Effects of teriparatide on morphology of aortic calcification in aged hyperlipidemic mice

Calcific aortic vasculopathy correlates with bone loss in osteoporosis in an age-independent manner. Prior work suggests that teriparatide, the bone anabolic treatment for postmenopausal osteoporosis, may inhibit onset of aortic calcification. Whether teriparatide affects progression of pre-existing aortic calcification, widespread among this patient population, is unknown. Female apolipoprotein E-deficient mice were aged for over one year to induce aortic calcification, treated for 4.5 weeks with daily injections of control vehicle (PBS), teriparatide 40 µg/kg (PTH40) or 400 µg/kg (PTH400), and assayed for aortic calcification by micro-computed tomography (microCT) before and after treatment. In a follow-up cohort, aged female apolipoprotein E-deficient mice were treated with PBS or PTH400, and assayed for aortic calcification by serial microCT and micro-positron emission tomography (microPET). In both cohorts, aortic calcification detected by microCT progressed similarly in all groups. Mean aortic 18F-NaF incorporation, detected by serial microPET, increased in the PBS group (+14{plus minus}5%). In contrast, 18F-NaF incorporation decreased in the PTH400 group (-33{plus minus}20%; p=0.03). Quantitative histochemical analysis by Alizarin red staining revealed a lower mineral surface area index in the PTH400 group compared with the PBS group (p=0.04). Furthermore, Masson trichrome staining showed a significant increase in collagen deposition in the left ventricular myocardium of mice receiving PTH400 (2.1{plus minus}0.6% vs. controls, 0.5{plus minus}0.1%; p=0.02). In summary, while teriparatide may not affect the calcium mineral content of aortic calcification, it reduces 18F-NaF uptake in calcified lesions, suggesting the possibility that it may reduce mineral surface area with potential impact on plaque stability.