Pilot Study of Bone Mineral Density Changes During Anti-PD-1 Immunotherapy

May 4, 2026 updated by: Jessica Mezzanotte Sharpe

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

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and work by blocking protein interactions that normally prevent the immune system from recognizing and destroying cancer cells. However, these agents, now approved for over 15 types of cancers and for both early-stage and metastatic disease, are capable of causing inflammation in any organ system of the body that can lead to organ damage, dysfunction, and even death in rare cases. Some patients may suffer acute and treatable complications like joint pain, but some may have irreversible complications like hypothyroidism that requires daily, life-long medication. It is therefore important to fully understand the different types of damage ICIs can cause to better monitor patients receiving ICI therapy.

A rising concern from recent reports in the literature is that ICIs may weaken bone and increase the risk of fractures. In this study, the investigators aim to characterize how ICIs impact the bone by examining several factors in patients undergoing curative-intent ICI treatment either alone or in combination with chemotherapy: bone mineral density, bone volume, and markers of bone turnover in the blood. The study will use two imaging techniques to assess bone mineral density and volume. DXA (dual X-ray absorptiometry) imaging uses low-dose X-rays to measure how dense (or strong) bones are and is often used to diagnose or assess the risk of osteoporosis. High-resolution peripheral quantitative computed tomography (HRpQCT) is a 3D imaging technology that can quantify bone structure and volume and offers high resolution that can be used to assess bone in smaller bones of the peripheral skeleton.

The investigators hypothesize that ICI treatment will weaken bones and increase the risk of fractures. As ICI therapy is relatively new, a rising number of patients may be at risk of fractures or have low bone density that is not being monitored because there are no guidelines in place notifying physicians of this potential risk to patients. This is study will provide important preliminary data that will be the basis for larger studies in the future aiming to better monitor and potentially treat bone weakening in patients treated with ICIs to reduce the pain, inconvenience, and complications from fragility fractures.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

25

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt-Ingram Cancer Center
        • Contact:
        • Principal Investigator:
          • Jessica Sharpe, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bone mineral density scans (DXA and HRpQCT)
Patients undergo two research bone mineral density scans (DXA and HRpQCT) at three time points: baseline, 4-6 months during immunotherapy, and after 12 months of immunotherapy
Device: Dual-Energy X-ray Absorptiometry (DXA)
Research participants undergo both DXA scans at baseline (within 1 month of starting immunotherapy), 4-6 months after starting immunotherapy, and after 12 months of immunotherapy
Device: High Resolution peripheral Quantitative Computed Tomography (HRpQCT)
Research participants undergo both HRpQCT scans at baseline (within 1 month of starting immunotherapy), 4-6 months after starting immunotherapy, and after 12 months of immunotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in BMD using DXA
Time Frame: At 12 months after starting immunotherapy
Assess changes in BMD on DXA scans in patients undergoing anti-PD-1 therapy over the course of a year.
At 12 months after starting immunotherapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in plasma markers of bone resorption and formation
Time Frame: At 12 months after starting immunotherapy
Examine plasma markers of bone resorption and formation over the course of a year in patients undergoing neoadjuvant treatment.
At 12 months after starting immunotherapy
Fracture incidence
Time Frame: To be completed within 30 days of the end of study (12 months +/-30 days)
Monitor fracture incidence in patients being treated with anti-PD-1 therapy and explore whether these are correlated with an increased risk of BMD loss.
To be completed within 30 days of the end of study (12 months +/-30 days)
Rates of documented immune-related adverse events (irAE)
Time Frame: To be completed within 30 days of the end of study (12 months +/-30 days)
Monitor rates of irAEs in patients being treated with anti-PD-1 therapy and explore whether these are correlated with an increased risk of BMD loss.
To be completed within 30 days of the end of study (12 months +/-30 days)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bone microarchitecture using HRpQCT
Time Frame: At 12 months after starting immunotherapy
Assess changes in bone microarchitecture using HRpQCT scans in patients undergoing anti-PD-1 therapy and correlate these findings with DXA results.
At 12 months after starting immunotherapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jessica Mezzanotte Sharpe

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 25, 2025

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

July 1, 2028

Study Registration Dates

First Submitted

April 21, 2026

First Submitted That Met QC Criteria

April 21, 2026

First Posted (Actual)

April 29, 2026

Study Record Updates

Last Update Posted (Actual)

May 6, 2026

Last Update Submitted That Met QC Criteria

May 4, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VICCMD25019
  • #242079 (Other Identifier: VUMC IRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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