Effects of 3- and 5-Year Treatment With Risedronate on Bone Mineralization Density Distribution in Triple Biopsies of the Iliac Crest in Postmenopausal Women

Abstract

Long-term effects of risedronate on bone mineralization density distribution in triple transiliac crest biopsies of osteoporotic women were evaluated. In this double-blinded study, 3-and 5-year treatment with risedronate increased the degree and homogeneity of mineralization without producing hypermineralization. These changes at the material level of bone could contribute to risedronate's antifracture efficacy.Introduction: Risedronate, a nitrogen-containing bisphosphonate, is widely used in the treatment of osteoporosis. It reduces bone turnover, increases BMD, and decreases fracture risk. To date, there are no data available on the long-term effects of risedronate on bone mineralization density distribution (BMDD) in humans. Materials and Methods: Osteoporotic women enrolled in the VERT-NA trial received either risedronate (5 mg/day, orally) or placebo for up to 5 years. All subjects received calcium and vitamin D supplementation if deficient at baseline. Triple iliac crest biopsies were collected from a subset of these subjects at baseline and 3 and 5 years. BMDD was measured in these biopsies using quantitative backscattered electron imaging, and the data were also compared with a normal reference group. Results: At baseline, both risedronate and placebo groups had a lower degree and a greater heterogeneity of mineralization as well as an increase in low mineralized bone compared with the normal reference group. The degree of mineralization increased significantly in the risedronate as well as in the placebo group after 3-and 5-year treatment compared with baseline. However, the degree of mineralization did not exceed that of normal. Three-year treatment with risedronate significantly increased the homogeneity of mineralization and slightly decreased low mineralized bone compared with placebo. Surprisingly with 5-year risedronate treatment, heterogeneity of mineralization increased compared with 3-year treatment, which might indicate an increase in newly formed bone. Conclusions: Long-term treatment with risedronate affects the homogeneity and degree of mineralization without inducing hypermineralization of the bone matrix. These changes at the material level of the bone matrix may contribute to risedronate's antifracture efficacy in osteoporotic patients.

Effects of preexisting microdamage, collagen cross‐links, degree of mineralization, age, and architecture on compressive mechanical properties of elderly human vertebral trabecular bone

“…Also, despite a greater than fourfold range in the heterogeneity index in our samples (i.e., from 0.12 to 0.53 g/cm 3 ), there was no association between the heterogeneity index and trabecular bone mechanical properties. This indicates that the reported decrease in heterogeneity index due to bisphosphonate treatment [52][53][54][55] is not likely to be deleterious to trabecular bone mechanical properties.…”

The degree of bone mineralization is maintained with single intravenous bisphosphonates in aged estrogen-deficient rats and is a strong predictor of bone strength

“…However, prevention of OVX induced bone loss with prolonged bisphosphonates treatment, appeared to increase the DBM, and was associated with improved bone strength [1,3,19]. Postmenopausal women were treated with oral risedronate or placebo for 5 years, and the average degree of bone mineralization, estimated from iliac crest biopsies, increased by 4.2% after 3 years of treatment, which was sustained for another 2 years [27]. Risedronate also prevented the age-associated and estrogen deficiency-related elevation in mineral maturity/crystallinity and collagen cross-link ratios [13].…”

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

“…After 5 to 10 years of BP treatment, BMDD was restored to within the normal premenopausal range. (40)(41)(42)(43) Effects of reducing remodeling on microdamage accumulation. Excessive bone remodeling results in microarchitectural deterioration and consequent loss of bone mass and strength and increased susceptibility to fragility fractures.…”