Advances in pathogenesis and therapeutic strategies for osteoporosis

Song, Shasha; Guo, Yuanyuan; Yang, Yueping; Fu, Dehao

doi:10.1016/j.pharmthera.2022.108168

Cited by 219 publications

(116 citation statements)

References 295 publications

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“…Bone mineral density (BMD) is considered as the key standard for determining osteoporosis. 533 Vitamin D, one of the important metabolites of cholesterol, induces synthesis of calcium-binding proteins to promote Ca 2+ absorption and enhances BMD. 534 Interestingly, epidemiological evidence indicates that high serum cholesterol levels represent a risk factor for osteoporosis.…”

Section: Cholesterol-related Diseases and Interventionsmentioning

confidence: 99%

Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics

Duan

Gong

et al. 2022

Sig Transduct Target Ther

167

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Disturbed cholesterol homeostasis plays critical roles in the development of multiple diseases, such as cardiovascular diseases (CVD), neurodegenerative diseases and cancers, particularly the CVD in which the accumulation of lipids (mainly the cholesteryl esters) within macrophage/foam cells underneath the endothelial layer drives the formation of atherosclerotic lesions eventually. More and more studies have shown that lowering cholesterol level, especially low-density lipoprotein cholesterol level, protects cardiovascular system and prevents cardiovascular events effectively. Maintaining cholesterol homeostasis is determined by cholesterol biosynthesis, uptake, efflux, transport, storage, utilization, and/or excretion. All the processes should be precisely controlled by the multiple regulatory pathways. Based on the regulation of cholesterol homeostasis, many interventions have been developed to lower cholesterol by inhibiting cholesterol biosynthesis and uptake or enhancing cholesterol utilization and excretion. Herein, we summarize the historical review and research events, the current understandings of the molecular pathways playing key roles in regulating cholesterol homeostasis, and the cholesterol-lowering interventions in clinics or in preclinical studies as well as new cholesterol-lowering targets and their clinical advances. More importantly, we review and discuss the benefits of those interventions for the treatment of multiple diseases including atherosclerotic cardiovascular diseases, obesity, diabetes, nonalcoholic fatty liver disease, cancer, neurodegenerative diseases, osteoporosis and virus infection.

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Section: Cholesterol-related Diseases and Interventionsmentioning

confidence: 99%

Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics

Duan

Gong

et al. 2022

Sig Transduct Target Ther

167

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“…Osteoporosis is a metabolic disease characterized by microarchitectural deterioration of bone tissue with a consequent increase in the risk of fractures, chronic pain and disability, ending in loss of independence. Osteoporosis is currently considered a major global public health issue by the World Health Organization (WHO) affecting millions of people all over the world, especially the aging population and postmenopausal women, leading to a poor quality of life and generating enormous direct health care costs [ 1 , 2 , 3 ]. Among other risks related to an unhealthy lifestyle such as unbalanced diet, stress and being sedentary, the maintenance of bone health strictly depends on the continuous and correct bone remodeling based on the coordinated interaction and balanced activity of bone reforming cells called osteoblasts (OBs), and bone-resorbing cells called osteoclasts (OCs) [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Osteoporosis is currently considered a major global public health issue by the World Health Organization (WHO) affecting millions of people all over the world, especially the aging population and postmenopausal women, leading to a poor quality of life and generating enormous direct health care costs [ 1 , 2 , 3 ]. Among other risks related to an unhealthy lifestyle such as unbalanced diet, stress and being sedentary, the maintenance of bone health strictly depends on the continuous and correct bone remodeling based on the coordinated interaction and balanced activity of bone reforming cells called osteoblasts (OBs), and bone-resorbing cells called osteoclasts (OCs) [ 3 , 4 ]. The excessive differentiation/activity of the OCs, which are multinucleated cells derived from the fusion of hematopoietic mononuclear precursors of monocytic lineage, is responsible for unbalanced bone resorption causing osteoporosis [ 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Among other risks related to an unhealthy lifestyle such as unbalanced diet, stress and being sedentary, the maintenance of bone health strictly depends on the continuous and correct bone remodeling based on the coordinated interaction and balanced activity of bone reforming cells called osteoblasts (OBs), and bone-resorbing cells called osteoclasts (OCs) [ 3 , 4 ]. The excessive differentiation/activity of the OCs, which are multinucleated cells derived from the fusion of hematopoietic mononuclear precursors of monocytic lineage, is responsible for unbalanced bone resorption causing osteoporosis [ 3 , 4 , 5 ]. Several factors, such as chronic use of drugs, hormones, immobilization, malnutrition, and low-grade chronic inflammation, predispose to bone loss, further predisposing to fragility, morbidity and mortality [ 3 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

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KYMASIN UP Natural Product Inhibits Osteoclastogenesis and Improves Osteoblast Activity by Modulating Src and p38 MAPK

et al. 2022

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The imbalance in osteoblast (OB)-dependent bone formation in favor of osteoclast (OC)-dependent bone resorption is the main cause of loss of tissue mineral mass during bone remodeling leading to osteoporosis conditions. Thus, the suppression of OC activity together with the improvement in the OB activity has been proposed as an effective therapy for maintaining bone mass during aging. We tested the new dietary product, KYMASIN UP containing standardized Withania somnifera, Silybum marianum and Trigonella foenum-graecum herbal extracts or the single extracts in in vitro models mimicking osteoclastogenesis (i.e., RAW 264.7 cells treated with RANKL, receptor activator of nuclear factor kappa-Β ligand) and OB differentiation (i.e., C2C12 myoblasts treated with BMP2, bone morphogenetic protein 2). We found that the dietary product reduces RANKL-dependent TRAP (tartrate-resistant acid phosphatase)-positive cells (i.e., OCs) formation and TRAP activity, and down-regulates osteoclastogenic markers by reducing Src (non-receptor tyrosine kinase) and p38 MAPK (mitogen-activated protein kinase) activation. Withania somnifera appears as the main extract responsible for the anti-osteoclastogenic effect of the product. Moreover, KYMASIN UP maintains a physiological release of the soluble decoy receptor for RANKL, OPG (osteoprotegerin), in osteoporotic conditions and increases calcium mineralization in C2C12-derived OBs. Interestingly, KYMASIN UP induces differentiation in human primary OB-like cells derived from osteoporotic subjects. Based on our results, KYMASIN UP or Withania somnifera-based dietary supplements might be suggested to reverse the age-related functional decline of bone tissue by re-balancing the activity of OBs and OCs, thus improving the quality of life in the elderly and reducing social and health-care costs.

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“…Hormone status strongly affects women's health and quality of life, with age-associated estrogen deficiency and hormonal imbalance having been implicated in the pathogenesis of various diseases, including osteoporosis [ 1 ]. Postmenopausal osteoporosis is the most common type of osteoporosis and is characterized by low bone mineral density (BMD), which increases the risk of fractures [ 2 , 3 ]. The cause of postmenopausal osteoporosis, however, remains to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Association between Serum Total Testosterone Level and Bone Mineral Density in Middle-Aged Postmenopausal Women

Yang

Kong

Yao

et al. 2022

International Journal of Endocrinology

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Background. Hormone status strongly affects women’s health and quality of life. To date, studies investigating the association between total testosterone (T) level and bone mineral density (BMD) in women are limited and have yielded contradictory conclusions. The aim of our study was to examine the association between serum total T level and lumbar BMD in postmenopausal women aged 40–59 years. Methods. The study group included 1,058 women from the 2011–2016 National Health and Nutrition Examination Survey. Multiple regression analyses were used to evaluate the association between serum total T level and lumbar BMD. Results. After adjusting for covariates, there was a positive association between the serum total T level and lumbar BMD (β, 1.07; 95% confidence interval, 0.17–1.97). A non-linearity in this association was identified, with a point of inflection at 30 ng/dL. Conclusions. Serum total T level was positively associated with lumbar BMD in middle-aged postmenopausal women up to a T level >30 ng/dL. Therefore, increasing T level in women with a low serum total T level may have beneficial outcomes on bone health.

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Advances in pathogenesis and therapeutic strategies for osteoporosis

Cited by 219 publications

References 295 publications

Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics

Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics

KYMASIN UP Natural Product Inhibits Osteoclastogenesis and Improves Osteoblast Activity by Modulating Src and p38 MAPK

Association between Serum Total Testosterone Level and Bone Mineral Density in Middle-Aged Postmenopausal Women

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