Genetic Regulators of Bone Health That Are Unique to Vertebral Bone

NCT05946278 | Recruiting

• 1 other identifier: 23-0602
• Study Type: observational
• Target: 550
• Locations: 1 country
• Sites: 1

Brief Summary

Osteoporosis is an age related disease in which a person's bone slowly becomes weaker with time. The bones may become so weak that they break easily such as a fall from standing height. The most commonly broke bones in osteoporosis are those of the hip, the spine or the wrist. Osteoporosis runs in families meaning that genetic differences explain why some people break bones in old age and other do not. Genetic studies have been done that show the the genes associated with spine (vertebral) fractures (broken bones) and hip fractures are different, suggesting that osteoporosis of the spine is not the exact same disease as osteoporosis of the hip. Genetic studies tell us what part of the genome (i.e. genes) are associated with a disease, but do not tell us how these genes act biologically to cause that disease. In this study, we seek to determine how the genes uniquely associated with spine osteoporosis behave in normal and aged bone, to determine how they interact with each other as a team to impact spine bone. In this study, we will measure gene activity (so called gene expression) in bone samples taken from people undergoing major spine deformity surgery. We will using genetic data from these patients to determine how gene activity is controlled in bone and how that relates to measures of bone health such as bone mineral density data. The results of this study will provide critical data regarding how osteoporosis of the spine happens, and these data will be used to find better and safer treatments to prevent bone fractures of the spine that happen with age.

Conditions

Age-Related Osteoporosis

Keywords

Bone mineral density, gene transcription, spine, genetic disease

Outcome Measures

Primary Outcomes (2)

• Gene and transcript quantification

  The abundances (in transcripts per million, TPM) of all known transcripts will be quantified in each bone sample via next generation RNA-sequencing.

  Baseline

• Genotypes

  Low coverage whole genome sequence data will be obtained from all participants and the yielded outcome will be high quality genotypes for millions of single nucleotide polymorphism (SNPs) across the patient's genome. As this is low coverage genotyping, the coverage rate will be between 1 and 0.4X representation for each spot in the genome per patients, so the data will be imputed to ensure coverage to 1X for all patients. Each patient will be genotyped and therefore, data on a per participant level will be yielded.

  Baseline

Secondary Outcomes (4)

• Expression quantitative trait loci (eQTL)

  Baseline

• Co-localization

  Baseline

• Expression-phenotype correlation

  Baseline

• Co-expression Network

  Baseline

Study Arms (1)

Patients undergoing deformity correction surgery

Patients undergoing deformity correction surgery undergoing a multi-level spinal fusion (i.e. a T10 (or higher) fusion to the pelvis) -OR- a 3 column osteotomy with a corpectomy from for short segment surgeries -OR- a vertebral column resection (VCR) involving a corpectomy -OR- any deformity correction surgery wherein the attending surgeon determines that a large amount of bone containing trabecular elements will be removed and discarded

Other: Sample collection for gene expression

Interventions

Sample collection for gene expression OTHER

This is a cross-sectional sample collection study. Vertebral bone tissue that would otherwise be discarded is collected from patients undergoing surgery to correct a spine deformity and gene expression is measure in these tissues.

Patients undergoing deformity correction surgery

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing deformity correction surgery undergoing a multi-level spinal fusion (i.e. a T10 (or higher) fusion to the pelvis) -OR- a 3 column osteotomy with a corpectomy from for short segment surgeries -OR- a vertebral column resection (VCR) involving a corpectomy -OR- any deformity correction surgery wherein the attending surgeon determines that a large amount of bone containing trabecular elements will be removed and discarded. Patients Patients will be recruited through the Spine Center at the University of Colorado Hospital.

You may qualify if:

• Men and women between the ages of 18 and 85 undergoing a multi-level spinal fusion (i.e. a T10 (or higher) fusion to the pelvis) -OR- a 3 column osteotomy with a corpectomy from for short segment surgeries -OR- a vertebral column resection (VCR) involving a corpectomy -OR- any deformity correction surgery wherein the attending surgeon determines that a large amount of bone containing trabecular elements will be removed and discarded.
• Willing and able to provide informed consent

You may not qualify if:

• End stage renal disease.
• Any history of cancer.
• Reliance on a wheelchair for 70% or greater of their mobility for longer than 12 months.
• Quadra or paraplegia due to spinal cord injury.
• Current use of epilepsy medications.
• Confirmed Marfans, osteogenesis imperfecta or other genetic syndrome known to impact bone formation (Guacher's, Vit D independent rickets, etc).
• Current glucocorticoid use lasting longer than 3 months, or greater than 6 months lifetime use.
• Current or suspected current infection associated with orthopedic hardware.
• HIV or Hep C positive and or currently on anti-viral medications.
• History of gastric bypass surgery and or weigh loss exceeding 100 pounds.
• Primary or secondary hyperparathyroidism.
• Paget's disease

Sponsors & Collaborators

• University of Colorado, Denver: lead
• University of Virginia: collaborator

Study Sites (1)

Univeristy of Colorado Denver

Aurora, Colorado, 80045, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

At the time of surgery, peripheral blood (5 mL of whole blood) is drawn into a DNA/RNA Shield Blood collection tube (Zymo Research) and DNA is extracted.

MeSH Terms

Conditions

Osteoporosis; Genetic Diseases, Inborn

Interventions

Specimen Handling; Gene Expression

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Phenomena

Study Officials

• Cheryl L Ackert-Bicknell, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cheryl L Ackert-Bicknell, PhD

CONTACT

3037246623; CHERYL.ACKERT-BICKNELL@CUANSCHUTZ.EDU

Study Design

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

Study Record Dates

• First Submitted: July 7, 2023
• First Posted: July 14, 2023
• Study Start: April 1, 2024
• Primary Completion (Estimated): August 30, 2030
• Study Completion (Estimated): August 30, 2030
• Last Updated: April 3, 2024

Record last verified: 2024-04

Locations

US (1)