Effect of Vitamin K Supplementation on Circulating Levels of Osteocalcin on the Bone Metabolism and Aging

NCT04669782 | Terminated DMC

• 1 other identifier: OstMARK
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

Brief Summary

This is an interventional study on nutraceuticals. It is a randomized controlled, open-label, prospective, single-center study that involves the enrollment of 82 patients with osteoporosis and 41 subjects without osteoporosis. The hypothesis the decarboxylated form of Osteocalcin (OC), called GluOC, represents a clinically useful marker for monitoring the effects of supplementation with vitamin K in association with anabolic treatment with teriparatide will be analyzed not only on bone but also on skeletal muscle and energy metabolism in patients with severe osteoporosis.

Conditions

Bone Metabolism Disorder; Aging Disorder; Osteoporosis

Keywords

osteocalcin; vitamin k

Outcome Measures

Primary Outcomes (1)

• Circulating levels of GluOC

  Circulating levels of GluOC measured after 18 months of treatment with vitamin K

  18 months

Secondary Outcomes (1)

• Circulating levels of OC isoforms

  18 months

Study Arms (3)

Patients with osteoporosis treated with teriparatide + Vitamin K

EXPERIMENTAL

Patients will have to take teriparatide (standard of care) + Vitamin K (MK7) at the dosage of 375 microg / day

Dietary Supplement: Vitamin K (MK7); Drug: Teriparatide

Patients with osteoporosis treated with teriparatide

ACTIVE COMPARATOR

Patients will have to take teriparatide (standard of care)

Drug: Teriparatide

Controls

NO INTERVENTION

Subject without osteoporosis, no treatment will be administered.

Interventions

Vitamin K (MK7) DIETARY_SUPPLEMENT

MK-7 will be administered at a dose of 375 microg / day

Patients with osteoporosis treated with teriparatide + Vitamin K

Teriparatide DRUG

Teriparatide will be administered as standard of care

Patients with osteoporosis treated with teriparatide; Patients with osteoporosis treated with teriparatide + Vitamin K

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age ≥ 65 years
• Serum levels of 25OHD\> 30 ng / ml (as per clinical practice)
• Adequate calcium intake (assessed by questionnaire)
• Diagnosis of severe primary osteoporosis
• Criteria for the prescription and reimbursement of treatment with Teriparatide 20 microg / day subcutaneous according to the Italian Agency of Pharma (AIFA) 79
• Patient suitable for treatment with MK-7
• Informed consent freely acquired before the person was enrolled
• Age ≥ 65 years
• Serum levels of 25OHD\> 30 ng / ml (as per clinical practice)
• Adequate calcium intake (assessed by questionnaire).
• Informed consent freely acquired before the person was enrolled

You may not qualify if:

• causes of secondary osteoporosis: current glucocorticoid therapy, active and uncontrolled rheumatic diseases, endogenous hypercortisolism, uncontrolled hyperthyroidism or hypothyroidism (except known hypothyroidism well compensated with L-thyroxine), chronic renal failure (IRC) with glomerular filtration rate (GFR) \<30 ml / min, multiple myeloma, liver failure (chronic liver disease of CHILD class B and C), heart failure (New York Heart Association, also said NHYA) NHYA\> 2, active neoplasms, type 1 and type 2 diabetes mellitus
• ongoing therapies: glucocorticoids, antiepileptics, aromatase inhibitors and similar gonadotropin-releasing hormone (GnRH, contraindicated for teriparatide).
• ongoing therapies: glucocorticoids, antiepileptics, diphosphonates, teriparatide, denosumab, statins, oral or injective hypoglycemic agents, aromatase inhibitors, similar GnRH or other oncological therapies
• diagnosis of osteoporosis (according to World Health Organization, WHO) T-score \<-2.5 standard deviation (SD), at any site evaluated with ''Dual-Energy X-ray Absorptiometry'' (DXA)
• diagnosis of sarcopenia (according to ''Appendicular Skeletal Muscle Mass'', ASMMI) ASMMI \<7.59 kg / m2 for males and 5.47 kg / m2 for females evaluated with DXA
• diagnosis of IRC with estimated GFR \<30 ml / minute, liver failure (chronic liver disease of CHILD class B and C), heart failure with NHYA\> 2 , active neoplasms, endocrinopathies (except known hypothyroidism well compensated with L-thyroxine ), type 1 and type 2 diabetes mellitus.

Sponsors & Collaborators

• University of Milano Bicocca: lead

Study Sites (1)

Istituto Ortopedico Galeazzi IRCCS

Milan, Italy

Location

Related Publications (8)

• Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003 Aug;35(8):1381-95. doi: 10.1249/01.MSS.0000078924.61453.FB.

  PMID: 12900694 BACKGROUND

• Airoldi C, Giovannardi S, La Ferla B, Jimenez-Barbero J, Nicotra F. Saturation transfer difference NMR experiments of membrane proteins in living cells under HR-MAS conditions: the interaction of the SGLT1 co-transporter with its ligands. Chemistry. 2011 Nov 25;17(48):13395-9. doi: 10.1002/chem.201102181. Epub 2011 Oct 27. No abstract available.

  PMID: 22031470 BACKGROUND

• Anastasilakis A, Goulis DG, Koukoulis G, Kita M, Slavakis A, Avramidis A. Acute and chronic effect of teriparatide on glucose metabolism in women with established osteoporosis. Exp Clin Endocrinol Diabetes. 2007 Feb;115(2):108-11. doi: 10.1055/s-2007-967090.

  PMID: 17318770 BACKGROUND

• Ebina K, Hashimoto J, Shi K, Kashii M, Hirao M, Yoshikawa H. Comparison of the effect of 18-month daily teriparatide administration on patients with rheumatoid arthritis and postmenopausal osteoporosis patients. Osteoporos Int. 2014 Dec;25(12):2755-65. doi: 10.1007/s00198-014-2819-x. Epub 2014 Aug 1.

  PMID: 25082556 BACKGROUND

• Ferron M, McKee MD, Levine RL, Ducy P, Karsenty G. Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice. Bone. 2012 Feb;50(2):568-75. doi: 10.1016/j.bone.2011.04.017. Epub 2011 Apr 29.

  PMID: 21550430 BACKGROUND

• Grasso D, Corsetti R, Lanteri P, Di Bernardo C, Colombini A, Graziani R, Banfi G, Lombardi G. Bone-muscle unit activity, salivary steroid hormones profile, and physical effort over a 3-week stage race. Scand J Med Sci Sports. 2015 Feb;25(1):70-80. doi: 10.1111/sms.12147. Epub 2013 Oct 31.

  PMID: 24433517 BACKGROUND

• Gundberg CM, Lian JB, Booth SL. Vitamin K-dependent carboxylation of osteocalcin: friend or foe? Adv Nutr. 2012 Mar 1;3(2):149-57. doi: 10.3945/an.112.001834.

  PMID: 22516722 BACKGROUND

• Knapen MHJ, Jardon KM, Vermeer C. Vitamin K-induced effects on body fat and weight: results from a 3-year vitamin K2 intervention study. Eur J Clin Nutr. 2018 Jan;72(1):136-141. doi: 10.1038/ejcn.2017.146. Epub 2017 Sep 27.

  PMID: 28952607 BACKGROUND

MeSH Terms

Conditions

Bone Diseases, Metabolic; Osteoporosis

Interventions

Vitamin K; Teriparatide

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Naphthoquinones; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phytol; Diterpenes; Terpenes; Polycyclic Compounds; Parathyroid Hormone; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2020
• First Posted: December 17, 2020
• Study Start: November 24, 2020
• Primary Completion: July 4, 2024
• Study Completion: July 4, 2024
• Last Updated: July 29, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)