Long-term parenteral administration of 2-hydroxypropyl-β-cyclodextrin causes bone loss

Area of Science:

• Pharmacology and Toxicology
• Bone Metabolism Research
• Drug Delivery Systems

Background:

• Cyclodextrins, including 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), are utilized in pharmaceuticals as solubilizing agents for poorly soluble drugs.
• Parenteral administration of HP-β-CD is common, but its long-term effects on bone health require thorough investigation.

Purpose of the Study:

• To evaluate the long-term impact of subcutaneous HP-β-CD administration on bone mineral density and resorption markers.
• To assess potential organ toxicity associated with chronic HP-β-CD treatment in an animal model.

Main Methods:

• Adult rats underwent sham-operation or ovariectomy and received daily subcutaneous injections of saline, 50 mg/kg, or 200 mg/kg HP-β-CD for 4 months.
• Bone mineral density (BMD), serum biochemical markers (transaminases, albumin), and urinary deoxypyridinoline excretion were analyzed.

Main Results:

• The 200 mg/kg HP-β-CD dose significantly reduced body weight in ovariectomized rats and uterine weight in sham-operated rats.
• Hepatotoxicity was observed at 200 mg/kg HP-β-CD, evidenced by elevated serum transaminases and reduced albumin.
• Decreased vertebral and tibial BMD, cortical thinning, and increased bone resorption markers (deoxypyridinoline) were noted at 200 mg/kg HP-β-CD.
• Even at 50 mg/kg, HP-β-CD administration showed increased bone resorption without overt organ toxicity or BMD impairment.

Conclusions:

• Subcutaneous administration of HP-β-CD, particularly at 200 mg/kg daily, induces significant bone resorption and subsequent bone loss.
• HP-β-CD exhibits dose-dependent hepatotoxicity and negatively impacts bone metabolism, warranting caution in its long-term parenteral use.