Pathophysiology of Paget's Disease of Bone

NCT02802384 | Completed

• 1 other identifier: IRB00077130
• Study Type: observational
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Paget's disease of the bone is a skeletal disorder which results in increased and disorganized bone remodeling, leading to dense but fragile and expanding bones. The identified genetic causes of Paget's disease of bone only explain why bone is destroyed, but not why the bone formed in its place is abnormal. Current treatment for people with Paget's disease of the bone is limited to patients with bone pain, thought to be related to high rate of bone turnover (breakdown and rebuilding of bone) and works by slowing down the rate of bone breakdown. The current treatment does not address the excess blood vessels and bone formed. This research is being done to understand factors that may promote blood vessel and bone formation in Paget's disease of the bone.

Conditions

Paget's Disease of Bone

Keywords

Paget's Disease of Bone; Healthy controls

Outcome Measures

Primary Outcomes (1)

• Serum chemokine level

  Compare the serum chemokine concentrations in research participants with Paget's disease of bone to research participants without Paget's disease of bone

  Day 1

Secondary Outcomes (4)

• Correlation of chemokine level to Paget's Disease of Bone Pain

  Day 1

• Correlation of chemokine level to alkaline phosphatase concentration

  Day 1

• Correlation of chemokine level to proportion of affected skeleton

  Day 1

• Correlation of chemokine level to number of circulating stem cells

  Day 1

Study Arms (2)

Cases

People with active Paget's Disease of Bone

Controls

Age and sex matched people without history of Paget's Disease of Bone

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adults with active Paget's Disease of Bone but without other medical conditions or use of medications known to directly affect the bone. Healthy controls similar to age and gender will also be recruited.

You may qualify if:

• Men and women between the ages of 18-99 years who have evidence of active Paget's disease of bone as clinically and/or radiographically defined by:
• Increased serum alkaline phosphatase or increased serum collagen type 1 c-telopeptide (CTX) or increase in urinary pyridinoline at diagnosis
• AND history of at least one of the following signs/symptoms: Pagetoid lesions(s) on x-ray/CT/MRI, increased uptake of radioactive substance by bone scan, bone pain, fracture, hearing loss, headache, hypercalcemia, or bony deformity.
• Men and women between the ages of 18-99 years who match age within 5 years of cases and gender who do NOT have evidence of Paget's disease of bone as defined by:
• No bone pain or bony deformity
• Normal serum alkaline phosphatase

You may not qualify if:

• Osteosarcoma or other blastic bony metastases alone
• Fibrous dysplasia of bone
• Hyperostosis frontalis interna
• All men and women \< 18 years or \> 99 years
• Pregnancy (women) determined by self-report
• Current use of oral contraceptive tablets or Depo-Provera™ (women)
• Current use of hormone replacement therapy
• Creatinine clearance \< 60 ml/min./1.73 m2 by Cockcroft-Gault based on most recent serum creatinine level (if greater than 1 year since last assessment, will be measured on collected blood sample to verify eligibility)
• Current smoking or tobacco use
• Alcohol use greater than 3 units daily
• Use of thiazolidinediones within the last year
• Use of medications known to impact bone and mineral metabolism, including use of a bisphosphonate in the last 11 months; ever use of teriparatide or denosumab; use of calcitonin, selective estrogen receptor modulators (SERMs), or estrogen within the past 6 months, prednisone \> 5 mg for over 10 days in the last three months, anti-epileptic medications (e.g. phenytoin, carbamezapine, phenobarbitol, and primidone); current or use within the past year of aromatase inhibitors; leuprolide; histrelin
• History of a thyroid problem that is currently uncontrolled as defined by most recent thyroid stimulating hormone levels \< 0.1 microIU/mL (if greater than 6 months since last assessment, will be measured on collected blood sample to verify eligibility)
• Other known metabolic or structural bone disease other than low bone density (e.g. hyperparathyroidism, multiple myeloma, sarcoid or other granulomatous disease, celiac disease, osteopetrosis, osteomalacia, osteitis fibrosa cystica)
• Other significant medical illness (heart disease, pulmonary disease, inflammatory bowel disease, malignancy other than ductal carcinoma in situ (DCIS) or non-melanoma skin cancer, rheumatologic conditions including rheumatoid arthritis, systemic lupus, renal disease requiring dialysis, etc.)

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Human blood samples with be collected. One tube of blood will be utilized to measure specific serum chemokine concentrations. One tube will be utilized to extract DNA for potential future studies if permission is provided. The remainder of the blood sample will be utilized to count the number of stem cells.

MeSH Terms

Conditions

Osteitis Deformans

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases

Study Officials

• Janet L Crane, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2016
• First Posted: June 16, 2016
• Study Start: April 1, 2016
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: November 20, 2024

Record last verified: 2024-11

Locations

US (1)