Effects of long-term alendronate treatment on postmenopausal osteoporosis bone material properties.

Abstract

Raman microspectroscopic analysis of iliac crest from patients that were treated with alendronate (ALN) for 10years revealed minimal, transient alterations in bone material properties confined to actively forming bone surfaces compared to patients that were on ALN for 5years. These changes were not encountered in the bulk tissue. Alendronate (ALN) and other bisphosphonates (BPs) are the most widely prescribed therapy for postmenopausal osteoporosis. Despite their overall excellent safety record and efficacy in reducing fractures, questions have been raised regarding potential detrimental effects that may be related to prolonged bone turnover reduction, although no definite cause-effect relationship has been established to date. The purpose of the present study was to evaluate bone material properties in patients that were receiving ALN for 5 or 10years. Raman microspectroscopic analysis was used to analyze iliac crest biopsies from postmenopausal women with osteoporosis who had been treated with ALN for 5years and were then re-randomized to placebo (PBO, N = 14), 5mg/day ALN (N = 10), or 10mg/day ALN (N = 6) for another 5years. The parameters monitored and expressed as a function of tissue age were (i) the mineral/matrix ratio (MM), (ii) the relative proteoglycan content (PG), (iii) the relative lipid content (LPD), (iv) the mineral maturity/crystallinity (MMC), and (v) the relative pyridinoline content (PYD). The obtained data indicate that 10-year ALN use results in minimal, transient bone tissue composition changes compared to use for 5years, confined to actively forming trabecular surfaces, implying potential differences in bone matrix maturation that nevertheless did not result in differences of these values in bulk tissue. The data suggest that prolonged reduction in bone turnover during 10years of therapy with ALN by itself is unlikely to be associated with adverse effects on bone material properties.