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Correlations Between Changes in Undercarboxylated Osteocalcin and Muscle Function in Hypoparathyroidism.

ABSTRACT: BACKGROUND:Muscles and bones are interconnected. Recent studies suggest that undercarboxylated osteocalcin from bone may affect muscle mass and strength. There are, however, no prospective human data on this relationship. METHODS:We previously treated patients with hypoparathyroidism with intact Parathyroid Hormone (PTH) or placebo in a six-month randomized, placebo-controlled trial and demonstrated a marked increase in undercarboxylated osteocalcin (ucOC) in the PTH-treated group. We therefore investigated if this increase correlated with changes in muscle mass, strength or function. Primarily, the muscle mass using Dual energy X-ray Absorptiometry (DXA) was measured and the maximal voluntary isometric muscle strength at the upper and lower extremities, using dynamometry, was assessed. Furthermore, repeated chair stands test, Timed Up and Go test were performed and postural stability using a stadiometer was assessed. Finally, the relationship between change in ucOC or the ratio of the changes in ucOC and total OC (ucOC%/OC%) and different measures of muscle function were analyzed, using regression analyses. RESULTS:The findings indicated that ucOC%/OC% was positively and significantly associated with percentage change in max force production during elbow extension (? = 0.28, P = 0.034), however, all other associations were non-significant. CONCLUSIONS:Given the number of statistical tests that were carried out, our one significant finding may represent a false positive. Thus the results do not support the role of ucOC in muscle function in humans with hypoparathyroidism. Our results are inconsistent with previous data from a human cross-sectional study; however, cross-sectional studies, do not allow for inference of causality. The analyses should be repeated in larger, randomized trials including healthy individuals.

SUBMITTER: Harslof T

PROVIDER: S-EPMC5138377 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Correlations Between Changes in Undercarboxylated Osteocalcin and Muscle Function in Hypoparathyroidism.

Harslof Torben T Sikjaer Tanja T Mosekilde Leif L Langdahl Bente L BL Rejnmark Lars L

International journal of endocrinology and metabolism 20160701 3

<h4>Background</h4>Muscles and bones are interconnected. Recent studies suggest that undercarboxylated osteocalcin from bone may affect muscle mass and strength. There are, however, no prospective human data on this relationship.<h4>Methods</h4>We previously treated patients with hypoparathyroidism with intact Parathyroid Hormone (PTH) or placebo in a six-month randomized, placebo-controlled trial and demonstrated a marked increase in undercarboxylated osteocalcin (ucOC) in the PTH-treated group ...[more]

PMID: 27942265

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Project description:INTRODUCTION:The global burden of type 2 diabetes (T2DM) is steadily increasing. Experimental studies have demonstrated that a novel hormone secreted by bone cells, osteocalcin (OC), can stimulate beta-cell proliferation and improve insulin sensitivity in mice. Observational studies in humans have investigated the relationship between OC and metabolic parameters, and T2DM. Importantly, few studies have reported on the undercarboxylated form of OC (ucOC), which is the putative active form of OC suggested to affect glucose metabolism. OBJECTIVES:We will conduct a systematic review and meta-analysis to: (1) compare the levels of serum OC and ucOC between T2DM and normal glucose-tolerant controls (NGC); (2) investigate the risk ratios between serum OC and ucOC, and T2DM; (3) determine the correlation coefficient between OC and ucOC and fasting insulin levels, homeostatic model assessment-insulin resistance, haemoglobin A1c and fasting glucose levels and (4) explore potential sources of between-study heterogeneity. The secondary objective is to compare the serum OC and ucOC between pre-diabetes (PD) and NGC and between T2DM and PD. HODS AND ANALYSIS:This study will report items in line with the guidelines outlined in preferred reporting items for systematic reviews and meta-analysis of observational studies in epidemiology. We will include observational studies (cohort, case-control and cross-sectional studies) and intervention studies with baseline data. Three databases (MEDLINE, EMBASE and SCOPUS) will be searched from inception until July 2018 without language restrictions. Two reviewers will independently screen the titles and abstracts and conduct a full-text assessment to identify eligible studies. Discrepancies will be resolved by consensus with a third reviewer. The risk of bias assessment will be conducted by two reviewers independently based on the Newcastle-Ottawa Scale. Potential sources of between-study heterogeneity will be tested using meta-regression/subgroup analyses. Contour-enhanced funnel plots and Egger's test will be used to identify potential publication bias. ETHICS AND DISSEMINATION:Formal ethical approval is not required. We will disseminate the results to a peer-reviewed publication and conference presentation. PROSPERO REGISTRATION NUMBER:CRD42017073127.

Project description:CONTEXT:Animal studies indicate that osteocalcin (OC), particularly the undercarboxylated isoform (unOC), affects insulin sensitivity and secretion, but definitive data from humans are lacking. OBJECTIVE:The objectives of the study were to determine whether total OC and unOC are independently associated with insulin sensitivity and ?-cell response in overweight/obese adults; whether glucose tolerance status affects these associations; and whether the associations are independent of bone formation, as reflected in procollagen type 1 amino propeptide (P1NP). DESIGN, SETTING, AND PARTICIPANTS:This was a cross-sectional study conducted at a university research center involving 63 overweight/obese adults with normal (n = 39) or impaired fasting glucose (IFG; n = 24). MAIN OUTCOME MEASURES:Serum concentrations of total/undercarboxylated OC and P1NP were assessed by RIA; insulin sensitivity was determined by iv glucose tolerance test (S(I)-IVGTT), liquid meal test (S(I) meal), and homeostasis model assessment of insulin resistance; ?-cell response to glucose [basal ?-cell response to glucose; dynamic ?-cell response to glucose; static ?-cell response to glucose; and total ?-cell response to glucose] was derived using C-peptide modeling of meal test data; and intraabdominal adipose tissue was measured using computed tomography scanning. RESULTS:Multiple linear regression, adjusting for intraabdominal adipose tissue and P1NP, revealed that total OC was positively associated with S(I)-iv glucose tolerance test (P < .01) in the total sample. OC was not associated with S(I) meal or homeostasis model assessment of insulin resistance. In participants with IFG, unOC was positively associated with static ?-cell response to glucose and total ?-cell response to glucose (P < .05), independent of insulin sensitivity. CONCLUSIONS:In overweight/obese individuals, total OC may be associated with skeletal muscle but not hepatic insulin sensitivity. unOC is uniquely associated with ?-cell function only in individuals with IFG. Further research is needed to probe the causal inference of these relationships and to determine whether indirect nutrient sensing pathways underlie these associations.

Project description:Osteocalcin in its undercarboxylated form (ucOC) may influence diabetes risk; however, its relationship with all-cause and cause-specific mortality is unclear. Whether other bone turnover markers (BTMs) are associated with mortality risk differently from ucOC also remains uncertain. Our aim was to determine associations of serum ucOC with all-cause and cause-specific mortality and compare these with the corresponding associations of serum total osteocalcin (TOC), procollagen type I N-propeptide (PINP), and collagen type 1 C-terminal cross-linked telopeptide (CTX) in older men. We conducted a prospective cohort study of 3871 community-dwelling men, aged 77.0 ± 3.6 years at baseline, followed for a median of 12.3 years. Exposure variables were ucOC, TOC, PINP, and CTX concentrations assayed in serum. Outcomes were incidence of all deaths and deaths due to cardiovascular disease (CVD) or cancer, ascertained using death registry data. Cox regression analyses adjusted for cardiovascular risk factors and prevalent CVD and for prevalent cancer in analyses of cancer-related mortality. Higher concentrations of ucOC, PINP, and CTX were associated with all-cause mortality (hazard ratio [HR] per 1 standard deviation increase: ucOC 1.12, 95% confidence interval [CI] 1.06-1.18, p < 0.001; PINP HR = 1.06, 95% CI 1.01-1.11, p = 0.009; CTX HR = 1.13, 95% CI 1.08-1.19, p < 0.001), but TOC was not associated. Similar results were found after excluding men with an incident fracture during follow-up. Higher ucOC and CTX were associated with CVD mortality (ucOC HR per 1 SD increase 1.13, 95% CI 1.05-1.22, p = 0.001; CTX HR = 1.12, 95% CI 1.04-1.20, p = 0.003), but this result was not significant in competing risks analysis. Higher CTX was also associated with cancer mortality (HR = 1.12, 95% CI 1.01-1.23, p = 0.024). In conclusion, in older men, higher bone turnover, assessed by BTMs including ucOC, is a biomarker for all-cause mortality risk. Undercarboxylated osteocalcin was a more informative biomarker for this outcome than TOC. Higher CTX was associated with all-cause and cancer-related mortality. Further evaluation of causality and potential underlying mechanisms is warranted. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Dataset Information

Correlations Between Changes in Undercarboxylated Osteocalcin and Muscle Function in Hypoparathyroidism.

Publications

Correlations Between Changes in Undercarboxylated Osteocalcin and Muscle Function in Hypoparathyroidism.

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