The Effect of Dietary Calcium Intake Level on the Slow Phase of Postmenopausal Bone Loss in Letrozole-Treated Ovariectomized Rats
Abstract
Although aromatase inhibitors (AIs) are a mainstay for treatment of estrogen receptor positive breast cancer in postmenopausal women, they have been associated with significant bone loss and increased fracture risk. Dietary calcium (Ca) has been shown to reduce bone loss in healthy postmenopausal women. However, its effectiveness has not been evaluated in AI-induced bone loss. We hypothesized that improved Ca intake would reduce bone loss induced by AIs. We tested this hypothesis using a 2 by 3 factorial design in an ovariectomized (OVX) rat model which represents the slow phase of postmenopausal bone loss. 6-month-old OVX rats (n=72) were fed a 0.2% low Ca diet during a 2-month post-OVX stabilization period. Six rats were sacrificed at baseline and the rest (n=66) were randomized to one of three levels of dietary Ca: 0.2%, 0.4%, or 1.0% for 12 weeks. Half of the rats within each diet group received a subcutaneous letrozole pellet that delivered 2.5 mg over 90 days while the other half received a placebo pellet. Contrary to our expectation, letrozole did not induce bone loss. Of the 16 bone phenotypes we measured across femur and spine, only femur bone mineral density (BMD) and femur midshaft total cross-sectional area significantly decreased in response to letrozole. However, we observed a strong positive impact of increased dietary Ca intake on almost all bone endpoints. Compared to the 0.2% and 0.4% Ca diets, the 1.0% Ca diet reduced the loss of spine bone mineral content (BMC) and BMD significantly, and increased femur BMC and BMD. At the 4th lumbar spine, trabecular bone volume, number, thickness were significantly higher while trabecular separation was significantly lower in the 1.0% Ca diet group. The 1.0% Ca diet also resulted in thicker cortical bone, enlarged cortical area, and increased cortical area fraction at femur midshaft. In contrast to the 1.0% Ca diet group, feeding the 0.4% Ca diet did not consistently improve these bone endpoints compared to feeding the 0.2% low Ca diet. We conclude that 1.0% high Ca intake is beneficial by reducing postmenopausal slow bone loss and by protecting bone microstructure.
Degree
M.S.
Advisors
Fleet, Purdue University.
Subject Area
Nutrition
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