Baseline Glucocorticoid Dose and Bone Mineral Density Response with Teriparatide or Alendronate Therapy in Patients with Glucocorticoid-induced Osteoporosis

Abstract

ABSTRACT. Objective. This post-hoc analysis studied the effect of baseline glucocorticoid dose on the 18-month bone mineral density (BMD) response to teriparatide 20 µg/day or alendronate 10 mg/day in 387 patients with glucocorticoid-induced osteoporosis (GIO) from a randomized, double-blind trial. Methods. Lumbar spine (LS), femoral neck (FN), and total hip (TH) BMD were measured at baseline and 18 months. Mean baseline glucocorticoid dose was categorized as low (≤ 5 mg/day), medium (> 5 and < 15 mg/day), or high (≥ 15 mg/day). Results. Baseline LS, FN, and TH BMD were similar between groups, and between glucocorticoid dose categories within each group. LS BMD increases at the low, medium, and high glucocorticoid doses were 8.1%, 6.6%, and 4.6%, respectively, with teriparatide, and 3.6%, 2.8%, and 2.3% with alendronate. Analyzed as a continuous variable, higher glucocorticoid doses had a negative, but nonsignificant, effect on the percentage increase in LS BMD in both groups. Glucocorticoid dose did not significantly affect FN or TH BMD increases in either group. Across the 3 glucocorticoid dose categories, the overall LS BMD increases were different for both treatments combined (p = 0.033), but the relative differences between the treatment groups were not different (interaction, p = 0.52). Glucocorticoids effectively treat inflammatory conditions but are associated with an array of side effects 1 , including secondary osteoporosis 2 . The pathophysiology of glucocorticoid-induced osteoporosis (GIO) involves multiple mechanistic pathways, including early increases in bone resorption along with decreased bone formation, and alterations in bone microarchitecture 3 . Daily or cumulative oral glucocorticoid doses are related to decreased bone mass and the occurrence of fractures 2,4 . However, patients treated with oral glucocorticoids experience fractures at a higher bone mineral density (BMD) than patients with postmenopausal osteoporosis 5 , and the fracture risk is greater than predicted by decreased bone mass alone 6 , suggesting that glucocorticoids can also negatively affect bone quality 1,2,5 . Other mechanisms of bone fragility, such as osteocyte apoptosis and reduced repair of local defects, may contribute to the increased fracture risk observed in patients treated with chronic glucocorticoids 7 . Current guidelines for management of GIO include assessment of patients for osteoporosis risk factors prior to initiating glucocorticoid therapy, concomitant use of calcium and vitamin D supplements, and for prolonged treatment of the underlying disease, minimizing the glucocorticoid dose and/or tapering the glucocorticoid dose in low disease Conclusion