J Clin Pharmacol. 2019 Nov;59(11):1543-1550. doi: 10.1002/jcph.1451. Epub 2019 Jun 6.

Disease Progression Modeling Analysis of the Change of Bone Mineral Density  by Postoperative Hormone Therapies in Postmenopausal Patients With Early Breast Cancer.

Yoon S, Bae KS, Cho YS, Han S, Kim H, Lim HS.

Abstract

The osteoporosis incidence in postmenopausal patients on aromatase inhibitors (AI) is much higher than in those on tamoxifen, and adverse effects other than musculoskeletal disorders are less on AI than on tamoxifen. In this study we performed disease-progression modeling in postmenopausal patients with early breast cancer who had received 5 years of postoperative hormone  therapy. Clinical data from postmenopausal patients who had received postoperative hormonal therapy and met the predefined selection criteria were retrospectively collected in an anonymized way. Disease-progression modeling and simulations were performed using NONMEM version 7.42. A first-order deterioration model with a combination of a symptomatic model (when a drug effect provides a transient bad effect by offsetting the severity of the disease) and a disease-modifying model (when a drug affects the disease progression rate) was used. Vitamin D supplementation was found to have a disease-modifying effect in osteoporosis, whereas AI decreased the bone mineral density by a t score of -0.21. However, after stopping the AI, the estrogen level reverted to normal, thereby reexercising protective effects against bone loss. In the simulation the probability of osteoporosis increased by 10% in the AI group compared with the other groups (tamoxifen, no-treatment group) during the medication period. Tamoxifen showed no significant effects in the final model.

KEYWORDS:

Aromatase inhibitor; Bone mineral density; Disease progression modeling; Osteoporosis; Tamoxifen

PMID:

31172521

DOI:

10.1002/jcph.1451