Role of Osteocytes in Myeloma Bone Disease

Progress in the treatment of myeloma and myeloma bone disease has substantially increased overall survival, but relapse is inevitable and better treatment is needed. The bone microenvironment is tremendously complex, so that targeting single interactions between tumor and bone is unlikely to be effective. Treatments need to block centrally important, multifunctional pathways. The investigators data point to a central role of the osteocyte to induce heparanase, a multifunctional mediator of myeloma bone disease. Increased heparanase due to FGF23 may make systemic inhibitors of heparanase less effective in bone than elsewhere. FGF23 neutralizing antibodies have been developed for non-cancer conditions of FGF23 excess, such as chronic kidney disease (Shimada & Fukamoto, 2012), and could be used in MM alone or in combination with heparanase inhibitors. Complete neutralization of FGF23 has adverse effects, but neutralization of FGF23 excess may be practical, or in the future, suppression of excess FGF23 biosynthesis by osteocytes.

The investigators hope to determine serum FGF23 and heparanase, Dkk1 and plasma klotho levels in patients with newly diagnosed and relapsed myeloma compared to healthy controls with this exploratory study.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma

• Study Type: Observational
• Enrollment (Actual): 67

Contacts and Locations

• Study Contact: Name: Attaya Suvannasankha, M.D.; Phone Number: 317-278-9306; Email: asuvanna@iu.edu

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • VA Roudebush Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Oncology Clinics at Indiana University Roudebuch VA Medical Center Community sample

Description

Inclusion Criteria:

1. Age > 18 years but ≤ 95 years at the time of consent
2. Subjects must be English-speaking
3. Must voluntarily sign the most current informed consent and HIPAA documents prior to study participation.
4. Have no prior history of malignancy in the past 5 years with the exception of basal cell and squamous cell carcinoma of the skin. Other cancers with low potential for metastasis, such as in situ cancers can also be enrolled as healthy volunteers.
5. Have no known liver or kidney disorders

Exclusion Criteria:

1. Pregnant females will be excluded from the study.
2. Subjects allergic to xylocaine will be excluded.
3. Subjects with an acute illness (Ex. upper respiratory infection, viral illness) in the past seven days will be excluded.
4. History of bleeding disorders.
5. Subjects deemed incompetent by treating physician
6. Institutionalized, mentally disabled subjects
7. Subjects who are prisoners

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Multiple Myeloma Patients; Patients with multiple myeloma will undergo a blood draw and a bone marrow aspirate. Extra bone marrow will be taken for study purposes only.
Healthy subjects; Healthy subjects and multiple myeloma patients will undergo a blood draw

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular interactions between multiple myeloma and osteocytes	To determine FGF23 and heparanase, Dkk1 and plasma klotho levels increase in patients with newly diagnosed and relapsed myeloma compared to healthy controls.	Up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multiple Myeloma osteocytes and tumor staging	To correlate the FGF23, heparanase, Dkk1 and plasma klotho to tumor staging	Up to 4 years
Multiple Myeloma osteocytes and Type I collagen fragments on bone resorption	To correlate the FGF23, heparanase, Dkk1 and plasma klotho to extent of bone resorption using serum type I collagen fragments ICTP and CTX	Up to 4 years

Collaborators and Investigators

• Sponsor: Attaya Suvannasankha
• Investigators: Principal Investigator: Attaya Suvannasankha, M.D., Indiana University

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2014
• Primary Completion (Actual): February 5, 2022
• Study Completion (Actual): February 5, 2022

Study Registration Dates

• First Submitted: July 31, 2014
• First Submitted That Met QC Criteria: August 7, 2014
• First Posted (Estimated): August 8, 2014

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: September 5, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Musculoskeletal Diseases; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Bone Diseases
• Other Study ID Numbers: IUCRO-0498