Perspective on post-menopausal osteoporosis: establishing an interdisciplinary understanding of the sequence of events from the molecular level to whole bone fractures

Abstract

Current drug treatments for post-menopausal osteoporosis cannot eliminate bone fractures, possibly because the mechanisms responsible for bone loss are not fully understood. Although research within various disciplines has significantly advanced the state of knowledge, fundamental findings are not widely understood between different disciplines. For that reason, this paper presents noteworthy experimental findings from discrete disciplines focusing on post-menopausal osteoporosis. These studies have established that, in addition to bone loss, significant changes in bone micro-architecture, tissue composition and micro-damage occur. Cellular processes and molecular signalling pathways governing pathological bone resorption have been identified to a certain extent. Ongoing studies endeavour to determine how such changes are initiated at the onset of oestrogen deficiency. It emerges that, because of the discrete nature of previous research studies, the sequence of events that lead to bone fracture is not fully understood. In this paper, two sequences of multi-scale changes are proposed and the experimental challenges that need to be overcome to fully define this sequence are outlined. Future studies must comprehensively characterize the time sequence of molecular-, cellular-and tissue-level changes to attain a coherent understanding of the events that ultimately lead to bone fracture and inform the future development of treatments for post-menopausal osteoporosis.

Low-molecular weight fucoidan inhibits the differentiation of osteoclasts and reduces osteoporosis in ovariectomized rats

“…The results demonstrated that 4 weeks after treatment with LMWF, BMD was higher in the LMWF group when compared with the OVX group, and 8 weeks after surgery BMD increased further. BMD has been identified as an important factor for the evaluation of osteoporosis-related fractures; a previous study revealed that in accordance with BMD criteria, only 10-53% of patients are diagnosed with osteoporosis following an osteoporotic fracture (36). Micro-CT voxel-based test unit may be used for the early detection of lesions and bone structure deterioration (37,38).…”

Upregulated Cellular Expression of IL-17 by CD4+ T-Cells in Osteoporotic Postmenopausal Women

“…Our results were in agreement with their reports. It is known that TNFα and IL-6 are potent osteoclastogenic cytokines; the increased production of TNFα and IL-6 can promote osteoclastogenesis and then stimulates bone loss [7,23] . TNFα and IL-6 contain nuclear factor kappa B binding sites in their promoter, and when present in abundance, TNFα and IL-6 can directly target osteoclast precursors to accelerate their differentiation and then increase osteoclast formation [11,24] .…”

Mechanisms of osteocyte stimulation in osteoporosis

“…the coordinated bone formation by osteoblasts and resorption by osteoclasts) were at first surprising. A recent study sought to establish the sequence with which complex changes in molecular and cellular biology, tissue composition, tissue integrity and architecture arise in the bone loss cascade of osteoporosis (McNamara 2010). It was proposed that the complex heterogeneous changes in bone tissue composition might be explained by the mechanical environment, which varies considerably in magnitude according to anatomical location.…”