1% ALENDRONATE GEL AS LOCAL DRUG

DELIVERY IN THE TREATMENT OF CLASS II

FURCATION DEFECTS: A RANDOMIZED
CONTROLLED CLINICAL TRIAL
BY-DR. RUPALI BORADE
• Periodontitis is a term used to describe an inflammatory process, initiated by the plaque biofilm,
that leads to loss of periodontal attachment to the root surface and adjacent alveolar bone and
ultimately results in tooth loss.

• Molars are the tooth type demonstrating the highest rate of periodontal destruction in untreated
disease and suffer the highest frequency of loss for periodontal reasons.
• Furcations are frequently not accessible for adequate professional debridement because the
entrance is very small for the size of periodontal instruments, and they present with ridges,
convexities, and concavities that frequently render the defect impossible to instrument
effectively.
• Therefore, furcation defects represent a formidable problem in the treatment of periodontal
disease, principally because of the complex and irregular anatomy of furcations.
• Periodontal regeneration is the restoration of the tooth-supporting tissues. Clinically, successful
regeneration at furcation sites is determined as the elimination or reduction of the horizontal and
vertical components of the lesion (i.E., A gain of clinical attachment level [CAL] and bone fill),
but the conclusive evidence of true regeneration can be achieved only by histologic means.
• The improvement of bone regeneration has included the use of biologic mediators to improve the
Quantity and quality of the bone being regenerated.
• Among these agents, bisphosphonates, which are Chemical analogs of pyrophosphate, are known
to Inhibit osteoclastic bone resorption. bisphosphonate are a class of drugs structurally similar to
pyrophosphate, A component of human metabolism.
• It binds To the hydroxyapatite crystals of bone and prevents Their dissolution by interfering with
osteoclast Function through a variety of direct and indirect Mechanisms.
• Bisphosphonates not only induce the osteoblasts to secrete inhibitors of osteoclast-mediated resorption
but also stimulate the formation of osteoblast precursors and mineralized nodules, thereby promoting
early osteoblastogenesis.
• Bisphosphonates are also proposed to have osteostimulative properties, both in vivo and in vitro, as
shown by the increase in matrix formation.
• Alendronate (ALN) is a second-generation bisphosphonate, which includes aminobisphosphonates
with an amino-terminal group. the antiresorptive properties of bisphosphonates change according to
their side chains. ALN binds to the crystals of hydroxyapatite in bone and binds preferentially to the
bone resorption surface, particularly to those undergoing active osteoclastic resorption.
 AIM

• The current study is designed as a single-center, randomized, controlled clinical trial to evaluate
the efficacy of 1% ALN gel as a local drug delivery agent adjunctively to SRP for the treatment
of class II furcation defects in comparison to placebo gel.
 MATERIAL AND METHOD

• A total of 69 systemically healthy patients (37 males and 32 females)

• Age range: 30 to 50 years
• Were selected from the outpatient section of the department of periodontics, government dental
college and research institute, bangalore, india.
 SELECTION CRIETERIA

• Inclusion crieteria.
• Presence of buccal class ii furcation defects.
• In endodontically vital, asymptomatic mandibular first molars with a radiolucency in the
furcation area on an intraoral periapical radiograph with pd ‡5 mm and horizontal pd ‡3 mm
following phase 1 therapy (srp).
• Exclusion crieteria
• 1) patients with known systemic disease.
• 2) patients with known or suspected allergy to the aln/bisphosphonate group.
• 3) patients receiving systemic aln/bisphosphonate therapy.
• 4) patients with aggressive periodontitis.
• 5) patients using tobacco in any form.
• 6) patients with alcoholism.
• 7) patients who were immunocompromised. And
• 8)pregnant or lactating females.
• In addition, teeth with gingival recession, endodontic (pulpal) involvement, or tooth mobility
‡class 2 were also excluded.
• Each patient was given careful instructions on proper oral hygiene measures. A full-mouth supra-
and subgingival SRP procedure was performed under local anesthesia.
• In the ALN group, sites were treated with SRP followed by 1% ALN gel (10 mg/ml) local drug
delivery,
• Where as in the placebo group,sites were treated with srp followed by placebo gel placement.
Only one site per patient was enrolled for either the ALN or the placebo group. The ALN and
control sites were not revealed to the patients.
 CLINICAL PARAMETERS

• No antibiotics or anti-inflammatory agents were prescribed after treatment.

• Clinical parameters, including modified sulcus bleeding index (msbi),
• full-mouth and site-specific plaque Index (PI) score
• ,Probing Depth, relative vertical CAL (RVCAL), and relative horizontal CAL (rhcal),were
recorded at baseline (before the SRP) and at 3, 6, and 12 months.
• A custom-made acrylic stent with grooves, a color-coded periodontal probe‡ (for vertical
measurement) and a furcation probe§ (for horizontal measurements) were used to standardize the
measurement of clinical parameters.
 RADIOGRAPHIC MEASUREMENTS

• Each bone defect (BD) was evaluated at baseline, 6 months, and 12 months. For the
measurement of BD depth, distance from the furcation fornix to the base of the defect was
considered.
 Figure 1.
BD was measured on the baseline radiograph by measuring the distance
from the furcation fornix to the base of the defect (4.10 mm).
• All radiographs were reviewed in a single reference center by a masked evaluator (NR). For
assessment, radiographs were scanned with a scanner at 6,400 DPI by the evaluator (NR) who
was masked to surgical procedure performed in patients.
• The radiographic bd depth was measured by a computer-aided software program¶ as used
previously.
 FORMULATION OF 1% ALN GEL

• ALN gel was prepared as described by reddy et al.

• ALN was dissolved in a required amount of distilled water to achieve 1% ALN concentration. A
weighed quantity of polymer# (2% wt/wt) was taken and added to the distilled water. The mixture
was stirred gradually, the polymer was allowed to soak for 2 hours, and 1% triethanolamine was
added to neutralize The polymer solutionandtoformthegel.The ph Was adjusted to 6.8. Finally, the
required amounts of Methyl paraben (0.1%) and propyl paraben (0.05%) Were dissolved in
ethanol and added to the gel.
• The placebo gel was prepared by the previously Mentioned procedure without adding the active
ingredient (Aln).
• Local drug delivery For standardization, 10 μl prepared ALN gel (10 mg/ Ml) was injected into
the furcation defects using a Syringe with a blunt cannula. Patients were instructed To refrain
from chewing hard or sticky foods, brushing Treated sites, or using any interdental aids for 1
week. Adverse effects were recorded at recall visits, and supragingival Deposits were removed.
 RESULTS

• Both the groups showed improvement in sitespecific PI, full-mouth PI score, and gingival index
(GI), but improvement was not statistically significantly different between the ALN group and
the placebo group at any time point (P >0.05) except for a significant difference in full-mouth PI
score at the 12-month follow-up (tables 1 and 2).
• This indicates that both groups maintained comparable levels of oral hygiene until the 6-month
follow-up but not a the end of the 1-year of study.
• The clinical parameters PD, RVCAL, and RHCAL also showed no difference in both groups at
baseline, but the ALN group showed a significantly greater PD reduction and RVCAL and
RHCAL gain (P <0.001) at 3, 6, and 12 months compared with the placebo group (tables 3 and
4).
• The radiographic parameter BD depth showed a statistically significant mean reduction in the
ALN group (1.27 – 0.28 mm, 1.29 – 0.27 mm) in comparison to the placebo group (0.11 – 0.03
mm, 0.07 – 0.06 mm) at 6 months and 12 months, respectively (table 4).
• The aln group sites presented with a significantl greater bd fill (32.11% – 6.18%) than the
placebo sites (2.71%– 0.61%) at 6months.
• Similarly, at the 12-month follow-up, a significantly greater BD fill of 32.66% – 5.86% in the
ALN group compared to 1.83% – 1.51% in the placebo group was shown (table 4).
 DISSCUSSION

• Bisphosphonates have a high affinity for calcium phosphate crystals, and they have been used in the
treatment of malignant hypercalcemia, paget disease, and osteoporosis because of their inhibitory effect
on osteoclast activity.
• ALN is an aminobisphosphonate, and once taken up by bone, it acts as an antiosteolytic agent.
ALN binds to resorption surfaces and is locally released during the acidification associated with
osteoclastic activity. This release leads to a rise in the local concentration of ALN, resulting in
an alteration in the ruffled border membrane characteristic of osteoclasts without destroying the
cells. therefore, ALN seems to have a potential to be used as an inhibitor of alveolar bone
resorption in the treatment of periodontitis.
• It has also been shown that the bisphosphonate ALN caused a rise in intracellular calcium levels
in an osteoclast-like cell line.
• this finding is of great interest because it could suggest the presence of a receptor for
bisphosphonates on osteoclasts. ALN appears to affect protein prenylation in osteoclasts through
inhibition of the mevalonate pathway, which is involved in cholesterol synthesis.
• Additionally, osteoclast function can be altered by the production of an osteoclast inhibitory
factor secreted by osteoblasts following exposure to ALN.
• The current study finds improvement in the clinical parameters PI and msbi compared to baseline
at all time intervals.
• However, there is a significant difference in the full-mouth PI score between the two groups at 12
months. There is also a significant decrease in PD, and significant gains in RVCAL and RHCAL,
in the ALN group in the current study, which is similar to the results of previous studies.
• The percentage of BD fill in the current study is 32.11% – 6.18% at 6 months and 32.66% –
5.86% at 12 months in the aln group, compared with 2.71%– 0.61% at 6 months and 1.83% –
1.51% at 12 months in the placebo group.
• Moreover, furcations are generally less responsive to therapy than non-furcated areas or single-
rooted teeth, as reflected by a limited gain in attachment levels and less reduction in the PD after
conventional non-surgical and open flap instrumentation of furcation surfaces. nevertheless,
furcation lesions are well-established and documented models for the clinical evaluation of
regenerative techniques, especially in mandibular molars.
• Compared with a systemic regimen, local delivery may offer important benefits in terms of
adverse reactions and patient compliance.
• the current study considers subgingivally delivered ALN in the treatment of class II furcation
defects because the local drug delivery systems offer the advantages of high concentrations of the
drug at the target site with a reduced dosage, fewer applications, and a high patient acceptability.
• polymer†† was used as a vehicle for preparation of ALN gel, which provides intimate contact
and prolongs the residence time of a dosage form in the periodontal pocket by means of specific
interfacial forces in a process commonly referred as mucoadhesion, after local drug delivery.
• Oral bisphosphonates (ALN, risedronate, and ibandronate), used mainly for the treatment of
osteoporosis, have been associated with adverse events from the upper gastrointestinal tract,
acute phase response, hypocalcaemia and secondary hyperparathyroidism, musculoskeletal pain,
osteonecrosis of the jaw, and ocularevents.
• Generally, intravenous bisphosphonates are more potent than oral bisphosphonates, and the
frequency and severity of some of the bisphosphonate associated adverse events are dose and
potency dependent.
• However, in this 12-month study period, no such complications were observed because ALN was
used locally at very low concentrations and dosage.
• Considering these facts and the results of the previous studies, direct subgingivally injected ALN
can be a better approach for periodontal healing of patients with furcation defects compared with
SRP alone.
 CONCLUSION

• The results of the present study show that local delivery of 1% ALN is effective in the treatment
of class II mandibular furcations.
• Within the limitations of this study, there is greater PD reduction and RVCAL and RHCAL gain
with significant BD fill when ALN is used in class II furcation defects in comparison to placebo.
• Further multicenter long-term randomized longitudinal prospective studies assessing bone
quality using suitable computerized tomographic images should be done to confirm the findings
of this study.