Philip Lee Miller, MD, Editor in Chief

Philip Lee Miller, MD • Clinical Insights

The Hidden Crisis in ADT Prostate Cancer Care

A critical examination of the unfulfilled promise in preventing ADT Prostate Cancer induced osteoporosis and sarcopenia. An urgent call for a paradigm shift in clinical practice.

Published January 6, 2026 | Evidence-Based Medicine

In the landscape of modern prostate cancer treatment, we’ve achieved remarkable progress in cancer control and survival rates. Yet beneath this success story lies a troubling reality. We are systematically failing to address one of the most devastating side effects of androgen deprivation therapy (ADT). The catastrophic loss of bone health (osteoporosis) and muscle mass (sarcopenia) that affects hundreds of thousands of men worldwide.

What is the current goal of androgen deprivation in prostate cancer therapy? To reduce total testosterone levels approaching 20 ng/dl. And a high sensitivity PSA less than 0.2 For men, it’s all a numbers game. Absolutely lower numbers assumes better cancer control. But as you will see, precision medicine demands a more global approach and perspective. [We really should be targeting DHT (dihydrotestosterone) levels. Since DHT is active testosterone metabolite at the site of action.]

A side note: I first want to give special thanks to Dr. Stephen Strumm, a renowned integrative prostate cancer oncologist. He taught me the value of QCT scans. And a special note of gratitude to Dr. William Grant. A tireless advocate of Vitamin D research.

Now, after conducting an extensive review of current clinical evidence, including recent trials on selective androgen receptor modulators (SARMs), intermittent ADT protocols, and advanced bone density measurement techniques, a stark picture emerges. Our current approach to bone health in ADT patients represents a fundamental misunderstanding of bone physiology and a massive missed opportunity for preventive intervention.

The scope of this crisis cannot be overstated. Men receiving ADT experience bone loss at rates that dwarf postmenopausal osteoporosis, yet fewer than 10% receive appropriate bone density monitoring, and our treatment arsenal remains limited to drugs that block normal bone remodeling rather than promoting healthy bone formation.

In This Article:

The Magnitude of Bone Loss
The DEXA Delusion vs. QCT
The Trap of Anti-Resorptive Drugs
Intermittent ADT & Recovery
Why SARMs Failed
The New Paradigm (Protocols)
FAQs
Peer Reviewed Citations

The Magnitude of ADT-Induced Bone Loss & Osteoporosis: Beyond What We Imagined

The clinical data reveals bone loss rates that should alarm every oncologist and urologist. Men receiving continuous ADT experience annual bone mineral density decrements of 1.4% to 4.6% at the lumbar spine and 0.6% to 3.9% at the femoral neck — rates that can reach 10% over just two years. To put this in perspective, healthy postmenopausal women typically lose 1-3% of bone density annually.

Key Clinical Findings:

Rapid Onset: Significant bone mineral density loss occurs as early as the first 6-12 months after starting ADT, with the most dramatic decreases happening in the first year.

Persistent Effect: Bone loss continues throughout treatment duration, with some studies showing progressive decline even up to year 10 of therapy.

Fracture Risk: ADT increases fracture risk by 39% overall, with some studies reporting up to 4-fold increased risk of skeletal fractures.

The DEXA Delusion: DEXA vs. QCT for Prostate Cancer

Why Standard Scans Miss Early Bone Loss in ADT Patients

Standard DEXA
2D Projection

17.1%
Osteoporosis Detection Rate

Averages density: Combines strong outer bone with weak inner bone.
Masks the problem: Healthy cortical bone hides trabecular decay.
Too Late: Often detects loss only after fracture risk is high.

QCT Scan
3D Volumetric Analysis

46.4%
Osteoporosis Detection Rate

Isolates Trabecular Bone: Measures the spongy interior directly.
High Sensitivity: Detects metabolic changes months earlier.
Actionable: Allows for intervention before structural failure.

Conventional DEXA Scanning

So, you can now see from our analysis the profound inadequacy of standard DEXA (Dual-Energy X-ray Absorptiometry) scanning for monitoring ADT patients. While DEXA still remains the overwhelming clinical standard, mounting evidence suggests it’s fundamentally inappropriate for this population. And to be honest, even this DEXA (Lunar Prodigy System or Hologic) convention has been largely abandoned for more “skimpy” cursory reporting. DEXA scan limitations in detecting trabecular bone loss in ADT prostate cancer

The Trabecular Bone Blind Spot

The primary site of ADT-induced bone loss is trabecular bone. That is the metabolically active, spongy interior bone tissue that has a turnover rate 10 times higher than cortical bone. Yet DEXA scans measure combined trabecular and cortical bone density. Thereby, missing early trabecular changes that herald impending fracture risk.

Comparison of normal bone vs osteopenia and osteoporosis trabecular architecture

This disparity isn’t theoretical — it’s clinical reality. Studies directly comparing DEXA and quantitative CT (QCT) in the same patients reveal that QCT detects osteoporosis in nearly half of patients where DEXA suggests normal or only mildly reduced bone density.

The Anti-Resorptive Trap: Treating Symptoms, Not Disease

Current bone health management for ADT patients relies heavily on bisphosphonates and denosumab. Drugs that block osteoclast activity and reduce bone resorption. While these medications can slow bone loss and reduce fracture risk, they represent a fundamentally flawed approach to bone health.

The Critical Insight

These “anti-resorptive” agents don’t promote healthy bone formation. They’re more accurately described as “anti-remodeling” drugs. They create a metabolic prison where bones become denser but increasingly brittle. Thereby, impairing healthy bone remodeling. The ability to repair microdamage and maintain normal bone architecture.

The Dark Side of Anti-Resorptive Therapy

Long-term use of these medications carries significant risks. Particularly concerning for ADT patients who may need treatment for years or decades:

Atypical Fractures: Paradoxically, long-term bisphosphonate use increases the risk of unusual femoral shaft fractures. With relative risk ratios reaching 47.5 in some studies.

Osteonecrosis of the Jaw: A devastating complication where jawbone tissue dies and fails to heal. Particularly problematic given the dental health challenges many cancer patients face.

Impaired Bone Quality: Anti-resorptive agents reduce bone remodeling rates. Leading to accumulation of microdamage and creation of more brittle bone despite increased density measurements.

Duration Limitations: Current guidelines recommend bisphosphonate treatment for only 3-5 years due to these risks. Just when many ADT patients require much longer treatment periods. This creates a clinical conundrum, How do we protect bone health during extended ADT when our primary tools have time limits?

Intermittent ADT: Can Cycling Therapy Prevent Bone Loss?

One of the most underexplored strategies for bone preservation lies in optimizing ADT delivery itself. Emerging evidence suggests that intermittent ADT protocols may offer significant bone health advantages while maintaining cancer control. That is where treatment is cycled on and off based on PSA levels.

Compelling but Limited Evidence

The data on intermittent ADT and bone health, while limited, is intriguing:

Reduced Osteoporosis Risk: Men receiving continuous ADT have more than double the odds of developing osteoporosis (OR: 2.14) compared to those on intermittent protocols.

Long-term Benefits: While bone loss patterns were similar in the first 2-4 years, patients on intermittent ADT demonstrated significantly less bone loss at 6 years. Despite having equivalently low testosterone levels during treatment periods.

Recovery Potential: During off-treatment periods, testosterone recovery can occur relatively rapidly (median 1.4-9 months depending on the ADT agent used). Potentially allowing bone remodeling to resume.

The Clinical Reality: Despite these promising signals, intermittent ADT remains underutilized. Furthermore, standardized protocols for optimizing bone health through ADT cycling haven’t been established. This represents a massive missed opportunity for improving patient outcomes. So, now let’s graphically summarize below

Continuous vs. Intermittent ADT

The Impact of “Cycling” Therapy on Bone Preservation

Continuous ADT
Standard Protocol

12-Month Timeline

2.14x
Higher Odds of Osteoporosis

Metabolic Freeze: Constant suppression prevents normal bone remodeling.
Cumulative Damage: Micro-fractures accumulate without repair periods.
Higher Risk: Rapid decline in spine and hip density.

Intermittent (IAD)
Cycling Protocol

12-Month Timeline (Example)

ADT

RECOVERY

ADT

High
Bone Recovery Potential

Recovery Windows: “Off” periods allow Testosterone to stimulate bone repair.
Long-term Safety: Significantly less bone loss at 6-year follow-up.
Quality of Life: periodic relief from other low-T side effects.

SARMs: The Theoretical Promise That Never Materialized

Our investigation into selective androgen receptor modulators (SARMs) as potential bone health preservers revealed both the tantalizing promise and crushing disappointment of this drug class.

Why SARMs Made Sense

The theoretical rationale for SARMs in ADT patients was compelling:

Tissue Selectivity: SARMs were designed to stimulate androgen receptors in bone and muscle while having minimal effects on the prostate. Exactly what ADT patients need. Ostarine is the flagship drug.

Anabolic Potential: Unlike anti-resorptive drugs, SARMs could theoretically promote actual bone formation and maintain normal bone remodeling cycles.

Dual Benefits: The drugs could potentially address both muscle wasting (cachexia) and bone loss simultaneously.

The Clinical Reality Check

Despite extensive clinical development, SARMs have largely failed to deliver on their bone health promise:

Phase III Failures: Ostarine (enobosarm), the most extensively studied SARM, failed to meet primary endpoints in Phase III trials for cancer cachexia. Leading to termination of development for this indication.

No Human Bone Benefits: While animal studies showed promising bone density improvements, no studies have demonstrated positive bone effects in humans.

Limited Efficacy: Even in successful trials, the gains in lean body mass were modest compared to those achieved with traditional androgens.

Current Status:

As of 2026, no SARMs have received FDA approval for any therapeutic use. The field has largely moved away from bone health applications, with remaining development focused on breast cancer treatment and body composition in specific populations.

The Path Forward: A New Paradigm for Bone Health

The failures in current bone health management for ADT patients aren’t just clinical disappointments. These are urgent calls for paradigm shifts in how we approach treatment-induced osteoporosis.

Essential Changes Needed:

- → QCT-Based Monitoring: Transition from DEXA to quantitative CT for more sensitive detection of trabecular bone loss
- → Intermittent ADT Optimization: Develop standardized protocols for cycling ADT to maximize bone recovery periods
- → True Anabolic Therapies: Invest in developing treatments that promote physiologic bone formation rather than just blocking resorption
- → Early Intervention: Implement bone protective strategies from ADT initiation, not after osteoporosis develops
- → Vitamin D / Vitamin K Fortification: Optimizing 25-OH Vitamin D levels
- → Personalized Protocols: Use biomarkers and advanced imaging to tailor bone health strategies to individual patient risk profiles

Emerging Opportunities

Sclerostin Inhibitors: Drugs like romosozumab that promote bone formation while reducing resorption may offer advantages over traditional anti-resorptive agents.

Combination Therapies: Strategic combinations of anabolic and anti-resorptive agents. Potentially with optimized timing relative to ADT cycles.

Lifestyle Interventions: Evidence-based exercise striving for Zone II optimum. Comprehensive nutritional protocols specifically designed for ADT patients. Implemented as standard of care rather than after thoughts. Calcium, Vitamin D3, Vitamin K2 supplementation.

Low dose Estradiol: Historically men were surgically treated with Orchiectomy. Excision of the testes. Hence the archaeic term – castrate sensitive or castrate resistant. At that time DES (Diethyl Stilbesterol), a potent but dangerous oral estrogen, was prescribed. Causing too many serious side effects in men and women. So, it was abandoned. Now there is a resurgence of interest in low dose 0.025 mg. topical Estradiol patches. Even in men, estradiol is a primary driver of healthy bone density. Validate: FDA approved to prevent Osteoporosis

The Fundamental Shift Required

We must move from a reactive model — where we treat osteoporosis after it develops — to a proactive model. Where bone health preservation is integrated into cancer treatment planning from day one. This isn’t just better medicine. It’s essential for the hundreds of thousands of men who will live for years or decades with prostate cancer.

Clinical Implications and Action Items

For clinicians managing ADT patients today, several immediate actions can improve bone health outcomes:

Enhanced Monitoring: Consider QCT scanning for high-risk patients. Particularly those with expected long-term ADT duration. Advocate for insurance coverage of more sensitive monitoring techniques.

Intermittent ADT Evaluation: For appropriate patients, consider intermittent ADT protocols that may preserve bone health while maintaining cancer control.

Early Intervention: Don’t wait for osteoporosis to develop. Consider bone protective therapy initiation based on fracture risk assessment and expected ADT duration.

Duration Awareness: Plan anti-resorptive therapy duration carefully, considering the limited treatment windows available with current agents.

A Call for Clinical Innovation

The current state of bone health management in ADT patients represents one of the most significant unmet needs in modern cancer care. We have the knowledge to do better. And we understand the mechanisms of ADT-induced bone loss. So, while superior monitoring techniques are available, there is evidence for alternative treatment approaches.

What we lack is the clinical will to implement comprehensive change. And the research investment to develop truly effective bone anabolic therapies. For the millions of men who will receive ADT in the coming decades, the time for incremental improvements has passed. We need a revolution in how we think about and manage treatment-induced bone disease.

The opportunity is clear. The need is urgent. The question is: will we seize this moment to transform bone health care for cancer patients, or will we continue to accept suboptimal outcomes as inevitable?

Frequently Asked Questions about ADT and Bone Health

A quick synopsis and overview

Does Androgen Deprivation Therapy (ADT) cause osteoporosis?

Yes. ADT causes rapid bone loss at a rate significantly higher than natural aging. Clinical data shows men on continuous ADT can lose bone density at a rate of 1.4% to 4.6% per year at the spine. Unlike postmenopausal osteoporosis which is gradual, ADT-induced bone loss is rapid, with the most dramatic decrease occurring in the first 6–12 months of treatment.

Why is a standard DEXA scan inaccurate for prostate cancer patients?

Standard DEXA scans measure the density of the entire bone, combining both the hard outer shell (cortical bone) and the spongy interior (trabecular bone). ADT primarily attacks the spongy trabecular bone first. Because DEXA averages these two types together, it often “masks” early bone loss. Studies show DEXA detects osteoporosis in only 17.1% of cases where a more sensitive QCT scan detected it in 46.4% of the same patients.

What is a QCT scan and why is it better for ADT patients?

Quantitative Computed Tomography (QCT) is a 3D imaging technique that can isolate and measure trabecular bone density separately from cortical bone. This allows it to detect the specific type of bone loss caused by hormone therapy much earlier than DEXA. It is the superior choice for monitoring “metabolically active” bone changes during cancer treatment.

Can bone loss from ADT be reversed?

Current “anti-resorptive” drugs (like bisphosphonates) generally stop further loss but do not build significant new bone. They essentially “freeze” normal and healthy bone remodeling. However, emerging strategies using intermittent ADT (cycling treatment) allow testosterone to recover periodically. Thereby encouraging physiologic bone remodeling and recovery. True reversal often requires a proactive approach combining specialized monitoring, nutritional protocols (Vitamin D3, K2), and potentially anabolic therapies.

Key Peer-Reviewed Sources:

QCT vs DEXA Studies:

Li, N., et al. (2013). “Comparison of QCT and DXA: Osteoporosis Detection Rates in Postmenopausal Women.” International Journal of Endocrinology, 2013, 895474.
- QCT detected osteoporosis in 46.4% vs DEXA’s 17.1%
Genant, H.K., et al. (2008). “Noninvasive assessment of bone mineral and structure: state of the art.” Journal of Bone and Mineral Research, 23(4), 425-441.
- Seminal paper on QCT superiority for trabecular bone assessment
Engelke, K., et al. (2013). “Clinical use of quantitative computed tomography-based advanced techniques in the management of osteoporosis.” Osteoporosis International, 24(6), 1651-1665.
- Clinical applications and advantages of QCT over DEXA
Janina M Patsch, (2011): Andrew J Burghardt, G lateia Kazakia, Sharmila Majumdar. Noninvasive imaging of bone microarchitecture. Ann NY Acad Sci. 2011 Dec 1240;77–87
- Excellent review with high quality images and extensive citations
Bouxsein ML. (2008) Technology insight: noninvasive assessment of bone strength in osteoporosis. Natures Review Rheumatology (Apr 2008). Nat Clin Pract Rheumatol. 2008 Jun;4(6):310-8.

SARMs Research:

Dobs, A.S., et al. (2013). “Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial.” Lancet Oncology, 14(4), 335-345.
- Phase II cancer cachexia trial showing lean mass benefits
Crawford, J., et al. (2016). “Study Design and Rationale for the Phase 3 Clinical Development Program of Enobosarm.” Current Oncology Reports, 18(6), 37.
- Details of failed Phase III trials and lessons learned

ADT Bone Loss Studies:

Greenspan, S.L., et al. (2005). “Bone loss after initiation of androgen deprivation therapy in patients with prostate cancer.” Journal of Clinical Endocrinology & Metabolism, 90(12), 6410-6417.
- Landmark study showing rapid BMD decline in first year
Smith, M.R., et al. (2001). “Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer.” New England Journal of Medicine, 345(13), 948-955.
- First major trial of bisphosphonates in ADT patients

Intermittent ADT Studies:

Hussain, M., et al. (2013). “Intermittent versus continuous androgen deprivation in prostate cancer.” New England Journal of Medicine, 368(14), 1314-1325.
- Major SWOG trial showing non-inferiority for survival — important study
Kiratli, B.J., et al. (2001). “Progressive decrease in bone density over 10 years of androgen deprivation therapy in patients with prostate cancer.” Urology, 57(1), 127-132.
- Demonstrates reduced bone loss with intermittent approach

Comprehensive Reviews:

Alibhai, S.M., et al. (2010). “Impact of Androgen-Deprivation Therapy on Physical Function and Quality of Life in Men With Nonmetastatic Prostate Cancer .” Journal Clinic Oncology, Vol 28 No 34
- Comprehensive review of ADT bone complications and management

The post ADT & Bone Loss: Why DEXA Fails Prostate Cancer Patients appeared first on Dr. Philip Lee Miller by Philip Miller.

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