Bone quality changes associated with aging and disease: a review

Boskey, Adele L.; Imbert, Laurianne

doi:10.1111/nyas.13572

Cited by 113 publications

(93 citation statements)

References 106 publications

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“…This is paradoxical because obesity is associated with normal or increased bone mass and is traditionally thought to be protective against fragility fractures because of higher bone mass caused by increased mechanical loading on the skeleton and higher estrogen levels (Wardlaw, 1996). Obesity is associated with increased bone marrow adipose tissue (BMAT) that alters bone marrow (BM) composition and thus may change bone architecture and bone material properties that contribute to reduced bone quality (Ambrosi et al, 2017;Boskey and Imbert, 2017;Naveiras et al, 2009;Rubin et al, 2007). However, the cellular mechanisms underlying these changes are not known.…”

Section: Introductionmentioning

confidence: 99%

Obesity-Associated Hypermetabolism and Accelerated Senescence of Bone Marrow Stromal Stem Cells Suggest a Potential Mechanism for Bone Fragility

et al. 2019

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Section: Introductionmentioning

confidence: 99%

Obesity-Associated Hypermetabolism and Accelerated Senescence of Bone Marrow Stromal Stem Cells Suggest a Potential Mechanism for Bone Fragility

et al. 2019

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“…One consequence of advances in modern medicine is an ageing global population and a concomitant increase in age-related conditions. Peak bone mass is typically reached in early adulthood, after which, bone quantity and quality decline with advancing years (Riggs & Melton 1986, Boskey & Imbert 2017. Osteoporosis is a prevalent skeletal disorder characterised by reduced bone strength with an associated increased risk of fracture (NIH Consensus Development Panel on Osteoporosis Prevention and Therapy 2001), and approximately 1 in 5 men and 1 in 3 women aged over 50 years will experience a fragility fracture in their remaining lifetime (Cooper & Ferrari 2017).…”

Section: Introductionmentioning

confidence: 99%

Novel actions of sclerostin on bone

Holdsworth

Roberts

2019

Journal of Molecular Endocrinology

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The discovery that two rare autosomal recessive high bone mass conditions were caused by the loss of sclerostin expression prompted studies into its role in bone homeostasis. In this article, we aim to bring together the wealth of information relating to sclerostin in bone though discussion of rare human disorders in which sclerostin is reduced or absent, sclerostin manipulation via genetic approaches and treatment with antibodies that neutralise sclerostin in animal models and in human. Together, these findings demonstrate the importance of sclerostin as a regulator of bone homeostasis and provide valuable insights into its biological mechanism of action. We summarise the current state of knowledge in the field, including the current understanding of the direct effects of sclerostin on the canonical WNT signalling pathway and the actions of sclerostin as an inhibitor of bone formation. We review the effects of sclerostin, and its inhibition, on bone at the cellular and tissue level and discuss new findings that suggest that sclerostin may also regulate adipose tissue. Finally, we highlight areas in which future research is expected to yield additional insights into the biology of sclerostin.

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“…Recently, using genome-wide association studies (GWASs), the PRDM6 gene has been shown to affect multiple, apparently unrelated inherited traits, including bone density and body mass index; therefore, it was regarded as a potentially pleiotropic gene [12,13]. The formation of the skeleton is part of the early development of an organism [14,15]. Hu et al found that the PRDM6 mutation was associated with bone development, bone density, and body mass index [12].…”

Section: Introductionmentioning

confidence: 99%

Screening of Deletion Variants within the Goat PRDM6 Gene and Its Effects on Growth Traits

Wang

Guo

et al. 2020

Animals

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Simple Summary: Genome-wide association studies found that the PR/SET Domain 6 (PRDM6) gene mutation was associated with bone development, bone density, and body mass index. This study found a 12 bp deletion variation within the PRDM6 gene in Shaanbei white cashmere goats in a large sample size (n = 1044). This variation polymorphism was associated with multiple goat growth traits in the yearling period, including heart girth (p = 0.027), cannon circumference (p = 0.008), chest depth (p = 2.10 × 10 −5 ), chest width (p = 0.004), body height (p = 0.032), body length (p = 0.044), and hip-width (p = 0.014). The effects of the 12 bp variation were found to make no difference on adult goat growth traits. Taken together, these results demonstrate that the 12 bp deletion variant plays an important role in the early growth and development of goats and could be considered as a useful and effective molecular marker for goat breeding selection in the growth stage.Abstract: By genome-wide association studies, the PRDM6 gene has been shown to affect multiple, apparently unrelated inherited traits, including bone density and body mass index. Therefore, it is considered a potentially pleiotropic gene. In this study, we identified a 12 bp deletion variant (NC_030814.1:rs651603667, g: 79985625-79985636delTTGACTGATCCA) within the PRDM6 gene in a large sample (SBWC goats; n = 1044). All goat samples were collected in Shaanxi province in July 2018. The frequency of the wt allele was higher than the frequency of the del allele, and this mutation polymorphism confirmed to be consistent with the Hardy-Weinberg equilibrium (p > 0.05). Further results showed that in a group of goats in the yearling period (18 months old, n = 567), this deletion variant of the PRDM6 gene was associated with heart girth (p = 0.027), cannon circumference (p = 0.008), chest depth (p = 2.10 × 10 −5 ), chest width (p = 0.004), body height (p = 0.032), body length (p = 0.044) and hip-width (p = 0.014). For adult SBWC goats (36 months old, n = 477), the effects of the 12 bp variation on growth-related traits were found to make no difference. These findings show that the 12 bp deletion within the goat PRDM6 gene plays an important role in the early growth and development of goats. Using the 12 bp mutation, breeders can quickly and effectively select excellent individual goats at an early stage.

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Bone quality changes associated with aging and disease: a review

Cited by 113 publications

References 106 publications

Obesity-Associated Hypermetabolism and Accelerated Senescence of Bone Marrow Stromal Stem Cells Suggest a Potential Mechanism for Bone Fragility

Obesity-Associated Hypermetabolism and Accelerated Senescence of Bone Marrow Stromal Stem Cells Suggest a Potential Mechanism for Bone Fragility

Novel actions of sclerostin on bone

Screening of Deletion Variants within the Goat PRDM6 Gene and Its Effects on Growth Traits

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