Relationship of serum GDF11 levels with bone mineral density and bone turnover markers in postmenopausal Chinese women

Growth differentiation factor 11 （GDF11） is an important circulating factor that regulates aging. However, the role of GDF11 in bone metabolism remains unclear. The present study was undertaken to investigate the relationship between serum GDF11 level, bone mass, and bone turnover markers in postmenopausal Chinese women. Serum GDF11 level, bone turnover biochemical markers, and bone mineral density （BMD） were determined in 169 postmenopausal Chinese women （47-78 years old）. GDF11 serum levels increased with aging. There were negative correlations between GDF11 and BMD at the various skeletal sites. After adjusting for age and body mass index （BMI）, the correlations remained statistically significant. In the multiple linear stepwise regression analysis, age or years since menopause, BMI, GDF11, and estradiol were independent predictors of BMD. A significant negative correlation between GDF11 and bone alkaline phosphatase （BAP） was identified and remained significant after adjusting for age and BMI. No significant correlation was noted between cross-linked N-telopeptides of type I collagen （NTX） and GDF11. In conclusion, GDF11 is an independent negative predictor of BMD and correlates with a biomarker of bone formation, BAP, in postmenopausal Chinese women. GDF11 potentially exerts a negative effect on bone mass by regulating bone formation.

Clinical application value of bone turnover markers in non-small-cell lung cancer patients with bone metastases

Objective:The purpose of this study was to assess the clinical application value of bone turnover markers in non-small-cell lung cancer(NSCLC) patients with bone metastases.Including diagnosing bone metastases,detecting bone metastatic spread.Methods:Alkaline phosphatase(AKP),β-C-terminal telopeptide of type I collagen(β-CTx),osteocalcin(OST) and bone alkaline phosphatase(BALP) were measured in 76 patients with bone metastases from NSCLC and 44 normal people.Results:The level of AKP,β-CTx and BALP in patients with bone metastasis was significantly higher than in the normal people.Significant correlation was observed among bone turnover markers.The levels of BALP and OST were significantly correlated with the extent of bone metastasis.The patients with high-level CTx and low-level BALP had higher risk of pathologic fracture.Conclusion:In NSCLC patients with bone metastases,bone turnover markers can help to make diagnosis and evaluate the severity.It will have a wide range of use in clinical practice.

Effect of Chongcao Bushen Capsule on bone turnover markers in patients with diabetic osteoporosis

Objective:To study the effect of Chongcao Bushen Capsules on bone turnover markers in patients with diabetic osteoporosis.Methods:107 patients with diabetic osteoporosis treated in the Hospital from December 2016 to November 2019were enrolled.They were divided into a control group(n=54)and an observation group(n=53)by random number table.The control group was treated with calcium carbonate,and the observation group was treated with Chongcao Bushen Capsules.The treatment effects,TCM syndrome scores,and bone turnover markers[including osteocalcin,type 1 procollagen amino-terminal propeptide(tP1NP),parathyroid hormone(PTH),25-hydroxyvitamin D,andβ-isomerized c-terminal peptide(β-CTx)],and the incidence of adverse reactions in the two groups were observed and compared.Results:After treatment,the total effective rate of treatment in the observation group(94.44%)was higher than that in the control group(73.58%),and the difference was statistically significant(P<0.05).The scores of symptoms including waist and knee weakness,back and waist pain,lower limb weakness,fatigue and tiredness,difficult walking and dizziness in the observation group were shown to be lower than the control group,and the difference was statistically significant(P<0.05).The levels of osteocalcin,PTH,tP1NP,andβ-CTx in the observation group were lower than those in the control group,and the difference was statistically significant(P<0.05).The 25-hydroxyvitamin D in the observation group was higher than the control group,and the difference was statistically significant(P<0.05).Bone density in both male and female in the observation group was higher than that in the control group,and the difference was statistically significant(P<0.05).Conclusion:For patients with diabetic osteoporosis,Chongcao Bushen Capsule can help improve their clinical symptoms,bone density and the level of bone turnover markers.

Correlation of Serum Leptin Level with Bone Mineral Density and Bone Turnover Markers in Chinese Adolescent Dancers

Objective To investigate plasma leptin concentrations in adolescent female dancers and to determine whether leptin has some effects on their bone mineral density （BMD） and bone turnover markers. Methods Sixty dancers aged 15-17 years and 77 healthy controls were enrolled in the study. Bone mineral density （BMD） and body composition were detected by dual energy X-ray absorptiometry. Serum leptin concentrations were measured by radioimmunoassay （RIA）. Two bone turnover markers, bone-specific alkaline phosphatase （BAP） and tartrate-resistant acid phosphatase（TRACP）, were determined by ELISA. Results The dancers had a lower fat mass and a lower leptin level than the controls, while they had a relatively higher BMD of the total body and legs after adjustment for BMI and age. The levels of bone resorption and formation of markers were higher in the dancers than in the controls. Leptin was positively correlated with BMI, body weight, fat mass, and percentage of body fat. In dancers, Leptin was positively correlated with the BMD of the total body and the left leg. However, after adjustment for BMI, no correlation of serum leptin concentrations with BMD values was found in either dancers or controls. Nor correlation was found between leptin and bone turnover markers after adjustment for BMI. Conelusion The leptin profile is different between the controls and the dancers with a lower BMI and a lower fat mass. Circulating plasma leptin level depends on BMI and is not a direct determinant of BMD in Chinese adolescent dancers.

Calcium-fortified fresh milk ameliorates postmenopausal osteoporosis via regulation of bone metabolism and gut microbiota in ovariectomized rats

The aging of the global population has made postmenopausal osteoporosis prevention essential;however,pharmacological treatments are limited.Herein,we evaluate the effect of calcium-fortified fresh milk(FM)in ameliorating postmenopausal osteoporosis in a rat model established using bilateral ovariectomy.After 3 months of FM(containing vitamin D,and casein phosphopeptides,1000 mg Ca/100 g)or control milk(110 mg Ca/100 g milk)supplementation,bone changes were assessed using dual-energy X-ray absorptiometry,microcomputed tomography,and bone biomechanical testing.The results revealed that FM can regulate bone metabolism and gut microbiota composition,which act on bone metabolism through pathways associated with steroid hormone biosynthesis,relaxin signaling,serotonergic synapse,and unsaturated fatty acid biosynthesis.Furthermore,FM administration significantly increased bone mineral content and density in the lumbar spine and femur,as well as femoral compressive strength,while improving femoral trabecular bone parameters and microarchitecture.Mechanistically,we found that the effects may be due to increased levels of estrogen,bone formation marker osteocalcin,and procollagen typeⅠN-propeptide,and decreased expression of the bone resorption marker C-telopiptide and tartrate-resistant acid phosphatase 5b.Overall,the findings suggest that FM is a potential alternative therapeutic option for ameliorating postmenopausal osteoporosis.

Unveiling osteoprotective potential of biologically active naringenin in rats with dexamethasone-induced osteoporosis

Objective To investigate the protective effects of naringenin(NRG)against dexamethasone(DEX)-induced osteoporosis(OP)in rats.Methods Molecular docking of NRG was done with AutoDock Vina 1.2.0 software.Forty-eight female Wistar rats were randomly divided into six groups(n=8 each):normal control(NC),DEX(7 mg/kg,i.m.),NRG-low(NRG-L;25 mg/kg,i.g.),NRG-medium(NRG-M;50 mg/kg,i.g.),NRG-high(NRG-H;100 mg/kg,i.g.),and alendronate(ALN;0.25 mg/d,i.g.)groups.OP was induced by administering DEX once a week for five weeks in all groups except NC group.Begining in the third week after the initial DEX administration,the rats in NRG-L,NRG-M,NRG-H,and ALN groups received the corresponding treatments daily for three weeks,while NC and DEX groups received no additional treatment.Serum samples were collected at the end of the experiment for biochemical,bone turnover,antioxidant,lipid profile,and inflammatory cytokine analyses.Femur bones underwent physical parameter testing and histopathological examination.Results The molecular docking results illustrated that NRG docked with calcitonin(CT),lowdensity lipoprotein(LDL),bone morphogenetic protein(BMP),vascular endothelial growth factor(VEGF)receptor,forkhead transcription factors,and osteoprogenitor cells showed good binding energy.In rats administered with 25,50,and 100 mg/kg NRG,there was a significant enhancement in serum biochemical indices,characterized by a reduction in tartrate-resistant acid phosphatase(TRAP),parathyroid hormone(PTH),and an elevation in osteocalcin(OC)and CT levels(P<0.05,P<0.01,and P<0.001,respectively).Despite no significant changes in thickness,weight,and length(P>0.05),there was a marked increase in bone mineral density(BMD)(P<0.01,P<0.001,and P<0.001,respectively).Antioxidant enzyme markers showed significant upregulation,with higher glutathione,superoxide dismutase,and catalase,and a concurrent decrease in malondialdehyde(MDA)(P<0.05,P<0.01,and P<0.001,respectively).The lipid profile also improved significantly,with lower cholesterol(CH),triglycerides(TG),and low-density lipoprotein(LDL)levels,and an increase in high-density lipoprotein(HDL)level(P<0.05,P<0.01,and P<0.001,respectively).Inflammatory cytokine levels were reduced,as evidenced by decreases in tumor necrosis factor(TNF),interleukin(IL)-6,and IL-1β(P<0.05,P<0.01,and P<0.001,respectively).Furthermore,histological alterations revealed obvious improvements,and the body weight of rats treated with NRG showed an increase compared with DEX group.Conclusion These findings imply that NRG exhibited a protective effect against DEX-induced OP in rats as it promotes the bone formation process by increasing the number of bone turnover markers including OC and CT,and restoring of antioxidant status,lipid metabolism,and inflammatory markers.

Bone mineral density in lifelong trained male football players compared with young and elderly untrained men

Purpose: The purpose of the present controlled cross-sectional study was to investigate proximal femur and whole-body bone mineral density(BMD), as well as bone turnover profile, in lifelong trained elderly male football players and young elite football players compared with untrained age-matched men.Methods: One hundred and forty healthy, non-smoking men participated in the study, including lifelong trained football players(FTE, n = 35)aged 65—80 years, elite football players(FTY, n = 35) aged 18—30 years, as well as untrained age-matched elderly(UE, n = 35) and young(UY,n = 35) men. All participants underwent a regional dual-energy X-ray Absorptiometry(DXA) scan of the proximal femur and a whole-body DXA scan to determine BMD. From a resting blood sample, the bone turnover markers(BTMs) osteocalcin, carboxy-terminal type-1 collagen crosslinks(CTX-1), procollagen type-1 amino-terminal propeptide(P1NP), and sclerostin were measured.Results: FTE had 7.3%—12.9% higher(p < 0.05) BMD of the femoral neck, wards, shaft, and total proximal femur in both legs compared to UE,and 9.3%—9.7% higher(p < 0.05) BMD in femoral trochanter in both legs compared to UY. FTY had 24.3%—37.4% higher(p < 0.001) BMD in all femoral regions and total proximal femur in both legs compared to UY. The whole-body DXA scan confirmed these results, with FTE showing similar whole-body BMD and 7.9% higher(p < 0.05) leg BMD compared to UY, and with FTY having 9.6% higher(p < 0.001) wholebody BMD and 18.2% higher(p < 0.001) leg BMD compared to UY. The plasma concentration of osteocalcin, CTX-1, and P1NP were 29%,53%, and 52% higher(p < 0.01), respectively, in FTY compared to UY.Conclusion: BMD of the proximal femur and whole-body BMD are markedly higher in lifelong trained male football players aged 65—80 years and young elite football players aged 18—30 years compared to age-matched untrained men. Elderly football players even show higher BMD in femoral trochanter and leg BMD than untrained young despite an age difference of 47 years.

Effect of chronic sleep deprivation on peak bone mass in rats: An experimental study

Objective:To investigate the effects of chronic sleep deprivation(CSD)on bone microstructure and peak bone mass(PBM)in SD rats.Methods:Twenty-four SD rats were randomly divided into CSD group and control group.In the CSD group,a CSD model was established using a new sleep deprivation instrument for rats and mice,and intervened for 5 weeks.Bone turnover markers including P1NP and CTX-1 before and after the experiment were observed.After the experiment,the left femur were scanned by Micro-CT,and the cortical bone and bone trabecula were three-dimensionally reconstructed,respectively.The bone mineral density(BMD)and relevant parameters were detected.Results:CT images of the femur(proximal ends)showed significant trabecular loss in CSD rats.Trabecular parameters including bone volume fraction(BV/TV),trabecular number(Tb.N)and trabecular separation(Tb.Sp)in the CSD group were all lower than those in the control group.The bone cortex of the middle segment of the femur and tibia in CSD rats was also lower than that in the control group.The parameters of bone cortex including total tissue area(Tt.Ar),cortical bone area(Ct.Ar)and cortical bone thickness(Ct.Th)in the CSD group were significantly lower than those in the control group(P<0.01).After chronic CSD,BMD of both bone trabecula and bone cortex of the femur was lower,while the corresponding P1NP and CTX-1 were significantly higher than those in the control group.Conclusion:Sleep plays an important role in PBM formation.CSD accelerates bone turnover and thus significantly reducing PBM in SD rats.

Bone Loss in Women with Type 1 Diabetes

Background: Although osteoporosis has been investigated and debated in the diabetic population over the past decades, very little is known about the spontaneous changes in bone mineral density (BMD) and biochemical markers of bone turnover in pre- and postmenopausal type 1 diabetic (T1DM) women over time. Aim: To measure spontaneous changes in BMD and biochemical markers of bone turnover in pre- and postmenopausal T1DM women. Subjects: 53 T1DM women (31 premenopausal and 22 postmenopausal) from the outpatient clinic were enrolled in the study in 1993 and 35 (22 premenopausal, 13 postmenopausal) were reexamined in 1997. Method: BMD was measured at femoral neck (f.n.), spine (L2 - L4), total body and forearm with DXA or SXA in 53 T1DM women. 4 years later a re-scan was carried out on 35 T1DM. Results: In premenopausal subjects a yearly decrease less than 1% at f.n., spine, forearm and total body was observed, though only statistically significant (s.s.) at f.n., p ≤ 0.05. In postmenopausal subjects a s.s. decrease less than 2% was observed at f.n., forearm and total body, p ≤ 0.05. In general, osteopenic or osteoporotic values were observed at the measured skeletal sites. Only at f.n. a lower s.s. BMD compared to age-matched reference women was seen. Conclusion: Small or non-significant changes in BMD and biochemical markers of bone turnover were observed in pre- and postmenopausal T1DM subjects after a 4-year period.

Urinary cross-linked N-telopeptides of type Ⅰ collagen and bone metabolic diseases

Objective To evaluate the type I collagen cross linked N telopeptide (NTx) levels in human urine as an indicator of bone resorption rate in different ages, sex and in bone metabolic diseases.Methods Urinary NTx was determined by immunoassay in 591 Beijing healthy subjects aged from 0 to 86 years and 379 patients with bone metabolic diseases.Results The levels of urinary NTx were significantly higher in children than in adults (P<0.001) and higher in boys than in girls (P<0.01) and increased 1.4-2.2 times in postmenopausal females than in men and premenopausal women. Urine NTx had a positive linear correlation with urine HOP/Cr (r= 0.778, P< 0.01) and Ca/Cr ratio (r=0.320, P< 0.01 ), and a negative linear correlation with age (r= -0.523, P<0.01) and lumbar spine BMD (r= -0.426, P<0.01). The levels of urine NTx increased for 3.6 times in pregnancy, 1.5 times in osteoporosis, 1.9 times in fragility fracture, 3.6 times in chronic renal failure, 2.1 times in rickets and 7.2 times in multiple myeloma compared to age matched controls.Conclusions NTx in urine is a specific and sensitive indicator of bone resorption and is able to distingish normal premenopause from late osteoporotic patients. NTx could be used as diagnostic information about metabolic bone diseases, and to monitor antiresorptive therapy.