Exercise and Zoledronic Acid on Lipid Profile and Bone Remodeling in Ovariectomized Rats: a Paradoxical Negative Association?
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Exercise (EXE) and amino-bisphosphonates (BP) are both considered as useful strategies in the prevention of post-menopausal bone loss. Exercise reduces lipid levels, and BP may induce increase in high-density lipoprotein cholesterol (HDL-C). We hypothesized that combined effects of BP and exercise would produce a better improvement of lipid profile. We studied the specific and combined effects of zoledronic acid (Z) and EXE on lipid profile and bone remodeling in mature ovariectomized (OVX) rats. Six-month old female rats were randomly assigned to either a sham-ovx group (n = 12) or one of four OVX groups (n = 12): vehicle-treated sedentary (OVX); OVX + EXE (OVX-E, running on a treadmill for 12 weeks); OVX + Z (20 μg/kg, i.v.), (OVX-Z); OVX + Z+EXE (OVX-ZE). Total cholesterol (TC), HDL-C and bone remodeling markers were measured at baseline and at the end of the study. We demonstrated that both Z and EXE prevented the increase in bone resorption resulting from OVX, and individually improved the atherosclerotic risk index. Therapy with Z resulted in significant increase (39.00 ± 0.03 vs. 53.6 ± 0.01 mg/dl; +37.4%, P < 0.05) in serum concentration of HDL-C and a non significant decrease in TC (135.30 ± 0.03 vs. 144.80 ± 0.05 mg/dl; −5.8%) in the OVX-Z group compared to the OVX group. Post-menopausal women have elevated risk of CVD and bone resorption, hence, these data ultimately demonstrate (except for the elevated ratio in the combined group) that exercise and zoledronic acid are useful in minimizing the impact of these two processes in women and the combination of the two may be clinically relevant.
KeywordsLipid metabolism Atherosclerosis
C terminal collagen cross-links
Farnesyl pyrophosphate synthetase
High-density lipoprotein cholesterol
Lean body mass
Low-density lipoprotein cholesterol
Ovariectomized + Exercise trained animal
Ovariectomized + Zoledronic acid treated animal
Ovariectomized + Zoledronic acid treated + Exercise trained animal
Total serum cholesterol
Tumor necrosis factor alpha
Whole body bone mineral content
Whole body bone mineral density
E. Lespessailles was the recipient of a fellowship research grant from Novartis.
Conflict of interest statement
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
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