leptin and Spinal-Fractures

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

Adiponectin and leptin are adipokines that influence bone metabolism in vitro and in animal models. However, less is known about the longitudinal association of leptin and adiponectin with fracture. We tested the hypothesis that low leptin and high adiponectin levels are each individually associated with fracture risk in a prospective cohort study in Memphis and Pittsburgh among 3075 women and men aged 70 to 79 years from the Health Aging and Body Composition (Health ABC) study. There were 406 incident fractures (334 nonvertebral and 72 vertebral) over a mean of 6.5 ± 1.9 years. Cox regression was used to estimate the hazard ratios for fracture. Sex modified the association between adiponectin and fracture (p = .025 for interaction). Men with the highest adiponectin level (tertile 3) had a 94% higher risk of fracture [hazard ratio (HR) = 1.94; 95% confidence interval (CI) 1.20-3.16] compared with the lowest tertile (tertile 1; p = .007 for trend) after adjusting age, race, body mass index (BMI), education, diabetes, weight change, and hip bone mineral density (BMD). Among women, after adjusting for age and race, this association was no longer significant (p = .369 for trend). Leptin did not predict fracture risk in women (p = .544 for trend) or men (p = .118 for trend) in the multivariate models. Our results suggest that adiponectin, but not leptin, may be a novel risk factor for increased fracture risk independent of body composition and BMD and that these relationships may be influenced by sex. More research is needed to understand the physiologic basis underlying these sex differences.

Topics: Adiponectin; Adult; Aged; Female; Fractures, Bone; Humans; Leptin; Male; Proportional Hazards Models; Risk Factors; Sex Characteristics; Spinal Fractures

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