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Relationships Between the Changes of Serum Levels of OPG and RANKL with Age, Menopause, Bone Biochemical Markers and Bone Mineral Density in Chinese Women Aged 20-75

The correlations between the serum levels of OPG, RANKL with age, menopause, bone markers, and bone mineral densities (BMDs) at the lumbar spine and proximal femur were studied in 504 pre- and postmenopausal Chinese women aged 20–75 years. We found that age was positively and negatively correlated with serum concentrations of OPG (r = 0.442, P < 0.001) and RANKL (r = −0.263, P < 0.001), respectively. Compared with premenopausal women, postmenopausal women showed higher serum OPG levels (107.6 ± 3.0 vs 72.0 ± 1.8 pg/ml, P < 0.001), lower serum RANKL concentrations (4.7 ± 0.4 vs. 5.8 ± 0.3 pg/ml, P < 0.001) and RANKL/OPG ratios (0.045 ± 0. 004 vs. 0.099 ± 0.008, P < 0.001). Neither serum levels of OPG nor RANKL or RANKL/OPG ratio correlated with BMDs after adjustment of age and menopause. They also showed no differences among normal, osteopenic and osteoporotic postmenopausal women. Serum levels of OPG were positively correlated with urinary excretion of NTx (r = 0.1453, P = 0.006). Serum levels of RANKL (r = −0.1928, P < 0.001) and RANKL/OPG ratio (r = −0.1303, P = 0.013) were inversely correlated with serum concentrations of OC. In multiple regression analysis, up to 20% variance (R2 = 0.106–0.224) of the OPG-RANKL system in peripheral circulation can be explained by age, menopause and bone markers.These results suggest that although serum OPG and RANKL concentrations were unrelated with BMDs, the age– and menopause– dependent changes of serum OPG and RANKL might be a protective mechanism against the accelerated bone loss in postmenopausal women.

IGF-1 as an early marker for low bone mass or osteoporosis in premenopausal and postmenopausal women.

To find out which of the following parameters—serum levels of insulin-like growth factor 1 (IGF-1), osteoprotegerin (OPG), leptin, osteocalcin (OC), and urinary excretion of N-terminal telopeptide of type I collagen (NTx), can be used as an early marker for osteopenia/osteoporosis in women diagnosed by dual-energy X-ray absorptiometry (DXA), 282 premenopausal and 222 postmenopausal women aged 20–75 years were investigated by the measurement of bone mineral densities (BMDs) at lumbar spine (LS) and femoral neck (FN) by DXA, together with serum concentrations of IGF-1, OPG, leptin, OC, and urinary NTx. The characteristics of the earliest marker(s) were tested with the receiver operating characteristic (ROC) analysis. The area under the curve (AUC), sensitivity, and specificity parameters were determined. It was revealed that serum levels of IGF-1 and leptin changed the earliest, with both markers significantly decreasing (P < 0.0001) or increasing (P = 0.020), respectively, at age 30. However, in ROC analysis, IGF-1 was the only early parameter that had the capacity to differentiate the low bone mass/osteoporosis women from the normal ones (P < 0.0001). If the serum level of IGF-1 at 1.5 SD below its peak was adopted as a cutoff point, it could identify women with low bone mass/osteoporosis with a sensitivity of 73% and specificity of 67%. In the premenopausal women subgroup analysis, the low bone mass women (30/282, 10.6%) were older (38.2 ± 1.7 vs. 34.5 ± 0.5 years; P = 0.026), with lower serum levels of IGF-1 (215.1 ± 22.4 vs. 278.8 ± 9.4 ng/ml; P = 0.02) and less lean mass (33.1 ± 0.6 vs. 34.8 ± 0.2 kg; P = 0.010) than the normal ones. After controlling for age, the serum level of IGF-1 had a weak, but still significant, positive correlation with lean mass (r = 0.17, P < 0.001). In conclusion, measurement of serum IGF-1 in young women may help in the early identification of those at risk for developing low bone mass and osteoporosis.

The effects of bisphenol A (BPA) exposure on fat mass and serum leptin concentrations have no impact on bone mineral densities in non-obese premenopausal women

OBJECTIVES Bisphenol A (BPA) exposure may promote obesity, but its effect on bone mineral density (BMD) has not been reported in humans. We aimed to examine the relationships between BPA exposure, body composition, serum estradiol, leptin, osteocalcin levels and BMDs in healthy premenopausal women. DESIGN AND METHODS In this cross-sectional study, a total of 246 healthy premenopausal women aged 20 years and older with regular menstrual cycles were investigated. Body mass index (BMI), fat mass, fat-free mass and BMDs were measured by DXA. Serum estradiol, leptin, osteocalcin, urinary BPA and NTx levels were also tested. RESULTS Urinary BPA levels were positively associated with fat mass (r=0.193, p=0.006) and leptin (r=0.236, p=0.001) but not with fat-free mass after adjusting for age and BMI. BPA was not associated with serum estradiol levels, BMDs, or bone resorption marker NTx and bone formation parameter osteocalcin, either. A multivariate stepwise regression analysis confirmed that serum leptin levels were positively influenced by fat mass (β=0.746, p<0.001) and BPA (β=0.127, p=0.01) but negatively correlated with fat-free mass (β=-0.196, p<0.001). However, the changes of BMDs at the lumbar spine (β=0.298, p<0.001) and femoral neck (β=0.305, p<0.001) were primarily explained by fat-free mass, and were irrelevant of the fat mass, leptin or BPA exposure. CONCLUSIONS Although BPA exposure is related with increased amount of fat mass and elevated serum leptin levels, it has neutral effect on BMDs in premenopausal women, possibly due to the exclusive role of fat-free mass, which is unrelated to BPA in determining BMDs.

Relationships between insulin-like growth factor-I (IGF-I) and OPG, RANKL, bone mineral density in healthy Chinese women

SummarySerum IGF-I level was negatively correlated with OPG and OPG/RANKL ratio, but positively correlated with RANKL. Serum OPG level in the highest quintile of IGF-I was significantly lower than that in the lowest. We conclude that the effect of IGF-I on bone remodeling may be mediated by the OPG/RANKL system.IntroductionInsulin-like growth factor I (IGF-I) is an important factor in coupling bone remodeling, activating both formation and resorption. Compared with the many studies on the role of IGF-I in bone formation, the information regarding its effects on bone resorption is limited and conflicting. The balance of the two peptides produced by osteoblasts, osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL), is critical for the bone resorption process. Our study was designed to analyze the relationships of serum concentrations of IGF-I with OPG, RANKL, OPG/RANKL ratio as well as BMDs in healthy Chinese women.MethodsBMDs at lumbar spine and proximal femur in 504 pre- and postmenopausal women were measured by DXA. Serum levels of IGF-I, OPG and RANKL were also measured. Pearson’s correlation and partial correlation analysis, ANOVA, covariance analysis and stepwise multiple regression analysis were used as appropriate.ResultsAge was negatively correlated with serum levels of IGF-I (r = −0.702, p < 0.001). IGF-I was negatively correlated with OPG and OPG/RANKL ratio, but positively correlated with RANKL. The relationship between IGF-I and BMDs disappeared after adjustment for age. In postmenopausal women, IGF-I was lower in women with osteoporosis than in those with normal BMD (p = 0.056), but no differences were found among OPG, RANKL and OPG/RANKL ratio. Serum levels of OPG in the highest quintile of IGF-I were significantly lower than those in the lowest quintile of IGF-I, while no difference was found in RANKL. In the multiple regression analysis model, serum levels of IGF-I were the main determinants of the bone mass in Chinese women.ConclusionsIn conclusion, the relationship between decreasing IGF-I and BMDs in healthy Chinese women influenced by age, whereas the effect of IGF-I on bone remodeling (bone resorption) may be mediated by the OPG/RANKL system.

An Independent Positive Relationship Between the Serum Total Osteocalcin Level and Fat-Free Mass in Healthy Premenopausal Women

CONTEXT It is widely reported that osteocalcin is negatively associated with fat mass. However, there are few reports describing its correlation with fat-free mass, particularly in women. OBJECTIVES The objective of the current study was to investigate the possible relationship between osteocalcin and fat-free mass in healthy, nonobese women. DESIGN AND SETTING This study was performed in a tertiary university teaching hospital. SUBJECTS A total of 504 healthy women aged 20-75 years were enrolled. MAIN OUTCOME MEASURES Body composition was measured using a bioelectronics impedance analyzer. The serum concentrations of total osteocalcin, estradiol, leptin, osteoprotegerin, the receptor activator of nuclear factor-κB ligand, IGF-I, fasting plasma glucose, and urinary N-terminal telopeptide of type I collagen were tested. The bone mineral densities (BMDs) at the lumbar spine and proximal femoral neck were measured by dual-energy X-ray absorptiometry. RESULTS The serum total osteocalcin level had a significant positive association with fat-free mass (r = 0.168, P = .007) after adjusting for age, fat mass, menopausal status, estradiol, fasting glucose, leptin, osteoprotegerin, receptor activator of nuclear factor-κB ligand, IGF-I, N-terminal telopeptide of type I collagen, BMDs, and waist and hip circumference. Analysis in pre- and postmenopausal women demonstrated that this association was only present in premenopausal women (r = 0.190, P = .005). The multiple stepwise regression analysis revealed that hip circumference, femoral neck-BMD, fat mass, leptin, osteocalcin, and age are the contributors to the changes in fat-free mass in premenopausal women (adjusted R(2) = 0.521, P < .001). CONCLUSION The serum level of total osteocalcin was positively associated with fat-free mass independent of age, fat mass, leptin, and other confounders in premenopausal women.

Association of Serum Fetuin-A Levels With the Risk of Albuminuria in Middle-Aged and Elderly Chinese

CONTEXT Fetuin-A is an important hepatokine associated with many cardiometabolic abnormities. The association between fetuin-A and albuminuria has not been investigated in a prospective cohort. OBJECTIVE The objective of the study was to prospectively investigate whether serum fetuin-A levels were associated with albuminuria in middle-aged and elderly Chinese. DESIGN, SETTING, AND PARTICIPANTS A community-based study was conducted at baseline in 2009, including 3102 individuals aged 40 years or older and followed up for 4 years. MAIN OUTCOME MEASURES Baseline and follow-up urine samples were collected to measure urinary albumin and creatinine concentrations. Albuminuria was defined as urinary albumin to creatinine ratio (UACR) of 30 mg/g or greater. RESULTS A total of 194 participants (8.5%) developed albuminuria during the follow-up. Men who developed albuminuria had significantly higher baseline levels of fetuin-A compared with those who did not (338.2 vs 292.9 mg/L, P = .02). Among men, after adjustment for traditional risk factors, each 1-SD increase of fetuin-A level (131.6 mg/L) was associated with a 32% higher risk for developing albuminuria (odds ratio 1.32, 95% confidence interval 1.07-1.62). In addition, among men, compared with participants in the lowest tertile (<253.1 mg/L) of serum fetuin-A levels, those in the highest tertile (>338.2 mg/L) had a 2-fold risk for developing albuminuria (odds ratio 2.07, 95% confidence interval 1.04-4.12) after multivariate adjustment. No association between fetuin-A levels and incident albuminuria was observed in women. CONCLUSIONS High serum fetuin-A levels were independently associated with an increased risk of developing albuminuria in middle-aged and elderly men, whereas no significant associations were found in women.

Two unusual cases of intractable hyperthyroidism responsive to octreotide: Munchausen syndrome or not?

BACKGROUND The effective treatment for patients with resistant hyperthyroidism is difficult. METHODS In this case report with 4-year follow-up data, we present 2 unusual cases of hyperthyroidism that were unresponsive to almost all antithyroid treatments including total thyroidectomy, but both were controlled with octreotide. RESULTS Cases 1 and 2 were both middle-aged women. They presented thyrotoxicosis with a low serum concentration of TSH and thyroidal radioactive iodine uptake (RAIU). The underlying causes, such as thyroiditis, metastatic thyroid cancer and struma ovarii were explored. Iodine-induced hyperthyroidism, particularly factitious hyperthyroidism was highly suspected, but there was no direct evidence to establish these diagnoses. In spite of good compliance, their thyrotoxicosis could not be controlled with large doses of PTU or MMI. β-blocker, methylprednisolone, radio-iodine therapy and even thyroidectomy were all attempted and failed. Short-acting octreotide was first administered to case 1 and then to case 2. Thyroid function improved greatly within 3 days in both cases. The doses of octreotide were tapered down to twice a week with consistent efficacy. During the follow-up periods, case 1 required octreotide 0.1mg twice per week and case 2 is on thyroid replacement therapy due to hypothyroidism. The recurrences of hyperthyroidism in both cases were again rapidly controlled with the increased dose of octreotide in case 1 and re-started the usage of octreotide in case 2. CONCLUSIONS The etiology of thyrotoxicosis in these 2 cases is not clear. In the absence of struma ovarii or wide-spread follicular thyroid cancer, factitious hyperthyroidism due to Munchausen syndrome should be considered first. The efficacy of the off-label use of octreotide in hyperthyroidism was highly effective (only) in these 2 cases.