The BEST Trial: Biomarkers for Evaluating Spine Treatments

Inclusion Criteria: To be eligible, an individual must meet all of the following inclusion criteria: * Ability to read and understand English * Provision of signed and dated informed consent form(s) * Willing and able to receive study-related messages and survey links via email * Willing and able to receive study-related phone calls * Age 18 years old or older * Low-back pain for at least 3 months and occurring on at least half the days in the past 6 months * Contraindicated to no more than one of the study interventions at the time of eligibility assessment(s) * Eligible to receive at least three of the four study interventions and willing to receive any intervention for which they are eligible * A PEG score 4 or higher prior to the Run-in period * Willing and able to undergo required phenotyping * Regular reliable access to an internet-enabled device such as a smart phone, tablet, or laptop computer * Meet Run-in period engagement eligibility criteria: o Completion of two Run-in study information modules prior to period 1 randomization (Visit 0) * Low-back pain more severe than pain in other parts of the body * Available to complete the full study protocol (approximately 9 months) Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation in this study: * Pregnant at the time of Visit 0 (Baseline) * Affirmative participant response to any of the following conditions: * Progressive neurodegenerative disease * History of discitis osteomyelitis (spine infection) or spine tumor * History of ankylosing spondylitis, rheumatoid arthritis, polymyalgia rheumatica, psoriatic arthritis, or lupus * History of cauda equina syndrome or spinal radiculopathy with functional motor deficit (strength \<4/5 on manual motor testing) * Diagnosis of any vertebral fracture in the last 6 months * Osteoporosis requiring pharmacologic treatment other than vitamin D, calcium supplements, or bisphosphonates. * History of any bone-related cancer or cancer that metastasized to the bone * Currently in treatment for any non-skin cancer or plan to start non-skin cancer treatment in the next 12 months * History of any non-skin cancer treatment in the last 24 months * Visual or hearing difficulties that would preclude participation * Uncontrolled drug/alcohol addiction * Individuals actively pursuing disability or workers compensation or involved in active personal injury-related litigation * Currently participating in another intervention…