Effect of zoledronic acid on muscle metabolism in mice with osteoporosis combined with sarcopenia

BMC Musculoskelet Disord. 2024 Nov 21;25(1):937. doi: 10.1186/s12891-024-08054-0.

Abstract

Objective: To investigate the effects of zoledronic acid on muscle metabolism in mice with osteoporosis and sarcopenia and elucidate the possible underlying mechanism.

Methods: Twenty-four 8-week-old male C57BL/6J mice were randomly divided into four groups: non-suspension (N-SUS), suspension (SUS), suspension + zoledronic acid (ZA), and suspension + PTH(PTH) groups. Equal doses of saline, zoledronic acid, and PTH were administered subcutaneously. After 4 weeks, the mice were sacrificed, and body weight and muscle mass (gastrocnemius and soleus) were measured, the right tibia of mice was taken for micro-CT examination, and the muscle specimens were analyzed using HE staining, ATPase staining, western blotting, and real-time PCR.

Results: Compared with the N-SUS group, the bone mineral density (BMD), trabecular bone relative volume (BV/TV) and trabecular bone number (Tb.N) were significantly decreased in the SUS group (P < 0.01), the trabecular bone separation(Tb.Sp)was significantly increased (P < 0.01), which was reversed in ZA and PTH group (P < 0.01).Compared to the SUS group, the body and muscle weights of the ZA and PTH groups were significantly increased. Compared to the SUS group, the muscle structure was less damaged, the proportion of type I muscle fibers was increased, and the protein expression of β-catenin and AKT were upregulated in the ZA and PTH groups(P < 0.05). In addition, the mRNA expression levels of Wnt3a, Wnt16, Myf5, and PI3K were significantly increased (P < 0.05), where as those of Myogenic Differentiation Antigen(MyoD )and Myogenin (MyoG) were significantly decreased (P < 0.05). No significant differences were observed between the ZA and PTH groups.

Conclusions: Zoledronic acid can reduce muscle loss and damage by upregulating the mRNA expression of Wnt and PI3K and the protein expression of β-catenin and AKT.Our results provide a novel basis for the development of drugs for the treatment of osteoporosis combined with sarcopenia.

Keywords: Muscle metabolism; Osteoporosis; Sarcopenia; Zoledronic acid.

MeSH terms

  • Animals
  • Bone Density / drug effects
  • Bone Density Conservation Agents* / pharmacology
  • Bone Density Conservation Agents* / therapeutic use
  • Disease Models, Animal
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Muscle, Skeletal* / drug effects
  • Muscle, Skeletal* / metabolism
  • Muscle, Skeletal* / pathology
  • Osteoporosis* / drug therapy
  • Osteoporosis* / metabolism
  • Sarcopenia* / drug therapy
  • Sarcopenia* / etiology
  • Sarcopenia* / metabolism
  • X-Ray Microtomography
  • Zoledronic Acid* / pharmacology
  • Zoledronic Acid* / therapeutic use

Substances

  • Zoledronic Acid
  • Bone Density Conservation Agents