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Effect of recombinant human parathyroid hormone and zoledronic acid on osteoblast gene expression using multifaceted

Vandana Dhiman1, Sanjay Kumar Bhadada1, Poonam Kanta2

  • 1Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Indian Journal of Pharmacology
|June 13, 2025
PubMed
Abstract

Insights

Recombinant human parathyroid hormone (rhPTH) followed by zoledronic acid (ZOL) demonstrated the most effective bone-forming activity. This sequential treatment enhances osteogenesis, offering potential for improved osteoporosis prevention.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Endocrinology

Background:

  • Bone remodeling is a continuous process involving bone cell turnover.
  • The precise molecular mechanisms of anti-fracture drugs like bisphosphonates and recombinant human parathyroid hormone (rhPTH) remain incompletely understood.
  • This study investigates the effects of zoledronic acid (ZOL) and rhPTH on human osteogenic sarcoma cells (U2OS).

Purpose of the Study:

  • To elucidate the molecular mechanisms of action for ZOL and rhPTH.
  • To assess the combined effects of ZOL and rhPTH on osteogenesis.
  • To identify optimal drug sequencing for maximizing anabolic bone effects.

Main Methods:

  • Assessed cellular viability, mineralization, and osteogenic gene expression.
  • Treated U2OS cells with varying concentrations of ZOL and rhPTH, both individually and sequentially.
  • Analyzed alkaline phosphatase activity, COL1A1, and osteocalcin gene expression.

Main Results:

  • Neither ZOL nor rhPTH affected cellular viability.
  • Sequential treatment of rhPTH followed by ZOL significantly increased osteoblastic activity and alkaline phosphatase levels.
  • Osteoblastic genes COL1A1 and osteocalcin were significantly modulated by the rhPTH-ZOL sequential treatment.

Conclusions:

  • Sequential administration of rhPTH (5 μg) followed by ZOL (1 μM) yielded the most significant anabolic (bone-forming) effect.
  • These findings suggest that combining anti-fracture drugs in a specific sequence can augment osteogenesis.
  • Further research is warranted to explore similar drug combinations for enhanced osteoporosis prevention.
Keywords:
Bisphosphonateboneosteocalcinosteoporosiszoledronic acid

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