Long-term safety of antiresorptive treatment: bone material, matrix and mineralization aspects

Abstract

It is well established that long-term antiresorptive use is effective in the reduction of fracture risk in high bone turnover osteoporosis. Nevertheless, during recent years, concerns emerged that longer bone turnover reduction might favor the occurrence of fatigue fractures. However, the underlying mechanisms for both beneficial and suspected adverse effects are not fully understood yet. There is some evidence that their effects on the bone material characteristics have an important role. In principle, the composition and nanostructure of bone material, for example, collagen cross-links and mineral content and crystallinity, is highly dependent on tissue age. Bone turnover determines the age distribution of the bone structural units (BSUs) present in bone, which in turn is decisive for its intrinsic material properties. It is noteworthy that the effects of bone turnover reduction on bone material were observed to be dependent on the duration of the antiresorptive therapy. During the first 2-3 years, significant decreases in the heterogeneity of material properties such as mineralization of the BSUs have been observed. In the long term (5-10 years), the mineralization pattern reverts towards normal heterogeneity and degree of mineralization, with no signs of hypermineralization in the bone matrix. Nevertheless, it has been hypothesized that the occurrence of fatigue fractures (such as atypical femoral fractures) might be linked to a reduced ability of microdamage repair under antiresorptive therapy. The present article examines results from clinical studies after antiresorptive, in particular long-term, therapy with the aforementioned potentially positive or negative effects on bone material.

Graphene‐Based MicroRNA Transfection Blocks Preosteoclast Fusion to Increase Bone Formation and Vascularization

“…However, according to recent discoveries, POCs barely resorb bone matrix, on the contrary, they are beneficial for angiogenesis through secreting platelet derived growth factor‐BB (PDGF‐BB) 8, 9, 10. This is why current long‐term antiresorptive therapy is not satisfying and even increases risk of atypical fractures 11. Herein, we assumed that depletion of mature OCs while preserving POCs will be a more effective strategy in treating osteoporosis.…”

Alendronate induces osteoclast precursor apoptosis via peroxisomal dysfunction mediated ER stress

“…However, nitrogencontaining bisphosphonates including ALN seem to have no selectivity in depleting osteoclasts (Drake et al, 2008;Rachner et al, 2011). This potentially explained why current long-term antiresorptive therapy is not satisfying and even increases risk of atypical fractures (Adler et al, 2016;Misof et al, 2015). We assumed that depletion of mature OCs while preserving POCs will be a more effective strategy in treating osteoporosis.…”

Review: Breaking From Bisphosphonates

“…Fracture is a composite risk based on age, sex, race, anatomy, the structural integrity of bone with aging, the quality of mineralization, and the impact that occurs with a fall. Is there some quality of aging bone that is compromised by prolonged bisphosphonate therapy at the tissue level ? The proportion of women who continue to have fractures while receiving treatment would suggest that this might be true.…”