Role of Osteocytes in Myeloma Bone Disease

Attaya Suvannasankha67 enrolled

Overview

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 Type

OBSERVATIONAL

Enrollment

Conditions

Multiple Myeloma

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: Up to 4 years

Secondary Outcomes

Multiple Myeloma osteocytes and tumor staging

To correlate the FGF23, heparanase, Dkk1 and plasma klotho to tumor staging

Time frame: 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

Time frame: Up to 4 years

Role of Osteocytes in Myeloma Bone Disease

Overview

Conditions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes