevalence of osteoporosis and osteopenia significantly increased from 10% and 58–22% and 70%, respectively21. In our study, patients who had been on ADT for more than a year showed a significant decrease in their minimal T-scores and a higher proportion meeting the criteria for osteoporosis, echoing these findings. Although older patients on long-term ADT might initially overlook bone health issues, our study revealed that this group showed a significant increase in willingness to accept calcium supplements and bone-modifying agents after BMD screening. This indicates that these patients are not unwilling to take action to protect themselves, but rather they are unaware of their bone health status. Therefore, patient education and awareness initiatives are crucial to empower individuals to advocate for their bone health and pursue appropriate screening and preventive interventions22.

This study has several limitations. First, although it is a prospective cohort study, most patients lacked baseline BMD data prior to initiating ADT, which may affect the accuracy of osteoporosis data analysis. To address this issue, we simultaneously established a bone-health database aimed at facilitating long-term and comprehensive data analysis regarding the impact of ADT on bone health. Second, although the auto-recruit path in the outpatient system was associated with a significant increase in screening rates, other factors—such as heightened clinician awareness, patient education initiatives, and evolving clinical practices over time—may also have contributed to this rise. Our current study design does not allow us to isolate the impact of each of these factors. Future research will focus on examining the effects of different clinical policies over time to better assess the specific contribution of the auto-recruit system. Third, while many patients took preventive and therapeutic measures for bone health after BMD screening, there is still no direct evidence that these measures effectively reduce SREs. Long-term follow-up and comparison of cohort differences are necessary to establish this evidence. Furthermore, in this study, we referred to ‘patient willingness’ regarding the increased uptake of calcium supplementation and BMA use. However, without direct patient-reported outcomes, we lack definitive evidence to attribute the increase solely to patient willingness. Other factors, such as increased clinician awareness or prioritization, may have also played a role. Therefore, it is challenging to fully distinguish the contributions of each factor in this context. Lastly, this study was conducted at a single medical center. Although the implementation relied on simple diagnostic and medication codes, not all healthcare electronic systems may support such configurations, potentially limiting the generalizability of the system. Further validation in diverse healthcare settings is needed to assess its broader applicability.

Conclusion

Bone health screening for patients with prostate cancer undergoing ADT remains an unmet need. The convenience of the system plays a crucial role in influencing physicians’ decisions to screen for this issue. The auto-recruit path within the outpatient management system can effectively remind physicians of the appropriate inclusion criteria, significantly increasing the bone health screening rate. Additionally, it enhances patient education and awareness initiatives. Such programs allow us to effectively identify and treat high-risk patients for fractures while avoiding unnecessary side effects and medical waste.

Materials and methods

Auto-recruit path and study design

To enhance the BMD screening rate and assist physicians in arranging the necessary examinations, we implemented a mandatory pop-up reminder within the outpatient management system, launched in March 2021. This reminder activates whenever ADT is prescribed for a prostate cancer patient who has not undergone a DXA screening within the past year.

If the physician opts to proceed with the screening, the system prompts for DXA, spinal X-rays, serum testosterone levels, other relevant laboratory tests, and the Fracture Risk Assessment Tool (FRAX) score. Additionally, we collaborated with the Osteoporosis Prevention and Treatment Center, osteoporosis specialists, and the dental department, which play crucial roles in preventing complications associated with bone-modifying agents (BMAs) (Fig. 1).

Fig. 1
figure 1

Workflow for Bone Health Screening in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy (ADT).

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Study cohort and bone-health database

The system identifies prostate cancer patients (ICD10: C61) in the outpatient system who are receiving ADT (Drug ID) and have not undergone a DXA exam within the past year. This includes patients receiving ADT-based therapy for metastatic prostate cancer and those undergoing combination therapy of ADT and radiotherapy for localized prostate cancer.

We established a prostate cancer-related bone health database to collect and analyze data. The study protocol was approved by the Institutional Review Board (IRB) of Taichung Veterans General Hospital (IRB No. CG20068A). All research was conducted in accordance with relevant guidelines and regulations, and all participants provided written informed consent.

Factors influencing screening and outcomes

We assessed all eligible patients and divided them into participants and non-participants to identify factors affecting the overall screening rate, including age, height, weight, body mass index (BMI), duration of ADT use, percentage of castration-resistant prostate cancer (CRPC), and usage of BMAs.

Within the participant group, we analyzed the impact of ADT duration on bone health outcomes. Additionally, we evaluated changes in the usage rates of calcium supplements and BMAs before and after the screening protocol. This analysis aimed to understand factors influencing participation in screening and the effectiveness of the intervention in improving bone health management.

To assess the impact of the auto-recruit system, we retrospectively reviewed prostate cancer patients who underwent ADT from 2000 to 2018, focusing on the number and results of DXA tests to evaluate the BMD screening rate. This review was conducted under the same IRB approval from Taichung Veterans General Hospital (IRB No. CE21454B).

Statistical analysis

Descriptive statistics were presented as medians with interquartile ranges (IQR) for continuous variables and as frequencies with percentages for categorical variables. The Chi-square test was used for comparing categorical variables, while the Mann-Whitney U test was applied to continuous variables. Additionally, changes in the usage rates of calcium supplements and BMAs before and after the implementation of the screening protocol were analyzed using the McNemar test for paired nominal data. All statistical analyses were conducted using SAS software version 9.2 (SAS Institute Inc., Cary, NC, USA), with statistical significance determined by a p-value of less than 0.05.