adiponectin AND osteoporosis(脂联素与骨质疏松症)
检索式：adiponectin AND (osteoporosis OR osteoporotic OR patients with osteoporosis) AND bone metabolic disease
篇名： N-Acetylcysteine (NAC) Ameliorates Lipid-Related Metabolic Dysfunction in Bone Marrow Stromal Cells-Derived Adipocytes.
作 者： Raffaele, M ; Barbagallo, I ; Licari, M ; Vanella, L ;等
出 处： Evid Based Complement Alternat Med.2018 ;2018 :5310961
摘要： Recent experimental data suggest that fatty acids and lipotoxicity could play a role in the initiation and evolution of metabolic bone diseases such as osteoporosis. A functional bone marrow adipose tissue (BMAT) may provide support to surrounding cells and tissues or may serve as a lipid reservoir that protects skeletal osteoblasts from lipotoxicity. The present study examined the effect of N-acetylcysteine (NAC), a powerful antioxidant and precursor of glutathione, commonly used to treat chronic obstructive pulmonary disease, on triglycerides accumulation in bone marrow stromal cells-derived adipocytes. Quantification of Oil Red O stained cells showed that lipid droplets decreased following NAC treatment. Additionally, exposure of bone marrow stromal cells (HS-5) to NAC increased adiponectin, PPARγ, HO-1, and SIRT-1 and increased beta-oxidation markers such as PPARα and PPARδ mRNA levels. As there is now substantial interest in alternative medicine, the observed therapeutic value of NAC should be taken into consideration in diabetic patients.
篇名：Lung, Fat and Bone: Increased Adiponectin Associates with the Combination of Smoking-Related Lung Disease and Osteoporosis.
作 者： Suh, YJ ; McDonald, MN ; Washko, GR ; COPDGene Investigators ;等
出 处： Chronic Obstr Pulm Dis.2018 Apr 01 ;5(2) :134-143
摘要： Background: Adiponectin has been proposed as a biomarker of disease severity and progression in chronic obstructive pulmonary disease (COPD) and associated with spirometry-defined COPD and with computed tomography (CT)-measured emphysema. Increased adiponectin plays a role in other diseases including diabetes/metabolic syndrome, cardiovascular disease and osteoporosis. Previous studies of adiponectin and COPD have not assessed the relationship of adiponectin to airway disease in smokers and have not evaluated the effect of other comorbid diseases on the relationship of adiponectin and lung disease. We postulated that adiponectin levels would associate with both airway disease and emphysema in smokers with and without COPD, and further postulated that body composition and the comorbid diseases of osteoporosis, cardiovascular disease and diabetes might influence adiponectin levels. Methods: Current and former smokers from the COPD Genetic Epidemiology study (COPDGene) (n= 424) were assigned to 4 groups based on CT lung characteristics and volumetric Bone Density (vBMD). Emphysema (% low attenuation area at -950) and airway disease (Wall area %) were used to assess smoking-related lung disease (SRLD). Group 1) Normal Lung with Normal vBMD; Group 2) Normal Lung and Osteoporosis; Group 3) SRLD with Normal vBMD; Group 4) SRLD with Osteoporosis. Cardiovascular disease (CVD), diabetes, C-reactive protein (CRP) and T-cadherin (soluble receptor for adiponectin) levels were defined for each group. Body composition was derived from chest CT. Multivariable regression assessed effects of emphysema, wall area %, bone density, comorbid diseases and other key factors on log adiponectin. Results: Group 4, SRLD with Osteoporosis, had significantly higher adiponectin levels compared to other groups and the effect persisted in adjusted models. Systemic inflammation (by CRP) was associated with SRLD in Groups 3 and 4 but not with osteoporosis alone. In regression models, lower bone density and worse emphysema were associated with higher adiponectin. Airway disease was associated with higher adiponectin levels when T-cadherin was added to the model. Male gender, greater muscle and fat were associated with lower adiponectin. Conclusions: Adiponectin is increased with both airway disease and emphysema in smokers. Bone density, and fat and muscle composition are all significant factors predicting adiponectin that should be considered when it is used as a biomarker of COPD. Increased adiponectin from chronic inflammation may play a role in the progression of bone loss in COPD and other lung diseases.
主题词：C-reactive protein ;
T cadherin ;
airway disease ;
body composition ;
bone mineral density ;
muscle area ;
smoking-related lung disease ;
subcutaneous fat area ;
systemic inflammation ;
visceral fa ;
volumetric BMD ;
篇名：Soybean-Hop Alleviates Estrogen Deficiency-Related Bone Loss and Metabolic Dysfunction in Ovariectomized Rats Fed a High-Fat Diet.
作 者： Noh, D ; Lim, Y ; Lee, H ; Kwon, O ;等
出 处： Molecules.2018 May 17 ;23(5)
摘要： Soybeans and hops have been traditionally used as a natural estrogen replacement therapy and their major active ingredients, isoflavones and prenylflavanones, are known to have estrogenic/antiestrogenic effects depending on the target organ. However, their potential benefits are still subject to controversies. The present study investigated the dual effect of soy isoflavones plus hop prenylflavanones (Soy-Hop) on bone loss and metabolic dysfunction under estrogen deficient condition. Rats were sham-operated (n = 10) or ovariectomized (OVX; n = 40) and then fed a high-fat diet (HFD) to develop hyperlipidemia in OVX rats within the experimental period of 8 weeks. The OVX/HFD rats were assigned to four groups to receive different doses of Soy-Hop (0, 30, 100, and 300 mg/kg) by oral gavage for 8 weeks. High-dose Soy-Hop significantly suppressed OVX/HFD-induced increases in food intake, body weight gain, fat mass, and circulating levels of leptin, adiponectin, LDL-cholesterol, total cholesterol, triglycerides, glucose, and insulin. High-dose Soy-Hop also attenuated OVX/HFD-induced elevation of osteocalcin, alkaline phosphatase, and CTX in plasma and RANKL/OPG gene expression ratio in femur. These findings were confirmed visually by confocal analysis of GLUT4 translocation in soleus muscle cells and micro-computed tomography scanning of the distal femoral epiphysis, respectively. These results suggest that Soy-Hop may have potential to ameliorate estrogen deficiency-related alterations in both metabolism and bone quality, at least in part, by hormonal factors secreted by adipocytes.
主题词：bone loss ;
metabolic dysfunction ;
ovariectomized rats ;
篇名：Role of Fat and Bone Biomarkers in the Relationship Between Ethnicity and Bone Mineral Density in Older Men.
作 者： Chan, GMF ; Riandini, T ; Ng, SHX ; Venkataraman, K ;等
出 处： Calcif Tissue Int.2018 01 ;102(1) :64-72
摘要： Osteoporosis is an important health issue for older adults, and has been relatively understudied in older men. This study aimed to examine ethnic differences in bone mineral density (BMD), and elucidate the role of bone turnover markers (BTMs), fat and fat biomarkers on these ethnic differences. BMD at the lumbar spine and femoral neck, marrow fat at femoral neck, visceral adipose tissue (VAT) and subcutaneous adipose tissue, bone and fat biomarkers were evaluated in 120 healthy men aged ≥ 60 years. Indians had higher BMD values compared to Chinese at the lumbar spine (β = 20.336, SE = 4.749, p < 0.001) and the femoral neck (e β = 1.105, SE = 0.032, p < 0.001), after adjusting for BTMs, fat composition and lifestyle choices. Marrow fat, VAT and adiponectin were independent predictors of BMD. However, these factors did not explain the lower BMD observed in older Chinese men. Our findings suggest that older Chinese men are at significant risk of osteoporotic fractures due to lower BMD. Fat appears to be a key factor associated with lower BMD, and warrants further longitudinal studies to elucidate the complex interactions between adipose tissue and bone strength.
主题词： Adipokines ; Adiposity ; Bone biomarkers ; Bone mineral density ; Osteoporosis ;
篇名： Bone structural changes after gastric bypass surgery evaluated by HR-pQCT: a two-year longitudinal study.
作 者： Shanbhogue, VV ; St?ving, RK ; Frederiksen, KH ; Hansen, S ;等
出 处： Eur J Endocrinol.2017 Jun ;176(6) :685-693
摘要： OBJECTIVE, DESIGN AND
METHODS:Roux-en-Y gastric bypass (RYGB) has proved successful in attaining sustained weight loss but may lead to metabolic bone disease. To assess impact on bone mass and structure, we measured a real bone mineral density at the hip and spine by dual-energy X-ray absorptiometry, and volumetric BMD (vBMD) and bone microarchitecture at the distal radius and tibia by high-resolution peripheral quantitative CT in 25 morbidly obese subjects (15 females, 10 males) at 0, 12 and 24 months after RYGB. Bone turnover markers (BTMs), calciotropic and gut hormones and adipokines were measured at the same time points.
RESULTS:After a 24.1% mean weight loss from baseline to month 12 (P?<?0.001), body weight plateaued from month 12 to 24 (-0.9%, P?=?0.50). However, cortical and trabecular vBMD and microarchitecture deteriorated through the 24 months, such that there was a 5 and 7% reduction in estimated bone strength at the radius and tibia respectively (both P?<?0.001). The declines observed in the first 12 months were matched or exceeded by declines in the 12- to 24-month period. While a significant increase in BTMs and decrease in leptin and insulin were seen at 24 months, these changes were maximal at month 12 and stabilized from month 12 to 24.
CONCLUSIONS:Despite weight stabilization and maintenance of metabolic parameters, bone loss and deterioration in bone strength continued and were substantial in the second year. The clinical importance of these changes in terms of increased risk of developing osteoporosis and fragility fractures remain an important concern.
主题词：Absorptiometry, Photon 【吸收测定法, 光子】
Bone Density 【骨密度】
Bone Diseases, Metabolic 【骨疾病, 代谢性】
Bone Diseases, Metabolic 【骨疾病, 代谢性】
Bone Remodeling 【骨重建】
Gastric Bypass/adverse effects* 【胃旁路术/副作用*】
Hip Joint/diagnostic imaging 【髋关节/影像诊断】
Longitudinal Studies 【纵向研究】
篇名：Association between omentin-1, adiponectin and bone health under consideration of osteoprotegerin as possible mediator.
作 者： Menzel, J ; Di Giuseppe, R ; Biemann, R ; Weikert, C ;等
出 处： J Endocrinol Invest.2016 Nov ;39(11) :1347-1355
摘要： PURPOSE:Several studies implicated a crosstalk between bone and fat in the pathogenesis of osteoporosis. Few studies indicated an association between adiponectin and omentin-1 on the bone remodeling process and bone mineral density, and suggested osteoprotegerin (OPG) as a mediator of this relationship. However, only limited evidence on this relationship is available in humans. Therefore, this study aimed to investigate the association between omentin-1, adiponectin and broadband ultrasound attenuation (BUA) in peri-/premenopausal and postmenopausal women, and to assess the role of OPG as a possible mediator.
METHODS:Data from the German population-based EPIC-Potsdam cohort comprising 637 women were analyzed. Multivariable-adjusted ANCOVA including age, BMI, waist circumference, smoking status, education, physical activity, adiponectin or omentin-1 and hormone use was used to investigate potential relationships between the adipokines and BUA levels. A mediation analysis assessed the mediating effect of OPG on the association of BUA and omentin-1 levels.
RESULTS:Peri-/premenopausal women had higher BUA levels (112.5 ± 10.1 dB/MHz), compared to postmenopausal women (106.3 ± 10.0 dB/MHz). In peri-/premenopausal women neither adiponectin nor omentin-1 was significantly associated with BUA. In postmenopausal women, adiponectin was not associated with BUA, but 10 % increase in the omentin-1 concentration was significantly associated with 0.44 dB/MHz lower BUA levels (p = 0.01). Omentin-1 was positively associated with OPG (p = 0.02); however, OPG was not significantly related to BUA (p = 0.62).
CONCLUSION:Our study provides evidence for an inverse association between circulating omentin-1 and BUA levels in postmenopausal women. However, the present findings do not support a mediating effect of OPG in the adipose tissue-bone pathway.
主题词：Bone mineral density ;
Broadband ultrasound attenuation ;
Osteoclastogenesis inhibitory factor ;
篇名：Effect of Two-Year Caloric Restriction on Bone Metabolism and Bone Mineral Density in Non-Obese Younger Adults: A Randomized Clinical Trial.
作 者： Villareal, DT ; Fontana, L ; Das, SK ; CALERIE Study Group ;等
出 处： J Bone Miner Res.2016 Jan ;31(1) :40-51
摘要： Although caloric restriction (CR) could delay biologic aging in humans, it is unclear if this would occur at the cost of significant bone loss. We evaluated the effect of prolonged CR on bone metabolism and bone mineral density (BMD) in healthy younger adults. Two-hundred eighteen non-obese (body mass index [BMI] 25.1?±?1.7?kg/m(2) ), younger (age 37.9?±?7.2 years) adults were randomly assigned to 25% CR (CR group, n?=?143) or ad libitum (AL group, n?=?75) for 2 years. Main outcomes were BMD and markers of bone turnover. Other outcomes included body composition, bone-active hormones, nutrient intake, and physical activity. Body weight (-7.5?±?0.4 versus 0.1?±?0.5?kg), fat mass (-5.3?±?0.3 versus 0.4?±?0.4?kg), and fat-free mass (-2.2?±?0.2 versus -0.2?±?0.2?kg) decreased in the CR group compared with AL (all between group p < 0.001). Compared with AL, the CR group had greater changes in BMD at 24 months: lumbar spine (-0.013?±?0.003 versus 0.007?±?0.004?g/cm(2) ; p < 0.001), total hip (-0.017?±?0.002 versus 0.001?±?0.003?g/cm(2) ; p < 0.001), and femoral neck (-0.015?±?0.003 versus -0.005?±?0.004?g/cm(2) ; p?=?0.03). Changes in bone markers were greater at 12 months for C-telopeptide (0.098?±?0.012 versus 0.025?±?0.015?μg/L; p < 0.001), tartrate-resistant acid phosphatase (0.4?±?0.1 versus 0.2?±?0.1?U/L; p?=?0.004), and bone-specific alkaline phosphatase (BSAP) (-1.4?±?0.4 versus -0.3?±?0.5?U/L; p?=?0.047) but not procollagen type 1 N-propeptide; at 24 months, only BSAP differed between groups (-1.5?±?0.4 versus 0.9?±?0.6?U/L; p?=?0.001). The CR group had larger increases in 25-hydroxyvitamin D, cortisol, and adiponectin and decreases in leptin and insulin compared with AL. However, parathyroid hormone and IGF-1 levels did not differ between groups. The CR group also had lower levels of physical activity. Multiple regression analyses revealed that body composition, hormones, nutrients, and physical activity changes explained ～31% of the variance in BMD and bone marker changes in the CR group. Therefore, bone loss at clinically important sites of osteoporotic fractures represents a potential limitation of prolonged CR for extending life span. Further long-term studies are needed to determine if CR-induced bone loss in healthy adults contributes to fracture risk and if bone loss can be prevented with exercise.
主题词：BONE-FAT INTERACTIONS ;
BONE-MUSCLE INTERACTIONS ;
FRACTURE PREVENTION ;
篇名：Adiponectin exacerbates collagen-induced arthritis via enhancing Th17 response and prompting RANKL expression.
作 者： Sun, X ; Feng, X ; Tan, W ; Zhang, M ;等
出 处： Sci Rep.2015 Jun 11 ;5 :11296
摘要： We previously reported adiponectin (AD) is highly expressed in the inflamed synovial joint tissue and correlates closely with progressive bone erosion in Rheumatoid arthritis (RA) patients. Here, we investigate the role of adiponectin in regulating Th17 response and the expression of receptor activator of nuclear factor-κB ligand (RANKL) in mice with CIA mice by intraarticularly injection of adiponectin into knee joints on day 17, day 20 and day 23 post first collagen immunization. The increased adiponectin expression was found in inflamed joint tissue of collagen-induced arthritis (CIA) mice. Adiponectin injection resulted in an earlier onset of arthritis, an aggravated arthritic progression, more severe synovial hyperplasia, bone erosion and osteoporosis in CIA mice. CD4(+)IL-17(+) Th17 cells, IL-17 mRNA and RANKL mRNA expression were markedly increased in the joint tissue of adiponectin treated CIA mice. Moreover, adiponectin treatment markedly enhanced Th17 cell generation from naive CD4(+) T cells in vitro, which accompanied by the high expression of Th17 transcription factor ROR-γt, and Th17 cytokine genes included IL-22 and IL-23. This study reveals a novel effect of adiponectin in exacerbating CIA progression by enhancing Th17 cell response and RANKL expression.
Arthritis, Experimental 【关节炎】
Cells, Cultured 【细胞, 培养的】
Disease Models, Animal 【疾病模型, 动物】
Knee Joint 【膝关节】
Nuclear Receptor Subfamily 1, Group F, Member 3/biosynthesis 【细胞核受体，亚科1，F组，成员3/生物合成】
RANK Ligand/biosynthesis* 【RANK配体/生物合成*】
RANK Ligand/genetics 【RANK配体/遗传学】
RNA, Messenger/biosynthesis 【RNA, 信使/生物合成】
Synovial Membrane/physiopathology 【滑膜/病理生理学】
Th17 Cells/immunology* 【Th17细胞/免疫学*】
篇名： Associations among endocrine, inflammatory, and bone markers, body composition and weight loss induced bone loss.
作 者： Labouesse, MA ; Gertz, ER ; Piccolo, BD ; Van Loan, MD ;等
出 处： Bone.2014 Jul ;64 :138-46
摘要： INTRODUCTION:Weight loss reduces co-morbidities of obesity, but decreases bone mass. PURPOSE:Our aims were to (1) determine if adequate dairy intake attenuates weight loss-induced bone loss; (2) evaluate the associations of endocrine, inflammatory and bone markers, anthropometric and other parameters to bone mineral density and content (BMD, BMC) pre- and post-weight loss; and (3) model the contribution of these variables to post weight-loss BMD and BMC.
METHODS:Overweight/obese women (BMI: 28-37 kg/m2) were enrolled in an energy reduced (-500 kcal/d; -2092 kJ/d) diet with adequate dairy (AD: 3-4 servings/d; n=25, 32.2±8.8 years) or low dairy (LD: ≤1 serving/d; n=26, 31.7±8.4 years). BMD, BMC and body composition were measured by DXA. Bone markers (CTX, PYD, BAP, OC), endocrine (PTH, vitamin D, leptin, adiponectin, ghrelin, amylin, insulin, GLP-1, PAI-1, HOMA) and inflammatory markers (CRP, IL1-β, IL-6, IL-8, TNF-α, cortisol) were measured in serum or plasma. PA was assessed by accelerometry.
RESULTS:Following weight loss, AD intake resulted in significantly greater (p=0.004) lumbar spine BMD and serum osteocalcin (p=0.004) concentration compared to LD. Pre- and post-body fat was negatively associated with hip and lumbar spine BMC (r=-0.28, p=0.04 to -0.45, p=0.001). Of note were the significant negative associations among bone markers and IL-1β, TNFα and CRP ranging from r = -0.29 (p=0.04) to r = -0.34 (p=0.01); magnitude of associations did not change with weight loss. Adiponectin was negatively related to change in osteocalcin. Factor analysis resulted in 8 pre- and post-weight loss factors. Pre-weight loss factors accounted for 13.7% of the total variance in pre-weight loss hip BMD; post-weight loss factors explained 19.6% of the total variance in post-weight loss hip BMD. None of the factors contributed to the variance in lumbar spine BMD.
CONCLUSION:AD during weight loss resulted in higher lumbar spine BMD and osteocalcin compared to LD. Significant negative associations were observed between bone and inflammatory markers suggesting that inflammation suppresses bone metabolism. Using factor analysis, 19.6% of total variance in post-weight loss hip BMD could be explained by endocrine, immune, and anthropometric variables, but not lumbar spine BMD.
Endocrine and inflammatory markers ;
Physical activity ;
Weight loss induced bone loss ;
篇名： Adiponectin as a biomarker of osteoporosis in postmenopausal women: controversies.
作 者： Lubkowska, A ; Dobek, A ; Mieszkowski, J ; Chlubek, D ;等
出 处： Dis Markers.2014 ;2014 :975178
摘要： The literature reports indicating a link between plasma levels of adiponectin and body fat, bone mineral density, sex hormones, and peri- and postmenopausal changes, draw attention to the possible use of adiponectin as an indicator of osteoporotic changes, suggesting that adiponectin may also modulate bone metabolism. In this study, we attempted to analyze the available in vitro and in vivo results which could verify this hypothesis. Although several studies have shown that adiponectin has an adverse effect on bone mass, mainly by intensifying resorption, this peptide has also been demonstrated to increase the proliferation and differentiation of osteoblasts, inhibit the activity of osteoclasts, and reduce bone resorption. There are still many ambiguities; for example, it can be assumed that concentrations of adiponectin in plasma do not satisfactorily reflect its production by adipose tissue, as well as conflicting in vitro and in vivo results. It seems that the potential benefit in the treatment of patients with osteoporosis associated with the pharmacological regulation of adiponectin is controversial.
Adipose Tissue, White/metabolism 【脂肪组织,白色/代谢】
Case-Control Studies 【病例对照研究】
Energy Metabolism 【能量代谢】
Osteoporosis, Postmenopausal/blood* 【骨质疏松, 绝经后/血液*】
篇名： Deficiency of adiponectin protects against ovariectomy-induced osteoporosis in mice.
作 者： Wang, F ; Wang, PX ; Wu, XL ; Pang, XF ;等
出 处： PLoS One.2013 ;8(7) :e68497
摘要： Adipokine adiponectin (APN) has been recently reported to play a role in regulating bone mineral density (BMD). To explore the mechanism by which APN affects BMD, we investigated BMD and biomechanical strength properties of the femur and vertebra in sham-operated (Sham) and ovariectomized (OVX) APN knockout (KO) mice as compared to their operated wild-type (WT) littermates. The results show that APN deficiency has no effect on BMD but induces increased ALP activity and osteoclast cell number. While OVX indeed leads to significant bone loss in both femora and vertebras of WT mice with comparable osteogenic activity and a significant increase in osteoclast cell number when compared to that of sham control. However, no differences in BMD, ALP activity and osteoclast cell number were found between Sham and OVX mice deficient for APN. Further studies using bone marrow derived mesenchymal stem cells (MSCs) demonstrate an enhanced osteogenic differentiation and extracellular matrix calcification in APN KO mice. The possible mechanism for APN deletion induced acceleration of osteogenesis could involve increased proliferation of MSCs and higher expression of Runx2 and Osterix genes. These findings indicate that APN deficiency can protect against OVX-induced osteoporosis in mice, suggesting a potential role of APN in regulating the balance of bone formation and bone resorption, especially in the development of post-menopausal osteoporosis.
主题词：Absorptiometry, Photon 【吸收测定法, 光子】
Alkaline Phosphatase 【碱性磷酸酶】
Bone Density 【骨密度】
Bone Marrow Cells 【骨髓细胞】
Cell Differentiation 【细胞分化】
Cell Proliferation 【细胞增殖】
篇名：Adiponectin is a candidate biomarker of lower extremity bone density in men with chronic spinal cord injury.
作 者： Doherty, AL ; Battaglino, RA ; Donovan, J ; Morse, LR ;等
出 处： J Bone Miner Res.2014 Jan ;29(1) :251-9
摘要： Adipose tissue is a major regulator of bone metabolism and in the general population obesity is associated with greater bone mineral density (BMD). However, bone-fat interactions are multifactorial, and may involve pathways that influence both bone formation and resorption with competing effects on the skeleton. One such pathway involves adipocyte production of adipokines that regulate bone metabolism. In this study we determined the association between BMD, walking status, and circulating adipokines (adiponectin and leptin) in 149 men with chronic spinal cord injury (SCI). Although adipokine levels did not vary significantly based on walking status, there was a significant inverse association between adiponectin and BMD in wheelchair users independent of body composition. We found no association between adiponectin and BMD in the walkers and no association between leptin and BMD in either group. These findings suggest that for subjects with chronic SCI, walking may mitigate the effect of adiponectin mediated bone loss. For wheelchair users, adipose-derived adiponectin may contribute to SCI-induced osteoporosis because the osteoprotective benefits of obesity appear to require mechanical loading during ambulation.
主题词： ADIPONECTIN ;
REHABILITATION MEDICINE ;
SPINAL CORD INJURY ;
篇名： Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin: parathyroid hormone (1-84) or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study).
作 者： Schafer, AL ; Sellmeyer, DE ; Schwartz, AV ; Black, DM ;等
出 处： J Clin Endocrinol Metab.2011 Dec ;96(12) :E1982-9
摘要： CONTEXT:The undercarboxylated form of the osteoblast-secreted protein osteocalcin has favorable effects on fat and glucose metabolism in mice. In human subjects, cross-sectional studies suggest a relevant association.
OBJECTIVE:We investigated whether changes in undercarboxylated osteocalcin (ucOC) during osteoporosis treatment are associated with changes in metabolic parameters. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS:We measured ucOC in sera from a subset of osteoporotic postmenopausal women who were treated with PTH(1-84) or alendronate (n = 64 and n = 33, respectively) during the Parathyroid Hormone and Alendronate study. MAIN OUTCOME MEASURES:We measured serum adiponectin, leptin, and insulin and analyzed existing data on body weight, fat mass, and serum glucose concentration. Three-month changes in ucOC levels were evaluated as predictors of 12-month changes in indices of fat and glucose metabolism.
RESULTS:ucOC levels increased with PTH(1-84) and decreased with alendronate administration (P ≤ 0.01 for both treatment groups). Three-month change in ucOC was inversely associated with 12-month changes in body weight (standardized β = -0.25, P = 0.04) and fat mass (β = -0.23, P = 0.06), after adjustment for the treatment group. Three-month change in ucOC was positively associated with a 12-month change in adiponectin (β = 0.30, P = 0.01), independent of change in fat mass. There were no interactions between treatment and change in ucOC on changes in weight, fat mass, or adiponectin.
CONCLUSIONS:PTH(1-84) increases and alendronate decreases ucOC levels. Changes in ucOC induced by PTH(1-84) and alendronate are associated with changes in metabolic indices. These associations are consistent with observations from animal models and support a role for ucOC in the skeletal regulation of energy metabolism in humans.
Body Weight 【体重】
Bone Density 【骨密度】
Bone Density Conservation Agents 【骨密度保护剂】
Double-Blind Method 【双盲法】
Middle Aged 【中年人】
Osteoporosis, Postmenopausal 【骨质疏松, 绝经后】
Parathyroid Hormone 【甲状旁腺素】
篇名：Zinc finger protein 467 is a novel regulator of osteoblast and adipocyte commitment.
作 者： Quach, JM ; Walker, EC ; Allan, E ; Martin, TJ ;等
出 处： J Biol Chem.2011 Feb 11 ;286(6) :4186-98
摘要： Osteoblasts and adipocytes are derived from common mesenchymal progenitor cells. The bone loss of osteoporosis is associated with altered progenitor differentiation from an osteoblastic to an adipocytic lineage. cDNA microarrays and quantitative real-time PCR (Q-PCR) were carried out in a differentiating mouse stromal osteoblastic cell line, Kusa 4b10, to identify gene targets of factors that stimulate osteoblast differentiation including parathyroid hormone (PTH) and gp130-binding cytokines, oncostatin M (OSM) and cardiotrophin-1 (CT-1). Zinc finger protein 467 (Zfp467) was rapidly down-regulated by PTH, OSM, and CT-1. Retroviral overexpression and RNA interference for Zfp467 in mouse stromal cells showed that this factor stimulated adipocyte formation and inhibited osteoblast commitment compared with controls. Regulation of adipocyte markers, including peroxisome proliferator-activated receptor (PPAR) γ, C/EBPα, adiponectin, and resistin, and late osteoblast/osteocyte markers (osteocalcin and sclerostin) by Zfp467 was confirmed by Q-PCR. Intra-tibial injection of calvarial cells transduced with retroviral Zfp467 doubled the number of marrow adipocytes in C57Bl/6 mice compared with vector control-transduced cells, providing in vivo confirmation of a pro-adipogenic role of Zfp467. Furthermore, Zfp467 transactivated a PPAR-response element reporter construct and recruited a histone deacetylase complex. Thus Zfp467 is a novel co-factor that promotes adipocyte differentiation and suppresses osteoblast differentiation. This has relevance to therapeutic interventions in osteoporosis, including PTH-based therapies currently available, and may be of relevance for the use of adipose-derived stem cells for tissue engineering.
Antigens, Differentiation 【抗原, 分化】
Cell Differentiation* 【细胞分化*】
Nuclear Proteins 【核蛋白质类】
Response Elements* 【反应元件*】
Transcription Factors 【转录因子】
Transcriptional Activation* 【转录激活*】
Transduction, Genetic 【转导, 遗传】
篇名：Review of the Literature Examining the Association of Serum Uric Acid with Osteoporosis and Mechanistic Insights into Its Effect on Bone Metabolism.
作 者： Kaushal, N ; Vohora, D ; Jalali, RK ; Jha, S ;等
出 处： Endocr Metab Immune Disord Drug Targets.2019 ;19(3) :259-273
摘要： BACKGROUND AND
OBJECTIVE:Osteoporosis is a common bone disorder that increases susceptibility to fragility bone fractures. The clinical and public health repercussions of osteoporosis are huge due to the morbidity, mortality, and cost of medical care linked with fragility fractures. Clinical assessment of osteoporotic risk factors can help to identify candidates at an early stage that will benefit from medical intervention and potentially lowering the morbidity and mortality seen with fractures and complications. Given this, research is ongoing to evaluate the association of osteoporosis with some novel or less well-studied risk factors/bio-markers such as uric acid (UA).
DISCUSSION:Uric acid's antioxidant activity has been proposed to be one of the factors responsible for increasing longevity and lowering rates of age-related cancers during primate evolution, the level of which increased markedly due to loss of uricase enzyme activity (mutational silencing). Accumulated evidence shows that oxidative stress is the fundamental mechanism of age-related bone loss and acts via enhancing osteoclastic activity and increasing bone resorption. Antioxidant substances such as ascorbic acid scavenge free radicals and are positively related to bone health. Thus, it is hypothesized that uric acid holds bone-protective potential owing to its potent antioxidative property. Several correlation studies have been conducted globally to investigate the relationship between serum uric acid with bone mineral density and osteoporosis. Few pre-clinical studies have tried to investigate the interaction between uric acid and bone mineral density and reported important role played via Runt-related transcription factor 2 (RUNX2)/core-binding factor subunit alpha-1 (CBF-alpha-1), Wingless-related integration site (Wnt)-3a/β-catenin signaling pathway and 11β Hydroxysteroid Dehydrogenase type 1.
CONCLUSION:In this review, the authors provided a comprehensive summary of the literature related to association studies reported in humans as well work done until date to understand the potential cellular and molecular mechanisms that interplay between uric acid and bone metabolism.
主题词：Uric acid ;
Wnt-3a/β-catenin signaling pathway ;
bone mineral density ;
篇名：Novel insights into the relationship between diabetes and osteoporosis.
作 者： de Paula, FJ ; Horowitz, MC ; Rosen, CJ ;
出 处： Diabetes Metab Res Rev.2010 Nov ;26(8) :622-30
摘要： Only three decades ago adipose tissue was considered inert, with little relationship to insulin resistance. Similarly, bone has long been thought of purely in its structural context. In the last decade, emerging evidence has revealed important endocrine roles for both bone and adipose tissue. The interaction between these two tissues is remarkable. Bone marrow mesenchymal stem cells give rise to both osteoblasts and adipocytes. Leptin and adiponectin, two adipokines secreted by fat tissue, control energy homeostasis, but also have complex actions on the skeleton. In turn, the activities of bone cells are not limited to their bone remodelling activities but also to modulation of adipose cell sensitivity and insulin secretion. This review will discuss these new insights linking bone remodelling to the control of fat metabolism and the association between diabetes mellitus and osteoporosis.
主题词：Adipose Tissue/metabolism 【脂肪组织/代谢】
Bone Remodeling 【骨重建】
Bone and Bones 【骨和骨组织】
Diabetes Mellitus/physiopathology* 【糖尿病/病理生理学*】
Energy Metabolism 【能量代谢】 Adipose Tissue/metabolism 【脂肪组织/代谢】
Insulin Resistance 【胰岛素抗药性】
Insulin-Like Growth Factor I/metabolism 【胰岛素样生长因子Ⅰ/代谢】
篇名： The role of body mass index, insulin, and adiponectin in the relation between fat distribution and bone mineral density.
作 者： Zillikens, MC ; Uitterlinden, AG ; van Leeuwen, JP ; Rivadeneira, F ;等
出 处： Calcif Tissue Int.2010 Feb ;86(2) :116-25
摘要： Despite the positive association between body mass index (BMI) and bone mineral density (BMD) and content (BMC), the role of fat distribution in BMD/BMC remains unclear. We examined relationships between BMD/BMC and various measurements of fat distribution and studied the role of BMI, insulin, and adiponectin in these relations. Using a cross-sectional investigation of 2631 participants from the Erasmus Rucphen Family study, we studied associations between BMD (using dual-energy X-ray absorptiometry (DXA]) at the hip, lumbar spine, total body (BMD and BMC), and fat distribution by the waist-to-hip ratio (WHR), waist-to-thigh ratio (WTR), and DXA-based trunk-to-leg fat ratio and android-to-gynoid fat ratio. Analyses were stratified by gender and median age (48.0 years in women and 49.2 years in men) and were performed with and without adjustment for BMI, fasting insulin, and adiponectin. Using linear regression (adjusting for age, height, smoking, and use of alcohol), most relationships between fat distribution and BMD and BMC were positive, except for WTR. After BMI adjustment, most correlations were negative except for trunk-to-leg fat ratio in both genders. No consistent influence of age or menopausal status was found. Insulin and adiponectin levels did not explain either positive or negative associations. In conclusion, positive associations between android fat distribution and BMD/BMC are explained by higher BMI but not by higher insulin and/or lower adiponectin levels. Inverse associations after adjustment for BMI suggest that android fat deposition as measured by the WHR, WTR, and DXA-based android-to-gynoid fat ratio is not beneficial and possibly even deleterious for bone.
主题词：Absorptiometry, Photon 【吸收测定法, 光子】
Adipose Tissue 【脂肪组织】
Body Mass Index* 【人体质量指数*】
Bone and Bones 【骨和骨组织】
篇名： Relationship between osteoporosis and adipose tissue leptin and osteoprotegerin in patients with chronic obstructive pulmonary disease.
作 者： Pobeha, P ; Ukropec, J ; Skyba, P ; Tkacova, R ;等
出 处： Bone.2011 May 01 ;48(5) :1008-14
摘要： INTRODUCTION:The role of fat-bone interactions in the pathogenesis of osteoporosis in chronic obstructive pulmonary disease (COPD) is poorly understood. Our aim was to investigate expressions of leptin and osteoprotegerin (OPG) in the adipose tissue, and their relationships to osteoporosis in patients with COPD.
METHODS:In 39 patients with stable COPD, bone mineral density (BMD) and body composition was assessed by Dual Energy X-Ray Absorptiometry. Serum leptin was determined by the enzyme-linked immunosorbent assay, and bone turnover markers osteocalcin and β-crosslaps by the electrochemiluminiscence immunoassays. Subcutaneous adipose tissue samples were analyzed using real-time PCR.
RESULTS:Twenty-one patients without, and 18 with osteoporosis were enrolled (35 men; age 62.2 ± 7.3years). Compared to patients without osteoporosis, those with the disease had significantly lower serum levels and adipose tissue expressions of leptin, in association with increased serum β-crosslaps (p=0.028, p=0.034, p=0.022, respectively). Log adipose tissue leptin was inversely related to serum β-crosslaps (p=0.015), and directly to serum leptin (p<0.001) and to the total, femoral, and lumbar BMD and T-score (p<0.02 for all relationships). Adipose tissue OPG expression was related to all variables of bone density except for lumbar BMD and T-score (p<0.05 for all relationships). Log adipose tissue leptin and OPG expressions predicted femoral T-score independently of age, gender and pulmonary function (p<0.001, adjusted R(2)=0.383; p=0.008, adjusted R(2)=0.301, respectively). Introducing body mass (or fat mass) index into these models eliminated independent predictive value of leptin and OPG expressions.
CONCLUSION:Our results suggest that adipose tissue leptin and OPG expressions are related to osteoporosis in patients with COPD, and appear to act as mediators between fat mass and BMD.
主题词：Adipose Tissue/metabolism 【脂肪组织/代谢】
Bone Density 【骨密度】
Bone Remodeling 【骨重建】
Pulmonary Disease, Chronic Obstructive 【肺疾病, 慢性阻塞性】
Respiratory Function Tests 【呼吸功能试验】
篇名： Concentration of adipogenic and proinflammatory cytokines in the bone marrow supernatant fluid of osteoporotic women.
作 者： Pino, AM ; Ríos, S ; Astudillo, P ; Rodríguez, JP ;等
出 处： J Bone Miner Res.2010 Mar ;25(3) :492-8
摘要： Osteoporosis is characterized by low bone mass, microarchitectural deterioration of bone tissue leading to increased bone fragility, and a resulting susceptibility to fractures. Distinctive environmental bone marrow conditions appear to support the development and maintenance of the unbalance between bone resorption and bone formation; these complex bone marrow circumstances would be reflected in the fluid surrounding bone marrow cells. The content of regulatory molecules in the extracellular fluid from the human bone marrow is practically unknown. Since the content of cytokines such as adiponectin, leptin, osteoprogeterin (OPG), soluble receptor activator of nuclear factor kappaB ligand (s-RANKL), tumor necrosis factor alpha, and interleukin 6 (IL-6) may elicit conditions promoting or sustaining osteoporosis, in this work we compared the concentrations of the above-mentioned cytokines and also the level of the soluble receptors for both IL-6 and leptin in the extracellular fluid from the bone marrow of nonosteoporotic and osteoporotic human donors. A supernatant fluid (bone marrow supernatant fluid [BMSF]) was obtained after spinning the aspirated bone marrow samples; donors were classified as nonosteoporotic or osteoporotic after dual-energy X-ray absorptiometry (DXA) measuring. Specific commercially available kits were used for all measurements. The cytokines' concentration in BMSF showed differently among nonosteoporotic and osteoporotic women; this last group was characterized by higher content of proinflammatory and adipogenic cytokines. Also, osteoporotic BMSF differentiated by decreased leptin bioavailability, suggesting that insufficient leptin action may distinguish the osteoporotic bone marrow.
主题词：Absorptiometry, Photon 【吸收测定法, 光子】
Adipose Tissue/immunology* 【脂肪组织/免疫学*】
Bone Marrow 【骨髓】
Bone Resorption/blood* 【骨质吸收/血液*】
Osteoporosis, Postmenopausal/immunology* 【骨质疏松, 绝经后/免疫学*】
篇名：The relationship between serum adiponectin level and anthropometry, bone mass, osteoporotic fracture risk in postmenopausal women.
作 者： Ozkurt, B ; Ozkurt, ZN ; Altay, M ; Tabak, Y ;等
出 处： Eklem Hastalik Cerrahisi.2009 ;20(2) :78-84
摘要： OBJECTIVES:The aim of the present study was to evaluate the possible correlation between bone mass and serum adiponectin levels, and the correlation between adiponectin levels and osteoporotic fracture risk in a prospective clinical trial. PATIENTS AND
METHODS:Postmenopausal non-diabetic 105 women (mean age 63.4+/-8.1; range 52 to 64 years) with hip fracture were evaluated. Of these 105 patients, 46 had trochanteric fractures, 24 had subtrochanteric fractures and 35 had femoral neck fractures. Anthropometric measurements were performed. Serum adiponectin level was measured by means of ELISA. Total bone mineral density and bone mineral content of lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry (DEXA).
RESULTS:Lumbar bone mineral density and proximal femoral bone mineral density were not correlated with serum adiponectin levels. Serum adiponectin level was not found to have any significant effect on bone mass. Serum adiponectin levels were not significantly different between the patients with osteoporotic fractures and those with non-osteoporotic fractures.
CONCLUSION:Our study showed that serum adiponectin level is not associated with bone mass and osteoporotic fracture risk. Investigation of local adiponectin levels in bony tissue is needed to clarify the possible relation between adiponectin and bone mass, and risk of fractures associated with osteoporosis.
Bone Density* 【骨密度*】
Fractures, Bone/epidemiology* 【骨折/流行病学*】
Hip Fractures/blood* 【髋骨折/血液*】
Middle Aged 【中年人】
篇名：Sex differences in the association between adiponectin and BMD, bone loss, and fractures: the Rancho Bernardo study.
作 者： Araneta, MR ; von Mühlen, D ; Barrett-Connor, E ;
出 处： J Bone Miner Res.2009 Dec ;24(12) :2016-22
摘要： We evaluated sex differences in the prospective association between adiponectin with BMD, bone loss, and fractures. Adiponectin, an adipose-derived protein with insulin-sensitizing properties, is also expressed in bone-forming cells. Conflicting results and sex differences in the adiponectin-BMD association have been reported in cross-sectional studies. Serum adiponectin was measured in fasting blood samples obtained in 1984-1987 in 447 postmenopausal women (mean age: 76 yr) and 484 men (mean age: 75 yr). Four years later, BMD was measured at the midshaft radius by single photon absorptiometry and at the femoral neck, total hip, and lumbar spine by DXA. In 1992-1996, axial BMD was remeasured in 261 women and 264 men. Multivariable analysis adjusted for age, weight, calcium intake, type 2 diabetes, alcohol intake, and exercise. Among women, adiponectin was inversely associated with BMD at the femoral neck (beta = -0.002, p = 0.007), total hip (beta = -0.002, p = 0.009), lumbar spine (beta = -0.003, p = 0.008), and midshaft radius (beta = -0.002, p = 0.01) after 4.4 yr and at the femoral neck and total hip 8.6 yr later. Among men, adiponectin was inversely associated with BMD at the femoral neck, (beta = -0.002, p = 0.03), total hip (beta = -0.004, p < 0.001), and midshaft radius (beta = -0.003, p < 0.001) after 4.4 yr and at the hip 8.6 yr later. Adiponectin was not associated with 4-yr bone loss in either sex but was associated with vertebral fractures (adjusted OR: 1.13; 95% CI: 1.08-1.23; p = 0.009) among men only. Adiponectin was inversely associated with BMD; however, sex differences were observed by anatomical site and with regards to vertebral fractures.
Bone Density* 【骨密度*】
Fractures, Bone 【骨折】
Longitudinal Studies 【纵向研究】
Sex Factors* 【性别因素*】
篇名：Correlation of obesity and osteoporosis: effect of fat mass on the determination of osteoporosis.
作 者： Zhao, LJ ; Jiang, H ; Papasian, CJ ; Deng, HW ;等
出 处： J Bone Miner Res.2008 Jan ;23(1) :17-29
摘要： It was previously believed that obesity and osteoporosis were two unrelated diseases, but recent studies have shown that both diseases share several common genetic and environmental factors. Body fat mass, a component of body weight, is one of the most important indices of obesity, and a substantial body of evidence indicates that fat mass may have beneficial effects on bone. Contrasting studies, however, suggest that excessive fat mass may not protect against osteoporosis or osteoporotic fracture. Differences in experimental design, sample structure, and even the selection of covariates may account for some of these inconsistent or contradictory results. Despite the lack of a clear consensus regarding the impact of effects of fat on bone, a number of mechanistic explanations have been proposed to support the observed epidemiologic and physiologic associations between fat and bone. The common precursor stem cell that leads to the differentiation of both adipocytes and osteoblasts, as well the secretion of adipocyte-derived hormones that affect bone development, may partially explain these associations. Based on our current state of knowledge, it is unclear whether fat has beneficial effects on bone. We anticipate that this will be an active and fruitful focus of research in the coming years.
主题词：11-beta-Hydroxysteroid Dehydrogenases/physiology 【11-β-羟甾脱氢酶类/生理学】
Adipose Tissue/metabolism 【脂肪组织/代谢】
Bone Density 【骨密度】
原文获取：Correlation of obesity and osteoporosis: effect of fat mass on the determination of osteoporosis.
篇名： Association of adipokines and inflammatory markers with lipid control in type 2 diabetes.
作 者： Kap?on-Cie?licka, A ; Postu?a, M ; Rosiak, M ; Filipiak, KJ ;等
出 处： Pol Arch Med Wewn.2015 ;125(6) :414-23
摘要： INTRODUCTION:Data regarding the effect of certain adipokines on lipid metabolism are equivocal.
OBJECTIVES:The aim of this study was to evaluate the association of lipid control with adipokines and inflammatory markers in patients with type 2 diabetes. PATIENTS AND
METHODS:The analysis included 195 patients with type 2 diabetes. The achievement of treatment targets in terms of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides was assessed in accordance with the current guidelines. Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index as well as concentrations of highmolecular-weight (HMW) adiponectin, leptin, resistin, high-sensitivity C-reactive protein, interleukin 6, and tumor necrosis factor α (TNF-α) were measured in all patients. Logistic regression analyses were performed to determine the risk factors for inadequate lipid control.
RESULTS:Optimal control in terms of total cholesterol, LDL, HDL, and triglycerides was achieved in 61%, 43%, 53%, and 68% of the patients, respectively. In multivariate analyses, female sex, lower resistin concentrations, and the absence of statin treatment were predictors of total cholesterol levels above the treatment target; older age and lower statin dose--of LDL cholesterol levels above the treatment targets; female sex, higher HOMA-IR index, lower HMW adiponectin concentrations, and higher TNF-α concentration-o-f HDL levels below the treatment targets; and higher HOMA-IR, lower HMW adiponectin concentration, and the absence of statin treatment--of triglycerides above the treatment target.
CONCLUSIONS:In type 2 diabetes, lower HMW adiponectin concentrations are associated with inadequate triglyceride and HDL control; higher TNF-α, with inadequate HDL control, and lower resistin concentrations, with inadequate total cholesterol control.
C-Reactive Protein/analysis* 【C反应蛋白质/分析*】
Diabetes Mellitus, Type 2 【糖尿病, 2型】
Lipid Metabolism* 【脂类代谢*】
Lipoproteins, HDL 【脂蛋白类, HDL】
Tumor Necrosis Factor-alpha/blood* 【肿瘤坏死因子α/血液*】