In vivo impact on rabbit subchondral bone of viscosupplementation with a hyaluronic acid antioxidant conjugate

BMC Musculoskelet Disord. 2024 Dec 19;25(1):1018. doi: 10.1186/s12891-024-07921-0.

Abstract

Objective: This study aimed to assess the effects of an antioxidant-conjugated Hyaluronic Acid (HA), specifically HA-4-aminoresorcinol (HA4AR), on articular cartilage and subchondral bone in osteoarthritis (OA). We conducted a comparative analysis between HA4AR and a commercially available high molecular weight HA formulation in a rabbit model of OA.

Materials and methods: Eighteen rabbits underwent unilateral anterior cruciate ligament transection (ACLT) and were divided into three groups of six: Saline-group, HA-group, and HA4AR-group, based on the type of intra-articular injection received. Additionally, eight non-operated contralateral knees served as reference points (Contralateral-group). Six weeks post-surgery, iodine-enhanced micro-computed tomography imaging was used to evaluate articular cartilage volume and thickness, and to assess subchondral bone microarchitecture and mineral density.

Results: Cartilage thickness in both the HA and HA4AR groups was comparable to that of the Contralateral group. Notably, there was a significant reduction in subchondral bone plate tissue mineral density in the HA-group when compared to both the HA4AR and Saline groups (p < 0.05). However, no significant differences in trabecular subchondral bone microarchitectural parameters and mineral densities were observed between the HA4AR-group and the Saline-group. When compared to the Contralateral, Saline, and HA4AR groups, the HA-group exhibited a marked decrease in subchondral bone plate tissue mineral density (p < 0.05). Additionally, a significant reduction in trabecular bone volume fraction was noted in the HA-group compared to the Contralateral-group (p < 0.05).

Conclusions: The HA-4AR hydrogel demonstrated significant preservation of subchondral bone plate tissue mineral density compared to HA alone, while other bone microarchitectural parameters remained largely unchanged. These findings indicate that HA-4AR may provide enhanced osteoprotective benefits in the treatment of osteoarthritis.

Keywords: Hyaluronic acid, antioxidant conjugate, Viscosupplementation; Osteoarthritis; Rabbit model.; Subchondral bone.

MeSH terms

  • Animals
  • Antioxidants* / administration & dosage
  • Antioxidants* / pharmacology
  • Bone Density / drug effects
  • Cartilage, Articular* / diagnostic imaging
  • Cartilage, Articular* / drug effects
  • Cartilage, Articular* / pathology
  • Disease Models, Animal
  • Hyaluronic Acid* / administration & dosage
  • Hyaluronic Acid* / pharmacology
  • Injections, Intra-Articular
  • Male
  • Osteoarthritis, Knee / diagnostic imaging
  • Osteoarthritis, Knee / drug therapy
  • Osteoarthritis, Knee / pathology
  • Rabbits
  • Viscosupplementation* / methods
  • Viscosupplements / administration & dosage
  • Viscosupplements / pharmacology
  • X-Ray Microtomography*

Substances

  • Hyaluronic Acid
  • Antioxidants
  • Viscosupplements