Associations of fat mass and fat distribution with bone mineral density in pre- and postmenopausal Chinese women

Fu, Xiaohua; Ma, Xiaoguang; Han, Lu; He, Weiling; Wang, Z.; Zhu, Shankuan

doi:10.1007/s00198-010-1210-9

Cited by 92 publications

(70 citation statements)

References 48 publications

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“…First, in contrast to prior assumptions that fat mass begets bone mass, it is now clear from epidemiological studies that obesity tracks with osteoporosis (18)(19)(20). Notably, there is a negative correlation between bone mass and fat mass in both rodents and in people [e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, there is a negative correlation between bone mass and fat mass in both rodents and in people [e.g. (18,20)]. Second, during the menopausal transition, the rapid bone loss that leads to high fracture rates accompanies the onset of visceral fat accumulation (2, 3, 6); the latter, if left unchecked, predisposes to metabolic syndrome, cardiovascular disease, and cancer.…”

Section: Discussionmentioning

confidence: 99%

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Epitope-specific monoclonal antibodies to FSHβ increase bone mass

Liu

Yuen

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Pituitary hormones have long been thought solely to regulate single targets. Challenging this paradigm, we discovered that both anterior and posterior pituitary hormones, including FSH, had other functions in physiology. We have shown that FSH regulates skeletal integrity, and, more recently, find that the inhibition of FSH reduces body fat and induces thermogenic adipose tissue. A polyclonal antibody raised against a short, receptor-binding epitope of FSHβ was found not only to rescue bone loss post-ovariectomy, but also to display marked anti-obesity and pro-beiging actions. Questioning whether a single agent could be used to treat two medical conditions of public health importance -osteoporosis and obesity -we developed two further monoclonal antibodies, Hf2 and Mf4, against computationally defined receptor-binding epitopes of FSHβ. Hf2 has already been shown to reduce body weight, fat mass and cause beiging in mice on a high-fat diet. Here, we show that Hf2, which binds mouse Fsh in immunoprecipitation assays, also increases cortical thickness and trabecular bone volume, and microstructural parameters, in sham-operated and ovariectomized mice, noted on micro-computed tomography.This effect was largely recapitulated with Mf4, which inhibited bone resorption by osteoclasts and stimulated new bone formation by osteoblasts. These effects were exerted in the absence of alterations in serum estrogen in wild type mice. We also re-confirm the existence of Fshrs in bone by documenting the specific binding of fluorescently labeled FSH, FSH-CH, in vivo. Our study provides the framework for the future development of an FSH-based therapeutic that could potentially target both bone and fat. 3 SIGNIFICANCE STATEMENTWe have addressed the question whether osteoporosis and obesity, which often occur concurrently in postmenopausal women, can be targeted by a single agent. We have shown previously that the reproductive hormone FSH, the levels of which rise after menopause, regulates both body fat and bone mass. We now show that blocking FSH action using two purposefully designed epitope-specific antibodies protects against bone loss in mice. This positions both FSH antibodies as lead molecules for clinical development towards future use in people.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Epitope-specific monoclonal antibodies to FSHβ increase bone mass

Liu

Yuen

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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“…This led to a number of studies examining the relationship between childhood obesity and bone with conflicting results, with some suggesting a positive relationship between adiposity and bone with others suggesting that excess fat is detrimental to the developing skeleton [2]. The issue of 'obesity' and the effect on the developing and adult skeleton was perhaps considered overly simplistic and subsequent work focusing on fat distribution demonstrated that, as with other metabolic conditions, it is visceral fat that appears to have a deleterious effect on the skeleton [4,5] although again not all studies in adults are in agreement with this [3]. The advent of high resolution pQCT (HRpQCT) has allowed us to examine the in-vivo relationship between fat and bone at a microstructural level in children with results demonstrating that the trabecular architecture understanding of how adipokines affect and control energy regulation resulted in a shift from initial in vitro findings attempting to elucidate the direct and systemic effects of adipokines on skeletal cells, to determine how key areas of the brain such as the hypothalamus may control the skeleton.…”

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confidence: 99%

Fat and Bone: Where are We Now?

Dimitri

Rosen

2017

Calcif Tissue Int

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is more likely altered in response to obesity [6], although from cross sectional studies in adults that may not be the case [7]. Thus, the debate relating to the impact of obesity on the skeleton lives on. In this Special Edition of 'Fat and Bone', Farr, Dimitri and Walsh address the past and current research relating to the impact of obesity on bone in children and adults.A broad range of skeletal imaging techniques have been developed to aid our understanding of skeletal mass, size and architecture and engineering models such as finite element analysis have been applied to determine bone strength. DXA remains the gold-standard clinical means of assessing skeletal parameters [8,9], although challenges in interpreting DXA in relation to body size and proportions [10], particularly in obese children [2], and tissue thickness and distribution in [11,12] have called into question the accuracy of assessing bone mass and density in relation to increasing adiposity. At the limits of in vivo scanning resolutions, HR-pQCT provides a detailed view of trabecular and cortical microarchitecture but is limited to the distal extremities and may not reflect skeletal changes elsewhere in the skeleton. In this Special Edition, the clinical considerations and diagnostic challenges in relation to skeletal imaging of children are reviewed. The challenge ahead is the development of a scanning technique that provides an accurate assessment of skeletal microarchitecture in the appendicular and axial skeleton relevant to changes in factors affecting the skeleton such as hormonal changes and physical activity in children and adults.

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“…These diseases have remained the leading causes of death globally [5]. Osteoporosis is defined as a loss of basic metals from bones which increases susceptibility to bone fractures involving the lumbar spine, femoral neck and wrist [6] [7]. This research aimed to determine the relationship between obesity and bone density in Saudi women.…”

Section: Introductionmentioning

confidence: 99%

The Relationship between Bone Mineral Density and Obesity in Women

Albrahim¹

2018

FNS

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The aim of this study was to determine the relationship between obesity and osteoporosis. A total of 30 Saudi women, 20 -50 years of age, were randomly selected. We calculated the body mass index (BMI) and determined the lumbar and femur bone mineral density using dual-energy X-ray absorptiometry (DXA). We examined the interaction between obesity and bone mineral density (BMD) using logistic regression after adjusting for age, a family history of osteoporosis, maternal fractures, smoking, and sedentary lifestyle. BMI was shown to be the most effective independent variable with respect to bone density. We evaluated the Pearson correlation coefficients of BMI, BMD of the lumbar spine, and BMD of the femoral neck with the variables of the study and found a significant (P < 0.05) correlation between obesity and osteoporosis. In conclusion, we showed that obese women (BMI > 30 kg/m 2 ) are at increased risk for osteoporosis at the femoral neck and severe osteopenia in the lumbar spine.

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Associations of fat mass and fat distribution with bone mineral density in pre- and postmenopausal Chinese women

Cited by 92 publications

References 48 publications

Epitope-specific monoclonal antibodies to FSHβ increase bone mass

Epitope-specific monoclonal antibodies to FSHβ increase bone mass

Fat and Bone: Where are We Now?

The Relationship between Bone Mineral Density and Obesity in Women

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