Correlation between bone turnover and metabolic markers with age and gender: a cross-sectional study of hospital information system data.
ABSTRACT: BACKGROUND:Bone turnover and metabolic indicators are related to age and gender. Age and gender should be matched in subjects in disease control research of bone turnover and metabolism, but strict matching of gender and age increases the difficulty and cost of the research. Therefore, the aim of this study was to solve it is necessary to strictly match age and gender in clinical research in bone metabolism. METHODS:A cross-sectional study was conducted from the data were extracted from the HIS of ZhuJiang Hospital. Data relating to seven bone turnover and metabolic indicators from 1036 patients between January 2018 and October 2019 were analyzed. RESULTS:P1NP, ?-CTx and 25(OH)D were significant different in individuals younger than 20?years of age. ALP was significantly higher in those under 20?years of age and lower at age 20-39 compared with other age groups. The concentrations of Ca and P were different among the groups aged 0-19, 20-39, and 40-59?years of age groups but exhibited no difference above 60?years of age. PTH expression was not dependent on age. P1NP, ?-CTx and PTH concentrations were not significantly different between the genders within the same age group. ALP was significantly different between genders within the age range 20-59?years. Ca and 25(OH)D were significantly different between the genders for those older than 60. Serum P was significantly different in the two genders for those aged 40-79. Patients received both alfacalcidol and calcium treatment differently from the others in P1NP, ?-CTx, Serum Ca, P and ALP. CONCLUSION:P1NP and ?-CTx were highly correlated with age. If these two indictors require analysis in a case control study, the patients and controls should be strictly matched by age under 20?years. The demarcation point for ALP was 40?years of age. Ca and P were strongly recommended strict matching according to age in disease research. The difference in P1NP, ?-CTx, 25(OH)D and ALP between genders depends on age differences. Medication history should be considered in bone turnover and metabolic clinical research.
Project description:Phenylalanine hydroxylase (PAH) deficiency is a genetic disorder characterized by deficiency of the PAH enzyme. Patients follow a phenylalanine-restricted diet low in intact protein, and must consume synthetic medical food (MF) to supply phenylalanine-free protein. We assessed relationships between dietary intake and nutrient source (food or MF) on bone mineral density (BMD) and bone turnover markers (BTM) in PAH deficiency. Blood from 44 fasted females 11-52 years of age was analyzed for plasma phenylalanine, serum BTM [CTx (resorption), P1NP (formation)], vitamin D, and parathyroid hormone (PTH). BTM ratios were calculated to assess resorption relative to formation (CTx/P1NP). Dual energy X-ray absorptiometry measured total BMD and age-matched Z-scores. Three-day food records were analyzed for total nutrient intake, nutrients by source (food, MF), and compliance with MF prescription. Spearman's partial coefficients (adjusted for age, BMI, energy intake, blood phenylalanine) assessed correlations. All had normal BMD for age (Z-score >-2). Sixty-four percent had high resorption and normal formation indicating uncoupled bone turnover. CTx/P1NP was positively associated with food phenylalanine (r 2 = 0.39; p-value = 0.017), energy (r 2 = 0.41; p-value = 0.011) and zinc (r 2 = 0.41; p-value = 0.014). CTx/P1NP was negatively associated with MF fat (r 2 = -0.44; p-value = 0.008), MF compliance (r 2 = -0.34; p-value = 0.056), and positively with food sodium (r 2 = 0.43; p-value = 0.014). CTx/P1NP decreased significantly with age (p-value = 0.002) and higher PTH (p-value = 0.0002). Phenylalanine was not correlated with any bone indicator. Females with PAH deficiency had normal BMD but elevated BTM, particularly resorption. More favorable ratios were associated with nutrients from MF and compliance. Younger females had less favorable BTM ratios. Promoting micronutrient intake through compliance with MF may impact bone metabolism in patients with PAH deficiency. SYNOPSIS:Bone mineral density was normal in 44 females with PAH deficiency; however, bone turnover markers suggested uncoupling of bone resorption and formation, particularly in younger patients. Adequate nutrient intake from medical food and overall medical food compliance may positively impact bone turnover.
Project description:BACKGROUND:In patients with type 2 diabetes mellitus (T2DM), higher risks of impaired bone metabolism are widely reported. To evaluate bone metabolism, bone mineral density (BMD) and bone turnover levels should be included. In this article, we analyzed the relationship between them in T2DM. METHODS:We conducted a hospital-based cross-sectional study enrolling 1499 patients hospitalized for T2DM between October 2009 and January 2013. Multivariate linear regression models were used to identify the relationship between bone turnover markers (BTMs) and BMD levels. A two-sided P-value < .05 was considered statistically significant. RESULTS:After adjusting for confounding factors, osteocalcin (OC) showed a negative relationship with total lumbar, femur neck, and total hip BMD in men and women. N-terminal propeptides of type I collagen (P1NP) and alkaline phosphatase (ALP) showed a negative association with BMD at three sites in men and total lumbar BMD in women, whereas in the femur neck and total hip in women, the relationship was only found for P1NP with total hip. For ?-C-terminal telopeptides of type I collagen (?-CTX), a negative relationship was also found in all three sites for BMD in men and total lumbar BMD in women, whereas ?-CTX was not associated in the femoral neck and total hip in women. CONCLUSION:In patients with T2DM, serum levels of OC, P1NP, ?-CTX, and ALP were negatively correlated with BMD levels in men in three sites and with total lumbar BMD in women. The relationship varied in femur neck and total hip BMD in women.
Project description:<h4>Background</h4>Biochemical markers of bone turnover are lower in patients with type 2 diabetes, which may be explained by genetic variants being associated with type 2 diabetes and bone turnover as well as environmental factors. We hypothesized that bone turnover markers associate with and predict changes in glucose homeostasis after control for genetics and shared environment.<h4>Methods</h4>1071 healthy, non-diabetic (at baseline, 1997-2000) adult mono- and dizygotic twins participating in the prospective study GEMINAKAR were reassessed between 2010 and 2012 with clinical evaluation, biochemical tests and oral glucose tolerance test. Fasting bone turnover markers (CTX, P1NP and osteocalcin) were measured. The association between bone turnover, glucose homeostasis and the ability of bone turnover markers to predict changes in glucose homeostasis were assessed in cross-sectional and longitudinal analyses. Analyses were performed both at an individual level and adjusted for shared environmental and genetic factors.<h4>Results</h4>Glucose levels increased with age, and 33 (3%) participants had developed type 2 diabetes at follow-up. In women, bone turnover markers increased with age, whereas for men only osteocalcin increased with age. Bone turnover markers were not associated with fasting glucose, insulin, or HOMA-IR at baseline or follow-up before or after adjustment for age, sex, BMI, smoking, and use of medication at baseline. Variation in bone turnover markers was mainly explained by unique environmental factors, 70%, 70% and 55% for CTX, P1NP and osteocalcin, respectively, whereas additive genetic factors explained 7%, 13% and 45% of the variation in CTX, P1NP and osteocalcin.<h4>Conclusions</h4>Bone turnover markers were not associated with baseline plasma glucose levels and did not predict changes in glucose homeostasis. Variation in bone turnover markers is mainly explained by environmental factors, however, compared to CTX and P1NP, genetic factors have a larger impact on osteocalcin levels.
Project description:Objective:Bone health in SLE is adversely affected by vitamin D deficiency, inflammatory cytokines and glucocorticoid use. We hypothesised that vitamin D supplementation would increase markers of bone formation and decrease markers of bone resorption in SLE subjects. Methods:We studied 43 vitamin D-deficient SLE subjects who participated in a 12-week randomised controlled trial of 2000-4000?IU/day vitamin D supplementation versus placebo. Subjects had inactive SLE (SLE Disease Activity Index ?4) and were taking <20?mg prednisone daily at baseline. We assayed baseline and week 12 serum 25-hydroxyvitamin D, N-terminal propeptide of type 1 collagen (P1NP) and C-telopeptide (CTX). We tested the effect of vitamin D versus placebo on change (?) in P1NP and ?CTX in an intention-to-treat analysis. Secondary analyses evaluated whether vitamin D affected bone turnover among subjects achieving vitamin D repletion (?30?ng/mL) or currently taking glucocorticoids. Results:28 subjects were randomised to vitamin D and 15 to placebo. Mean age was 39 years and 40% were using glucocorticoids at enrolment. Repletion was achieved by 46% in the vitamin D group versus none in the placebo group. Changes in bone turnover markers were not significantly different in the vitamin D group versus placebo group (median ?P1NP -0.2 vitamin D group vs -1.1 placebo group (p=0.83); median ?CTX +3.5 vitamin D group vs -37.0 placebo group (p=0.50)). The effect of vitamin D did not differ based on achieving vitamin D repletion or baseline glucocorticoid use. Conclusion:Vitamin D supplementation did not affect the 12-week change in bone turnover markers among SLE subjects in this trial.
Project description:The osteocyte's role in orchestrating diurnal variations in bone turnover markers (BTMs) is unclear. We identified no rhythm in serum sclerostin (osteocyte protein). These results suggest that serum sclerostin can be measured at any time of day and the osteocyte does not direct the rhythmicity of other BTMs in men. INTRODUCTION:The osteocyte exerts important effects on bone remodeling, but its rhythmicity and effect on the rhythms of other bone cells are not fully characterized. The purpose of this study was to determine if serum sclerostin displays rhythmicity over a 24-h interval, similar to that of other bone biomarkers. METHODS:Serum sclerostin, FGF-23, CTX, and P1NP were measured every 2 h over a 24-h interval in ten healthy men aged 20-65 years. Maximum likelihood estimates of the parameters in a repeated measures model were used to determine if these biomarkers displayed a diurnal, sinusoidal rhythm. RESULTS:No discernible 24-h rhythm was identified for sclerostin (p = 0.99) or P1NP (p = 0.65). CTX rhythmicity was confirmed (p < 0.001), peaking at 05:30 (range 01:30-07:30). FGF-23 levels were also rhythmic (p < 0.001), but time of peak was variable (range 02:30-11:30). The only significant association identified between these four bone biomarkers was for CTX and P1NP mean 24-h metabolite levels (r = 0.65, p = 0.04). CONCLUSIONS:Sclerostin levels do not appear to be rhythmic in men. This suggests that in contrast to CTX, serum sclerostin could be measured at any time of day. The 24-h profiles of FGF-23 suggest that a component of osteocyte function is rhythmic, but its timing is variable. Our results do not support the hypothesis that osteocytes direct the rhythmicity of other bone turnover markers (CTX), at least not via a sclerostin-mediated mechanism.
Project description:Epidemiologic data suggest older adults receiving serotonergic antidepressants may have accelerated bone loss. We examined bone turnover marker changes and patient-level variables associated with these changes in older adults receiving protocolized antidepressant treatment.Open-label, protocolized treatment study.Medical centers in Pittsburgh, St Louis, and Toronto.Older adults with major depression (N = 168).Serum levels of the bone resorption marker C-terminal cross-linking telopeptide of type 1 collagen (CTX) and the bone formation marker procollagen type 1 N propeptide (P1NP) were assayed before and after 12 weeks of treatment with venlafaxine. Whether CTX and P1NP changes were associated with depression remission and duration of depression and genetic polymorphisms in the serotonin transporter (5HTTLPR) and 1B receptor (HTR1B) were also examined.CTX increased and P1NP decreased during venlafaxine treatment, a profile consistent with accelerated bone loss. Two individual-level clinical variables were correlated with bone turnover; participants whose depression did not go into remission had higher CTX levels, and those with chronic depression had lower P1NP levels. HTR1B genotype predicted P1NP change, whereas 5HTTLPR genotype was unrelated to either biomarker.Bone turnover markers change with antidepressant treatment in a pattern that suggests accelerated bone loss, although the clinical significance of these changes is unclear. These data are preliminary and argue for a larger, controlled study to confirm whether antidepressants are harmful to bone metabolism and whether certain individuals might be at increased risk.
Project description:The Maternal Vitamin D Osteoporosis (MAVIDOS) trial reported higher total body bone mineral content in winter-born infants of mothers receiving vitamin D supplementation [1000 IU/day cholecalciferol] compared with placebo from 14 weeks gestation until delivery. This sub-study aimed to determine whether antenatal vitamin D supplementation altered postnatal bone formation in response to mechanical stimulation. Thirty-one children born to MAVIDOS participants randomised to either placebo (n=19) or cholecalciferol (n=12) were recruited at age 4-5 years. Children received whole body vibration (WBV) for 10 minutes on 5 consecutive days. Fasting blood samples for bone homeostasis, 25 hydroxyvitamin D (25OHD), parathyroid hormone (PTH), and bone turnover markers (Pro-collagen Type 1 N-terminal propeptide, P1NP; Cross-linked C-telopeptide of Type I Collagen, CTX) were collected pre-WBV and on day 8 (D8). Mean changes (D) in P1NP (ng/ml) between baseline and D8 in the vitamin-D intervention and placebo groups were 40.6 and -92.6 respectively and mean changes (?) in CTX (ng/ml) were 0.034 (intervention) and -0.084 (placebo) respectively. Between-group DP1NP difference was 133.2ng/ml [95% CI 0.4, 266.0; p=0.049] and ?CTX 0.05ng/ml (95% CI -0.159, 0.26ng/mL; p=0.62). Antenatal vitamin-D supplementation resulted in increased P1NP in response to WBV, suggesting early life vitamin D supplementation increases the anabolic response of bone to mechanical loading in children.
Project description:OBJECTIVE:Bone turnover, which regulates bone mass, may exert metabolic consequences, particularly on markers of glucose metabolism and adiposity. To better understand these relationships, we examined cross-sectional associations between bone turnover markers (BTMs) and metabolic traits in a population with high bone mass (HBM, BMD Z-score ?+3.2). DESIGN:?-C-terminal telopeptide of type-I collagen (?-CTX), procollagen type-1 amino-terminal propeptide (P1NP) and osteocalcin were assessed by electrochemiluminescence immunoassays. Metabolic traits, including lipids and glycolysis-related metabolites, were measured using nuclear magnetic resonance spectroscopy. Associations of BTMs with metabolic traits were assessed using generalized estimating equation linear regression, accounting for within-family correlation, adjusting for potential confounders (age, sex, height, weight, menopause, bisphosphonate and oral glucocorticoid use). RESULTS:A total of 198 adults with HBM had complete data, mean [SD] age 61.6 [13.7] years; 77% were female. Of 23 summary metabolic traits, citrate was positively related to all BTMs: adjusted ??-CTX = 0.050 (95% CI 0.024, 0.076), P = 1.71 × 10-4 , ?osteocalcin = 6.54 × 10-4 (1.87 × 10-4 , 0.001), P = .006 and ?P1NP = 2.40 × 10-4 (6.49 × 10-5 , 4.14 × 10-4 ), P = .007 (? = increase in citrate (mmol/L) per 1 µg/L BTM increase). Inverse relationships of ?-CTX (? = -0.276 [-0.434, -0.118], P = 6.03 × 10-4 ) and osteocalcin (-0.004 [-0.007, -0.001], P = .020) with triglycerides were also identified. We explored the generalizability of these associations in 3664 perimenopausal women (age 47.9 [4.4] years) from a UK family cohort. We confirmed a positive, albeit lower magnitude, association between ?-CTX and citrate (adjusted ?women = 0.020 [0.013, 0.026], P = 1.95 × 10-9 ) and an inverse association of similar magnitude between ?-CTX and triglycerides (? = -0.354 [-0.471, -0.237], P = 3.03 × 10-9 ). CONCLUSIONS:Bone resorption is positively related to circulating citrate and inversely related to triglycerides. Further studies are justified to determine whether plasma citrate or triglyceride concentrations are altered by factors known to modulate bone resorption, such as bisphosphonates.
Project description:The balance between bone resorption and formation may be assessed by measurement of bone turnover markers (BTMs), like carboxyl-terminal cross-linked telopeptide of type 1 collagen (CTX-1) and procollagen type 1 amino-terminal propeptide (P1NP). Smoking has been shown to influence bone turnover and to reduce bone mass density (BMD), the exact mechanism for this is, however, not settled. In this post-hoc study including 406 subjects (mean age 51.9 years), we aimed to study the impact of smoking on bone turnover. Moreover, we wanted to assess the inter-correlation between substances regulating bone metabolism and BTMs, as well as tracking over time. BMD measurements and serum analyses of CTX-1, P1NP, osteoprotegerin (OPG), receptor activator of nuclear factor ?B ligand (RANKL), Dickkopf-1 (DKK1), sclerostin, tumor necrosis factor-? (TNF-?), and leptin were performed. Repeated serum measurements were made in 195 subjects after four months. Adjustments were made for sex, age, body mass index (BMI), smoking status, insulin resistance, serum calcium, parathyroid hormone, 25-hydroxyvitamin D and creatinine. Smokers had higher levels of DKK1 and OPG, and lower levels of RANKL, as reflected in lower BTMs and BMD compared to non-smokers. There were strong and predominantly positive inter-correlations between BTMs and the other substances, and there was a high degree of tracking with Spearman's rho from 0.72 to 0.92 (P < 0.001) between measurements four months apart. In conclusion, smokers exhibited higher levels of DKK1 and OPG and a lower bone turnover than did non-smokers. The strong inter-correlations between the serum parameters illustrate the coupling between bone resorption and formation and crosstalk between cells.