Emerging concepts in the epidemiology, pathophysiology, and clinical care of osteoporosis across the menopausal transition

Lizneva, Daria; Yuen, Tony; Sun, Li; Kim, Semin; Atabiekov, Ihor; Munshi, Lubna Bashir; Epstein, Sol; New, Maria I.; Zaidi, Mone

doi:10.1016/j.matbio.2018.05.001

Cited by 34 publications

(24 citation statements)

References 109 publications

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“…Individuals with osteoporosis are at a higher risk of fragility fractures ( Eastell et al, 2016 ). Over 200 million people worldwide suffer from this disease, and this number is gradually increasing ( Lizneva et al, 2018 ). Fractures caused by osteoporosis lead to functional disruption and pain along with an enormous therapeutic cost.…”

Section: Introductionmentioning

confidence: 99%

GAS5 protects against osteoporosis by targeting UPF1/SMAD7 axis in osteoblast differentiation

Xie

et al. 2020

eLife

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Osteoporosis is a common systemic skeletal disorder resulting in bone fragility and increased fracture risk. It is still necessary to explore its detailed mechanisms and identify novel targets for the treatment of osteoporosis. Previously, we found that a lncRNA named GAS5 in human could negatively regulate the lipoblast/adipocyte differentiation. However, it is still unclear whether GAS5 affects osteoblast differentiation and whether GAS5 is associated with osteoporosis. Our current research found that GAS5 was decreased in the bones and BMSCs, a major origin of osteoblast, of osteoporosis patients. Mechanistically, GAS5 promotes the osteoblast differentiation by interacting with UPF1 to degrade SMAD7 mRNA. Moreover, a decreased bone mass and impaired bone repair ability were observed in Gas5 heterozygous mice, manifesting in osteoporosis. The systemic supplement of Gas5-overexpressing adenoviruses significantly ameliorated bone loss in an osteoporosis mouse model. In conclusion, GAS5 promotes osteoblast differentiation by targeting the UPF1/SMAD7 axis and protects against osteoporosis.

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Section: Introductionmentioning

confidence: 99%

GAS5 protects against osteoporosis by targeting UPF1/SMAD7 axis in osteoblast differentiation

Xie

et al. 2020

eLife

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“…and Vitamin D homeostasis and conditionally promoting upregulation of cytokines that either incite or inhibit bone resorption (Lizneva et al, 2018). That OP is overwhelmingly presented by post-menopausal women (four times more common in women over 50 than similarly aged men) further solidifies the preponderance of estrogen in disease pathology.…”

Section: Advancement In Current Treatmentsmentioning

confidence: 99%

The Role of Chronic Inflammatory Bone and Joint Disorders in the Pathogenesis and Progression of Alzheimer's Disease

Culibrk

Hahn

2020

Front. Aging Neurosci.

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Late-onset Alzheimer's Disease (LOAD) is a devastating neurodegenerative disorder that causes significant cognitive debilitation in tens of millions of patients worldwide. Throughout disease progression, abnormal secretase activity results in the aberrant cleavage and subsequent aggregation of neurotoxic Aβ plaques in the cerebral extracellular space and hyperphosphorylation and destabilization of structural tau proteins surrounding neuronal microtubules. Both pathologies ultimately incite the propagation of a disease-associated subset of microglia—the principle immune cells of the brain—characterized by preferentially pro-inflammatory cytokine secretion and inhibited AD substrate uptake capacity, which further contribute to neuronal degeneration. For decades, chronic neuroinflammation has been identified as one of the cardinal pathophysiological driving features of AD; however, despite a number of works postulating the underlying mechanisms of inflammation-mediated neurodegeneration, its pathogenesis and relation to the inception of cognitive impairment remain obscure. Moreover, the limited clinical success of treatments targeting specific pathological features in the central nervous system (CNS) illustrates the need to investigate alternative, more holistic approaches for ameliorating AD outcomes. Accumulating evidence suggests significant interplay between peripheral immune activity and blood-brain barrier permeability, microglial activation and proliferation, and AD-related cognitive decline. In this work, we review a narrow but significant subset of chronic peripheral inflammatory conditions, describe how these pathologies are associated with the preponderance of neuroinflammation, and posit that we may exploit peripheral immune processes to design interventional, preventative therapies for LOAD. We then provide a comprehensive overview of notable treatment paradigms that have demonstrated considerable merit toward treating these disorders.

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“…Thirteen per cent of trabecular bone loss in postmenopausal women can be attributed to the decrease in trabecular numbers and the increase in trabecular perforation . It is important to note that trabecular perforation is considered an irreversible microarchitectural change, so that bone loss, strength and microarchitecture that occurs during transmenopause are permanent …”

Section: Introductionmentioning

confidence: 99%

“…3 It is important to note that trabecular perforation is considered an irreversible microarchitectural change, so that bone loss, strength and microarchitecture that occurs during transmenopause are permanent. 4 More knowledge is needed about the factors that may identify women who are at high risk for bone loss or fracture as they enter menopause and therefore are more likely to require future management.…”

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confidence: 99%

Trabecular bone score and bone remodelling markers identify perimenopausal women at high risk of bone loss

Restituto¹,

Botella

Monreal

et al. 2019

Clinical Endocrinology

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Context Bone loss is accelerated in the late perimenopause and early menopause. The date of the final menstrual period cannot be stated until 1 year after it has ended, and at that time, most of the rapid bone loss phase will have elapsed. Therefore, early detection of bone loss is crucial. Objectives To evaluate the utility of bone turnover markers (BTM) to identify the women who are more likely to lose more bone mass during the transition to menopause and quantify the loss of bone quality measured by trabecular bone score (TBS). Design, patients and setting Sixty‐four healthy premenopausal women, mean age between 44 and 57 years old, were enrolled and followed up for 5 years. Clinical features, lifestyle, bone densitometry, TBS and BTM (CTX, P1NP and osteocalcin) were measured at baseline and follow‐up. Results All women had densitometrically normal bone at the time of enrolment. After 5 years, 48.4% had normal bone mineral density, 45.8% low bone mass and 6.3% osteoporosis. Women with osteopenia/osteoporosis at follow‐up had higher CTX and P1NP at enrolment compared with women with densitometrically normal bone. The areas under the curve for the prediction of low bone mass or osteoporosis were 0.69 (P = 0.011) for P1NP, 0.69 for CTX (P = 0.013) and 0.77 (P 0.001) for OC. A significant correlation was found between P1NP increase after 5 years and the decrease in lumbar bone density (r = −0.383, P = 0.002). At baseline, 7 (10.9%) women had deteriorated microarchitecture (TBS < 1.3). Three of these women developed osteoporosis and four osteopenia at follow‐up. Conclusions Women with higher P1NP and CTX and lower TBS at baseline had lower BMD in the transition to menopause suggesting these novel tools could have potential use in identifying women at high risk of rapidly decreasing bone mass.

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Emerging concepts in the epidemiology, pathophysiology, and clinical care of osteoporosis across the menopausal transition

Cited by 34 publications

References 109 publications

GAS5 protects against osteoporosis by targeting UPF1/SMAD7 axis in osteoblast differentiation

GAS5 protects against osteoporosis by targeting UPF1/SMAD7 axis in osteoblast differentiation

The Role of Chronic Inflammatory Bone and Joint Disorders in the Pathogenesis and Progression of Alzheimer's Disease

Trabecular bone score and bone remodelling markers identify perimenopausal women at high risk of bone loss

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