Sost Haploinsufficiency Provokes Peracute Lethal Cardiac Tamponade without Rescuing the Osteopenia in a Mouse Model of Excess Glucocorticoids

Javaheri, Behzâd; Herbert, Eleanor; Hopkinson, Mark; Aljazzar, Ahmed; Pitsillides, Andrew A.

doi:10.1016/j.ajpath.2018.12.007

Cited by 10 publications

(10 citation statements)

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“…Population aging is expected to escalate the prevalence of osteoporosis over the next decades. A better grasp of these mechanisms is crucial if new effective treatments to combat or indeed reverse this age-related decline are to be pinpointed [5].…”

Section: Introductionmentioning

confidence: 99%

Aging and Mechanoadaptive Responsiveness of Bone

Javaheri

Pitsillides

2019

Curr Osteoporos Rep

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Purpose of Review Osteoporosis is an age-related disorder characterized by bone loss and increased fracture susceptibility. Whether this is due to reduced loading in less active elderly individuals or inherent modifications in bone cells is uncertain. We suppose that osteoporosis is nonetheless prima facie evidence for impaired mechanoadaptation; either capacity to accrue new bone declines, or the stimulus for such accrual is absent/can no longer be triggered in the aged. Herein, we provide only sufficient background to enable a focus on recent advances which seek to address such dilemmas. Recent Findings Recent advances from innovative high-impact loading regimes emphasize the priming of mechanoadaptation in the aged, such that low-to-moderate intensity loading becomes beneficial. These new findings lead us to speculate that aged bone mechanoadaptation is not driven solely by strain magnitude but is instead sensitive to high strain gradients. Summary Impaired mechanoadaptation is a feature of the aged skeleton. Recent advances indicate that novel interventional loading regimes can restore mechanoadaptive capacity, enabling new approaches for retaining bone health in the aged. Innovative exercise paradigms appear to be capable of "hacking" into the osteogenic signal produced by exercise such that low-to-moderate intensity activities may also become more beneficial. Deciphering the underpinning mechanism(s) will also enable new pharmacological intervention for retaining bone health in the aged.

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Section: Introductionmentioning

confidence: 99%

Aging and Mechanoadaptive Responsiveness of Bone

Javaheri

Pitsillides

2019

Curr Osteoporos Rep

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“…Increased sclerostin, from either source, was found to be protective against aortic aneurysm formation and atherosclerosis. This was further supported by data from experiments in which a murine model of glucocorticoid-induced osteopenia was crossed with a Sost-deficient (and therefore sclerostin-deficient) mouse [109], with resultant sudden death in ~ 10% of mice. On post-mortem, histopathological evidence of peracute haemopericardium and cardiac tamponade was observed.…”

Section: Romosozumabmentioning

confidence: 79%

Assessment of Cardiovascular Safety of Anti-Osteoporosis Drugs

Fuggle

Cooper

Harvey

et al. 2020

Drugs

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The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theoretically cause atheroma formation via calcium deposition, and in one study was found to be associated with myocardial infarction, but this has not been replicated. Vitamin D supplementation has been extensively investigated for cardiac benefit, but no consistent effect has been found. Despite findings in the early 21st century that menopausal hormone therapy was associated with coronary artery disease and venous thromboembolism (VTE), this therapy is now thought to be potentially safe (from a cardiac perspective) if started within the first 10 years of the menopause. Selective estrogen receptor modulators (SERMs) are associated with increased risk of VTE and may be related to fatal strokes (a subset of total strokes). Bisphosphonates could theoretically provide protection against atheroma. However, data from randomised trials and observational studies have neither robustly supported this nor consistently demonstrated the potential association with atrial fibrillation. Denosumab does not appear to be associated with cardiovascular disease and, although parathyroid hormone analogues are associated with palpitations and dizziness, no association with a defined cardiovascular pathology has been demonstrated. Finally, romosozumab has been shown to have a possible cardiovascular signal, and therefore post-market surveillance of this therapy will be vital.

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“…Site Specificity follows a very simple workflow with open source MATLAB-executed code. Similar workflows have also been described by others (Javaheri et al, 2019b). Application of Site Specificity allows quantitative discrimination between regional and global changes in cortical mass in response to changes in loading, ageing, genetic mutations and hormonal treatment (Galea et al, 2015, Orriss et al, 2018.…”

Section: Introductionmentioning

confidence: 82%