Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis.

Abstract

Treatment effects on bone quality and remodeling was assessed in postmenopausal women with osteoporosis treated with oral alendronate. One transiliac bone biopsy was obtained from 231 women at either 24 mo ( n ϭ 11) or 36 mo ( n ϭ 120) from the start of treatment with alendronate at doses of between 5 and 20 mg/d, or placebo. 64 biopsies at 24 mo (31 from the placebo group and 33 alendronatetreated patients) and 95 biopsies at 36 mo (40 from the placebo group and 55 alendronate-treated patients) provided adequate cancellous tissue, and were analyzed by histomorphometry. Mineral apposition rate was unaffected by treatment. At 24 and 36 mo, osteoid thickness, volume, and surface significantly decreased. At each of the doses studied, mineralizing surface and activation frequency significantly decreased at each time point (e.g., Ϫ 92% and Ϫ 87%, respectively, for the 10 mg daily dose after 2 yr). These diminutions were of the same magnitude for each dose at 24 mo, and for the two highest doses at 36 mo. A significant increase in wall thickness accompanied by a reduction in erosion depth was detected in biopsies obtained at 24 mo. These findings confirm that mineralization is normal, and trabecular bone turnover markedly decreased in patients receiving long-term dosing with alendronate. The findings also suggest that the observed increases in bone mineral density could result both from a reduction in the remodeling space due to a decreased activation frequency and a possible trend to a positive bone balance. In addition, further studies focused on a possible increase in the degree of mineralization of bone are required. (

The potential value of monitoring bone turnover markers among women on alendronate

“…Overall, treatment resulted in an increase in this marker of bone formation in approximately 16.7% of women. This finding was unexpected: despite reports that bisphosphonates may stimulate osteoblast formation, (29,30) there is no histomorphometric evidence of an increase in bone formation with treatment (31) and in general bisphosphonates are thought to be antiresorptive and not anabolic. (32) Other studies, similar to the present one, are needed to support or refute this finding.…”

Bisphosphonate effects on bone turnover, microdamage, and mechanical properties: What we think we know and what we know that we don't know

“…These studies consistently show alendronate suppresses remodeling more than risedronate [8,9] while zoledronate suppresses more than risedronate [10]. No head-tohead assessments of bone remodeling among the BPs has been conducted using histology as an outcome, yet based on iliac crest biopsy studies from the major clinical trials the percent suppression of remodeling relative to placebo-treated controls tends to be quite similar over 3 years with daily risedronate (-40%) [11], daily alendronate (-92%) [12], intermittent oral ibandronate (-50%) [13], and zoledronate (-63%) [14].…”

Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice

“…Unstained 8-μm-thick longitudinal sections were used for fluorescence microscopy to assess mineral apposition rate (MAR, μm/day). Area of mineralising surfaces was expressed as alizarin red-labelled surfaces per bone surfaces (MS/BS, %) and the bone formation rate was calculated as MS/BS×MAR (BFR/BS, μm3/μm2/day) (47). Alternatively, sections were stained for tartrate-resistant acid phosphatase (TRAP) (Leucognost® SP; Merck, Germany) and counterstained with Mayer's haematoxylin solution.…”