Alterations of GCF Levels of Sclerostin and DKK-1 in Postmenopausal Osteoporosis

• Sponsor: Ondokuz Mayıs University (Other)
• Overall Status: Completed
• CT.gov ID: NCT04149405
• Collaborator: (none)
• Enrollment: 43
• Arms: 4
• Actual Duration (Months): 29.9

Study Details

Study Description

Brief Summary

Symptoms of periodontal disease are tissue destruction and destruction of the alveolar bone which supports the tooth. Wnt way (wingless-type MMTV integration site family) plays a role in the regulation of bone homeostasis in periodontal disease-induced bone resorption. The Wnt / β-catenin signal is controlled by physiological antagonists, including dickkopf released from osteocytes-associated protein 1 (DKK-1) and sclerostin (SOST). Thus, Wnt inhibitors SOST and DKK-1 affect bone mass changes. Bisphosphonates used in osteoporous treatment are selective inhibitors of bone resorption. In the serum of postmenopausal osteoporotic women treated with bisphosphonate, short-term and decreased DKK-1 level during the treatment, and increased SOST in the late period were reported. Increased bone formation after bisphosphonate treatment in postmenopausal osteoporotic patients has been associated with increased serum SOST level. The aim of our study is to investigate the effect of bisphosphonate in patients with post-menopausal osteoporosis on the bone demolition metabolism in periodontally healthy and periodontally diseased tooth regions and gingival health with the clinical data by investigating the SOST and DDK-1 molecules that play role in bone destruction mechanism.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis, Postmenopausal; Periodontitis	Procedure: Phase 1 periodontal therapy; Drug: Bisphosphonate therapy	Phase 4

Detailed Description

This study aims to reveal the effect of initial periodontal treatment together with bisphosphonate on sclerostin (SOST) and dickkopf-related protein-1 (DKK-1) in gingival crevicular fluid (GCF) of patients with osteoporosis.

Clinical recordings and GCF were obtained from postmenopausal women; with chronic periodontitis and those using bisphosphonate (Group A, n=12), with chronic periodontitis and otherwise healthy (Group B, n=10), without chronic periodontitis and those using bisphosphonate (Group C, n=11), systemically and periodontally healthy controls (Group D, n=10) at the baseline.

GCF sampling were recorded and repeated at the 6th and 12th months in Group A, B and C. SOST and DKK-1 values were measured by ELISA.

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Diagnostic
• Official Title: Investigation of the Effects of Bisphosphonate on the Gingival Crevicular Fluid Levels of Sclerostin and the DKK-1 in Individuals With Postmenopausal Osteoporosis With Periodontal Changes
• Actual Study Start Date: Jun 30, 2016
• Actual Primary Completion Date: Dec 6, 2017
• Actual Study Completion Date: Dec 28, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group A Subjects with chronic periodontitis and osteoporosis. Phase 1 periodontal therapy and bisphosphonate therapy ( Aclasta: intravenous infusion of 5 mg of zoledronic acid once a year) were administered to the subjects.	Procedure: Phase 1 periodontal therapy; Scaling and root planning with ultrasonic and hand instruments under local anesthesia.; Other Names: Periodontal treatment ; Drug: Bisphosphonate therapy; Using aclasta: intravenous infusion of 5 mg of zoledronic acid once a year; Other Names: Osteoporosis treatment
Active Comparator: Group B Subjects with chronic periodontitis and systemically healthy. Phase 1 periodontal theraphy was administered to the subjects.	Procedure: Phase 1 periodontal therapy; Scaling and root planning with ultrasonic and hand instruments under local anesthesia.; Other Names: Periodontal treatment
Active Comparator: Group C Subjects with periodontally healthy and osteoporosis. Bisphosphonate therapy ( Aclasta: intravenous infusion of 5 mg of zoledronic acid once a year) were administered to the subjects.	Drug: Bisphosphonate therapy; Using aclasta: intravenous infusion of 5 mg of zoledronic acid once a year; Other Names: Osteoporosis treatment
No Intervention: Group D Systemically and periodontally healthy controls No intervention has been made.

Outcome Measures

Primary Outcome Measures

1. Sost Values for 6th Month [6 months]

   levels of sclerostin in 6th month

2. Dkk-1 Values for 6th Month [6 months]

   levels of dickkopf-related protein-1 in 6th month

Secondary Outcome Measures

1. Sost Values for 12th Month [12 month]

   levels of sclerostin in 12th month

2. Dkk-1 Values for 12th Month [12 months]

   levels of dickkopf-related protein-1 in 12th month

Eligibility Criteria

Criteria

• Ages Eligible for Study: 51 Years to 66 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Women with T scores less than -2.5 (groups A and C)

• The periodontitis patients were selected based on the radiographical evidence of bone loss, presence of four or more sites with bleeding on probing (BOP), ≥5 mm pocket depth (PD) and ≥6 mm clinical attachment loss (CAL).

• The clinically healthy control groups were selected on the basis of no radiographic bone loss or CAL and PD≤3 mm.

Exclusion Criteria:

• Any known systemic disease rather than osteoporosis

• Smoking

• Antibiotic therapy within the last 3 months

• Periodontal treatment in the last 6 months

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Ondokuz Mayıs University

Investigators

• Study Director: Eser Acarel, PhD,Prof.Dr., Ondokuz Mayıs University, School of Dentistry, Department of Periodontology

Study Documents (Full-Text)

• Informed Consent Form - Jun 30, 2016
• Study Protocol and Statistical Analysis Plan - Dec 28, 2018

More Information

Publications

• Hampson G, Edwards S, Conroy S, Blake GM, Fogelman I, Frost ML. The relationship between inhibitors of the Wnt signalling pathway (Dickkopf-1(DKK1) and sclerostin), bone mineral density, vascular calcification and arterial stiffness in post-menopausal women. Bone. 2013 Sep;56(1):42-7. doi: 10.1016/j.bone.2013.05.010. Epub 2013 May 20.
• Juluri R, Prashanth E, Gopalakrishnan D, Kathariya R, Devanoorkar A, Viswanathan V, Romanos GE. Association of Postmenopausal Osteoporosis and Periodontal Disease: A Double-Blind Case-Control Study. J Int Oral Health. 2015 Sep;7(9):119-23.
• Papapoulos SE, Landman JO, Bijvoet OL, Löwik CW, Valkema R, Pauwels EK, Vermeij P. The use of bisphosphonates in the treatment of osteoporosis. Bone. 1992;13 Suppl 1:S41-9. Review.

• Responsible Party: Feyza Otan ÖZDEN, Principal Investigator, Ondokuz Mayıs University
• ClinicalTrials.gov Identifier: NCT04149405
• Other Study ID Numbers: KAEK 2016/100
• First Posted: Nov 4, 2019
• Last Update Posted: Mar 11, 2021
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Feyza Otan ÖZDEN, Principal Investigator, Ondokuz Mayıs University: sclerostin; dickkopf-related protein-1
• Additional relevant MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal; Periodontitis; Diphosphonates

Study Results

Participant Flow

Recruitment Details	Postmenopausal women who were admitted to Ondokuz Mayıs University (OMU), Faculty of Medicine, Department of Endocrinology and Metabolism between 2016 and 2018. Patients eligible for the study were directed to OMU, Faculty of Dentistry, Department of Periodontology for periodontal examination after obtaining medical records.
Pre-assignment Detail	Smokers and subjects who had received antibiotic treatment in the last 3 months and/or periodontal treatment in the last 6 months were excluded from the study.

Arm/Group Title	Group A	Group B	Group C	Group D
Arm/Group Description	subjects with chronic periodontitis and osteoporosis	subjects with chronic periodontitis and systemically healthy	subjects with periodontally healthy and osteoporosis	systemically and periodontally healthy controls
Period Title: Overall Study
STARTED	12	10	11	10
COMPLETED	12	10	11	10
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Group A	Group B	Group C	Group D	Total
Arm/Group Description	subjects with chronic periodontitis and osteoporosis	subjects with chronic periodontitis and systemically healthy	subjects with periodontally healthy and osteoporosis	systemically and periodontally healthy controls	Total of all reporting groups
Overall Participants	12	10	11	10	43
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.67 (4.77)	57.00 (4.39)	56.45 (3.88)	56.30 (3.91)	56.88 (4.15)
Sex: Female, Male (Count of Participants)
Female	12 100%	10 100%	11 100%	10 100%	43 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	12 100%	10 100%	11 100%	10 100%	43 100%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Turkey	12 100%	10 100%	11 100%	10 100%	43 100%
baseline sost values (ng/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/ml]	494.096 (99.840)	634.731 (152.554)	1023.071 (512.733)	2131.87 (485.784)	1103.417 (751.080)
baseline dkk-1 levels (ng/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/ml]	1031.323 (506.985)	1264.632 (492.691)	2630.430 (1679.080)	4269.394 (1734.732)	2358.505 (1801.692)

Outcome Measures

1. Primary Outcome

Title	Sost Values for 6th Month
Description	levels of sclerostin in 6th month
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A	Group B	Group C	Group D
Arm/Group Description	scaling and root planning, bisphosphonate therapy (zoledronic acid) periodontal phase 1 therapy: periodontal phase 1 therapy consisted of scaling and root planning with ultrasonic and hand instruments under local anesthesia. bisphosphonate therapy: bisphosphonate therapy refers to the use of zoledronic acid 5 mg/year (i.v.) GCF: gingival crevicular fluid collection by the same investigator.	scaling and root planning, no bisphosphonate therapy periodontal phase 1 therapy: periodontal phase 1 therapy consisted of scaling and root planning with ultrasonic and hand instruments under local anesthesia. GCF: gingival crevicular fluid collection by the same investigator.	bisphosphonate therapy (zoledronic acid) bisphosphonate therapy: bisphosphonate therapy refers to the use of zoledronic acid 5 mg/year (i.v.) GCF: gingival crevicular fluid collection by the same investigator.	Systemically and periodontally healthy controls No intervention has been made
Measure Participants	12	10	11	10
Mean (Standard Deviation) [ng/ml]	1389.177 (670.834)	1085.405 (618.136)	1596.585 (841.026)	2131.87 (485.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A, Group B, Group C, Group D
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	Kruskal-Wallis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.01
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Dkk-1 Values for 6th Month
Description	levels of dickkopf-related protein-1 in 6th month
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A	Group B	Group C	Group D
Arm/Group Description	Subjects with chronic periodontitis and osteoporosis. Phase 1 periodontal therapy and bisphosphonate therapy ( Aclasta: intravenous infusion of 5 mg of zoledronic acid once a year) were administered to the subjects. Phase 1 periodontal therapy: Scaling and root planning with ultrasonic and hand instruments under local anesthesia. Bisphosphonate therapy: Using aclasta: intravenous infusion of 5 mg of zoledronic acid once a year	Subjects with chronic periodontitis and systemically healthy. Phase 1 periodontal theraphy was administered to the subjects. Phase 1 periodontal therapy: Scaling and root planning with ultrasonic and hand instruments under local anesthesia.	Subjects with periodontally healthy and osteoporosis. Bisphosphonate therapy ( Aclasta: intravenous infusion of 5 mg of zoledronic acid once a year) were administered to the subjects. Bisphosphonate therapy: Using aclasta: intravenous infusion of 5 mg of zoledronic acid once a year	Systemically and periodontally healthy controls No intervention has been made
Measure Participants	12	10	11	10
Mean (Standard Deviation) [ng/ml]	3358.265 (1477.199)	1963.185 (966.451)	3263.665 (2298.590)	4269.39 (1734.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A, Group B, Group C, Group D
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Kruskal-Wallis
	Comments

3. Secondary Outcome

Title	Sost Values for 12th Month
Description	levels of sclerostin in 12th month
Time Frame	12 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A	Group B	Group C	Group D
Arm/Group Description	Subjects with chronic periodontitis and osteoporosis. Phase 1 periodontal therapy and bisphosphonate therapy ( Aclasta: intravenous infusion of 5 mg of zoledronic acid once a year) were administered to the subjects. Phase 1 periodontal therapy: Scaling and root planning with ultrasonic and hand instruments under local anesthesia. Bisphosphonate therapy: Using aclasta: intravenous infusion of 5 mg of zoledronic acid once a year	Subjects with chronic periodontitis and systemically healthy. Phase 1 periodontal theraphy was administered to the subjects. Phase 1 periodontal therapy: Scaling and root planning with ultrasonic and hand instruments under local anesthesia.	Subjects with periodontally healthy and osteoporosis. Bisphosphonate therapy ( Aclasta: intravenous infusion of 5 mg of zoledronic acid once a year) were administered to the subjects. Bisphosphonate therapy: Using aclasta: intravenous infusion of 5 mg of zoledronic acid once a year	Systemically and periodontally healthy controls No intervention has been made
Measure Participants	12	10	11	10
Mean (Standard Deviation) [ng/ml]	1702.265 (1012.124)	1347.330 (876.383)	1114.988 (368.840)	2131.87 (485.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A, Group B, Group C, Group D
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Kruskal-Wallis
	Comments

4. Secondary Outcome

Title	Dkk-1 Values for 12th Month
Description	levels of dickkopf-related protein-1 in 12th month
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A	Group B	Group C	Group D
Arm/Group Description	-Subjects with chronic periodontitis and osteoporosis.	-Subjects with chronic periodontitis and systemically healthy.	-Subjects with periodontally healthy and osteoporosis.	Systemically and periodontally healthy controls No intervention has been made
Measure Participants	12	10	11	10
Mean (Standard Deviation) [ng/ml]	3440.67 (2347.112)	3203.802 (1706.081)	2490.553 (841.512)	4269.39 (1734.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A, Group B, Group C, Group D
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Kruskal-Wallis
	Comments

Adverse Events

Time Frame	Adverse Events were not monitored/assessed
Adverse Event Reporting Description	All-Cause Mortality, Serious, and Other (Not Including Serious) Adverse Events were not monitored/assessed in any participants.
Arm/Group Title	Group A		Group B		Group C		Group D
Arm/Group Description	Participants received periodontal phase 1 treatment and used bisphosphonate.		Participants received periodontal phase 1 treatment.		Participants used bisphosphonate.		Participants did not receive any treatment.
All Cause Mortality
	Group A		Group B		Group C		Group D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Group A		Group B		Group C		Group D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Group A		Group B		Group C		Group D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.