Bone density changes with anti-PD-1 immunotherapy

Pilot Study Assessment of Bone Mineral Density Changes During Treatment With Anti-PD-1 Immunotherapy Agents

This pilot will test if anti-PD-1 immunotherapy changes bone density in adults starting approved anti-PD-1 treatment for certain early-stage cancers.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Vanderbilt-Ingram Cancer Center (other)
• Drugs / interventions: denosumab, chemotherapy, immunotherapy
• Locations: 1 site (Nashville, Tennessee)
• Trial ID: NCT07555210 on ClinicalTrials.gov

What this trial studies

This pilot enrolls adults with non-metastatic cancers who are planning to start or are within four weeks of starting FDA-approved anti-PD-1 therapy. Participants undergo bone mineral density measurement by dual-energy X-ray absorptiometry (DXA) and microarchitectural imaging by high-resolution peripheral quantitative CT (HR-pQCT) to track changes over time. The protocol excludes patients with metastatic disease, known osteoporosis/osteopenia, recent bisphosphonate or denosumab use, planned dual checkpoint therapy, and certain endocrine or advanced renal disorders. The goal is to characterize changes in bone mass and structure during anti-PD-1 therapy to inform monitoring and preventive care.

Who should consider this trial

Good fit: Adults (≥18) with non-metastatic triple-negative breast cancer, renal cell carcinoma, melanoma, non-small cell lung cancer, or MSI-H/dMMR rectal cancer who are planning to start or are within four weeks of starting FDA-approved anti-PD-1 therapy and have a life expectancy of at least 12 months.

Not a fit: Patients with metastatic disease, known osteoporosis/osteopenia, recent treatment with bisphosphonates or denosumab, planned dual immune checkpoint therapy, or certain parathyroid/advanced renal disorders would be excluded and are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the study could help clinicians detect bone loss early and guide monitoring or preventive treatments to reduce fracture risk.

How similar studies have performed: Case reports and small observational studies have raised concerns that immune checkpoint inhibitors may affect bone health, but prospective imaging studies using DXA and HR-pQCT are limited, so this pilot is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years.
2. Patients planning to start or within the first four weeks of treatment with anti-PD-1 immune checkpoint inhibitor therapy either alone or in combination with chemotherapy for curative intent for a known cancer diagnosis (use of immunotherapy must be FDA-approved and not experimental).
3. Life expectancy of at least 12 months per the discretion of the treating physician.

Exclusion Criteria:

1. Patients ineligible for anti-PD-1 therapy.
2. Patients with metastatic disease.
3. Patients planning treatment with dual immune checkpoint inhibitor therapy.
4. Bony fractures in the pelvis, bilateral hips/femurs, thoracic spine, or lumbar spine.
5. Known osteoporosis or osteopenia.
6. Planned or previous treatment with denosumab, zoledronic acid, or other bisphosphonate therapy in the last six months.
7. Parathyroid gland disorders, rheumatoid arthritis (unless well-controlled off active biologic therapy without chronic steroid use), CKD stage IV/V, or ESRD.
8. Inability to comply with study procedures.
9. Inability to lie flat for 20-25 minutes during an imaging session.
10. Pregnant or breastfeeding patients.
11. Medical or psychiatric co-morbidities that, in the opinion of the treating physician, would prevent the patient from successfully participating in the study.

Where this trial is running

Nashville, Tennessee

• Vanderbilt-Ingram Cancer Center — Nashville, Tennessee, United States (RECRUITING)

Study contacts

• Study coordinator: Jessica Sharpe, MD, PhD

Conditions: Breast Cancer), Renal Cell Carcinoma, Melanoma, Non-Small Cell Lung Cancer, MSI-H/dMMR Rectal Cancer, Squamous Cell Carcinoma Mouth, Invasive Mammary Carcinoma, Classic Hodgkin Lymphoma