Faculty Opinions recommendation of Relationship between placental expression of the imprinted PHLDA2 gene, intrauterine skeletal growth and childhood bone mass.

Appreciation of the role of the gut microbiome in regulating vertebrate metabolism has exploded recently. However, the effects of gut microbiota on skeletal growth and homeostasis have only recently begun to be explored. Here, we report that colonization of sexually mature germ-free (GF) mice with conventional specific pathogen-free (SPF) gut microbiota increases both bone formation and resorption, with the net effect of colonization varying with the duration of colonization. Although colonization of adult mice acutely reduces bone mass, in long-term colonized mice, an increase in bone formation and growth plate activity predominates, resulting in equalization of bone mass and increased longitudinal and radial bone growth. Serum levels of insulin-like growth factor 1 (IGF-1), a hormone with known actions on skeletal growth, are substantially increased in response to microbial colonization, with significant increases in liver and adipose tissue IGF-1 production. Antibiotic treatment of conventional mice, in contrast, decreases serum IGF-1 and inhibits bone formation. Supplementation of antibiotic-treated mice with short-chain fatty acids (SCFAs), products of microbial metabolism, restores IGF-1 and bone mass to levels seen in nonantibiotic-treated mice. Thus, SCFA production may be one mechanism by which microbiota increase serum IGF-1. Our study demonstrates that gut microbiota provide a net anabolic stimulus to the skeleton, which is likely mediated by IGF-1. Manipulation of the microbiome or its metabolites may afford opportunities to optimize bone health and growth.

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Recovery from osteoporosis through skeletal growth: early bone mass acquisition has little effect on adult bone density

The FASEB Journal ◽

10.1096/fj.01-0640fje ◽

2002 ◽

Vol 16 (7) ◽

pp. 736-738 ◽

Cited By ~ 44

Author(s):

Rachel I. Gafni ◽

Edward F. McCarthy ◽

Tracy Hatcher ◽

Jodi L. Meyers ◽

Nozomu Inoue ◽

...

Keyword(s):

Bone Density ◽

Bone Mass ◽

Skeletal Growth ◽

Adult Bone

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Skeletal growth in school children: Maturation and bone mass

American Journal of Physical Anthropology ◽

10.1002/ajpa.1330350319 ◽

1971 ◽

Vol 35 (3) ◽

pp. 399-407 ◽

Cited By ~ 43

Author(s):

Richard B. Mazess ◽

John R. Cameron

Keyword(s):

Bone Mass ◽

School Children ◽

Skeletal Growth

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Low Calcium-Phosphate Intakes Modulate the Low-Protein Diet-Related Effect on Peak Bone Mass Acquisition: A Hormonal and Bone Strength Determinants Study in Female Growing Rats

Endocrinology ◽

10.1210/en.2014-1308 ◽

2014 ◽

Vol 155 (11) ◽

pp. 4305-4315 ◽

Cited By ~ 8

Author(s):

C. Fournier ◽

R. Rizzoli ◽

P. Ammann

Keyword(s):

Bone Mass ◽

Peak Bone Mass ◽

Mineral Content ◽

Skeletal Growth ◽

Protein Diet ◽

Low Protein Diet ◽

Hepatic Gene Expression ◽

Mrna Levels ◽

Casein Diet ◽

Low Protein

Abstract Peak bone mass acquisition is influenced by environmental factors including dietary intake. A low-protein diet delays body and skeletal growth in association with a reduction in serum IGF-1 whereas serum FGF21 is increased by selective amino acid deprivation. Calcium (Ca) and phosphorous (P) are also key nutrients for skeletal health, and inadequate intakes reduce bone mass accrual in association with calciotropic hormone modulation. Besides, the effect of calcium supplementation on bone mass in prepubertal children appears to be influenced by protein intake. To further explore the interaction of dietary protein and Ca-P intake on bone growth, 1-month-old female rats were fed with an isocaloric 10%, 7.5%, or 5% casein diet containing normal or low Ca-P for an 8-week period (6 groups). Changes in tibia geometry, mineral content, microarchitecture, strength, and intrinsic bone quality were analyzed. At the hormonal level, serum IGF-1, fibroblast growth factor 21 (FGF21), PTH, 1,25-dihydroxyvitamin D3 (calcitriol), and FGF23 were investigated as well as the Ghr hepatic gene expression. In normal dietary Ca-P conditions, bone mineral content, trabecular and cortical bone volume, and bone strength were lower in the 5% casein group in association with a decrease in serum IGF-1 and an increase in FGF21 levels. Unexpectedly, the low-Ca-P diet attenuated the 5% casein diet-related reduction of serum IGF-1 and Ghr hepatic gene expression, as well as the low-protein diet-induced decrease in bone mass and strength. However, this was associated with lower cortical bone material level properties. The low-Ca-P diet increased serum calcitriol but decreased FGF23 levels. Calcitriol levels positively correlated with Ghr hepatic mRNA levels. These results suggest that hormonal modulation in response to a low-Ca-P diet may modify the low-protein diet-induced effect on Ghr hepatic mRNA levels and consequently the impact of low protein intakes on IGF-1 circulating levels and skeletal growth.

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The role of estrogens in male skeletal development

Reproduction Fertility and Development ◽

10.1071/rd00120 ◽

2001 ◽

Vol 13 (4) ◽

pp. 253 ◽

Cited By ~ 7

Author(s):

John P. Bilezikian

Keyword(s):

Bone Mass ◽

Skeletal Development ◽

Physiological Role ◽

Skeletal Growth ◽

Growth Spurt ◽

Primary Role ◽

Estrogen Synthesis ◽

Bone Mass Accrual ◽

Knockout Technology

The developing human skeleton is known to be influenced by the presence of sex steroids. In girls, estrogens have been considered to be the dominant hormone, whereas in boys, androgens have occupied a primary physiological role in terms of bone mass accrual. Although these views are still current, recent observations made of rare defects in estrogen receptor sensitivity or estrogen synthesis have called attention to the importance of estrogens in the developing male skeleton. In these human genetic models, the affected men have demonstrated continuous linear skeletal growth, open epiphyses, lack of pubertal growth spurt, and reduced bone mass. In the example of men with aromatase deficiency, lacking estrogens from birth, administration of estrogen led to impressive increases in bone density, maturation of the skeletal growth plates, and cessation of linear growth. Animal models mimicking these human syndromes by knockout technology, have tended to support these observations. The data argue for a primary role of estrogens in the developing male skeleton, while not diminishing the important role for androgens.

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Siglec-15-targeting therapy increases bone mass in rats without impairing skeletal growth

Bone ◽

10.1016/j.bone.2018.07.026 ◽

2018 ◽

Vol 116 ◽

pp. 172-180 ◽

Cited By ~ 8

Author(s):

Dai Sato ◽

Masahiko Takahata ◽

Masahiro Ota ◽

Chie Fukuda ◽

Eisuke Tsuda ◽

...

Keyword(s):

Bone Mass ◽

Skeletal Growth ◽

Targeting Therapy

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Deficiency of Thrombospondin-4 in Mice Does Not Affect Skeletal Growth or Bone Mass Acquisition, but Causes a Transient Reduction of Articular Cartilage Thickness

PLoS ONE ◽

10.1371/journal.pone.0144272 ◽

2015 ◽

Vol 10 (12) ◽

pp. e0144272 ◽

Cited By ~ 5

Author(s):

Anke Jeschke ◽

Martin Bonitz ◽

Maciej Simon ◽

Stephanie Peters ◽

Wolfgang Baum ◽

...

Keyword(s):

Articular Cartilage ◽

Bone Mass ◽

Cartilage Thickness ◽

Skeletal Growth ◽

Thrombospondin 4

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The skeletal endocannabinoid system: clinical and experimental insights

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2015-0073 ◽

2016 ◽

Vol 27 (3) ◽

Cited By ~ 6

Author(s):

Bitya Raphael ◽

Yankel Gabet

Keyword(s):

Bone Resorption ◽

Bone Formation ◽

Bone Mass ◽

Cannabinoid Receptors ◽

Endocannabinoid System ◽

Skeletal Growth ◽

Therapeutic Approaches ◽

Skeletal Disorders ◽

Strain Dependent

AbstractRecently, there has been a rapidly growing interest in the role of cannabinoids in the regulation of skeletal remodeling and bone mass, addressed in basic, translational and clinical research. Since the first publications in 2005, there are more than 1000 publications addressing the skeletal endocannabinoid system. This review focuses on the roles of the endocannabinoid system in skeletal biology via the cannabinoid receptors CB1, CB2 and others. Endocannabinoids play important roles in bone formation, bone resorption and skeletal growth, and are sometimes age, gender, species and strain dependent. Controversies in the literature and potential therapeutic approaches targeting the endocannabinoid system in skeletal disorders are also discussed.

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