Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Osteoporosis International
Published in: Osteoporosis International 10/2019

01-10-2019 | Original Article

Effects of calcium supplementation on circulating osteocalcin and glycated haemoglobin in older women

Authors: J. R. Lewis, T. C. Brennan-Speranza, I. Levinger, E. Byrnes, E. M. Lim, L. C. Blekkenhorst, M. Sim, J. M. Hodgson, K. Zhu, W. H. Lim, L. A. Adams, R. L. Prince

Published in: Osteoporosis International | Issue 10/2019

Login to get access

Abstract

Summary

One year of calcium supplementation in older women led to modest reductions in total osteocalcin and undercarboxylated osteocalcin (ucOC), with no changes in muscle or fat mass, or glycated haemoglobin. Future studies should explore whether treatments with more profound effects of suppressing ucOC may lead to impaired glycaemic control.

Introduction

Total osteocalcin (TOC) is a marker of bone turnover, while its undercarboxylated form has beneficial effects on glucose metabolism in mice. This post hoc analysis of a randomised double-blind, placebo-controlled trial examined whether 1 year of calcium supplementation affected circulating TOC, undercarboxylated osteocalcin (ucOC) or glycated haemoglobin (HbA1c) in 1368 older community-dwelling women (mean age 75.2 ± 2.7 years).

Methods

Women enrolled in the Calcium Intake Fracture Outcome Study trial (1998–2003) were supplemented with 1.2 g/d of elemental calcium (in the form of calcium carbonate) or placebo. Circulating TOC, ucOC and HbA1c was measured at 1 year (1999).

Results

After 1 year of calcium supplementation, TOC and ucOC levels were 17% and 22% lower compared with placebo (mean 22.7 ± 9.1 vs. 27.3 ± 10.9 μg/L and 11.1 ± 4.9 vs. 13.0 ± 5.7 μg/L, both P < 0.001). Carboxylated osteocalcin/ucOC was 6% lower after calcium supplementation (P < 0.05). Despite this, no differences in HbA1c were observed (calcium, 5.2 ± 0.6 vs. placebo, 5.3 ± 0.8%; P = 0.08). Calcium supplementation did not affect BMI, whole body lean or fat mass. In exploratory analyses, total calcium (dietary and supplemental) was inversely related to TOC and ucOC, indicating calcium intake is an important dietary determinant of osteocalcin levels.

Conclusion

One year of calcium supplementation in older women led to modest reductions in TOC and ucOC, with no changes in muscle or fat mass, or HbA1c. Future studies should explore whether treatments with more profound effects of suppressing ucOC may lead to impaired glycaemic control.
Appendix
Available only for authorised users
Literature
1.
Karsenty G (1998) Transcriptional regulation of osteoblast differentiation during development. Front Biosci 3:834–837CrossRef
2.
Hauschka PV, Lian JB, Gallop PM (1975) Direct identification of the calcium-binding amino acid, gamma-carboxyglutamate, in mineralized tissue. Proc Natl Acad Sci U S A 72:3925–3929CrossRef
3.
Price PA, Otsuka AA, Poser JW, Kristaponis J, Raman N (1976) Characterization of a gamma-carboxyglutamic acid-containing protein from bone. Proc Natl Acad Sci U S A 73:1447–1451CrossRef
4.
Brennan-Speranza TC, Conigrave AD (2015) Osteocalcin: an osteoblast-derived polypeptide hormone that modulates whole body energy metabolism. Calcif Tissue Int 96:1–10CrossRef
5.
Hauschka PV, Lian JB, Cole DE, Gundberg CM (1989) Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev 69:990–1047CrossRef
6.
Ferron M, McKee MD, Levine RL, Ducy P, Karsenty G (2012) Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice. Bone 50:568–575CrossRef
7.
Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G (2007) Endocrine regulation of energy metabolism by the skeleton. Cell 130:456–469CrossRef
8.
Ferron M, Hinoi E, Karsenty G, Ducy P (2008) Osteocalcin differentially regulates β cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci U S A 105:5266–5270CrossRef
9.
Shen H, Grimston S, Civitelli R, Thomopoulos S (2015) Deletion of connexin43 in osteoblasts/osteocytes leads to impaired muscle formation in mice. J Bone Min Res 30:596–605CrossRef
10.
Lin X, Hanson E, Betik AC, Brennan-Speranza TC, Hayes A, Levinger I (2016) Hindlimb immobilization, but not castration, induces reduction of undercarboxylated osteocalcin associated with muscle atrophy in rats. J Bone Min Res 31:1967–1978CrossRef
11.
Ferron M, Lacombe J (2014) Regulation of energy metabolism by the skeleton: osteocalcin and beyond. Arch Biochem Biophys 561:137–146CrossRef
12.
Booth SL, Centi A, Smith SR, Gundberg C (2012) The role of osteocalcin in human glucose metabolism: marker or mediator? Nat Revs Endocrinol 9:43–55CrossRef
13.
Bullo M, Moreno-Navarrete JM, Fernandez-Real JM, Salas-Salvado J (2012) Total and undercarboxylated osteocalcin predict changes in insulin sensitivity and beta cell function in elderly men at high cardiovascular risk. Am J Clin Nutr 95:249–255CrossRef
14.
Pittas AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B (2009) Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 94:827–832CrossRef
15.
Schafer AL, Sellmeyer DE, Schwartz AV, Rosen CJ, Vittinghoff E, Palermo L, Bilezikian JP, Shoback DM, Black DM (2011) Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin: parathyroid hormone (1-84) or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study). J Clin Endocrinol Metab 96:E1982–E1989CrossRef
16.
Ngarmukos C, Chailurkit LO, Chanprasertyothin S, Hengprasith B, Sritara P, Ongphiphadhanakul B (2012) A reduced serum level of total osteocalcin in men predicts the development of diabetes in a long-term follow-up cohort. Clin Endocrinol 77:42–46CrossRef
17.
Shea M, Dawson-Hughes B, Gundberg CM, Booth SL (2017) Reducing undercarboxylated osteocalcin with vitamin K supplementation does not promote lean tissue loss or fat gain over 3 years in older women and men: a randomized controlled trial. J Bone Min Res 32:243–249CrossRef
18.
Schwartz AV, Schafer AL, Grey A, Vittinghoff E, Palermo L, Lui LYL, Wallace RB, Cummings SR, Black DM, Bauer DC, Reid IR (2013) Effects of antiresorptive therapies on glucose metabolism: results from the FIT, HORIZON-PFT, and FREEDOM trials. J Bone Min Res 28:1348–1354CrossRef
19.
Diaz-Lopez A, Bullo M, Juanola-Falgarona M, Martinez-Gonzalez MA, Estruch R, Covas MI, Aros F, Salas-Salvado J (2013) Reduced serum concentrations of carboxylated and undercarboxylated osteocalcin are associated with risk of developing type 2 diabetes mellitus in a high cardiovascular risk population: a nested case-control study. J Clin Endocrinol Metab 98:4524–4531CrossRef
20.
21.
Institute of Medicine (2011) Dietary reference intakes for calcium and vitamin D, Washington DC, USA
22.
National Health and Medical Research Council (Australia)., New Zealand. Ministry of Health., Australia. Dept. of Health and Ageing (2006) Nutrient reference values for Australia and New Zealand : including recommended dietary intakes. National Health and Medical Research Council, Canberra
23.
Zhu K, Bruce D, Austin N, Devine A, Ebeling PR, Prince RL (2008) Randomized controlled trial of the effects of calcium with or without vitamin D on bone structure and bone-related chemistry in elderly women with vitamin D insufficiency. J Bone Min Res 23:1343–1348CrossRef
24.
Prince RL, Devine A, Dhaliwal SS, Dick IM (2006) Effects of calcium supplementation on clinical fracture and bone structure: results of a 5-year, double-blind, placebo-controlled trial in elderly women. Arch Intern Med 166:869–875CrossRef
25.
Bruce DG, Devine A, Prince RL (2002) Recreational physical activity levels in healthy older women: the importance of fear of falling. J Am Geriatr Soc 50:84–89CrossRef
26.
Britt H, Scahill S, Miller G (1997) ICPC PLUS for community health? A feasibility study. J Health Info Manage Assoc Aust 27:171
27.
Gundberg CM, Lian JB, Gallop PM (1983) Measurements of gamma-carboxyglutamate and circulating osteocalcin in normal children and adults. Clin Chim Acta 128:1–828CrossRef
28.
Hodge A, Patterson AJ, Brown WJ, Ireland P, Giles G (2000) The Anti Cancer Council of Victoria FFQ: relative validity of nutrient intakes compared with weighed food records in young to middle-aged women in a study of iron supplementation. Aust N Z J Public Health 24:576–583CrossRef
29.
Ireland P, Jolley D, Giles G, O’Dea K, Powles J, Ritishauser I, Wahlqvist ML, Williams J (1994) Development of the Melbourne FFQ: a food frequency questionnaire for use in an Australian prospective study involving an ethnically diverse cohort. Asia Pac J Clin Nutr 3:19–31PubMed
30.
US Department of Agriculture ARS, and Nutrient Data Laboratory (2015) USDA National Nutrient Database for Standard Reference, Release 28
31.
Schurgers LJ, Vermeer C (2001) Determination of phylloquinone and menaquinones in food. Pathophysiol Haemost Thromb 30:298–307CrossRef
32.
Manoury E, Jourdon K, Boyaval P, Fourcassie P (2013) Quantitative measurement of vitamin K 2 (menaquinones) in various fermented dairy products using a reliable high-performance liquid chromatography method. J Dairy Sci 96:1335–1346CrossRef
33.
Lambert LJ, Challa AK, Niu A, Zhou L, Tucholski J, Johnson MS, Nagy TR, Eberhardt AW, Estep PN, Kesterson RA, Grams JM (2016) Increased trabecular bone and improved biomechanics in an osteocalcin-null rat model created by CRISPR/Cas9 technology. Dis Model Mech 9:1169–1179CrossRef
34.
Levinger I, Jerums G, Stepto NK, Parker L, Serpiello FR, McConell GK, Anderson M, Hare DL, Byrnes E, Ebeling PR, Seeman E (2014) The effect of acute exercise on undercarboxylated osteocalcin and insulin sensitivity in obese men. J Bone Min Res 29:2571–2576CrossRef
35.
Levinger I, Zebaze R, Jerums G, Hare DL, Selig S, Seeman E (2011) The effect of acute exercise on undercarboxylated osteocalcin in obese men. Osteoporos Int 22:1621–1626CrossRef
36.
Liu DM, Guo XZ, Tong HJ, Tao B, Sun LH, Zhao HY, Ning G, Liu JM (2015) Association between osteocalcin and glucose metabolism: a meta-analysis. Osteoporos Int 26:2823–2833CrossRef
37.
Levinger I, Seeman E, Jerums G et al (2016) Glucose-loading reduces bone remodeling in women and osteoblast function in vitro. Physiol Rep 4(3):e12700CrossRef
Metadata
Title
Effects of calcium supplementation on circulating osteocalcin and glycated haemoglobin in older women
Authors
J. R. Lewis
T. C. Brennan-Speranza
I. Levinger
E. Byrnes
E. M. Lim
L. C. Blekkenhorst
M. Sim
J. M. Hodgson
K. Zhu
W. H. Lim
L. A. Adams
R. L. Prince
Publication date
01-10-2019
Publisher
Springer London
Published in
Osteoporosis International / Issue 10/2019
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-019-05087-3

Other articles of this Issue 10/2019

Osteoporosis International 10/2019 Go to the issue

Concise Clinical Review

Practical tips for prescribing exercise for fall prevention

Original Article

A population-based study of postfracture care in Manitoba, Canada 2000/2001–2014/2015

Original Article

A multicenter, randomized, rater-blinded, parallel-group, phase 3 study to compare the efficacy, safety, and immunogenicity of biosimilar RGB-10 and reference once-daily teriparatide in patients with osteoporosis

Review

Risk of fracture with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors in real-world use: systematic review and meta-analysis of observational studies

Original Article

The renin-angiotensin aldosterone system and osteoporosis: findings from the Women’s Health Initiative

Original Article

Thoracic kyphosis assessment in postmenopausal women: an examination of the Flexicurve method in comparison to radiological methods