Skip to main content
OpenTrials
Recruiting

NCT Number: NCT07555210

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Breast Cancer (Triple Negative Breast Cancer (TNBC)) Adenocarcinoma Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Carcinoma, Renal Cell Carcinoma, Squamous Cell Classic Hodgkin Lymphoma Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Head and Neck Neoplasms Invasive Mammary Carcinoma Kidney Diseases Kidney Neoplasms Lung Diseases Lung Neoplasms MSI-H/dMMR Rectal Cancer Male Urogenital Diseases Melanoma Melanoma (Skin Cancer) Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Non-small Cell Lung Cancer Renal Cell Carcinoma (Kidney Cancer) Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Squamous Cell Carcinoma Mouth Squamous Cell Carcinoma of Head and Neck Thoracic Neoplasms Triple Negative Breast Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location status: Recruiting

Location contact

Jennifer Whisenant, PhD

CONTACT

[email protected]

615-936-8422

Jessica Sharpe, MD, PhD

PRINCIPAL_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥ 18 years.
  • 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).
  • Life expectancy of at least 12 months per the discretion of the treating physician.

Exclusion criteria

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

Treatment and study plan

dual-energy X-ray absorptiometry (DXA)

Device

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

High Resolution peripheral Quantitative Computed Tomography (HRpQCT)

Device

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

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

Other outcomes

  1. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Jessica Sharpe, MD, PhD

CONTACT

[email protected]

615-936-8422

Sponsors and collaborators

Lead sponsor

Jessica Mezzanotte Sharpe

Other

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Apr 29, 2026
Registry last updated
May 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.