Circulating Myokine Levels and Bone Metabolism

NCT04206618 | Completed FDA Drug

• 1 other identifier: MYOBONE
• Study Type: observational
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

Circulating levels of several myokines will be measured in serum samples obtained from women in various categories of bone density and according to the presence of fracture or not as well as before and after treatment with teriparatide and denosumab

Conditions

Osteoporosis, Postmenopausal

Outcome Measures

Primary Outcomes (1)

• follistatin

  circulating levels of myokine follistatin at baseline and their changes at 3 and 12 months with treatment

  0,3,12 months

Secondary Outcomes (4)

• activin-A

  0,3,12 months

• FSTL3

  0,3,12 months

• activin-B

  0,3,12 months

• irisin

  0,3,12 months

Study Arms (8)

premenopausal normal

premenopausal women with normal BMD who will be subjected to a single morning, fasting blood drainage

postmenopausal normal

postmenopausal women with normal BMD who will be subjected to a single morning, fasting blood drainage

postmenopausal osteopenia

postmenopausal women with osteopenia who will be subjected to a single morning, fasting blood drainage

postmenopausal osteoporosis

postmenopausal women with osteoporosis who will be subjected to a single morning, fasting blood drainage

hip fracture

postmenopausal women at the moment of hip fracture who will be subjected to a single, fasting blood drainage right before osteosynthesis

controls (knee osteoarthitis)

postmenopausal women with knee osteoarthritis who will be subjected to a single, fasting blood drainage right before arthroplasty and serve as controls

teriparatide group

postmenopausal women with osteoporosis who will be treated with teriparatide (Forsteo) 1 injection of 20mcg subcutaneously daily for 12 months

Drug: Teriparatide

denosumab group

postmenopausal women with osteoporosis who will be treated with denosumab (Prolia) 1 injection of 60mg subcutaneously every 6 months for 12 months

Drug: Denosumab

Interventions

Teriparatide DRUG

1 subcutaneous injection daily for 12 months

Also known as: rhPTH 1-34

teriparatide group

Denosumab DRUG

1 subcutaneous injection every 6 months for 12 months

Also known as: RANKL inhibitor

denosumab group

Eligibility Criteria

• Age: 20 Years - 85 Years
• Gender Eligibility Details: Postmenopausal women
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Substudy 1: equal groups (n=25) of premenopausal women with normal BMD, postmenopausal women with normal BMD, postmenopausal women with osteopenia, and postmenopausal women with osteoporosis Substudy 2: postmenopausal women with an incident hip fracture (n=40) compared with controls (postmenopausal women with knee osteoarhtritis) Substudy 3: postmenopausal women with osteoporosis will receive treatment with either teriparatide or denosumab for 12 months

You may qualify if:

• Substudy 1:
• adult women
• Substudy 2:
• postmenopausal women with an incident hip fracture
• Substudy 3:
• postmenopausal women with osteoporosis

You may not qualify if:

• secondary osteoporosis
• any disease that could affect muscle and/or bone metabolism
• any medication that could affect muscle and/or bone metabolism

Sponsors & Collaborators

• 424 General Military Hospital: lead
• Beth Israel Deaconess Medical Center: collaborator

Study Sites (1)

424 General Military Hospital

Thessaloniki, Northern Greece, 56429, Greece

Location

Related Publications (11)

• Bowser M, Herberg S, Arounleut P, Shi X, Fulzele S, Hill WD, Isales CM, Hamrick MW. Effects of the activin A-myostatin-follistatin system on aging bone and muscle progenitor cells. Exp Gerontol. 2013 Feb;48(2):290-7. doi: 10.1016/j.exger.2012.11.004. Epub 2012 Nov 21.

  PMID: 23178301 BACKGROUND

• Lotinun S, Pearsall RS, Horne WC, Baron R. Activin receptor signaling: a potential therapeutic target for osteoporosis. Curr Mol Pharmacol. 2012 Jun;5(2):195-204. doi: 10.2174/1874467211205020195.

  PMID: 21787285 BACKGROUND

• Anastasilakis AD, Polyzos SA, Makras P, Gkiomisi A, Savvides M, Papatheodorou A, Terpos E. Circulating activin-A is elevated in postmenopausal women with low bone mass: the three-month effect of zoledronic acid treatment. Osteoporos Int. 2013 Jul;24(7):2127-32. doi: 10.1007/s00198-012-2198-0. Epub 2012 Nov 3.

  PMID: 23124716 BACKGROUND

• Lodberg A, Eijken M, van der Eerden BCJ, Okkels MW, Thomsen JS, Bruel A. A soluble activin type IIA receptor mitigates the loss of femoral neck bone strength and cancellous bone mass in a mouse model of disuse osteopenia. Bone. 2018 May;110:326-334. doi: 10.1016/j.bone.2018.02.026. Epub 2018 Feb 28.

  PMID: 29499419 BACKGROUND

• Lotinun S, Pearsall RS, Davies MV, Marvell TH, Monnell TE, Ucran J, Fajardo RJ, Kumar R, Underwood KW, Seehra J, Bouxsein ML, Baron R. A soluble activin receptor Type IIA fusion protein (ACE-011) increases bone mass via a dual anabolic-antiresorptive effect in Cynomolgus monkeys. Bone. 2010 Apr;46(4):1082-8. doi: 10.1016/j.bone.2010.01.370. Epub 2010 Jan 18.

  PMID: 20080223 BACKGROUND

• Ruckle J, Jacobs M, Kramer W, Pearsall AE, Kumar R, Underwood KW, Seehra J, Yang Y, Condon CH, Sherman ML. Single-dose, randomized, double-blind, placebo-controlled study of ACE-011 (ActRIIA-IgG1) in postmenopausal women. J Bone Miner Res. 2009 Apr;24(4):744-52. doi: 10.1359/jbmr.081208.

  PMID: 19049340 BACKGROUND

• Fahmy-Garcia S, Farrell E, Witte-Bouma J, Robbesom-van den Berge I, Suarez M, Mumcuoglu D, Walles H, Kluijtmans SGJM, van der Eerden BCJ, van Osch GJVM, van Leeuwen JPTM, van Driel M. Follistatin Effects in Migration, Vascularization, and Osteogenesis in vitro and Bone Repair in vivo. Front Bioeng Biotechnol. 2019 Mar 1;7:38. doi: 10.3389/fbioe.2019.00038. eCollection 2019.

  PMID: 30881954 BACKGROUND

• Lodberg A, van der Eerden BCJ, Boers-Sijmons B, Thomsen JS, Bruel A, van Leeuwen JPTM, Eijken M. A follistatin-based molecule increases muscle and bone mass without affecting the red blood cell count in mice. FASEB J. 2019 May;33(5):6001-6010. doi: 10.1096/fj.201801969RR. Epub 2019 Feb 13.

  PMID: 30759349 BACKGROUND

• Anastasilakis AD, Polyzos SA, Makras P, Savvidis M, Mantzoros CS. The comparative effect of teriparatide and denosumab on activins, follistatins, and inhibins in women with postmenopausal osteoporosis. J Bone Miner Res. 2024 Sep 2;39(9):1306-1314. doi: 10.1093/jbmr/zjae106.

  PMID: 38976019 DERIVED

• Anastasilakis AD, Polyzos SA, Savvidis M, Anastasilakis DA, Sarridimitriou A, Kumar A, Kalra B, Makras P, Mantzoros CS. Association of activins, follistatins and inhibins with incident hip fracture in women with postmenopausal osteoporosis: a proof of concept, case-control study. Endocrine. 2023 Sep;81(3):573-578. doi: 10.1007/s12020-023-03402-x. Epub 2023 May 23.

  PMID: 37221430 DERIVED

• Anastasilakis AD, Polyzos SA, Rodopaios NE, Makras P, Kumar A, Kalra B, Mantzoros CS. Activins, follistatins and inhibins in postmenopausal osteoporosis: A proof of concept, case-control study. Metabolism. 2023 Apr;141:155397. doi: 10.1016/j.metabol.2022.155397. Epub 2022 Dec 30.

  PMID: 36587801 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

serum samples

MeSH Terms

Conditions

Osteoporosis, Postmenopausal

Interventions

Teriparatide; Denosumab

Condition Hierarchy (Ancestors)

Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Parathyroid Hormone; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Athanasios Anastasilakis, phD

  424 General Military Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 18, 2019
• First Posted: December 20, 2019
• Study Start: June 1, 2019
• Primary Completion: September 30, 2020
• Study Completion: November 10, 2020
• Last Updated: January 12, 2021

Record last verified: 2021-01

Locations

GR (1)