J Korean Soc Endocrinol.  2005 Oct;20(5):476-487. 10.3803/jkes.2005.20.5.476.

Effects of alpha-Lipoic Acid on Bone Metabolism in Rats with Low Bone Mass

Affiliations
  • 1Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Korea.
  • 2Asan Institute for Life Science, Korea.

Abstract

BACKGROUND: Growing evidence has shown a biochemical link between increased oxidative stress and reduced bone density. In our previous study, alpha-lipoic acid (alpha-LA), a thiol antioxidant, suppressed both osteoclastogenesis and bone resorption, and also prevented TNF-alpha-induced apoptosis of osteoblast lineages. The effects of alpha-LA were investigated on bone metabolism in rats with a low bone mass.
METHODS
An ovariectomy (OVX) or Talc injection (inflammation-mediated osteopenia, IMO) was performed in 12 week old female Sprague-Dawley rats. Diets containing either 0.3%, 0.5% or 1.0% alpha-LA were administered to the OVX rats for 16 weeks, and to the IMO rats for 21 days. The bone mineral densities (BMD) of the anterior-posterior lumbar spine and total femur were measured using dual-energy X-ray absorptiometry (Hologic QDR 4500-A), with small animal software. The plasma bone specific alkaline phosphatase activity (BSAP) and urinary free deoxypyridinoline concentration (DPD) were determined using enzyme immunoassay methods.
RESULTS
The body weights were significantly decreased in the OVX rats on the diets containing 0.3 and 0.5% alpha-LA than in the OVX control. No significant differences in the BMD at either site were noted between rats administered the diets with or without alpha-LA. However, the administration of various doses of alpha-LA noticeably decreased the level of urinary DPD in both the OVX and IMO rats. High doses of alpha-LA (0.5% and/or 1.0%) also decreased the levels of plasma BSAP in both models.
CONCLUSION
Although no increase in BMD was demonstrated by the administration of alpha-LA, these results suggest that alpha-LA suppresses the rates of bone turnover in rats with a low bone mass


MeSH Terms

Absorptiometry, Photon
Alkaline Phosphatase
Animals
Antioxidants
Apoptosis
Body Weight
Bone Density
Bone Diseases, Metabolic
Bone Resorption
Diet
Female
Femur
Humans
Immunoenzyme Techniques
Metabolism*
Osteoblasts
Osteoporosis
Ovariectomy
Oxidative Stress
Plasma
Rats*
Rats, Sprague-Dawley
Spine
Talc
Thioctic Acid*
Alkaline Phosphatase
Antioxidants
Talc
Thioctic Acid

Figure

  • Fig. 1 Experimental protocols in ovariectomized rats (A) and inflammation-mediated osteopenia model (B).

  • Fig. 2 Change in body weights during the experiment with ovariectomized rats. Study groups consist of sham operated rats with standard diet (I), ovariectomized rats with standard diet (II), ovariectomized rats with diet containing 0.3% α-lipoic acid (α-LA) (IV), and ovariectomized rats with diet containing 0.5% α-LA (V). The OVX pair-fed control (III) was ovariectomized rats given the same amount of standard diet as that consumed by 0.5% α-LA group. *P < 0.05, **P < 0.001 vs. sham OP control.

  • Fig. 3 Bone mineral density (BMD) at the lumbar spine (A) and total femur (B) during the experiment with ovariectomized rats. Study groups consist of sham operated rats with standard diet (I), ovariectomized rats with standard diet (II), ovariectomized rats with diet containing 0.3% α-lipoic acid (α-LA) (IV), and ovariectomized rats with diet containing 0.5% α-LA (V). The OVX pair-fed control (III) was ovariectomized rats given the same amount of standard diet as that consumed by 0.5% α-LA group. *P < 0.05, **P < 0.01 vs. sham OP control.

  • Fig. 4 Body weights (A), and bone mineral density (BMD) at the lumbar spine (B) and total femur (C) during the experiment with inflammation-mediated osteopenia models (IMO). Study groups consist of saline injected rats with standard diet (I), IMO rats with standard diet (II), IMO rats with diet containing 0.3% (III), 0.5% (IV) and 1.0% α-lipoic acid (α-LA) (V). *P < 0.05, vs. saline control.


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