title: Long-term parenteral administration of 2-hydroxypropyl-β-cyclodextrin causes bone loss.
abstract: Cyclodextrins are oligosaccharides which are used in the pharmaceutical industry and research as vehicles for application of apolar substances such as steroids. The aim of this study was to examine the long-term effects of parenteral administration of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on bone. Sham-operated (SHAM) or ovariectomized (OVX) adult rats were subcutaneously injected with physiological saline, 50, or 200 mg/kg HP-β-CD daily. After 4 months, body weight in OVX rats and uterine weight in SHAM rats were significantly lower after administration of 200 mg/kg HP-β-CD, relative to vehicle controls. At 200 mg/kg, HP-β-CD was hepatotoxic as measured by increased serum transaminases, and reduced serum albumin. Moreover, 200 mg/kg HP-β-CD led to decreased vertebral and tibial bone mineral density (BMD), and to cortical thinning at the tibial shaft. Bone loss in HP-β-CD-treated rats was associated with increased bone resorption as measured by increased renal deoxypyridinoline excretion. Although 50 mg/kg HP-β-CD was devoid of overt signs of organ toxicity and did not impair BMD, bone resorption was already increased. In summary, subcutaneous long-term administration of HP-β-CD at a daily dose of 200 mg/kg led to increased bone resorption and subsequent bone loss. Minor alterations in bone metabolism were also seen at 50 mg/kg.
authors.affiliation: Institute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kantner
authors.forename: Reinhold G
authors.initials: RG
authors.lastname: Erben
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D015519:Bone Density / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000503:physiopathology*; D001862:Bone Resorption / Q000150:complications / Q000503:physiopathology*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D010052:Ovariectomy; D010288:Parenteral Nutrition / Q000379:methods; D051381:Rats; D011916:Rats, Inbred F344; D013131:Spine / Q000187:drug effects / Q000503:physiopathology; D013977:Tibia / Q000187:drug effects / Q000503:physiopathology; D013997:Time Factors; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000596:Amino Acids; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C036020:deoxypyridinoline