Old age causes de novo intracortical bone remodeling and porosity in mice

Piemontese, Marilina; Almeida, Maria; Robling, Alexander G.; Kim, Ha‐Neui; Xiong, Jinhu; Thostenson, Jeff D.; Weinstein, Robert S.; Manolagas, Stavros C.; O’Brien, Charles A.; Jilka, Robert L.

doi:10.1172/jci.insight.93771

Cited by 145 publications

(165 citation statements)

References 76 publications

(106 reference statements)

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“…12D and E). (22) Osteocyte senescence has also been reported by Farr and colleagues. (73) As discussed earlier, MMP13 and SDF1 are likely candidates for the loss of cortical bone caused by estrogen deficiency.…”

Section: The Contribution Of Old Osteocytes To Skeletal Involutionsupporting

confidence: 54%

“…Reproduced with permission from Piemontese and colleagues. (22) N.Oc/B.Pm = number of osteoclasts per bone perimeter.…”

Section: Figmentioning

confidence: 99%

“…Reproduced with permission from Piemontese and colleagues. (22 ) γH2AX = phosphorylated histone H2AX; GATA4 = GATA binding protein 4.…”

Section: Figmentioning

confidence: 99%

“…Reproduced with permission from Piemontese and colleagues. (22) * p < 0.05 versus 6-month-old or 7-month-old mice of the same sex and strain. …”

Section: Figmentioning

confidence: 99%

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The Quest for Osteoporosis Mechanisms and Rational Therapies: How Far We've Come, How Much Further We Need to Go

Manolagas

2018

Journal of Bone and Mineral Research

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During the last 40 years, understanding of bone biology and the pathogenesis of osteoporosis, the most common and impactful bone disease of old age, has improved dramatically thanks to basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies. Culprits of osteoporosis are no longer a matter of speculation based on in vitro observations. Instead, they can be identified and dissected at the cellular and molecular level using genetic approaches; and their effect on distinct bone envelopes and anatomic regions can be functionally assessed in vivo. The landscape of pharmacotherapies for osteoporosis has also changed profoundly with the emergence of several potent antiresorptive drugs as well as anabolic agents, displacing estrogen replacement as the treatment of choice. In spite of these major positive developments, the optimal duration of the available therapies and their long-term safety remain matters of conjecture and some concern. Moreover, antiresorptive therapies are used indiscriminately for patients of all ages on the assumption that suppressing remodeling is always beneficial for bone, but rebound remodeling upon their discontinuation suggests otherwise. In this invited perspective, I highlight the latest state of knowledge of bone-intrinsic and extrinsic mechanisms responsible for the development of osteoporosis in both sexes; differences between the mechanisms responsible for the effects of aging and estrogen deficiency; and the role of old osteocytes in the development of cortical porosity. In addition, I highlight advances toward the goal of developing drugs for several degenerative diseases of old age at once, including osteoporosis, by targeting shared mechanisms of aging. © 2018 American Society for Bone and Mineral Research.

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Section: The Contribution Of Old Osteocytes To Skeletal Involutionsupporting

confidence: 54%

“…Reproduced with permission from Piemontese and colleagues. (22) N.Oc/B.Pm = number of osteoclasts per bone perimeter.…”

Section: Figmentioning

confidence: 99%

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The Quest for Osteoporosis Mechanisms and Rational Therapies: How Far We've Come, How Much Further We Need to Go

Manolagas

2018

Journal of Bone and Mineral Research

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“…A recent study has shown that osteon size positively correlates with body mass in mammals and suggested that the lack of clear osteons in small mammals may be related to the need to avoid fractures (56). Be that as it may, dysregulation of Haversian remodeling, such as may occur with aging, remains difficult to study in rodents (57). …”

Section: Genetic Manipulation Of Animalsmentioning

confidence: 99%

Modeling Rare Bone Diseases in Animals

O’Brien

Morello

2018

Curr Osteoporos Rep

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Gene editing after creation of double-stranded breaks in chromosomal DNA is increasingly being used to modify animal genomes. Multiple tools can be used to create such breaks, with the newest ones being based on the bacterial adaptive immune system known as CRISPR/Cas. Advances in gene editing have increased the ease and speed, while reducing the cost, of creating novel animal models of disease. Gene editing has also expanded the number of animal species in which genetic modification can be performed. These changes have significantly increased the options for investigators seeking to model rare bone diseases in animals.

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Cribra orbitalia and porotic hyperostosis: A biological approach to diagnosis

Brickley

2018

American J Phys Anthropol

129

109

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ObjectivesPorotic lesions of the skull (cribra orbitalia and porotic hyperostosis) are one of the most common types of lesion identified in archaeological human bone and have also been found in hominins and non‐human primates. Because of the frequency with which such lesions are found there has been extensive debate on the possible causes and whether they are linked, with much of the debate centering on anemia. The biological approach to diagnosis in paleopathology used by Don Ortner and recently proposed more formally as a technique to facilitate diagnosis in paleopathology by Simon Mays may offer a means of answering some of the questions surrounding these lesions.Materials and MethodsA review was undertaken of biomedical information on changes in the distribution of marrow type and pattern of conversion of red and mixed marrow, and the potential for re‐conversion of yellow marrow with age. The range and type of other conditions that might result in the development of porous lesions were also considered.ResultsCombining information from the biomedical literature on marrow type and patterns of conversion with age, with careful evaluation of the type and location of porous lesions in the skull and across the rest of the skeleton will assist in suggesting a diagnosis.DiscussionA wide range of conditions can produce porous lesions in the cranial vault and the orbital roof, but due to anatomical structures and physiological factors such lesions are more likely to occur in the orbital roof. Anemia can produce lesions in both locations, but evidence of marrow expansion is required to confirm it as a cause.

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Old age causes de novo intracortical bone remodeling and porosity in mice

Abstract: Reference information: JCI Insight. 2017;2(17):e93771. https://

Cited by 145 publications

References 76 publications

The Quest for Osteoporosis Mechanisms and Rational Therapies: How Far We've Come, How Much Further We Need to Go

The Quest for Osteoporosis Mechanisms and Rational Therapies: How Far We've Come, How Much Further We Need to Go

Modeling Rare Bone Diseases in Animals

Cribra orbitalia and porotic hyperostosis: A biological approach to diagnosis

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