Detrimental Effect of Low-Magnitude High-Frequency Vibration in an Ex Vivo Model of Intervertebral Disc Degeneration Despite Estrogen Treatment.

Abstract

Introduction: Postmenopausal females are at increased risk of intervertebral disc (IVD) degeneration due to estrogen decline. While both estrogen supplementation and low-magnitude high-frequency vibration (LMHFV) are proposed as therapies for osteoporosis, their effects and potential interactions on IVD degeneration remain unclear. Therefore, the aim of this work was to investigate the individual and combined effects of 17β-oestradiol (E2) and LMHFV in a papain (PP)-induced ex vivo model of IVD degeneration.

Methods: Bovine IVDs were degraded with PP (65 U/mL) and subsequently treated with E2 (10^-7 M), LMHFV (45 Hz, 0.3 g, 20 min/day), or both; untreated discs served as controls. Gene expression was analyzed on Day 8. On Day 21, cell viability, DNA content, extracellular matrix components (glycosaminoglycan [GAG], collagen), inflammatory (interleukin-6 [IL-6]) and catabolic (matrix metalloproteinase-3 [MMP-3]) markers, and annular stiffness and strength were assessed.

Results: PP digestion reduced cell viability and decreased GAG content, while increasing IL-6 and MMP-3 production. Treatment with E2 partially restored ESR1 expression but did not affect cell viability or matrix metabolism. LMHFV (PP + LMHFV group) significantly increased DNA and GAG content compared with PP alone, whereas the combined treatment (PP + E2 + LMHFV) further elevated IL-6 and MMP-3 production. Annular stiffness was higher following PP treatment but was normalized by all subsequent treatments.

Conclusion: In a severely degenerated IVD model, LMHFV promoted catabolic and inflammatory responses, and E2 treatment was insufficient to counteract these effects. These findings suggest that LMHFV, commonly used to support bone health in osteoporotic patients, may pose risks to IVD integrity in advanced degeneration.