Clinical trial NCT05946278: Genetic Regulators of Bone Health That Are Unique to Vertebral Bone
Official title: Identification and Characterization of Genetic Regulators of Bone Health That Are Unique to Vertebral Bone.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Age-Related Osteoporosis
Keywords: Bone mineral density, gene transcription, spine, genetic disease
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: University of Virginia
First posted: 2023-07-14
Enrollment: 550
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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.

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Gene and transcript quantification
timeFrame: Baseline
measure: Genotypes
timeFrame: Baseline
Secondary outcomes:
measure: Expression quantitative trait loci (eQTL)
timeFrame: Baseline
measure: Co-localization
timeFrame: Baseline
measure: Expression-phenotype correlation
timeFrame: Baseline
measure: Co-expression Network
timeFrame: Baseline
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Univeristy of Colorado Denver
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Cheryl L Ackert-Bicknell, PhD
role: PRINCIPAL_INVESTIGATOR
References: