PTH and Vibration in OSteoporosis Study (PaVOS)

• ClinicalTrials.gov Identifier: NCT02563353
• Recruitment Status: Completed
• First Posted: September 30, 2015
• Last Update Posted: September 18, 2020
• Sponsor: Odense University Hospital
• Collaborators: University of Southern Denmark; Copenhagen University Hospital, Denmark; Hospital of South West Denmark; Sygehus Lillebaelt; Odense Patient Data Explorative Network; Region of Southern Denmark
• Information provided by (Responsible Party): Lars Matzen, Odense University Hospital

Study Description

Brief Summary:

Objective:

This is a randomized controlled trial (RCT) in osteoporosis patients randomized to standard parathyroid hormone (PTH) treatment alone or to standard PTH treatment and Whole-body vibration (WBV). PTH is an effective but expensive anabolic treatment for osteoporosis. WBV stimulates muscles and bones. A combined treatment might have synergistic or additive beneficial effects on bone, reducing fracture risk making treatment more effective and cost-effective. A beneficial effect on muscles and thereby falls risk of WBV may improve fracture risk even further.

If the results of this pilot study are promising then a strong case can be made for a large multi-centre RCT using strong endpoints including fractures and falls.

Condition or disease	Intervention/treatment	Phase
Osteoporosis	Other: whole-body vibration; Drug: teriparatide	Not Applicable

Detailed Description:

Study Objectives

1. To determine if WBV in addition to standard PTH treatment has a greater effect on bone mass in osteoporosis patients compared to standard PTH treatment alone.
2. To determine if WBV in addition to standard PTH treatment has a greater effect on bone microarchitecture in osteoporosis patients compared to standard PTH treatment alone, as assessed by high resolution peripheral quantitative computed tomography (HR-pQCT).
3. To determine if WBV in addition to standard PTH treatment has a greater effect on markers of bone formation and resorption in osteoporosis patients compared to standard PTH treatment alone.
4. To study the effects of WBV on muscle function and balance in osteoporosis
5. To assess the safety and adherence to WBV in osteoporotic patients

Study Design:

General Design This will be a multi-center randomized controlled trial (RCT) in osteoporosis patients being started on standard PTH treatment according to Danish Osteoporosis guidelines. Participants will be randomized to standard PTH treatment alone or to standard PTH treatment and WBV.

Statistical Plan:

Sample Size Determination The inclusion of 32 participants (16 in both groups) would give the study 80% power to detect a clinically significant additional increase of 22% with WBV (assuming a 9% increase of BMD in the PTH alone group and 11% increase in the combined PTH+WBV group, and assuming a SD of the BMD increase of 2%. Allowing for a 20% dropout rate, the plan is to include 40 participants (20 in each group). From previous research on WBV by one of the investigators (TM), statistically significant differences were found in bone formation markers and in muscle strength at 3 months between the WBV and control groups with a sample size of 35. The number of participants in the latter pilot work is reassuringly consistent with the sample size calculations. The number needed to be included is far less (34%) than the actual number of patients treated with PTH in the recruiting departments in a similar time period last year.

Statistical Methods:

STATA/SPSS will be used for data analysis. For the primary endpoint (BMD at 12 months) the mean percentage changes in BMD between the two groups will be compared using Analysis of Variance (ANOVA) provided the distribution is normal. For the other endpoints parametric tests will be used to assess differences in the two groups for normally distributed data and non-parametric tests for data not normally distributed.

The randomization will be done online in the data capture program Red Cap. There will be created a Data dictionary that contains detailed descriptions of each variable used by the registry, including the source of the variable, and normal ranges if relevant.

Information:

Participants will be recruited during their attendance at the outpatient clinics. At that time the subjects will be given a full explanation of the study as well as the patient information sheet and invited to participate in the study. At an interval of not less than 24 hours, patients will be invited to consent prior to starting their PTH treatment.

The information will be sufficient for subjects to make an informed decision about their participation in this study. The subject will complete and sign a consent form to indicate they are giving valid consent to participate in the trial.

Withdrawal of Subjects:

Patients who withdraw consent from participation in the trial will be withdrawn from the trial. This will not affect their standard medical management and not cause any adverse effect on the subject.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: PTH and Vibration in OSteoporosis (PaVOS) Study
• Actual Study Start Date: November 2015
• Actual Primary Completion Date: November 2018
• Actual Study Completion Date: November 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: controlgroup; Teriparatide, 20 microgram/day. 24 months of treatment	Drug: teriparatide; Teriparatide, 20 microgram/day. 24 months of treatment.; Other Name: PTH
Experimental: studygroup 1; Teriparatide, 20 microgram/day. 24 months of treatment. 12 months of Whole-body vibration on vibration platforms.	Other: whole-body vibration; Whole-body vibration on vibration platforms. 30-40 Hertz, from 2 mm (low) to 4 mm (high) amplitude, 1 minutes x 6 with 1 minute break between. 3 times a week.; Other Name: vibration therapy; Drug: teriparatide; Teriparatide, 20 microgram/day. 24 months of treatment.; Other Name: PTH
Experimental: studygroup 2; Teriparatide, 20 microgram/day. 24 months of treatment. 24 months of Whole-body vibration on vibration platforms	Other: whole-body vibration; Whole-body vibration on vibration platforms. 30-40 Hertz, from 2 mm (low) to 4 mm (high) amplitude, 1 minutes x 6 with 1 minute break between. 3 times a week.; Other Name: vibration therapy; Drug: teriparatide; Teriparatide, 20 microgram/day. 24 months of treatment.; Other Name: PTH

Outcome Measures

Primary Outcome Measures :

1. Changes in the BMD, Bone Mineral Density of hip and spine region (Hologic DXA machine) [ Time Frame: at the time the participants start treatment and in an interval as close as possible to after 6, 12, 18, 24 months from baseline ]
   DXA scan of hip and spine regions, BMD (g/cm^2)

Secondary Outcome Measures :

1. Changes in the Bone microarchitecture at the tibia [ Time Frame: at the time the participants start treatment and in an interval as close as possible to after 6, 12, 18 and 24 months from baseline ]
   HRpQCT assesses parameters of bone microarchitecture at the tibia.
2. Changes in the Bone microarchitecture at the radius [ Time Frame: at the time the participants start treatment and in an interval as close as possible to after 6, 12, 18 and 24 months from baseline ]
   HRpQCT assesses parameters of bone microarchitecture at the radius.
3. changes in muscle mass [ Time Frame: at the time the participants start treatment and in an interval as close as possible to after 12 and 24 months from baseline ]
   Full body DXA
4. Changes from baseline in the markers of bone resorption [ Time Frame: at the time the participants start treatment and in an interval as close as possible to after 3, 6, 12, 18, 24 months from baseline ]
   CTX, sclerostin
5. Changes from baseline in the markers of bone formation [ Time Frame: at the time the participants start treatment and in an interval as close as possible to after 3, 6, 12, 18, 24 months from baseline ]
   P1NP
6. Changes in Muscle strength [ Time Frame: at the time the participants start treatment and in an interval as close as possible to after 3,6,12,18 and 24 months from baseline ]
   Measurements of muscle strength (leg extensor power)
7. Changes in handgrip strength [ Time Frame: at the time the participants start treatment and in an interval as close as possible to after 3,6,12,18 and 24 months from baseline ]
   Measurements of muscle strength (handgrip strength)
8. Changes in Balance [ Time Frame: at the time the participants start treatment and in an interval as close as possible to after 3, 6 ,12, 18 and 24 months from baseline ]
   Short Physical Performance Battery (SPPB)
9. Adherence to WBV [ Time Frame: During 2 years from the start of the treatment ]
   Self Reporting training log
10. Changes in physical activity [ Time Frame: at the time the participants start treatment and in an interval as close as possible to after 12, and 24 months from baseline ]
    IPAQ short version
11. Changes in quality of life [ Time Frame: at the time the participants start treatment and in an interval as close as possible to after 12, and 24 months from baseline ]
    EQ5D questionaire.
12. Changes in basic mobility [ Time Frame: at the time the participants start treatment and in an interval as close as possible to after 3,6,12,18 and 24 months from baseline ]
    Time up and go test
13. Changes in The Falls Efficacy Scale International [ Time Frame: at the time the participants start treatment and in an interval as close as possible to after 12, and 24 months from baseline ]
    FES-I

Eligibility Criteria

• Ages Eligible for Study: 50 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Women starting PTH treatment for osteoporosis according to Danish Osteoporosis guidelines

Exclusion Criteria:

• Women currently taking oral glucocorticoids
• Women unable to give informed consent
• Women unable to stand for 2 minutes at a time on the vibration platform
• Women who have contraindications to WBV (e.g. joint prosthesis, pacemakers)

Contacts and Locations

Locations

Denmark

Odense University Hospital

Odense, Denmark, 5000

Sponsors and Collaborators

Odense University Hospital

University of Southern Denmark

Copenhagen University Hospital, Denmark

Hospital of South West Denmark

Sygehus Lillebaelt

Odense Patient Data Explorative Network

Region of Southern Denmark

Investigators

• Principal Investigator: Lars Matzen, Clin.Ass.Pro; Odense University Hospital
• Principal Investigator: Ditte Jepsen, MD, ph.d. student; University of Southern Denmark

More Information

Publications:

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Chow JW, Fox S, Jagger CJ, Chambers TJ. Role for parathyroid hormone in mechanical responsiveness of rat bone. Am J Physiol. 1998 Jan;274(1):E146-54. doi: 10.1152/ajpendo.1998.274.1.E146.

Li J, Duncan RL, Burr DB, Gattone VH, Turner CH. Parathyroid hormone enhances mechanically induced bone formation, possibly involving L-type voltage-sensitive calcium channels. Endocrinology. 2003 Apr;144(4):1226-33.

Roberts MD, Santner TJ, Hart RT. Local bone formation due to combined mechanical loading and intermittent hPTH-(1-34) treatment and its correlation to mechanical signal distributions. J Biomech. 2009 Nov 13;42(15):2431-8. doi: 10.1016/j.jbiomech.2009.08.030. Epub 2009 Sep 26.

Wysocki A, Butler M, Shamliyan T, Kane RL. Whole-body vibration therapy for osteoporosis: state of the science. Ann Intern Med. 2011 Nov 15;155(10):680-6, W206-13. doi: 10.7326/0003-4819-155-10-201111150-00006. Review.

Gusi N, Raimundo A, Leal A. Low-frequency vibratory exercise reduces the risk of bone fracture more than walking: a randomized controlled trial. BMC Musculoskelet Disord. 2006 Nov 30;7:92.

Cardinale M, Pope MH. The effects of whole body vibration on humans: dangerous or advantageous? Acta Physiol Hung. 2003;90(3):195-206. Review.

Cardinale M, Rittweger J. Vibration exercise makes your muscles and bones stronger: fact or fiction? J Br Menopause Soc. 2006 Mar;12(1):12-8. Review.

Cardinale M, Wakeling J. Whole body vibration exercise: are vibrations good for you? Br J Sports Med. 2005 Sep;39(9):585-9; discussion 589. Review.

Eisman JA. Good, good, good... good vibrations: the best option for better bones? Lancet. 2001 Dec 8;358(9297):1924-5. Review.

Rubin C, Xu G, Judex S. The anabolic activity of bone tissue, suppressed by disuse, is normalized by brief exposure to extremely low-magnitude mechanical stimuli. FASEB J. 2001 Oct;15(12):2225-9.

Xie L, Jacobson JM, Choi ES, Busa B, Donahue LR, Miller LM, Rubin CT, Judex S. Low-level mechanical vibrations can influence bone resorption and bone formation in the growing skeleton. Bone. 2006 Nov;39(5):1059-1066. doi: 10.1016/j.bone.2006.05.012. Epub 2006 Jul 7.

Judex S, Lei X, Han D, Rubin C. Low-magnitude mechanical signals that stimulate bone formation in the ovariectomized rat are dependent on the applied frequency but not on the strain magnitude. J Biomech. 2007;40(6):1333-9. Epub 2006 Jun 30.

Xie L, Rubin C, Judex S. Enhancement of the adolescent murine musculoskeletal system using low-level mechanical vibrations. J Appl Physiol (1985). 2008 Apr;104(4):1056-62. doi: 10.1152/japplphysiol.00764.2007. Epub 2008 Feb 7.

Rubin C, Pope M, Fritton JC, Magnusson M, Hansson T, McLeod K. Transmissibility of 15-hertz to 35-hertz vibrations to the human hip and lumbar spine: determining the physiologic feasibility of delivering low-level anabolic mechanical stimuli to skeletal regions at greatest risk of fracture because of osteoporosis. Spine (Phila Pa 1976). 2003 Dec 1;28(23):2621-7.

Bosco C, Iacovelli M, Tsarpela O, Cardinale M, Bonifazi M, Tihanyi J, Viru M, De Lorenzo A, Viru A. Hormonal responses to whole-body vibration in men. Eur J Appl Physiol. 2000 Apr;81(6):449-54.

Erskine J, Smillie I, Leiper J, Ball D, Cardinale M. Neuromuscular and hormonal responses to a single session of whole body vibration exercise in healthy young men. Clin Physiol Funct Imaging. 2007 Jul;27(4):242-8.

Fritton JC, Rubin CT, Qin YX, McLeod KJ. Whole-body vibration in the skeleton: development of a resonance-based testing device. Ann Biomed Eng. 1997 Sep-Oct;25(5):831-9.

Gilsanz V, Wren TA, Sanchez M, Dorey F, Judex S, Rubin C. Low-level, high-frequency mechanical signals enhance musculoskeletal development of young women with low BMD. J Bone Miner Res. 2006 Sep;21(9):1464-74.

Cardinale M, Lim J. Electromyography activity of vastus lateralis muscle during whole-body vibrations of different frequencies. J Strength Cond Res. 2003 Aug;17(3):621-4.

Hazell TJ, Kenno KA, Jakobi JM. Evaluation of muscle activity for loaded and unloaded dynamic squats during vertical whole-body vibration. J Strength Cond Res. 2010 Jul;24(7):1860-5. doi: 10.1519/JSC.0b013e3181ddf6c8.

Roelants M, Verschueren SM, Delecluse C, Levin O, Stijnen V. Whole-body-vibration-induced increase in leg muscle activity during different squat exercises. J Strength Cond Res. 2006 Feb;20(1):124-9.

Pollock RD, Woledge RC, Mills KR, Martin FC, Newham DJ. Muscle activity and acceleration during whole body vibration: effect of frequency and amplitude. Clin Biomech (Bristol, Avon). 2010 Oct;25(8):840-6. doi: 10.1016/j.clinbiomech.2010.05.004. Epub 2010 Jun 11.

Russo CR, Lauretani F, Bandinelli S, Bartali B, Cavazzini C, Guralnik JM, Ferrucci L. High-frequency vibration training increases muscle power in postmenopausal women. Arch Phys Med Rehabil. 2003 Dec;84(12):1854-7.

Torvinen S, Kannu P, Sievänen H, Järvinen TA, Pasanen M, Kontulainen S, Järvinen TL, Järvinen M, Oja P, Vuori I. Effect of a vibration exposure on muscular performance and body balance. Randomized cross-over study. Clin Physiol Funct Imaging. 2002 Mar;22(2):145-52.

Ward K, Alsop C, Caulton J, Rubin C, Adams J, Mughal Z. Low magnitude mechanical loading is osteogenic in children with disabling conditions. J Bone Miner Res. 2004 Mar;19(3):360-9. Epub 2004 Jan 27.

Tanaka SM, Alam IM, Turner CH. Stochastic resonance in osteogenic response to mechanical loading. FASEB J. 2003 Feb;17(2):313-4. Epub 2002 Dec 3.

Kerschan-Schindl K, Grampp S, Henk C, Resch H, Preisinger E, Fialka-Moser V, Imhof H. Whole-body vibration exercise leads to alterations in muscle blood volume. Clin Physiol. 2001 May;21(3):377-82.

Corrie H, Brooke-Wavell K, Mansfield NJ, Cowley A, Morris R, Masud T. Effects of vertical and side-alternating vibration training on fall risk factors and bone turnover in older people at risk of falls. Age Ageing. 2015 Jan;44(1):115-22. doi: 10.1093/ageing/afu136. Epub 2014 Oct 7.

Verschueren SM, Roelants M, Delecluse C, Swinnen S, Vanderschueren D, Boonen S. Effect of 6-month whole body vibration training on hip density, muscle strength, and postural control in postmenopausal women: a randomized controlled pilot study. J Bone Miner Res. 2004 Mar;19(3):352-9. Epub 2003 Dec 22.

Gómez-Cabello A, Ara I, González-Agüero A, Casajús JA, Vicente-Rodríguez G. Effects of training on bone mass in older adults: a systematic review. Sports Med. 2012 Apr 1;42(4):301-25. doi: 10.2165/11597670-000000000-00000. Review.

Sitjà Rabert M, Rigau Comas D, Fort Vanmeerhaeghe A, Santoyo Medina C, Roqué i Figuls M, Romero-Rodríguez D, Bonfill Cosp X. Whole-body vibration training for patients with neurodegenerative disease. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD009097. doi: 10.1002/14651858.CD009097.pub2. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Jepsen DB, Masud T, Holsgaard-Larsen A, Hansen S, Jørgensen NR, Ryg J. The combined effect of parathyroid hormone (1-34) and whole-body vibration exercise on physical performance in OSteoporotic women (PaVOS study): a secondary analysis from a randomised controlled trial. BMC Sports Sci Med Rehabil. 2020 Sep 5;12:54. doi: 10.1186/s13102-020-00204-w. eCollection 2020.

Jepsen DB, Ryg J, Hansen S, Jørgensen NR, Gram J, Masud T. The combined effect of Parathyroid hormone (1-34) and whole-body Vibration exercise in the treatment of postmenopausal OSteoporosis (PaVOS study): a randomized controlled trial. Osteoporos Int. 2019 Sep;30(9):1827-1836. doi: 10.1007/s00198-019-05029-z. Epub 2019 Jul 15.

Jepsen DB, Ryg J, Jørgensen NR, Hansen S, Masud T. The combined effect of Parathyroid hormone (1-34) and whole-body Vibration exercise in the treatment of OSteoporosis (PaVOS)- study protocol for a randomized controlled trial. Trials. 2018 Mar 16;19(1):186. doi: 10.1186/s13063-018-2551-5.

• Responsible Party: Lars Matzen, MD, Clin. Ass. Professor, Odense University Hospital
• ClinicalTrials.gov Identifier: NCT02563353
• Other Study ID Numbers: S-20150121
• First Posted: September 30, 2015
• Last Update Posted: September 18, 2020
• Last Verified: September 2020

Keywords provided by Lars Matzen, Odense University Hospital:

whole body vibration; PTH

Additional relevant MeSH terms:

Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Teriparatide; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Bone Density Conservation Agents