Effects of Gabapentin and Pregabalin on Calcium Homeostasis: Implications for Physical Rehabilitation of Musculoskeletal Tissues

• Published in: Current osteoporosis reports 2022-12, Vol.20 (6), p.365-378
• Main Authors: Reyes Fernandez, Perla C., Wright, Christian S., Warden, Stuart J., Hum, Julia, Farach-Carson, Mary C., Thompson, William R.
• Format: Article
• Language: English
• Subjects: Biomechanics (JS Nyman and V Ferguson; Calcium; Epidemiology; Gabapentin - pharmacology; gamma-Aminobutyric Acid - pharmacology; gamma-Aminobutyric Acid - therapeutic use; Homeostasis; Humans; Medicine; Medicine & Public Health; Orthopedics; Pregabalin - pharmacology; Pregabalin - therapeutic use; Section Editors; Topical Collection on Biomechanics
• ISSN: 1544-1873; 1544-2241
• DOI: 10.1007/s11914-022-00750-x

Purpose of Review In this review, we discuss the mechanism of action of gabapentinoids and the potential consequences of long-term treatment with these drugs on the musculoskeletal system. Recent Findings Gabapentinoids, such as gabapentin (GBP) and pregabalin (PGB) were designed as antiepileptic reagents and are now commonly used as first-line treatment for neuropathic pain and increasingly prescribed off-label for other pain disorders such as migraines and back pain. GBP and PGB exert their analgesic actions by selectively binding the α 2 δ 1 auxiliary subunit of voltage-sensitive calcium channels, thereby inhibiting channel function. Numerous tissues express the α 2 δ 1 subunit where GBP and PGB can alter calcium-mediated signaling events. In tissues such as bone, muscle, and cartilage, α 2 δ 1 has important roles in skeletal formation, mechanosensation, and normal tissue function/repair that may be affected by chronic use of gabapentinoids. Summary Long-term use of gabapentinoids is associated with detrimental musculoskeletal outcomes, including increased fracture risk. Therefore, understanding potential complications is essential for clinicians to guide appropriate treatments.