J Korean Soc Endocrinol JKSE Journal of Korean Society of Endocrinology 1015-6380 Korean Endocrine Society 10.3803/jkes.2005.20.5.476 Original Article Effects of alpha-Lipoic Acid on Bone Metabolism in Rats with Low Bone Mass Koh Jung-Min Lee Hee-Sook 1 Kim Duk Jae Kim Ghi Su Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Korea. Asan Institute for Life Science, Korea. 10 2005 20 10 2005 20 5 476 487 02 08 2004 14 09 2005 Copyright © 2005 Korean Endocrine Society 2005 Background

Growing evidence has shown a biochemical link between increased oxidative stress and reduced bone density. In our previous study, α-lipoic acid (α-LA), a thiol antioxidant, suppressed both osteoclastogenesis and bone resorption, and also prevented TNF-α-induced apoptosis of osteoblast lineages. The effects of α-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% α-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% α-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 α-LA. However, the administration of various doses of α-LA noticeably decreased the level of urinary DPD in both the OVX and IMO rats. High doses of α-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 α-LA, these results suggest that α-LA suppresses the rates of bone turnover in rats with a low bone mass.

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

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.

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.

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.

Plasma Bone Specific Alkaline Phosphatase (BSAP) and Urinary Deoxypyridinoline/Creatinine Ratio (DPD) at 16 weeks of Study day in Sham Controls, Ovariectomized (OVX) Controls, OVX Pair-Fed Controls, and OVX rats Treated with Diets Containing 0.3% and 0.5% α-lipoic acid (α-LA)

*P < 0.05, **P < 0.01 vs. sham OP, †P < 0.01 vs. OVX Pair-fed group

Plasma bone Specific Alkaline Phosphatase (BSAP) and Urinary Deoxypyridinoline/Creatinine Ratio (DPD) at 3 weeks of Study day in Saline Controls, Inflammation-Mediated Osteopenia (IMO) Controls, and IMO rats Treated with Diets Containing 0.3 %, 0.5% and 1.0% α--lipoic acid (α--LA)

*P < 0.05, **P < 0.01 vs. saline control, †P < 0.05, ††P < 0.01 vs. IMO control