Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02628197 |
| Other study ID # |
Perio 3 Aastha |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
December 9, 2015 |
| Last updated |
December 10, 2015 |
| Start date |
December 2013 |
| Est. completion date |
June 2015 |
Study information
| Verified date |
December 2015 |
| Source |
Postgraduate Institute of Dental Sciences Rohtak |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
India: Drugs Controller General of India |
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this interventional study was to investigate the impact of control of
systemic inflammation by scaling and root planing (SRP) on bone mineral density (BMD) in
osteopenic post-menopausal women with Chronic periodontitis(CP). Out of 68 osteopenic
postmenopausal women with CP, 34 participants each were included in test and control group.
BMD, hsCRP and periodontal parameters were recorded at baseline and 6 months.
Description:
Rapid estrogen level decline after menopause is associated with systemic bone loss in women
leading to osteopenia/osteoporosis. Estrogen therapy (ET) improves bone mineral density
(BMD) in postmenopausal women. Currently, ET has been associated with statistically
significant increased risk of breast cancer, stroke, and thromboembolic events. Easiest
lifestyle modification for the management of lower BMD is probably the adequate intake of
calcium and vitamin D.
Chronic inflammatory diseases are associated with systemic bone loss. Bone has been a target
in many inflammatory rheumatic diseases like rheumatoid arthritis (RA),and ankylosing
spondylitis (AS). Low bone mineral density has also been documented in patients with
Systemic lupus erythematosus (SLE).
Periodontitis is a chronic condition of supporting tissues of the teeth. It has been
reported that 30% of individuals above the age of 50 years suffer from severe
periodontitis.Hujoel et al has concluded that the mean periodontal surface area in patients
with periodontitis can be as large as 8-20cm2 . The inflamed and ulcerated subgingival
pocket epithelium may allow many gram negative and obligate anaerobic bacteria to enter
bloodstream. Bacterial components such as endotoxins and major outer membrane proteins may
also be disseminated. Studies on systemic influence of periodontitis have theorized that
locally produced pro-inflammatory cytokines such as interleukin-1(IL-1), tumour necrosis
factor-alpha(TNF-α), interleukin-6(IL-6) and prostaglandin-E2(PGE2) may be released into the
circulation and exercise distant effects. These inflammatory cytokines have been reported to
be implicated for the distinctive loss of bone density in osteoporosis through their effect
on osteoclast activity.
C-reactive protein (CRP) is an extremely sensitive and non-specific acute phase reactant
that is produced in response to tissue damage, inflammation, infection and hypoxia. It is a
serological marker of systemic inflammation. Previous studies on elderly females and a large
population based sample reported higher serum levels of CRP associated with lower BMD. A
study also implicated that CRP ≥ 4.2mg/l may be used to identify the groups having rapid
bone loss in older people. Various studies concluded higher levels of CRP in patients with
periodontitis than in control. D Auito reported CRP reduction of 0.5mg/l at 6 months after
non- surgical periodontal therapy in patients with chronic periodontitis(CP).Epidemiological
studies from Buffalo, New York, reported elevated CRP in blood plasma among patients with
severe periodontal attachment loss in comparison to individuals with minimal or no
attachment loss. Various cross sectional studies have reported association between
osteoporosis and periodontal disease in post-menopausal women. A recent study demonstrated
that severe clinical attachment loss (CAL) was independently associated with low BMD of the
femoral neck in postmenopausal women. These studies infer that osteoporosis is a risk factor
for periodontitis. It is difficult to infer cause and effect relationship from cross
sectional studies. The basis of association between osteoporosis and periodontitis may
either be osteoporosis influencing periodontitis and/or vice-versa and/or both of them
sharing common risk factors.
Inflammation has been reported to contribute towards post-menopausal deterioration in BMD.
Levels of inflammatory cytokines responsible for the loss of bone density e.g. IL-1β, IL-6,
TNF-α in osteoporosis are reported to be increased in the systemic circulation in CP. Hence,
it is hypothesized that CP, an inflammatory disorder with a large wound surface area, may
add to the systemic inflammatory burden and may consequently contribute towards
deterioration of BMD in post-menopausal women. So, controlling systemic inflammatory burden
by scaling and root planing(SRP) may have an adjunctive effect in the management of
osteopenia/osteoporosis in these patients.
Taking into consideration these observations, the present study was undertaken to evaluate
the impact of control of inflammation by SRP on BMD in osteopenic post-menopausal women with
periodontitis.
MATERIALS AND METHODS Study Population Patients for this interventional study were recruited
from the out-patient department of the department of Periodontics and Oral Implantology and
department of Oral Medicine, Post Graduate Institute of Dental Sciences, Rohtak. The study
protocol was carried out in accordance with the ethical standards outlined in the 1975
Declaration of Helsinki, as revised in 2013. The protocol was approved by the Institutional
Review Board, Pt. B. D. Sharma University of Health Sciences, Rohtak and the ethical
approval was obtained from the ethical committee of PGIDS, Rohtak. (PGIDS/IEC/2014/114).
Prior written informed consent was taken from each patient after explaining the procedure
along with the risks and benefits in their own language.
The patients accepted for the study met the following inclusion criteria: 1) osteopenic
post-menopausal women with CP with 20 or more natural teeth (excluding third molars); 2)
aged 52 -59 years; and 3) history of natural menopause since more than 5 years. Osteopenia
criteria as per the World Health Organization (WHO) criteria : standardized T-score between
-1.0 and -2.5 . CP criteria considered for the study were : at least 4 teeth on which one or
more sites with a probing depth ≥ 4mm, CAL ≥ 3mm and the presence of bleeding on probing at
the same site. Exclusion criteria included the following: 1) systemic disease known to
affect BMD and hsCRP levels including RA, AS, SLE, IBD, COPD; 2) systemic disease known to
affect the course of periodontal disease like diabetes mellitus or immunological disorder;
3) treatment with the following drugs in the previous 3 months: steroids, immune
suppressants, antibiotics, anti-inflammatories, statins, lipid lowering drugs,
anti-convulsants, thiazide diuretic agents, anti-coagulants or any other host modulatory
drug; 4) recent history or presence of acute or chronic infection; 5) history of metabolic
bone disease, thyroid and parathyroid disease and gastro-intestinal disorders; 6) early
onset of menopause; treatment with systemic medication for osteoporosis/osteopenia including
calcium and vitamin D supplementation, bisphosphonates etc.; 7) history of hysterectomy and
hormone replacement therapy; 8) current or former smokers or use of smokeless tobacco in any
form; and 9) periodontal treatment within past one year prior to inclusion into the study
STUDY GROUPS The test group consisted of 34 participants who received SRP along with calcium
(500mg) and vitamin D (250I.U.) supplementation (Shelcal, torrents pharmaceutical limited,
Gujarat, India) twice a day for 6 months while the control group consisted of 34
participants who received calcium (500mg) and vitamin D (250I.U.) supplementation* twice a
day for 6 months. Participants without any chief complaint with reference to periodontitis
who expressed their inability to undergo periodontal treatment immediately in near future
were included in the control group.
BMD measurement BMD of the participants was evaluated using Dual Energy X-ray Absorptimetry(
DXA, Hologic QDR explorer version 12.6:3; Hologic Inc., Bedford, MA, USA) in lumbar spine
region (L1-L4) with an exposure of .07mGy for 90 seconds at baseline and 6 month follow-up.
The improvement in BMD (T-score) at 6 months from baseline was taken as primary outcome.
Sample collection All the blood samples were collected at baseline and 6 month follow-up for
serum high-sensitivity C - reactive protein (hsCRP). Venous blood from anticubital vein was
collected after applying tourniquet in plain vacutainer tube without additive. It was
measured using serum samples.
hsCRP estimation Serum hsCRP levels were assessed using a kit with high-sensitivity
methodology‡( C - reactive protein (Latex) High-Sensitive Assay, Roche Diagnostics, GmbH,
Mannheim, USA) in an autoanalyser according to manufacturer's instructions. The test
principle was particle enhanced immune-turbidimetric assay, in which human CRP agglutinates
with latex particles coated with monoclonal anti-CRP antibodies. The turbidity induced by
the formation of immune complexes was measured at 546 nm.
Periodontal examination After their selection for the study, all participants underwent
full-mouth periodontal examination at baseline and 6 month in a standardized way using
illumination by a standard dental light, a mouth mirror, tweezer, manual calibrated probe(
PCP-UNC 15 Hu-Friedy, Chicago, IL, USA) and explorer. Following parameters were taken into
consideration: Plaque index (PI)(Silness & Loe); Gingival index (GI)(Loe & Silness);
Bleeding on probing (BOP); Pocket depth (PD); and Attachment loss (AL). To preclude inter
examiner variability, periodontal examination was performed by one trained and calibrated
examiner (AB). The calibration protocol included determination of examiner reproducibility,
which was recorded twice at the same visit on 10% of representative samples. Operator
calibration for GI was based on intra examiner exact reproducibility at 85% of sites. For PD
and AL, calibration was based on intra-examiner reproducibility within 1 mm at >90% and >85%
of sites.
Periodontal treatment Patients in TG received full mouth scaling and root planing (SRP)
using manual instruments and ultrasonic scaler (Suprasson P5 Booster; Satelec, Merignac
Cedex, France) in 2-4 sessions. The patients were further provided information on the
periodontal disease, and oral hygiene instructions were given at each appointment. The
patients were instructed to use only mechanical techniques such as toothbrushes and
interdental-floss during the study period. Mouthwashes and /or antimicrobials were not
prescribed. Patients were asked to bring the remaining tablets left with them so as to
assess the compliance. Patient compliance was considered when ≥90% of the tablets was
consumed. Weekly reminders were also given to the patients through personal phone calls.
Statistical analysis Post-hoc analysis was done using statistical software (G*Power
v.3.0.10, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany). Effect size was
determined following rule of the standardized difference in a given output variable (BMD)
with sample size of 62 with significance level of two sided α= 0.05. This came out to be 1.
With these measurements, statistical power exceeds 90% with allocation ratio of 1:1. The
normality of the data distribution was examined using Shapiro-wilk test. PD and hsCRP were
found to be normally distributed, whereas rests of the parameters were non-normally
distributed. The descriptives were expressed as mean±SD. The significance of difference
between groups for age, BMD, PI, GI, BOP and AL at baseline was compared by Mann-whitney U
test. Independent T test was used in hsCRP and PD for the same purpose. Wilcoxon signed rank
test and Paired T test were used to evaluate difference between baseline and 6 month follow
up in both groups. The difference between groups was assessed using Mann whitney U test or
Independent T test whichever was applicable. A binomial logistic regression model was fitted
to relate Normal T-score patients as the outcome variable and treatment groups as the
categorical predictor variable. The Hosmer-Lemeshow goodness of fit test was applied to
verify whether the present test fits well. Model was adjusted for the covariate and all
statistical analyses were 2 tailed, having a significance level at 0.05(SPSS v.21, IBM,
Chicago, IL).
