Abstract
Both tocotrienol and statins are suppressors of the mevalonate pathway. Supplementation of tocotrienol among statin users could potentially protect them against osteoporosis. This study aimed to compare the effects of tocotrienol and lovastatin co-supplementation with individual treatments on bone dynamic histomorphometric indices and bone morphogenetic protein-2 (BMP-2) gene expression in ovariectomized rats. Forty-eight female Sprague-Dawley rats were randomized equally into six groups. The baseline was sacrificed upon receipt. All other groups were ovariectomized, except for the sham group. The ovariectomized groups were administered orally daily with (1) lovastatin 11 mg/kg/day alone; (2) tocotrienol derived from annatto bean (annatto tocotrienol) 60 mg/kg/day alone; (3) lovastatin 11 mg/kg/day, and annatto tocotrienol 60 mg/kg/day. The sham and ovariectomized control groups were treated with equal volume of vehicle. After eight weeks of treatment, the rats were sacrificed. Their bones were harvested for bone dynamic histomorphometry and BMP-2 gene expression. Rats supplemented with annatto tocotrienol and lovastatin concurrently demonstrated significantly lower single-labeled surface, but increased double-labeled surface, mineralizing surface, mineral apposition rate and bone formation rate compared to individual treatments (p < 0.05). There was a parallel increase in BMP-2 gene expression in the rats receiving combined treatment (p < 0.05). The combination of annatto tocotrienol and lovastatin exerted either additively or synergistically on selected bone parameters. In conclusion, tocotrienol can augment the bone formation and mineralization in rats receiving low-dose statins. Supplementation of tocotrienol in statin users can potentially protect them from osteoporosis.
Highlights
Hypercholesterolemia is a prevalent condition among middle-aged and elderly populations worldwide [1,2,3]
Trabecular bone of the ovariectomized rats treated with annatto tocotrienol alone or lovastatin and annatto tocotrienol together showed more calcein double-labelled surface compared to untreated rats and rats treated with lovastatin alone (Figure 1)
The current study showed that co-supplementation of lovastatin and annatto tocotrienol was
Summary
Hypercholesterolemia is a prevalent condition among middle-aged and elderly populations worldwide [1,2,3]. The middle-aged and elderly populations are susceptible to osteoporosis. It is a condition characterized by degeneration of bone mass and deterioration of skeletal microarchitecture, leading to decreased bone strength and increased risk of fracture [5]. Meta-analyses have concluded that statins could increase bone mineral density of its users and protect them from osteoporosis [7,8,9]. This pleiotropic effect of statins on bone is mediated through the Nutrients 2017, 9, 143; doi:10.3390/nu9020143 www.mdpi.com/journal/nutrients
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