leptin and Osteoporosis--Postmenopausal

The clinical relevance of blood levels of adipokines in individuals with postmenopausal osteoporosis (PMOP) has not been previously clarified. We performed this meta-analysis to clarify the association between three common adipokines levels and the occurrence of PMOP. PubMed, Embase, Cochrane library, and China National Knowledgement Infrastructure (CNKI) were searched for collecting articles published before 31 October 2021, without language and status restrictions. Fourteen studies met the selection criteria. Meta-analysis revealed that blood leptin level was remarkably lower (mean difference [MD], -1.94; 95% confidence interval [CI], -3.83 to -0.06; I

Topics: Adipokines; Adiponectin; Bone Density; Female; Humans; Leptin; Osteoporosis, Postmenopausal

In recent decades the population of both elderly men and women has grown substantially worldwide. Aging is associated with a number of pathologies involving various organs including the skeleton. Age-related bone loss and resultant osteoporosis put the elderly population at an increased risk for fractures and morbidity. Fortunately, in parallel our understanding of this malady has also grown substantially in recent years. A number of clinical as well as translational studies have been pivotal in providing us with an understanding of the pathophysiology of this condition. This article discusses the current concepts of age-related modulation of the skeleton involving intrinsic factors such as genetics, hormonal changes, levels of oxidative stress, and changes in telomere length, as well as extrinsic factors such as nutritional and lifestyle choices. It also briefly outlines recent studies on the relationship between bone and fat in the marrow as well as the periphery.

Topics: Aged; Aging; Bone and Bones; Bone Remodeling; Elder Nutritional Physiological Phenomena; Exercise; Female; Humans; Leptin; Life Style; Male; Osteoporosis; Osteoporosis, Postmenopausal; Oxidative Stress; Serotonin; Telomere

Mesenchymal stem cells (MSCs) found in bone marrow stroma, are able to differentiate into osteoblasts and adipocytes, among other cellphenotypes. In normal bone marrow balance osteoblastic an adipocytes cell differentiation favour bone formation, while in osteoporosis there is an increased adipocytes content. Since osteoblasts and adipocytes originate from a common MSC precursor cell, here we discuss whether quantitative and qualitative stem cell defects may be the cause of alterations in the number and function of differentiated cells. This review analyzes some conditions that contribute to different osteogenic/adipogenic potentials in human bone marrow MSCs obtained from control and osteoporotic postmenopausal women. We analyze the protective effect exerted by locally generated factors like estradiol and leptin on MSCs differentiation, because altered bioavailability of these factors may play a role in osteoporosis. Osteoporotic MSCs (o-MSCs) are characterized by increased adipogenic potential as compared to control cells. Leptin exerted a direct protective action against adiposeness only in control cells. In contrast, leptin action on o-MSCs is hampered, suggesting that inadequate leptin action may be associated to lipid accumulation in bone marrow.

Topics: Adipogenesis; Aged; Cell Differentiation; Estradiol; Female; Humans; Leptin; Mesenchymal Stem Cells; Osteoporosis, Postmenopausal

Leptin a cytokine protein secreted by adipose tissue raises considerable interest as a potential mediator of the protective effects of fat mass on bone tissue. After menopause heavier women conserve bone mass better than those with lower body weight. The protective effect of obesity on bone mass has been ascribed to a high body fat content. As Leptin levels reflect the body fat content it has emerged as a possible mediator of these protective effects.. A search of the available literature focused on the role of leptin on bone tissue.. Both peripheral and central action of leptin on bone metabolism have been proposed. In vitro and in vivo evidence supports the hypothesis that leptin can act directly or indirectly on bone remodelling by modulating both osteoblast and osteoclast activities. However, studies in humans have not yet been able to confirm these actions possibly because of the shifting balance between stimulatory direct action and suppressive indirect action of leptin on bones via the hypothalamus. The effects of oestrogen decline and deficiency during natural or artificially induced menopause and administration of hormone replacement therapy has on leptin production remains controversial. Various studies have shown differences in leptin values in pre- and postmenopausal women. The existing clinical data on this issue are discordant.. Larger clinical studies are necessary to clarify leptin's role in vivo and to assess the contribution of the central and peripheral role of leptin in the overall maintenance of bone turnover in human beings.

Topics: Bone and Bones; Female; Humans; Leptin; Obesity; Osteoporosis, Postmenopausal; Postmenopause

There are three injectable and one oral bone-building (i.e., bone anabolic) parathyroid hormone (PTH) peptides. One of the four, Lilly's injectable teriparatide (Forteo), is currently being used, and the other three are in clinical trials. They are being used or assessed only for treating postmenopausal osteoporosis. However, their potential clinical targets now extend far beyond osteoporosis. They can accelerate the mending of even severe non-union fractures; they will probably be used to strengthen the anchorage of pros-theses to bone; they have been shown to treat psoriasis that has resisted other treatments; they can increase the size of haematopoietic stem cell proliferation and accelerate the endogenous repopulation or repopulation by donor transplants of bone marrow depleted by chemotherapeutic drugs; and they may prevent vascular ossification. Leptin, a member of the cytokine superfamily has a PTH-like osteogenic activity and may even partly mediate PTH action. But leptin has two drawbacks that cloud its therapeutic future. First, apart from directly stimulating osteoblastic cells, it targets cells in the hypothalamic ventromedial nuclei and through them it reduces oestrogenic activity by promoting osteoblast-suppressing adrenergic activity. Second, it stimulates vascular and heart valve ossification, which leads to such events as heart failure and diabetic limb amputations.

Topics: Animals; Humans; Leptin; Osteoporosis, Postmenopausal; Parathyroid Hormone; Peptide Hormones; Technology, Pharmaceutical

Osteoporosis is a disorder in which loss of bone strength leads to fragility fractures. This review examines the fundamental pathogenetic mechanisms underlying this disorder, which include: (a) failure to achieve a skeleton of optimal strength during growth and development; (b) excessive bone resorption resulting in loss of bone mass and disruption of architecture; and (c) failure to replace lost bone due to defects in bone formation. Estrogen deficiency is known to play a critical role in the development of osteoporosis, while calcium and vitamin D deficiencies and secondary hyperparathyroidism also contribute. There are multiple mechanisms underlying the regulation of bone remodeling, and these involve not only the osteoblastic and osteoclastic cell lineages but also other marrow cells, in addition to the interaction of systemic hormones, local cytokines, growth factors, and transcription factors. Polymorphisms of a large number of genes have been associated with differences in bone mass and fragility. It is now possible to diagnose osteoporosis, assess fracture risk, and reduce that risk with antiresorptive or other available therapies. However, new and more effective approaches are likely to emerge from a better understanding of the regulators of bone cell function.

Topics: Animals; Bone and Bones; Bone Density; Bone Remodeling; Calcium; Cell Differentiation; Collagen; Estrogens; Fractures, Bone; Glycoproteins; Hematopoietic Stem Cells; Hormones; Humans; Leptin; Ligands; Mice; Models, Biological; Neurons; NF-kappa B; Nitric Oxide; Osteoblasts; Osteoporosis; Osteoporosis, Postmenopausal; Osteoprotegerin; Parathyroid Hormone; Prostaglandins; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Vitamin D; Vitamin D Deficiency

In this work, I stand out the rich endocrine role of adipocytes, that together with its function of lipidic deposit and regulating of metabolism, this confers them a central place in physiology and pathology.

Topics: Adipocytes; Adiponectin; Adolescent; Adult; Aged; Animals; Child; Diabetes Mellitus, Type 2; Female; Humans; Hypothalamus; Infant, Newborn; Insulin Resistance; Interleukins; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Middle Aged; Obesity; Osteoporosis; Osteoporosis, Postmenopausal; Puberty; Rats; Tumor Necrosis Factor-alpha

Bone mass is maintained constant between puberty and menopause by the balance between osteoblasts and osteoclasts activity. The existence of a hormonal control of osteoblast activity has been speculated for years by analogy to osteoclast biology. Through the search for such humoral signal(s) regulating bone formation, leptin has been identified as a powerful inhibitor of bone formation. Furthermore, by means of intracerebroventricular infusion of leptin, it has been shown that the effect of this adipocyte-derived hormone on bone is mediated via a brain relay, like all its other functions. Subsequent studies have led to the identification of hypothalamic neurons involved in leptin's antiosteogenic function. In addition, it has been shown that those neurons or neuronal pathways are distinct from neurons responsible for the regulation of energy metabolism. Finally, the peripheral mediator of leptin's antiosteogenic function has been identified as being the sympathetic nervous system. Catecholamine-deficient mice have a high bone mass and sympathomimetics administered to mice decreased bone formation and bone mass. Conversely, beta-blockers increased bone formation and bone mass and blunt the bone loss induced by ovariectomy.

Topics: Adipocytes; Adrenergic beta-Antagonists; Animals; Body Weight; Bone Development; Energy Metabolism; Homeostasis; Humans; Immunity, Innate; Leptin; Mice; Mice, Obese; Neurons; Obesity; Organ Size; Osteoblasts; Osteoporosis, Postmenopausal; Receptors, Adrenergic, beta; Receptors, Leptin; Sympathetic Nervous System; Ventromedial Hypothalamic Nucleus

Body weight is among the most powerful predictors of bone status, and adipose tissue plays a substantial role in weight-related protective effects on bone. An understanding of the mechanisms underlying the relation between adipose tissue and bone may open up new perspectives for treatment. Leptin, which is known to regulate appetite and energy expenditures, may also contribute to mediate the effects of fat mass on bone. Although reported data are somewhat conflicting, there is some evidence that leptin may decrease bone formation via a central nervous effect and may stimulate both bone formation and bone resorption via direct peripheral effects on stromal precursor cells. The net result of these central and peripheral effects may depend on serum leptin levels and blood-brain barrier permeability, of which the first increase and the second decrease as obesity develops. Further work is needed to improve our understanding of these effects.

Topics: Adipose Tissue; Animals; Bone and Bones; Bone Density; Bone Remodeling; Cells, Cultured; Female; Humans; Leptin; Male; Obesity; Osteoporosis, Postmenopausal

Adiponectin and leptin, as the main circulating peptides secreted by adipose tissue, are potential contributors to bone metabolism. However, their association with bone mineral density (BMD) is unknown. We investigated whether these serum adipocytokines concentrations are associated with BMD and bone turnover markers.. Serum adiponectin, leptin concentrations, bone turnover biochemical markers, and BMD were determined in 265 premenopausal and 336 postmenopausal Chinese women.. In postmenopausal Chinese women, the multiple linear stepwise regression analysis showed that year since menopause, lean mass, estradiol, and adiponectin, but not fat mass, leptin, were independent predictors of BMD in postmenopausal Chinese women. However, in premenopausal Chinese women, adiponectin was not the predictor of BMD. The significant positive correlations between adiponectin and bone-specific alkaline phosphatase (BAP), bone cross-linked N-telopeptides of type I collagen (NTX) were found only in postmenopausal women. Serum BAP, and NTX, but not adiponectin, decreased in response to alendronate therapy.. Adiponectin was an independent predictor of BMD, and positively correlated with bone turnover biochemical markers in postmenopausal Chinese women, but not premenopausal women. It suggested that adiponectin may exert a negative effect on bone mass by promoting excessive bone resorption associated with bone loss. However, these effects may be mediated by menopausal status.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Alendronate; Alkaline Phosphatase; Biomarkers; Blood; Body Composition; Body Mass Index; Bone and Bones; Bone Density; Bone Remodeling; China; Collagen Type I; Double-Blind Method; Estradiol; Female; Humans; Leptin; Middle Aged; Osteoporosis, Postmenopausal; Peptides; Postmenopause; Premenopause; Treatment Outcome; Young Adult

One-year treatment of osteoporotic postmenopausal women with transdermal estrogen resulted in significant decreases in bone marrow adipocyte volume and prevented increases in adipocyte number as compared to placebo-treated controls. Estrogen treatment also prevented increases in mean adipocyte size over 1 year.. Aging is associated not only with bone loss but also with increases in bone marrow adipocytes. Since osteoblasts and adipocytes are derived from a common precursor, it is possible that with aging, there is a preferential "switch" in commitment of this precursor to the adipocyte over the osteoblast lineage. We tested the hypothesis that the apparent "age-related" increase in marrow adipocytes is due, at least in part, to estrogen (E) deficiency.. Reanalysis of bone biopsies from a randomized, placebo-controlled trial involving 56 postmenopausal osteoporotic women (mean age, 64 years) treated either with placebo (PL, n = 27) or transdermal estradiol (0.1 mg/d, n = 29) for 1 year.. Adipocyte volume/tissue volume (AV/TV) and adipocyte number (Ad#) increased (by 20%, P < 0.05) in the PL group, but were unchanged (Ad#) or decreased (AV/TV, by -24%, P < 0.001) in the E group. E treatment also prevented increases in mean adipocyte size over 1 year.. These findings represent the first in vivo demonstration in humans that not only ongoing bone loss, but also the increase in bone marrow adipocyte number and size in postmenopausal osteoporotic women may be due, at least in part, to E deficiency.

Topics: Adipocytes; Administration, Cutaneous; Aged; Anthropometry; Biopsy; Bone Density; Bone Marrow Cells; Cell Count; Cell Size; Estradiol; Estrogen Replacement Therapy; Female; Humans; Leptin; Lipids; Middle Aged; Osteoporosis, Postmenopausal

The aim of this study was to investigate the effects of strontium ranelate on insulin like growth factor-1 (IGF-1), leptin and osteocalcin levels in osteoporotic post-menopausal women.. Thirty-three women were given 2 g/day strontium ranelate for 6 months. Serum IGF-1, leptin and osteocalcin levels were measured before and after the treatment.. Strontium ranelate treatment increased IGF-1 levels significantly (P = 0.02). Leptin and osteocalcin levels did not change significantly before and after the treatment. There was no correlation between basal and 6-months treatment levels of IGF-1 and leptin.. Strontium ranelate increases serum IGF-1 levels in osteoporotic post-menopausal women.

Topics: Adult; Age Factors; Aged; Body Mass Index; Bone Density; Bone Density Conservation Agents; Female; Follow-Up Studies; Humans; Insulin-Like Growth Factor I; Leptin; Middle Aged; Organometallic Compounds; Osteocalcin; Osteoporosis, Postmenopausal; Prospective Studies; Thiophenes

To evaluate the effects of oral continuous 17beta-estradiol plus norethisterone acetate (E2/NETA) replacement therapy on abdominal subcutaneous fat, serum leptin level (SLL) and body composition in postmenopausal women.. A 6-month, prospective, randomized, double-blind and placebo-controlled study was conducted. Forty-three healthy naturally postmenopausal women aged 43-65 years were randomly assigned to receive E2/NETA (2 mg E2 plus 1 mg NETA, n = 22) or placebo (n = 21). Fasting SLL by enzyme-linked immunosorbent assay, subcutaneous abdominal fat thickness (STh) by ultrasound and the anthropometric indices of body weight (BW), body mass index (BMI), waist and hip circumference (WC, HC) and waist-to-hip ratio (WHR) were recorded at the beginning and the end of the study.. After 6 months of therapy, BW and SLL increased in the placebo group (p = 0.043 and 0.033, respectively). WC, HC and STh decreased significantly in the E2/NETA group (p = 0.002, 0.006 and 0.000, respectively) and they were also significantly lower in women receiving E2/NETA than in women taking placebo (p = 0.000, 0.034 and 0.000, respectively). At baseline, SLL and STh were positively correlated with all anthropometric indices except WHR.. Oral continuous combined regimen of E2/NETA significantly reduced central fat accumulation as assessed by WC and STh, and attenuated the increase in SLL. The observed changes in SLL were highly and positively related to changes in STh. The oral continuous combined E2/NETA regimen appears to have protective effects on cardiovascular function and probably on metabolic diseases by its slimming effect upon WC in postmenopausal women.

Topics: Administration, Oral; Adult; Aged; Body Composition; Body Mass Index; Body Weight; Double-Blind Method; Drug Therapy, Combination; Estradiol; Estrogen Replacement Therapy; Female; Humans; Leptin; Middle Aged; Norethindrone; Norethindrone Acetate; Osteoporosis, Postmenopausal; Placebos; Postmenopause; Subcutaneous Fat, Abdominal; Waist-Hip Ratio

To examine the relationships between serum leptin and bone metabolism, we measured bone mineral density (BMD) at the spine and the hip, fasting serum leptin, and osteocalcin and urinary excretion of C-terminal crosslinking telopeptide of type I collagen (CTX), as markers of bone formation and resorption, respectively, in 121 postmenopausal women aged 54 +/- 5 years. These parameters were also assessed at 6 months and 2 years of treatment with either 2.5 mg tibolone (n = 34), 1.25 mg tibolone (n = 45), or 2 mg estradiol plus 1 mg norethindrone acetate (n = 42). At baseline, serum leptin correlated positively with spine (r = 0.21, P = 0.02) and total hip (r = 0.26, P = 0.0044) BMD and negatively with CTX (r = -0.38, P < 0.0001) and osteocalcin (r = 0.21, P = 0.025). After adjustment for BMI and for fat mass, the association between serum leptin and CTX persisted with a partial correlation coefficient of -0.18 (P = 0.046) and of -0.22 (P = 0.03), respectively. Women in the highest quartile of leptin levels had 11% higher total hip (P = 0.0039) and lumbar spine BMD (P = 0.016), 21% lower osteocalcin (P = 0.01), and 38% lower CTX (P = 0.0005) than women in the lowest quartile (P < 0.05). During treatment, serum leptin levels increased (+14.7 +/- 47.3%, P = 0.019), without significant difference between the groups. This increase correlated with the increase in body weight (r = 0.46, P < 10(-4)). No correlation was found between the changes in leptin and the changes in bone parameters. In conclusion, leptin may play a role as a determinant of bone resorption in healthy, untreated postmenopausal women, but the effect of estradiol or tibolone on bone are not mediated by leptin.

Topics: Aged; Biomarkers; Bone Density; Bone Resorption; Double-Blind Method; Female; Humans; Leptin; Middle Aged; Norpregnenes; Osteoporosis, Postmenopausal; Postmenopause; Prospective Studies; Statistics, Nonparametric

Weight reduction reduces bone mineral density (BMD) and increases the risk of osteoporosis.. We investigated whether bone is mobilized in postmenopausal women during energy restriction and whether hormones regulate bone turnover and mass.. Twenty-seven obese postmenopausal women with a mean (+/-SD) age of 55.9 +/- 7.9 y and body mass index (in kg/m(2)) of 33.0 +/- 3.8 completed the 6-mo study. Fourteen women followed a moderate energy-restricted diet (WL group) and 13 control subjects maintained their body weight (WM group). Body weight, bone turnover markers, serum parathyroid hormone (PTH), and dietary intake were measured throughout the study. Total-body BMD, sex hormone binding globulin, leptin, and estrone were measured at baseline and at week 25.. In the WL group, body weight decreased by 10.2 +/- 5.5% (P < 0.001), body fat mass decreased by 18.7 +/- 11.3% (P < 0.001), and total-body BMD decreased by 1.2 +/- 1.2%; these changes were significantly different from those in the WM group (P < 0.05). Serial measurements showed chronically elevated rates of bone resorption and formation during energy restriction that were greater than in the WM group (P < 0.05). Serum sex hormone binding globulin increased and leptin decreased with weight loss (P < 0.05). Serum PTH tended to increase in the WL group but not in the WM group (P < 0.06). The reduction in fat mass with weight loss was directly associated with a decrease in serum estrone (P < 0.01, R(2) = 0.50).. Moderate energy restriction increases bone turnover in obese postmenopausal women and may be regulated in part by alterations in serum PTH and estrone.

Topics: Absorptiometry, Photon; Adipose Tissue; Body Composition; Bone Density; Bone Resorption; Diet, Reducing; Energy Intake; Estrone; Female; Humans; Leptin; Middle Aged; Obesity; Osteoporosis, Postmenopausal; Parathyroid Hormone; Postmenopause; Sex Hormone-Binding Globulin; Time Factors; Weight Loss

Osteoporotic fracture, a major complication which is known as the outcome postmenopausal osteoporosis, seriously threatens the health of postmenopausal women. At present, the traditional osteoporotic fracture prediction methods are characterized by inconvenient application and time-consuming statistical results, while predictive serum biomarkers can make up for this shortcoming. Accurate and advanced risk prediction of osteoporotic fracture is meaningful to early prevention and intervention, effectively avoiding the risk of this disease and the secondary fracture in the surgical treatment. In this study, based on the BEYOND cohort, a 2-year follow-up study was conducted after subjects participated to survey if OF occurred. Independent sample

Topics: Biomarkers; Bone Density; Female; Follow-Up Studies; Humans; Interleukin-6; Leptin; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Postmenopause; Risk Assessment; Risk Factors

Because the world's population is deficient in dietary calcium, it is important to search for new sources of this essential mineral for the bones and the entire body. One of the innovative foods that could act as such a source is pumpkin enriched with calcium lactate by means of osmotic dehydration. Providing the body with easily absorbable calcium may have beneficial effects on the reconstruction of bone tissue. Postmenopausal osteoporosis is associated with body weight and fat mass gain, and the aim of the present study was to evaluate the effect of consuming enriched pumpkin on the levels of adipokines and cytokines produced by the adipose tissue. This study was conducted on 12-month-old female Wistar rats that received nutritional intervention for 12 weeks. After termination of the rats, the levels of leptin, adiponectin, interleukin 31 and interleukin 33 in serum and adipose tissue were determined, and the femurs were examined histopathologically. It was demonstrated that calcium-enriched pumpkin reduced bone marrow femoral adipocytes and also markedly decreased serum leptin levels in groups of rats after ovariectomy, which was associated with a decrease of fat content. Additionally, it seems that calcium-enriched pumpkin may reduce body weight gain often observed after menopause.

Topics: Adiponectin; Adipose Tissue; Animals; Calcium, Dietary; Cucurbita; Disease Models, Animal; Female; Food, Fortified; Humans; Interleukins; Leptin; Osteoporosis, Postmenopausal; Ovariectomy; Rats; Rats, Wistar

Although associations among obesity, adipocytokines, and bone mineral density have been reported, the influence of adipocytokines on osteoporotic fractures remains unclear. This study aimed to assess the impact of the adipocytokines leptin and adiponectin on the risk of incident vertebral and long-bone fractures in postmenopausal women. Clinical data were obtained from the retrospective Nagano Cohort Study of outpatients followed at a single primary care institute in Nagano Prefecture, Japan, between 1993 and 2018. The primary outcome was the occurrence of incident vertebral or long-bone fractures. In total, 1167 Japanese postmenopausal women (mean age: 65.9 years) completed the follow-up and the average observation period was 7.2 years. The subjects were divided into 4 groups (quartile 1 to 4) based respective leptin and adiponectin values. Kaplan-Meier analysis demonstrated a significantly lower incident long-bone fracture rate in the higher quartiles of serum leptin levels (p = 0.002). A significantly higher and more rapid occurrence of incident vertebral fractures, but not long-bone fractures, was found in the highest adiponectin quartile (p < 0.001). A Cox proportional hazards model adjusted for confounders including age, body weight, and either leptin or adiponectin revealed lower leptin levels and higher adiponectin levels as significant independent risk factors for incident long-bone fractures (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.50-0.96; p = 0.03) and vertebral fractures (HR 1.18, 95% CI 1.02-1.37; p = 0.02), respectively. Therefore, serum leptin and adiponectin may be independent risk factors for osteoporotic fractures affecting different bone types and sites. Determining patient adipocytokine levels may help predict the occurrence of specific osteoporotic fractures, thereby enabling optimal treatment for osteoporosis and improving quality of life.

Topics: Adipokines; Adiponectin; Aged; Bone Density; Female; Humans; Japan; Leptin; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Postmenopause; Quality of Life; Retrospective Studies; Risk Factors; Spinal Fractures

Osteoporosis and obesity are considered civilisation diseases. Menopause is a time of increased bone resorption and increased mass of adipose tissue. Adipocytokines secreted by the adipose tissue are believed to be a potential factor in the pathogenesis of osteoporosis.. The aim of this research was to assess leptin, adiponectin, and resistin secretion in obese postmenopausal women with osteoporosis and determine whether obesity might be a factor mitigating the risk of osteoporosis. The study involved 80 postmenopausal women with osteoporosis divided into groups: I with BMI of 30.0 34.9, obese; and II with BMI of 18-24.9, normoweight. Leptin, adiponectin and resistin concentrations were assessed, and bone mineral density (BMD) was measured in the L1-L4 section of the spine using the DXA densitometric method.. The results of the comparison of the two groups indicate a statistically significant dependence in groups regarding leptin secretion; the group of obese women demonstrated significantly higher concentrations. No differences between the groups were demonstrated for adiponectin or resistin secretion.. Higher leptin concentration and a positive correlation with BMI was confirmed in obese postmenopausal women with osteoporosis. It was also demonstrated that BMD increases with growing BMI. No effect of obesity on the secretion of adiponectin or resistin in women with postmenopausal osteoporosis was found. From among the investigated adipocytokines, only leptin can be considered a bone tissue protective factor in postmenopausal women.

Topics: Adipokines; Adiponectin; Body Mass Index; Bone Density; Female; Humans; Leptin; Middle Aged; Obesity; Osteoporosis, Postmenopausal; Resistin; Risk Factors

To explore the relationship between circulating adiponectin, leptin and vaspin with bone mineral density (BMD), arterial stiffness and vascular calcification in post-menopausal women. We hypothesised that adipokines produced by adipose tissue may be mediators of bone and cardiovascular disease (CVD) and explain, in part, the observed association between osteoporosis and CVD.. We studied 386 ambulant community dwelling postmenopausal women aged (mean [SD] 61 [6.4] years). BMD at the lumbar spine, femoral neck (FN), and total hip (TH), body composition; fat mass (FM) and lean mass (LM) as well as abdominal aortic calcification (AAC) were determined by dual energy X-ray absorptiometry. Pulse wave velocity (PWV) and augmentation index, markers of arterial stiffness were measured. Fasting adiponectin, leptin and vaspin were quantified in serum.. A positive independent association was observed between vaspin and BMD at the FN (p = 0.009), TH (p = 0.037) in the whole study population adjusted for confounders including age, FM, LM and lifestyle variables. Using the same model, a negative association was seen between adiponectin and BMD at the FN in women with osteoporosis (p = 0.043). Serum adiponectin was significantly higher in women with fractures (20.8 [9.3] µg/ml compared to those without (18.5 [8.6] µg/ml, p = 0.018) and associated with a significant increased risk of fracture (HR 1.032, 95% CI 1.003-1.063, p = 0.032). Leptin was not associated with BMD or fracture risk after adjustment. Adiponectin was independently associated with AAC (p = 0.007) and significantly higher in women with AAC scores > 1; (19.2[9.2]) compared to those with no or low AAC scores (<1); 16.8 [8.0], p = 0.018). In adjusted analyses, PWV velocity was positively associated with circulating vaspin (p = 0.039) and AI was negatively associated with serum leptin (p = 0.002).. Adiponectin, leptin, vaspin are related to markers of bone and vascular health and may contribute to the observed association between osteoporosis and CVD.

Topics: Adiponectin; Adipose Tissue; Aged; Aged, 80 and over; Biomarkers; Body Composition; Bone Density; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Leptin; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause; Prognosis; Pulse Wave Analysis; Serpins; Vascular Stiffness

To assess the differential features of marrow adiposity between osteoarthritis (OA) and osteoporosis (OP) in postmenopausal women using water/fat MRI.. This cross-sectional study included 97 postmenopausal women (OA [n = 25], OA + osteopenia [n = 27], OA + OP [n = 23], and OP groups [n = 22]). Water/fat MRI, dual-energy x-ray absorptiometry and biochemical analysis were performed to assess vertebral marrow fat fraction, bone mineral density, and bone biomarkers, respectively. Harris Hip Score was recorded to evaluate hip function.. There were significant differences in marrow fat content among the OA, OA + osteopenia, and OA + OP groups, between OP and OA participants with normal bone mass or osteopenia (all P < 0.05); no significant difference was observed between OA + OP and OP groups. Serum levels of leptin and β-Crosslaps in OA with normal bone mass and osteopenic OA groups were higher than in OP group. Marrow fat fraction was inversely correlated with Harris Hip Score (r = -0.371, P = 0.013), bone mineral density (r = -0.554, P = 0.009) and leptin levels (r = -0.610, P < 0.001). In multivariate regression analysis, marrow fat fraction was found to have a consistent and unchanged inverse association with leptin levels (Sβ = -0.311, P = 0.002) and bone mineral density (Sβ =  -0.265, P = 0.006) after adjusting for age, years since menopause, and body mass index.. Postmenopausal OA with OP have a phenotype with higher marrow adiposity. OA and OP could coexist, for the presence of a specific subgroup of OA with increased marrow fat accumulation and high risk of developing OP.

Topics: Absorptiometry, Photon; Adiposity; Aged; Biomarkers; Bone Density; Bone Marrow; Cross-Sectional Studies; Female; Humans; Leptin; Magnetic Resonance Imaging; Middle Aged; Osteoarthritis; Osteoporosis, Postmenopausal; Postmenopause

To test the hypothesis that the relationship between fat mass (FM) and bone mineral density (BMD) is mediated by leptin. The study involved 611 individuals aged 20-89 years who were randomly sampled from Ho Chi Minh City (Vietnam). BMD at the femoral neck (FN), lumbar spine (LS), and whole body (WB) was measured by DXA. Lean mass and FM were derived from the WB DXA scan. Leptin was measured by ELISA (DRG Diagnostics, Germany). The regression method was used to partition the variance of leptin and FM on BMD. The mediated effect of leptin was analyzed by the mediation analysis model. In the multiple linear regression, leptin, FM, and age collectively accounted for ~34 % variation in FNBMD in men and women. However, only 0.5 % of this explained variance was due to leptin. Of the total effect of FM on FNBMD, the mediated effect of leptin accounted for 6.1 % (P = 0.38) in men and 7.1 % (P = 0.99) in women. The same trend was observed for LS and WBBMD. These data suggest that greater FM is associated with greater BMD, but the association is not mediated by leptin, and that leptin has a non-significant influence on bone mass.

Topics: Adipose Tissue; Adult; Aged; Aged, 80 and over; Aging; Body Composition; Body Mass Index; Bone Density; Female; Humans; Leptin; Male; Middle Aged; Osteoporosis, Postmenopausal; Young Adult

Present study was designed to find out whether leptin is a predictor of bone mass density (BMD) in premenopausal women (PMW) and postmenopausal osteoporotic women (PMOPW) or it has no association with BMD.. One hundred and ninety two women (98 PMOPW and 94 PMW) were recruited for this study. The control group was BMI matched with osteoporotic subjects. BMD assessment was done on calcaneus by peripheral ultrasound bone densitometry and T scores were determined. Serum leptin levels were measured by enzyme-linked immunosorbent assay (ELISA).. Serum leptin and BMD values were significantly different in both groups (leptin, 18.56 ± 8.65 ng/ml versus 21.64 ± 9.80 ng/ml, p = 0.02) and (BMD, -0.70 ± 0.19 versus -3.17 ± 0.59, p = 0.000), respectively. In PMOPW serum leptin and BMD were considerably correlated with weight (lep, r = 0.53, p = <0.001; BMD, r = -0.21, p = 0.02), BMI (lep, r = 0.52, p = <0.001; BMD, r = -0.27, p = 0.005), waist circumference (lep, r = 0.61, p = <0.001; BMD, r = 0.18, p = 0.04), hip circumference (lep, r = 0.58, p = <0.001). Multivariate linear stepwise regression analysis showed that weight and BMI in PMW and PMOPW were independent predictors of BMD. Serum leptin level was not found to be the predictor of BMD in both groups.. The present results indicate that body weight and BMI have an impact on BMD while serum leptin is not associated with BMD in PMW and PMOPW.

Topics: Absorptiometry, Photon; Bone Density; Female; Humans; Leptin; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause

Carotid artery calcifications (CAC) and high carotid artery intima-media thickness (cIMT) are associated with low bone mineral density (BMD) by unknown mechanisms in postmenopausal women. Leptin, adiponectin and estradiol may mediate these associations. Our aim was to study the relationships of the aforementioned factors to bone health (BMD) and carotid atherosclerosis (CAC and cIMT).. Participants (n = 290, mean age 73.6 years) for this cross-sectional OSTPRE-BBA study (Kuopio Osteoporosis Risk Factor and Prevention - Bone, Brain and Atherosclerosis) were randomly selected from the OSTPRE cohort in 2009. Femoral neck and total body BMDs, trunk and total body fat mass were measured with dual-energy X-ray absorptiometry, and cIMT (mm) and CAC (no/yes) were measured with B-type ultrasound. Free estradiol, adiponectin and leptin were measured from serum samples.. Circulating estradiol levels were associated with leptin (β = 0.131, p < 0.001), but not with adiponectin (p > 0.05), when adjusted for total body fat mass. There were no associations between estradiol tertiles and BMDs, or with cIMT or CAC. Adiponectin levels were inversely associated with femoral neck BMD (p = 0.019, β = -0.138) and total body BMD (p = 0.009, β = -0.142), adjusted for total body fat mass, age, current smoking and estradiol, but showed no relationship with CAC or cIMT. Leptin levels were not associated with BMDs or cIMT; but the odds ratio was 1.5 between the CAC and leptin quartiles (p = 0.014), adjusted for total body fat mass, age, statin use and calcium intake.. The adipokines are associated with vascular calcification and low BMD. Moreover, estradiol was not independently associated with BMD or CAC.

Topics: Adipokines; Adiponectin; Aged; Body Composition; Bone Density; Carotid Artery Diseases; Carotid Intima-Media Thickness; Cross-Sectional Studies; Estradiol; Female; Humans; Leptin; Osteoporosis, Postmenopausal; Postmenopause; Vascular Calcification

A significant change in serum leptin level and no change in homocysteine were observed with ibandronate treatment. No correlation of homocysteine and leptin was found with bone mass density (BMD). Results indicate that ibandronate reduces serum leptin levels but how does it help in reducing the osteoporosis. It needs to be explored.. The current study was planned to determine the effects of ibandronate on serum homocysteine and leptin levels in postmenopausal osteoporotic females and to correlate these with BMD.. Forty-two newly diagnosed and untreated postmenopausal osteoporotic females were selected on the basis of their BMD (BMD < -2.5) from Orthopaedic Out Patient Department of Shaikh Zayed Hospital, Lahore, Pakistan, and 36, age and BMI matched non-osteoporotic postmenopausal females, were also selected as a control group. Baseline physical and biochemical parameters were compared. In osteoporotic patients, changes in circulating leptin and homocysteine levels were studied after 6 months of therapy with ibandronate (150 mg). The collected data were analyzed on SPSS 16.. There was no significant difference observed in the mean value of all baseline parameters except BMD in both groups. After 6 months of treatment with ibandronate (150 mg), a significant change was observed in serum leptin levels (19.48 ± 1.60 ng/ml vs. 14.09 ± 0.85 ng/ml, p < 0.002), while no considerable change observed in serum homocysteine levels (16.22 ± 0.95 μmol/l vs. 16.80 ± 1.03 μmol/l, p < 0.63). Serum leptin was found significantly correlated with anthropometric parameters. No correlation of serum leptin and homocysteine was found with BMD (r = 0.09, p value = 0.54; r = -0.17, p value = 0.27).. Our results show that ibandronate reduces serum leptin levels while it has no effect on serum homocysteine levels. Further studies are needed to explain how the decrease in serum leptin level may help in reducing the progression of osteoporosis.

Topics: Bone Density; Bone Density Conservation Agents; Calcaneus; Case-Control Studies; Densitometry; Diphosphonates; Enzyme-Linked Immunosorbent Assay; Female; Homocysteine; Humans; Ibandronic Acid; Leptin; Middle Aged; Osteoporosis, Postmenopausal; Treatment Outcome; Ultrasonography

Zoledronic acid is known to induce a transient acute phase response (APR). The aim of the study was to investigate whether an APR caused by zoledronic acid administration can induce insulin resistance in post-menopausal osteoporotic women and the potential involvement of different inflammatory markers, cytokines and adipokines to this response. Insulin resistance was calculated by the homeostasis model assessment (HOMA-IR). APR symptoms appeared in 30 post-menopausal osteoporotic women within 24 h and attenuated on day 3 after zoledronic acid infusion. Twenty-eight age- and body mass index-matched, patients without an APR following zoledronic acid administration, served as a control group. In patients with APR, concurrently with a significant increase in serum high sensitive C-reactive protein (hsCRP), interleukin-6 (hsIL-6), tumour necrosis factor-alpha (hsTNF-α) and cortisol levels on days one and two, serum insulin was also significantly elevated, resulting in an increased HOMA-IR. Leptin and resistin significantly increased on day two in contrast to adiponectin which declined, though not statistically significant. The alterations in HOMA-IR were mainly associated to the increase of hsCRP and leptin. In conclusion, zoledronic acid induces an acute, short term insulin resistance, due to an APR, by altering the levels of various adipokines and cytokines.

Topics: Acute-Phase Reaction; Adiponectin; Bone Density Conservation Agents; C-Reactive Protein; Diphosphonates; Female; Humans; Hydrocortisone; Imidazoles; Insulin Resistance; Interleukin-6; Leptin; Middle Aged; Osteoporosis, Postmenopausal; Resistin; Tumor Necrosis Factor-alpha; Zoledronic Acid

In the present study, we aimed to investigate the association between genetic polymorphisms in period (PER) genes and bone mineral density (BMD) in postmenopausal Korean women.. The PER1 c.2247C> T and c.2884C> G polymorphisms; the PER2 c.661G> A and c.3731G> A polymorphisms; the PER3 c.2592G> A, c.3029C> T, c.3035C> T, and c.3083T> C polymorphisms, and the 54 bp variable number tandem repeats polymorphism were analyzed in 551 postmenopausal Korean women. Serum leptin, soluble leptin receptor, osteoprotegerin, soluble receptor activator of the nuclear factor-κB ligand, and bone markers including bone alkaline phosphatase and carboxy-terminal telopeptide of type I collagen were measured, and the lumbar spine and femoral neck BMDs were also determined.. The PER2 c.661G> A, PER3 c.3029C> T and c.3035C> T polymorphisms were not observed. The PER2 and PER3 polymorphisms evaluated were not related to BMD, whereas associations of the c.2247C> T and c.2884C> G polymorphisms in PER1 with the lumbar spine BMD were observed both singly and in combination. The CC haplotype homozygotes showed significantly lower lumbar spine BMD than participants with other genotypes. Additionally, 2.01-fold higher odds for osteoporosis of the lumbar spine were found in the CC haplotype homozygotes compared to women not carrying the haplotype CC allele. No significant differences in bone markers were detected according to the PER1 haplotype genotype.. Our results suggest that both the PER1 c.2247C> T and c.2884C> G polymorphisms may be genetic factors affecting the lumbar spine BMD in postmenopausal Korean women.

Topics: Aged; Alkaline Phosphatase; Asian People; Bone Density; Collagen Type I; Female; Femur Neck; Genotype; Haplotypes; Humans; Leptin; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Osteoprotegerin; Peptides; Period Circadian Proteins; Polymorphism, Genetic; Postmenopause; Receptors, Leptin

Obesity has a protective effect against osteoporosis and this effect has been attributed to a high body fat content. It has been shown that the leptin concentration is higher in obese patients. Leptin, the protein product of obesity gene, is a hormone produced in adipose tissue. Some studies suggest that endogenous leptin might influence bone metabolism in postmenopausal women. In this study, we investigated plasma leptin concentrations in postmenopausal women with osteoporosis and also analyzed the relationship between plasma leptin levels and bone mineral density (BMD) in order to understand the potential role of leptin in maintaining bone mass. Forty-two postmenopausal women with osteoporosis and thirty seven age and BMI-matched healthy postmenopausal women were included in the study. The mean femoral neck BMD value in the patient group was significantly lower than that in the control group (0.691±0.1 g/cm2 and 0.863±0.1 g/cm2, respectively; p<0.001). The mean plasma leptin concentration in the patient group was not significantly different from that in the control group (p>0.05). Plasma leptin levels were correlated with BMI in both groups (p<0.001 in the patient group and p=0.001 in controls). There was also a strong positive correlation between plasma leptin levels and %fat in both groups (p<0.001 in the patient group and p<0.001 in controls). But there was no correlation between plasma leptin levels and femoral neck BMD values in both groups. Our results do not support the hypothesis that leptin itself plays an important role in maintaining bone mass in postmenopausal women.

Topics: Body Composition; Body Mass Index; Bone and Bones; Bone Density; Enzyme-Linked Immunosorbent Assay; Female; Femur Neck; Humans; Leptin; Middle Aged; Obesity; Osteoporosis, Postmenopausal; Postmenopause

Clinical studies evaluating the role of leptin and adiponectin on bone metabolism had shown conflicting results, and data about the effect of anticatabolic drugs on these adipokines are scarce. Our aims were to determine adiponectin and leptin levels in osteoporotic postmenopausal women and their relationship with bone mass and bone turnover and to analyze changes on adiponectin and leptin levels after treatment with raloxifene or alendronate.. We selected 53 women (mean ± SD age, 63 ± 7 y) with postmenopausal osteoporosis divided into two treatment groups: raloxifene (60 mg/d; n = 20) or alendronate (70 mg/wk; n = 33) during a period of 1 year. Bone mineral density by dual-energy x-ray absorptiometry and serum levels of leptin, adiponectin, and bone turnovers markers were determined at baseline and at 1 year after treatment.. Baseline levels of leptin were correlated to body mass index (r = 0.47; P < 0.01), waist circumference (r = 0.38, P = 0.01), and estradiol (r = 0.4, P = 0.003). Adiponectin was inversely related to bone-specific alkaline phosphatase (r = -0.41, P < 0.01) and serum crosslaps (r = -0.35; P < 0.01). There was no correlation between bone mineral density, leptin, and adiponectin. After 12 months, no changes were observed in leptin and adiponectin in the alendronate group; however, a significant increase in leptin levels (973.5 ± 637.4 pM/mL vs 1,305.7 ± 793.5 pM/mL; P = 0.031) was detected in the raloxifene group, whereas adiponectin levels showed no significant changes (P = 0.46).. In postmenopausal women with osteoporosis, raloxifene induces a significant increase in leptin levels without significant changes in adiponectin serum levels. The antiresorptive effect of raloxifene and alendronate is not substantially influenced by changes in leptin or adiponectin levels.

Topics: Adiponectin; Aged; Alendronate; Body Mass Index; Bone Density; Bone Density Conservation Agents; Female; Humans; Leptin; Middle Aged; Osteoporosis, Postmenopausal; Raloxifene Hydrochloride

There is growing evidence that oxytocin, which regulates appetite, plays a role in bone remodelling and improves osteoporosis. We previously showed a significant decrease in circulating oxytocin levels in postmenopausal osteoporotic women compared to healthy controls. However, factors involved in the pathophysiology of osteoporosis, such as estrogens and leptin, are known to regulate oxytocin secretion. Herein, we evaluated the relationships between oxytocin and other hormonal factors known to regulate bone remodeling and body composition in postmenopausal osteoporotic women, compared to healthy controls.. In 20 postmenopausal women with severe osteoporosis compared to 16 healthy controls, we measured serum levels of oxytocin, high sensitive estradiol, testosterone, FSH, LH, SHBG, TSH, osteocalcin, serum type I collagen carboxy-terminal telopeptide, leptin. Bone mineral density and body composition were also measured with DXA.. Osteoporotic women had significantly lower oxytocin, leptin and LH serum levels and higher CTX and SHBG; all other biological parameters were similar in both groups. Fat mass and lean mass were significantly decreased in osteoporotic women. Oxytocin serum levels were significantly correlated to bone mineral density but not to any other measured parameter, including leptin, estradiol and age. In a logistic regression analysis, osteoporosis remained significantly correlated to oxytocin, regardless of age.. Low oxytocin serum levels appeared to be associated with severe osteoporosis, independently of other factors associated with osteoporosis or known to regulate oxytocin serum levels, such as estradiol or leptin, reinforcing the concept that oxytocin may be involved in the pathophysiology of postmenopausal osteoporosis.

Topics: Aged; Aged, 80 and over; Body Composition; Bone Density; Bone Remodeling; Case-Control Studies; Collagen Type I; Estradiol; Female; Humans; Leptin; Luteinizing Hormone; Middle Aged; Osteoporosis, Postmenopausal; Oxytocin; Peptides; Pituitary Hormones; Retrospective Studies; Severity of Illness Index; Sex Hormone-Binding Globulin

We investigated the relationship between the decrease in bone mineral mass (BMC) and bone mineral density (BMD) values with baseline adipocytokine and ghrelin concentrations in physically active postmenopausal women.. Leptin, adiponectin, ghrelin, BMC, BMD and different body composition values were measured in 35 women (age: 69.7+/-6.0 years) before and after a 12-month prospective study period.. Significant (P<0.05) decreases in fat-free mass (FFM) (by 2.56%) and BMC (by 1.63%) and increases in adiponectin (by 14.8%) were seen in older females as a result of the study period. The independent variables that were associated with decreases in total BMC were baseline fat mass (FM) and adiponectin explaining 30.6% (R(2)x100) of the total variance. In another model, baseline FFM and leptin were the independent variables that explained 20.6% (P<0.05) of the total variance in the decreases in total BMD value. The variables that were associated with decreases in femoral neck BMD were FM and leptin (R(2)=0.102; P<0.05), while the independent variables were baseline trunk fat:leg fat ratio and adiponectin in the model with decreases in lumbar spine BMD as the dependent variable, and accounted for 13.1% (P<0.05) of the decreases in BMD variance.. Initial adiponectin concentration together with specific body composition characteristics predicted loss in BMC and lumbar spine BMD values, while initial leptin concentration together with specific body composition parameters determined the loss in total and femoral neck BMD values in physically active older women.

Topics: Adiponectin; Aged; Aged, 80 and over; Aging; Biomarkers; Body Composition; Bone Density; Female; Femur Neck; Ghrelin; Humans; Leptin; Longitudinal Studies; Lumbar Vertebrae; Middle Aged; Motor Activity; Osteoporosis, Postmenopausal; Postmenopause; Predictive Value of Tests; Prospective Studies

The aim of this study was to identify and evaluate laboratory parameters associated with normal bone mineral density (BMD) and to test if -308 tumour necrosis factor (TNF) alpha gene promoter polymorphisms could influence BMD. We performed a comparative cross-sectional study of four main groups: young healthy individuals (20-30 years); subjects aged 50 years or over with normal BMD; osteoporotic subjects aged 50 years or over; osteoporotic women with active rheumatoid arthritis. Variables assessed included anthropometric features, diet intake, lifestyle, calcium-phosphorus balance, markers of bone turnover, sexual hormones, hormones related with body mass and growth, cytokines involved in inflammation and bone turnover, and -308 TNF alpha gene promoter polymorphisms. One hundred fifty-nine subjects were evaluated. Across the four groups, zinc serum levels were higher in men as compared to women. In addition, zinc serum levels were also higher in individuals with normal BMD as compared to osteoporotic subjects. Serum calcium levels were higher in normal BMD group. On the other hand, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were significantly higher in normal bone mass postmenopausal women and men as compared to age-matched osteoporotic groups. Finally, leptin was significantly lower in men, after correcting these results for body mass index values. The remaining variables assessed had a similar distribution among the different studied groups. In our population, low serum levels of leptin and high serum levels of zinc, calcium, FSH, and LH were associated with a higher BMD.

Topics: Adult; Aged; Bone Density; Calcium; Cross-Sectional Studies; Female; Humans; Leptin; Male; Middle Aged; Osteoporosis, Postmenopausal; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Sex Factors; Tumor Necrosis Factor-alpha; Zinc

The bone marrow contains mesenchymal stem cells (MSCs) that differentiate to the osteogenic and adipogenic lineages. The fact that the decrease in bone volume of age-related osteoporosis is accompanied by an increase in marrow adipose tissue implies the importance that the adipogenic process may have in bone loss. We previously observed that MSCs from control and osteoporotic women showed differences in their capacity to differentiate into the osteogenic and adipogenic pathways. In vitro studies indicate that bone marrow stromal cells are responsive to leptin, which increases their proliferation, differentiation to osteoblasts, and the number of mineralized nodules, but inhibits their differentiation to adipocytes. The aim of the present report was to study the direct effect of leptin on control and osteoporotic MSCs analyzing whether the protective effect of leptin against osteoporosis could be expressed by inhibition of adipocyte differentiation. MSCs from control, and osteoporotic donors were subjected to adipogenic conditions, in the absence or in the presence of 62.5 nM leptin. The number of adipocytes, the content of PPARgamma protein, and mRNA, and leptin mRNA were measured by flow cytometry, Western blot, and RT-PCR, respectively. Results indicate that control and osteoporotic MSCs differ in their adipogenic potential as shown by expression of active PPARgamma protein. Leptin exerted an antiadipogenic effect only on control MSCs increasing the proportion of inactive phosphorylated PPARgamma protein. Finally, results obtained during adipogenesis of osteoporotic cells suggest that this process is abnormal not only because of increased adipocyte number, but because of impaired leptin cells response.

Topics: Adipocytes; Adipogenesis; Aged; Aged, 80 and over; Bone Marrow Cells; Cell Differentiation; Female; Humans; Leptin; Mesenchymal Stem Cells; Osteoblasts; Osteoporosis, Postmenopausal; PPAR gamma

Topics: Adrenergic beta-Antagonists; Animals; Bone Density; Female; Fractures, Bone; Humans; Hypothalamus; Leptin; Osteoporosis; Osteoporosis, Postmenopausal; Receptors, Adrenergic, beta-2

Topics: Bone Remodeling; Bone Resorption; Humans; Leptin; Neuropeptide Y; Osteoclasts; Osteoporosis, Postmenopausal; Sympathetic Nervous System

Osteoporosis is less common in obese individuals with increased bone mineral density (BMD) and plasma leptin concentrations. The aim of this study was to determine the correlation between leptin levels and BMD in postmenopausal women. The study consisted of 90 postmenopausal women with a mean age of 53.45 +/- 0.87 years who visited our outpatient clinic for the evaluation of BMD. Thirty-six post-menopausal women with osteoporosis (mean age: 54.52 +/- 1.41 years and mean body mass index (BMI, kg/m2) 29.33 +/- 0.66), 30 age- and BMI-matched postmenopausal women with normal BMD, and 24 postmenopausal women (mean age: 52.79 +/- 1.48 years and mean BMI: 29.45 +/- 0.89) with osteopenic BMD were included in the study. Plasma concentrations of leptin after an overnight fast were measured by radioimmunoassay. BMD values were measured by dual-energy X-ray absorptiometry (DEXA) at the L2-L4 lumbar spine and femoral neck. The median spine BMD value in the patient group (0.67 +/- 0.08 g/cm2, mean +/- SEM) was significantly lower than that in the control group (1.02 +/- 0.25 g/cm2, mean +/- SEM) and osteopenic group (0.87 +/- 0.05 g/cm2, mean +/- SEM) (p < 0.005). The mean spine BMD value (T score -3.63 +/- 0.25, mean +/- SEM) and the mean femur neck BMD value (T score -2.55 +/- 0.18, mean +/- SEM) of the osteoporosis group were significantly lower than that in the normal BMD group (+ 0.33 +/- 0.14 and + 0.27 +/- 0.18, P < 0.001) and in the osteopenia group (-1.74 +/- 0,1 and -1.18 +/- 0.05, p < 0.005). The mean plasma leptin concentration in the osteoporotic group (17.03 +/- 1.40 ng/ml) was not significantly different from that in the normal BMD group and the osteopenia group (16.55 +/- 1.50 ng/ml; 16.16 +/- 1.60, respectively, p > 0.150). Plasma leptin concentrations were correlated with BMI in three groups (r(s) = 0.450, p = 0.025 in normal BMD group and r(s) = 0.4254, P = 0.009 in the osteoporotic group, and r(s) = 395, p = 0.015 in the osteopenia group. There was no correlation between plasma leptin concentrations and BMD values in three groups (r(s) = -0.89 in normal BMD group, r(s) = -0.124 in osteopenia group, and r(s) = -0.195 in osteoporosis group). From this study we conclude that circulating plasma leptin does not have a significant direct influence on bone mass in postmenopausal women.

Topics: Absorptiometry, Photon; Bone Density; Female; Femur Neck; Humans; Leptin; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause; Radioimmunoassay

the aim of this study was to evaluate the influence of serum leptin concentration on bone mass assessed by quantitative ultrasound (QUS) in a large sample of healthy pre and postmenopausal women.. 555 healthy pre and postmenopausal (n=261 and n=294) women (mean age, 49.5+/-17.2 years) not on hormone replacement therapy were recruited on the occasion of a routine gynecological visit. Before entry to the study, all women had answered a detailed questionnaire on important risk factors and gave written informed consent. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness index (SI) of the os Calcis were measured using the Achilles ultrasonometer (GE/lunar). We systematically investigated the relation of menopause, BMI and leptin on bone mass by allocating women into the following groups: (a) premenopausal women BMI<25 kg/m(2) (N=178); (b) premenopausal women BMI>25 kg/m(2) (N=83); (c) postmenopausal women BMI<25 kg/m(2) (N=125); and (d) postmenopausal women BMI>25 kg/m(2) (N=169). Additionally we investigated the relation of serum leptin concentrations, age and BMI on ultrasonometry variables by performing a multiple linear regression analyses.. in the initial analyses premenopausal women showed a significantly (P<0.001) lower mean age, weight, BMI, follicle stimulating hormone (FSH) and leptin concentration, a higher mean height, serum estradiol and ultrasonometry variables in comparison to postmenopausal women. Irrespective of the menopausal status, women with a BMI>25 kg/m(2) had significantly higher leptin concentrations (P<0.001) and BUA (P<0.05) whereas SOS and SI was not significant different, compared to women with a BMI<25 kg/m(2). The multiple linear regression analyses showed that only BMI but not Leptin was related to higher ultrasonometry variables, whereas increasing age was associated with a decrease in ultrasonometry variables. Furthermore, the multiple linear regression analyses confirmed that age and BMI were the only statistically significant independent predictor for ultrasonometry variables. There was no significant influence of leptin on ultrasonometry variables even after controlling for BMI or age, or BMI and age.. serum leptin concentrations are significantly higher in pre and postmenopausal obese women, compared with normal weight controls. Ultrasonometry variables are influenced by age and BMI but not by serum leptin concentrations.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Body Mass Index; Bone Density; Estradiol; Female; Germany; Humans; Leptin; Menopause; Middle Aged; Osteoporosis, Postmenopausal; Regression Analysis; Surveys and Questionnaires; Ultrasonography

We analyzed the relationship between serum leptin levels and bone mineral density (BMD) values as well as the relationship between serum leptin levels and whole body composition, whether or not they were associated. In addition, we also investigated whether lean mass or fat mass is a better predictor of BMD in postmenopausal Turkish women.. One hundred consecutive postmenopausal women with a mean age of 55.1 +/- 6.3 years who visited our outpatient clinic for the evaluation of osteoporosis were recruited. Skin fold thickness at four sites and waist:hip ratio were measured. Body mass index (BMI) was calculated in kg/m(2). Serum concentrations of leptin, insulin, and estradiol were evaluated. Bone formation and resorption markers were also determined. The BMD values were measured by dual energy X-ray absorptiometry (DEXA) at the lumbar spine and femoral neck. Whole body composition (lean mass, fat mass, and percentage of fat), total bone mineral content (BMC) in g, and total BMD were also measured by DEXA.. Serum leptin levels did not correlate with BMD values at all skeleton sites measured. Leptin correlated positively with fat mass, percentage of fat, and BMI (r = 0.738 and P = 0.00, r = 0.536 and P = 0.00, r = 0.356 and P = 0.00, respectively). Lean mass correlated with BMD at all sites measured (r = 0.339 and P = 0.00, r = 0.312 and P = 0.01, r = 0.523 and P = 0.00, r = 0.636 and P = 0.00). Lean mass correlated with BMI (r = 0.636, P = 0.00) but not with serum leptin (r = -0.021, P = 0.881), and it was an independent determinant of BMD at all skeleton sites measured.. Our study showed that lean mass is a better predictor than fat mass of bone mineral density and that serum leptin levels are not associated with BMD.

Topics: Body Composition; Bone Density; Bone Resorption; Female; Humans; Insulin; Leptin; Middle Aged; Osteogenesis; Osteoporosis, Postmenopausal; Predictive Value of Tests; Turkey

To determine whether leptin is involved in bone remodeling in patients with postmenopausal osteoporosis.. Cross-sectional study.. Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University.. Ninety postmenopausal osteoporotic women (37 obese and 53 nonobese) and 30 healthy premenopausal women from the same clinic served as controls. Lumbar spine bone mineral density (LS-BMD) of osteoporotic patients was more than 2.5 SD below the normal mean of healthy premenopausal women.. Serum levels of leptin, osteocalcin (OC), bone alkaline phosphatase (B-ALP), urinary deoxypyridinoline (DPyr), and N-telopeptide of type 1 collagen (NTX) as well as LS-BMD using dual energy X-ray absorptiometry (DEXA).. The serum leptin level in obese postmenopausal osteoporotic patients was significantly increased compared with nonobese osteoporotic patients. There were no significant differences of bone formation markers (B-ALP, OC), bone resorption markers (DPyr, NTX), or LS-BMD between the obese and nonobese groups. There were no significant correlations between serum leptin and any biomarkers of bone turnover and BMD.. In postmenopausal osteoporotic patients with increased bone turnover, serum leptin concentration is not correlated with BMD or with the biomarkers of bone formation or bone resorption.

Topics: Absorptiometry, Photon; Adult; Alkaline Phosphatase; Amino Acids; Bone Density; Bone Remodeling; Collagen; Collagen Type I; Cross-Sectional Studies; Female; Humans; Leptin; Lumbosacral Region; Middle Aged; Obesity; Osteocalcin; Osteoporosis, Postmenopausal; Peptides

Osteoprotegerin (OPG) is a recently identified citokine with an important role in bone remodeling, that acts as a decoy receptor for RANKL; OPG was shown to be an important inhibitor of osteoclast differentiation and activation. Leptin influences bone metabolism by acting on differentiated osteoblasts, having an anabolic effect on bone. The relationship between circulating OPG levels and osteoporosis in postmenopausal women is controversial. Thus, one of the aims of our study was to investigate the relationships between OPG levels and biochemical markers of bone turnover and bone density in women with and without osteoporosis. We have investigated 135 postmenopausal women, including a group with osteoporosis (n=76, mean age 59+/-8 years) and a group with severe osteoporosis (n=31, mean age 64+/-8 years), using healthy postmenopausal women (n=28, mean age 48+/-9 years) as controls. The serum concentrations of OPG were determinated by ELISA. Serum estradiol was measured by Enzyme Immunoassay (EIA). The markers of bone formation and resorption were measured by standard methods. Leptin was measured by ELISA. Bone mineral density at lumbar spine and femoral neck was measured by dual energy x-ray absorptiometry (DEXA). There was a significant positive association between serum OPG levels and age (r=0.27; p<0.001), both in the postmenopausal women as a whole and in the cohort with osteoporosis. Circulating OPG levels were significantly higher in both osteoporotic groups (p<0.005 and p<0.01, respectively) than in the control group. There were no significant associations between serum OPG levels and bone density, bone markers and serum estradiol. Serum leptin levels were significantly associated with age (r=0.18, p<0.03), estradiol (r=0.2, p<0.05) and BMD (r=0.25, p<0.008); there was no significant relationship between leptin and bone turnover markers. We conclude that serum OPG levels increase with age, both in healthy and osteoporotic postmenopausal women. This could represent a possible protective mechanism against bone loss. Serum leptin levels also increase with age and are positively associated with estradiol and BMD and not significantly associated with bone turnover markers.

Topics: Adult; Bone Density; Bone Resorption; Estradiol; Female; Glycoproteins; Humans; Leptin; Middle Aged; Osteoporosis, Postmenopausal; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Leptin; Receptors, Tumor Necrosis Factor

To investigate the effect of a low dose of fluoride on the plasma leptin concentration in postmenopausal women.. One hundred one healthy, postmenopausal women participated in this comparative study. To evaluate the influence of NaMFP treatment and body mass index (BMI) on leptin concentrations, patients were allocated to one of four groups: postmenopausal women (1) on NaMFP with BMI < 25 (n = 29), (2) on NaMFP with BMI > or = 25 (n = 26), (3) not on NaMFP with BMI > or = 25 (n = 24) and (4) not on NaMFP with BMI < 25 (n = 22). Plasma leptin levels were measured before and 12 months after the initiation of NaMFP or, in groups 3 and 4, after the start of the study. Ninety-eight women completed the study.. There were significant differences in leptin concentrations at baseline and 12 months between NaMFP users with BMI > or = 25 and BMI < 25 and between women not taking NaMFP with BMI > or = 25 and BMI < 25 (group 2 versus 1 and 3 versus 4). After controlling for BMI, the use of NaMFP was not found to be related to the leptin value (group 1 versus 4 and group 2 versus 3). Although plasma leptin concentrations tended to be decreased slightly at 12 months in NaMFP users, this decrease was not statistically significant (P = .065).. Leptin concentrations are significantly higher in obese, postmenopausal women than in nonobese, postmenopausal women. Plasma leptin concentrations are slightly but nonsignificantly influenced by long-term, low-dose fluoride treatment. Further studies are needed to elucidate the role of NaMFP on plasma leptin concentrations.

Topics: Body Mass Index; Female; Fluorides; Humans; Leptin; Middle Aged; Obesity; Osteoporosis, Postmenopausal; Phosphates

Although total fat body mass (FM) is considered to be one of the major determinants of bone mass, the mechanism by which FM and bone mass are positively correlated remains unclear. Leptin, the product of the obese (ob) gene, is secreted from adipocytes and its plasma levels are known to be positively correlated with %fat (FM divided by total body weight). There is recent evidence suggesting that leptin directly stimulates osteoblastic differentiation. Thus it is possible that the anabolic action of this hormone on bone may participate in the positive correlation between FM and bone mass. In this study, we analysed the relationships between either plasma leptin levels or %fat vs. bone mineral density (BMD) values as well as the presence of vertebral compression fractures, and evaluated whether or not plasma leptin levels were associated with BMD or bone fragility in a manner independent of FM.. One hundred and thirty-nine postmenopausal women (age 48-78 years, mean 62.5), who visited our outpatient clinic for the evaluation of osteoporosis.. Plasma concentrations of leptin after an overnight fast were measured by radioimmunoassay. BMD values were measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, femoral neck and whole body. Distal one-third of radius BMD was measured by single photon absorptiometry (SPA). Vertebral fractures were assessed by lateral thoracic and lumbar spine radiographs.. Although neither plasma leptin levels nor %fat correlated with age, there was a significant positive correlation between plasma leptin levels and %fat (r = 0.563, P < 0.001). Plasma leptin levels were significantly and positively correlated with BMD values at all skeleton sites measured, and multiple regression analysis revealed that this positive relationship was still observed with BMD values of the femoral neck and of the whole body, even after %fat and age were taken into account. Moreover, plasma leptin levels but not %fat were significantly lower in women with vertebral fractures than in those without fractures. When multiple logistic regression analysis was performed with either plasma leptin value or %fat employed as independent variables, plasma leptin values but not %fat were selected as an index affecting the presence of vertebral fractures.. Our study showed that plasma leptin levels but not %fat are associated with BMD and the presence of vertebral fractures in postmenopausal women, suggesting that circulating leptin might play a physiological role in maintaining bone mass as well as better bone quality.

Topics: Adipose Tissue; Aged; Body Composition; Bone Density; Female; Femur Neck; Humans; Leptin; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Radius; Regression Analysis; Spinal Fractures; Thoracic Vertebrae

The obese are usually protected against osteoporosis and have increased bone mineral density and plasma leptin concentrations. A recent in vitro study demonstrated that leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts, suggesting an influence of leptin on bone mass. However, little is known about the relationship between plasma leptin and bone mass in postmenopausal women with osteoporosis.. To investigate plasma leptin concentrations in postmenopausal women with osteoporosis to improve the understanding of the role of leptin in determining bone mass.. Fifty postmenopausal women with osteoporosis (ages 61.18+/-6.51 years; body mass index (BMI) 28. 91+/-3.44kg/m(2), mean+/-s.d.) and 30 age- and BMI-matched healthy postmenopausal women were included in the study. Bone mineral densities (BMD) were measured by dual energy X-ray absorptiometry. Plasma leptin concentrations were determined using an immunoradiometric assay.. The median spine BMD value in the patient group (0.695+/-8.26g/cm(2), median+/-s.e.m.) was significantly lower than that in the control group (1.006+/-1. 29g/cm(2), median+/-s.e.m.; z=-7.454, P<0.001). The median plasma leptin concentration in the patient group (18.70+/-1.78ng/ml, median+/-s.e.m.) was not significantly different from that in the control group (22.35+/-2.20ng/ml, median+/-s.e.m.; z=-1.630, P=0. 103). Plasma leptin concentrations were correlated with BMI in both groups (r(s)=0.394, P=0.031 in controls and r(s)=0.404, P=0.004 in the patient group). There was no correlation between plasma leptin concentrations and BMD values in controls (r(s)=-0.107, P=0.575) but a weak correlation was observed in the patient group (r(s)=0.285, P=0.045).. Our data suggest that circulating plasma leptin does not have a significant direct influence on bone mass in postmenopausal women.

Topics: Aged; Bone Density; Female; Humans; Leptin; Middle Aged; Osmolar Concentration; Osteoporosis, Postmenopausal; Reference Values