Alendronate prolongs the reversal-resorption phase in human cortical bone remodeling.

Bone

Molecular Bone Histology Team, Clinical Cell Biology, Research Unit of Pathology, Dept. of Clinical Research and Dept. of Molecular Medicine, University of Southern Denmark, Odense, Denmark; Dept. of Pathology, Odense University Hospital, Odense, Denmark; Dept. of Forensic Medicine, Aarhus University, Aarhus, Denmark. Electronic address:

Published: July 2022

AI Article Synopsis

  • Bisphosphonates like alendronate are effective in reducing fracture risk and increasing bone mineral density in osteoporotic women, but they may hinder new bone formation.
  • A study comparing cortical bone samples from alendronate-treated and placebo-treated patients found that new cortical remodeling is less activated in patients receiving alendronate, evidenced by lower percentages of formative pores and a higher contribution of eroded pores.
  • The differences in cortical remodeling between the two groups become significant after three years of alendronate treatment, suggesting a prolonged delay in the transition from resorption to new bone formation.

Article Abstract

Despite their ability to reduce fracture-risk and increase Bone Mineral Density (BMD) in osteoporotic women, bisphosphonates are reported to reduce formation of new bone. Reduced bone formation has been suggested to lead to accumulation of microfractures and contribute to rare side effects in cortical bone such as atypical femur fractures. However, most studies are limited to trabecular bone. In this study, the cortical bone remodeling in human iliac bone specimens of 65 non-treated and 24 alendronate-treated osteoporotic women was investigated using a new histomorphometric classification of intracortical pores. The study showed that only 12.4 ± 11% of the cortical pore area reflected quiescent pores/osteons in alendronate-treated patients versus 8.5 ± 5% in placebo, highlighting that new cortical remodeling events remain to be activated. The percent and size of eroded pores (events in resorption-reversal phase) remained unchanged, but their contribution to total pore area was 1.4-fold higher in alendronate versus placebo treated patients (66 ± 22% vs 48 ± 22%, p < 0.001). On the other hand, the mixed eroded-formative pores (events with mixed resorption-reversal-formation phases) was 2-fold lower in alendronate versus placebo treated patients (19 ± 14% vs 39 ± 23% of total pore area, p < 0.001), and formative pores (event in formation phase) was 2.2-fold lower in alendronate versus placebo treated patients (2.1 ± 2.4% vs 4.6 ± 3.6%, p < 0.01), and their contribution to total pore area was 2.4-fold lower (1.3 ± 2.1% vs 3.1 ± 4.4%, p < 0.05). Importantly, these differences between alendronate and placebo treated patients were significant in patients after 3 years of treatment, not after 2 years of treatment. Collectively, the results support that cortical remodeling events activated during alendronate treatment has a prolonged reversal-resorption phase with a delayed transition to formation, becoming increasingly evident after 3-years of treatment. A potential contributor to atypical femur fractures associated with long-term bisphosphonate treatment.

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http://dx.doi.org/10.1016/j.bone.2022.116419DOI Listing

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