Clinical and radiographic evaluation of effect of

Clinical and radiographic evaluation of effect of risedronate 5 mg as an adjunct to treatment of chronic periodontitis in postmenopausal women (12-month study) N. V. Bhavsar, S. R. Trivedi, K. Dulani, N. Brahmbhatt, S. Shah & D. Chaudhri

Osteoporosis International With other metabolic bone diseases ISSN 0937-941X Osteoporos Int DOI 10.1007/s00198-016-3577-8

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Author's personal copy Osteoporos Int DOI 10.1007/s00198-016-3577-8

ORIGINAL

Clinical and radiographic evaluation of effect of risedronate 5 mg as an adjunct to treatment of chronic periodontitis in postmenopausal women (12-month study) N. V. Bhavsar 1 & S. R. Trivedi 1 & K. Dulani 1 & N. Brahmbhatt 1 & S. Shah 1 & D. Chaudhri 2

Received: 28 September 2015 / Accepted: 21 March 2016 # International Osteoporosis Foundation and National Osteoporosis Foundation 2016

Abstract Summary Bisphosphonates are beneficial to women, after menopause, in treatment of gum diseases. In this study, significant improvement in the disease condition was found and that no further progress was noted, and no side effects were reported. Bisphosphonates can be safely and successfully be used to support oral health procedures. Introduction The purpose of this study was to evaluate host modulating effect of bisphosphonate adjunct with the treatment of chronic periodontitis in osteopenic and osteoporotic postmenopausal women. Methods Twenty-two osteopenic and osteoporotic postmenopausal women with moderate to severe chronic periodontitis were selected for the study. On intraoral examination,

* N. V. Bhavsar [email protected] S. R. Trivedi [email protected] K. Dulani [email protected] N. Brahmbhatt [email protected] S. Shah [email protected]

periodontal parameters like probing depth (PD), clinical attachment level (CAL), Plaque Index (PI) and Gingival Index (GI) were recorded. Scaling and root planing were done. Intraoral periapical X-rays were taken, and alveolar bone density (ABD) was measured with cone beam computed tomography (CBCT), and then, medications (risedronate 5 mg once daily (OD), calcium citrate 250 mg OD, vitamin D 400 IU OD) were given. Patients were recalled for follow-up at 3, 6 and 12 months. Intraoral periapical (IOPA) X-rays were taken at 6 and 12 months and ABD was measured at baseline and 12 months. Results There was a significant improvement in all the parameters. There was an increase of 0.02 ± 0.001 cm on CT scan and 0.38 ± 0.005 mm on IOPA in bone height over 12 months from baseline. Bone density increased by 118.56 ± 3.251 Hounsfield units (HU). There was no progress in the disease, and further bone loss was not noticed. This is in correlation with clinical parameters which showed highly significant gain in CAL (3.57 ± 0.234 mm) and reduction in PD (2.20 ± 0.229 mm) Conclusions Bisphosphonate therapy as an adjunct to scaling and root planing may have significant beneficial clinical effects on the periodontium of postmenopausal women with moderate to severe chronic periodontitis. Keywords Bisphosphonates . Chronic periodontitis . Host modulation . Osteoporosis . Postmenopausal women . Risedronate

D. Chaudhri [email protected]

Introduction 1

2

Department of Periodontology and Implantology, Government Dental College & Hospital, Asarwa, Ahmedabad, Gujarat 380016, India Department of Periodontology, Siddhpur Dental College, Siddhpur, Gujarat, India

Osteoporosis is a systemic skeletal disease which has manifestations in all the bones of the body, including alveolar processes of the maxilla and mandible. The WHO has defined osteoporosis as bone mineral density (BMD) ≥2.5 standard

Author's personal copy Osteoporos Int

deviations (SD) below the normal for Caucasian women. Low bone mass or osteopenia is defined as BMD between 1 and 2.5 SD below the mean for normal Caucasian women [1]. With the increasing longevity of Indian population, it is now being realized that osteoporotic fractures are major cause of morbidity and mortality amongst elderly population in India [2]. Based on 2001 census, approximately 163 million Indians are aged 50 years and above, and this number is expected to increase to 230 million by 2015; of these, approximately 20 % of women would be osteoporotic [2]. In most women, bone mass reaches its peak in the third decade of life and declines thereafter. This decline in bone mass is accelerated with the onset of menopause [3]. Oestrogen levels present prior to menopause are protective. Decrease in levels of oestrogen causes decrease in BMD and predisposes to osteopenia and subsequent osteoporosis [4]. The average bone loss after 30 years of age is 0.7 % per year, which increases to 2–5 % per year after menopause. Since cancellous bone is much more metabolically active than cortical bone, in periods of accelerated bone loss, cancellous bone loss is threefold greater [2]. Studies suggest that low oestrogen production after menopause is associated with increased production of interleukin (IL)-1, IL-6, IL-8, IL-10, tumour necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, which stimulates mature osteoclasts, modulates bone cell proliferation and induces resorption of both skeletal bones [5]. It is logical that if BMD is decreased systemically, the same effect should be apparent in the alveolar bone of the jaws. Crosssectional studies analyzing the relationship between systemic BMD and oral BMD tend to support this association [1]. Accumulation of bacterial plaque around gingival and subgingival tissues induces cascade of inflammatory process in the host periodontal tissues and subsequent loss of attachment (periodontitis). The periodontal disease process is a hostmediated process which involves mast cells, neutrophils, macrophages, lymphocytes and plasma cells. Macrophages play a direct role in IL production and secretion (IL-1, IL-6, IL-8 and TNF-α), and osteoclastic activity is upregulated [6]. Alveolar bone loss is a prominent feature of periodontal disease. In the light of these facts, it appears that cytokines play an important part in the pathogenesis of periodontitis and decrease in BMD after menopause. There exists a relationship between low BMD and increased risk of periodontitis in postmenopausal women [7–14]. Advances in the understanding of the aetiology and pathogenesis of periodontal disease have lead to use of pharmacological interventions along with mechanical and surgical periodontal treatment modalities. Host modulatory therapy (HMT) offers the potential to move periodontal treatment strategies to a new level. HMT is a treatment concept that aims to reduce tissue destruction and stabilize or even regenerate the periodontium by modifying or down regulating destructive aspects of host response and upregulate

protective or regenerative responses [13, 15, 16]. HMTs are systemically or locally delivered pharmaceuticals that are used as adjuncts to conventional periodontal treatments. Host modulatory agents used adjunct to periodontal treatment are nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates (BPs), tetracyclines, enamel matrix derivatives (EMDs), growth factors and bone morphogenetic proteins (BMPs). BPs are a group of medications that have become increasingly and more widely used in the management of postmenopausal osteoporosis [1]. BPs are agents that inhibit bone resorption by inducing down regulation of bone resorptive factors attributed to matrix metalloproteinases (MMPs) and inhibit osteoclast-mediated bone resorption by induction of osteoclastic apoptosis [15]. Randomized trials of risedronate, a second-generation BP, have shown to increase BMD in postmenopausal women with osteopenia or osteoporosis [1]. Long-term use of risedronate has been found to be safe on oral use [1]. Keeping in mind the pharmacological effect of BP and the pathophysiology of bone loss and decrease in BMD in periodontal disease and postmenopausal osteoporosis, effort has been made to evaluate the effect of BP on periodontitis in postmenopausal women. The purpose of this study was to evaluate periodontal status, alveolar bone density and alveolar bone height in postmenopausal women by administering BP [risedronate 5 mg once daily (OD)] for 12 months.

Methods This 12-month study composed of total 25 postmenopausal women with periodontitis reporting to Department of Periodontia, Government Dental College and Hospital, Ahmedabad. Patients were explained the nature and pattern of study. The study pattern was approved by The Ethical Committee of the institution. Subjects were selected according to the inclusion criteria, and a written consent was obtained. There were three dropouts during the study period. Therefore, the effective sample size was 22. Patients were either osteoporotic or osteopenic (BMD measured at calcaneus bone). According to power analysis, a sample size of 22 achieves 80 % power to detect difference of 0.3 between the null hypothesis mean of 1.4 and the alternative hypothesis mean of 1.1 with a known standard deviation of 0.5 and with a significance level (alpha) of 0.050 using a two-sided dependent t test. Subject inclusion criteria The subject inclusion criteria are as follows: (1) age 45 to 65 years, with history of at least 1 year of menopause; (2) patients with moderate to severe periodontitis (disease); and (3) subjects demonstrating good compliance in maintaining


good oral hygiene and willingness to come regularly for follow-up visits. Disease definition (Lane N et al. 2005 [17])

citrate 250 mg OD, vitamin D 400 IU OD [{thyrocal D(3) tablet, Abbott India Ltd (calcium citrate malate (250 mg), vitamin D3 (400 IU)}] were given. Instructions regarding medications were given which were the following:

The disease definitions of moderate periodontitis are as follows: mean clinical attachment level (CAL) loss 1.4 to 2.4 mm or ≥8 sites with CAL loss >3 mm distributed in at least three quadrants or in at least six teeth (not counting straight buccal and lingual surfaces and distal surfaces of the second molars) and severe periodontitis: mean CAL loss >2.5 mm or one or more sites in three out of four quadrants with CAL loss measurements >5 mm.

1. To take all medications in the morning with full glass of water in upright position before 30 min of meal. 2. Always take half an hour interval between BP and calcium supplements. 3. Sit or stand for at least 30 min after taking a BP. This helps prevent heartburn. Not to take a BP late in the day if morning dose is missed.

Subject exclusion criteria

Patients were recalled for follow-up at 3, 6 and 12 months and at every visit scaling, and root planing was done when needed. PD, CAL, PI and GI were recorded at every visit while IOPA X-rays were taken at 6 and 12 months, and ABD was done at baseline and 12 months.

The subject exclusion criteria are as follows (1) presence of generalized disease of bone (other than chronic periodontitis); (2) medically compromised patient; (3) presence of diseases that may affect bone metabolism like renal impairment, parathyroidism, malabsorption and hyperthyroidism; (4) gastrointestinal disturbances such as symptomatic peptic ulcer disease, inflammatory bowel disease, alcoholism and hepatic impairment; (5) physical condition, which hinders manual dexterity to maintain oral hygiene; (6) treatment with anabolic steroids, anticonvulsants or anticoagulants; (7) pharmacologic doses of vitamin A or D supplements within 1 year before start of the study; previous use of BPs (within 1 year), calcitonin (within 6 months) or fluoride therapy (>1 month) prior to start of study; and (8) trauma from occlusion. A thorough medical and dental history was obtained followed by complete medical, oral, clinical and radiographical examination. Impressions of upper and lower arches were made and poured immediately to avoid distortion. On intraoral examination, periodontal parameters like probing depth (PD), CAL, Plaque Index (PI: Turesky–Gilmore– Glickman modification of Quigley–Hein plaque index 1970) and Gingival Index (GI: LOE AND SILLNESS 1963) were recorded. PD and CAL were recorded on four surfaces of the tooth (mid-buccal, bucco-mesial, bucco-distal and mid-lingual). Customized acrylic occlusal stents with vertical grooves were prepared for each patient on their respective study cast to record the direction of insertion of periodontal probe (UNC-15 probe, InSci , Equinox) interproximally (bucco-mesial, buccodistal) and to standardize it for future measurements (Figs. 1 and 2). As a part of phase I therapy, supra-gingival and subgingival scaling and root planing were done and oral hygiene instructions (brushing technique) were given. After complete scaling and root planing, intraoral periapical (IOPA) X-rays (Fig. 1a) were taken and alveolar bone density (ABD) (Fig. 3a) was measured with cone beam computed tomography (CBCT), and then, medications [risedronate 5 mg OD{Risofos 5 mg, Cipla Ltd (risedronic acid)}], calcium

Intraoral periapical X-ray After phase I treatment, at least eight interproximal sites distributed in at least three quadrants, with CAL ≥1.4 to 2.4 mm, were selected. IOPAs were taken using long-cone paralleling technique. These were done at baseline, 6 months and 12 months. The indigenously developed standardized IOPA mm X-ray grid was placed in front of IOPA film on film holder, and the selected teeth were X-rayed. The measurement from cementoenamel junction (CEJ) to crest of the alveolar bone (CAB) (CEJ-CAB) in interproximal areas was calculated by counting the squares of the grid to nearest millimetre (Figs. 1a and 2a). Alveolar bone density—cone beam computed tomography Patient position prior to imaging The patients were informed about the investigation and instructed not to move or swallow during the scan. The investigation was performed in the sitting or standing position which is maintained with a head positioner and chin rest. Scanner protocol Dental CT images are displayed with a very low-contrast setting (bone window) due to the excellent contrast between the bone and soft tissue. The scan was obtained using NewTom GiANO cone beam 3D imaging (distributed by QR srl-Via Silvestrini, 20-37135 Verona, Italy) with the following protocol: 90 kVp, 10 mA and rotation time 18 s. Voxel size is 0.15 mm (can be adjusted between 0.15 to 5 mm), 521 × 512


Fig. 1 Baseline measurement of clinical parameters after phase I periodontal treatment. a Baseline IOPA. b CT scan at baseline for measurement of alveolar bone height

Fig. 2 Measurement of clinical parameters after 12 months. a IOPA at 12 months. b CT scan at 12 months for measurement of alveolar bone height


Fig. 3 a CT scan image, transverse section, at baseline showing area of measurement of ABD. b CT scan image, transverse section, at 12 months showing area of measurement of ABD

matrix and no added filtration. The ABD was recorded in Hounsfield units (HU).

Parameter ABD in HU and alveolar bone height (ABH) in centimetre from CEJ to CAB (Figs. 1b and 2b) as determined on CTscanned image at sites were selected for IOPA. Density was measured at interdental area (Fig. 3a, b).

Statistical analysis The data was collected and recorded as mean and standard deviation for clinical, radiographic and bone scan parameters. The mean changes of the variables over baseline to 6 months, 6 to 12 months and baseline to 12 months were calculated. This data was analyzed using mixed model analysis of variance (ANOVA) for intercorrelated data.

Result In the present study, a total of 22 (n) patients completed the study. There was a significant improvement in all the parameters: bone density with CBCT (Table 1); clinical: PD, CAL, PI and GI (Table 2); and radiographic (Table 3). A mean gain of 0.02 ± 0.001 cm was observed by CT scan at the end of 12 months (Table 1), and a 0.38 ± 0.005-mm increase in bone height was noted over 12 months from baseline on IOPA (Table 3). There was no progress in the disease and further bone loss was not noted. This was in correlation with clinical parameters which shows highly significant gain in CAL (3.57 ± 0.234* mm) and reduction in PD (2.20 ± 0.229* mm) (Table 2).

Discussion The purpose of this study was to evaluate the effect of BP (risedronate 5 mg OD) along with scaling and root planing on periodontal parameters and ABD in postmenopausal women suffering from periodontitis. Based on the pharmacological action of BP, it was hypothesized that an increase in density of the alveolar bone will inhibit the loss of bone in adjunct to periodontal treatment. It was found that there was an increase in ABD after a treatment time of 12 months (Table 1) and an increase in ABH (Tables 1 and 3). The periodontal parameters significantly improved over period of 12 months (Table 2). There was a reduction in Gingival Index scores as well as in Plaque Index scores (Table 2). The results of this study were consistent with the studies which evaluated the effect of BPs on periodontium of postmenopausal women [6, 15, 17–22]. Lane N et al. [17] found that BP therapy (alendronate at 10 mg/day or risedronate 5 mg/day) significantly improved CAL, PD and bleeding on probing (BOP) during the 12-month treatment period. The treatment group was compared with placebo group. However, there was no difference in the periodontal bone mass between the BP group and placebo group as measured by fractal analysis and DSR. A similar study conducted by Rocha ML et al. [18], which compared alendronate (ALN) with placebo, showed a greater Table 1 Comparison of mean change in bone density (in HU) and bone height (in cm) Parameter

Baseline (mean ± SD)

12 months (mean ± SD)

Mean change (mean ± SD)

Bone density (HU) Bone height (cm)

877.17 ± 181.493

995.73 ± 196.740

118.56 ± 3.251*

0.52 ± 0.061

0.50 ± 0.059

*High statistical significance; p value ≤0.0001

0.02 ± 0.001*

Author's personal copy Osteoporos Int Table 2

Comparison of clinical parameters over 12-month time interval (n = 22)

Parameter

Mean ± Std

Plaque Index Gingival Index

Mean differences

Baseline

6 months

12 months

Baseline to 6 months

6 to 12 months

Baseline to 12 months

3.64 ± 0.494 2.20 ± 0.398

1.71 ± 0.580 1.40 ± 0.368

0.80 ± 0.493 0.67 ± 0.324

1.33 ± 0.086* 0.80 ± 0.030

0.91 ± 0.087* 0.72 ± 0.044*

2.24 ± 0.001* 1.53 ± 0.074*

PD (in mm)

4.85 ± 0.390

3.12 ± 0.430

2.65 ± 0.619

1.73 ± 0.040*

0.47 ± 0.189*

2.20 ± 0.229*

CAL (in mm)

7.80 ± 1.084

5.49 ± 0.945

4.23 ± 0.850

2.30 ± 0.139*

1.27 ± 0.095*

3.57 ± 0.234*


improvement in PD and gingival bleeding in ALN group. Also, the CAB-CEJ distance on IOPA radiograph significantly diminished in ALN group. There was an increase in BMD of calcaneus bone in ALN group. The present study measured the periodontal bone density (ABD) with CBCT scans, which increased significantly after 12 months (Table 1). In the present study, tab. risedronate 5 mg, tab. calcium citrate and tab. vitamin D3 were given to patients for 12 months. Mostafa B et al. [19] gave BP (ALN) in osteoporotic women following non-surgical and surgical periodontal therapy along with calcium and vitamin D3 supplements. This group was compared with a control group in which calcium and vitamin D3 supplements were not given. They found improvement in both groups, but the study group showed higher percentages of improvement in the clinical as well as radiographic measurements. Tanna N.K. and Jeffcot M.K. [20] evaluated the effect of risedronate on periodontal parameters in patients with adult periodontitis. A statistically significant improvement in bone height was observed favouring the risedronate group over placebo at 9 months (p < 0.04). The magnitude of the mean difference was 0.30 mm at 6 months and 0.19 mm at 9 months. However, BMD was not measured. The prevention of the bone loss associated with periodontal disease progression by modulation of the host response may, therefore, be an adjunct approach to the management of periodontitis. Promising use of BPs in treatment of osteoporosis can also be an effective modality for controlling alveolar bone destruction in osteoporotic women [1, 21, 22]. BPs are highly potent inhibitors of osteoclastic bone resorption, with an initial

Table 3 Parameter

CEJ-CAB

filling of resorption cavities followed by increased mineralization that is the result of reduced bone turnover [22]. They also increase osteoblastic differentiation and inhibit osteoclast recruitment and activity. The nitrogen-containing BP, risedronate, has an affinity for hydroxyapatite (HAP) in the bone and acts as an anti-resorptive agent [23]. Risedronate is a highly potent inhibitor of farnesyl pyrophosphate synthase (FPPS) but does not bind to mineral as strongly as alendronate. In addition, risedronate dosing is simpler than the cyclical dosing regimen that is required for etidronate [24]. The bone sparing activities of BPs are as follows [25]: Mineral affinity (based on kinetic affinity constants): Risedronate < ibandronate < alendronate < pamidronate < zoledronate Farnesyl pyrophosphate synthase (FPPS) enzyme inhibition: Etidronate (extremely weak inhibitors) < pamidronate < alendronate < ibandronate < risedronate Positive change in surface charge as a result of BP binding to HAP: Risedronate < clodronate < etidronate < zoledronate < alendronate < ibandronate BPs are generally well tolerated and safe. According to the results obtained in the study done by Harris ST et al. [26], 5 mg daily and 35 mg weekly regimens of risedronate showed comparable safety profiles after both 1 and 2 years of treatment. The main adverse effects associated with risedronate and other BPs are gastrointestinal disturbances including oesophagitis, abdominal pain, dyspepsia, diarrhoea and constipation. Headache and musculoskeletal pain may also occur [24]. Other clinical

Comparison of mean change in bone level radiographically (IOPA) at baseline and 6 and 12 months (in mm) Baseline (mean ± SD)

5.70 ± 0.340


5.48 ± 0.330



5.32 ± 0.335

Bone gain Baseline to 6 months (mean ± SD)

6 months to 12 months (mean ± SD)

Baseline to 12 months (mean ± SD)

0.22 ± 0.010*

0.16 ± 0.005*

0.38 ± 0.005*


concerns associated with BP therapy are osteonecrosis of the jaw (ONJ), atrial fibrillation, oversuppression of bone turnover causing Bfrozen bone^, hypocalcaemia and acute inflammatory responses including ocular inflammation [23]. The risk of this is greater in patients receiving intravenous BPs than in patients receiving oral BPs for osteoporosis or Paget’s disease of bone [20, 27–29]. Multiple studies have shown that reductions in bone turnover are associated with increased bone density, more homogeneous mineralization and reduced fracture risk. The amount of BP retained in bone after 10 years of alendronate treatment was estimated at 75 mg per 2 kg mineral, using a pharmacokinetic model for a dose of 10 mg per day. This small fraction, which is unevenly distributed between cancellous and cortical bone, seems unlikely to change bone mechanical properties. Taken together, the known mechanism of action of potent BPs and the experience accrued from treating a large number of patients, including up to 10 years follow-up in controlled trials, have identified only beneficial BP effects on bone [30]. According to ADA, the risk of ONJ is reportedly between 0.7 and 1.5/100,000 [6]. No ONJ or other side effects were noted in this study. Hypovitaminosis D is common among many patients that are prescribed BP therapy and is common among elder patient who frequently have reduced dietary intake. This vitamin D insufficiency or deficiency limits dietary absorption of calcium leading to secondary hyperparathyroidism and loss of skeletal calcium to maintain normocalcaemia. So, maintenance of adequate calcium and vitamin D intake is crucial for all patients receiving BP therapy [31]. It appears that as people age, they take less dietary calcium and vitamin D possibly because of their decrease of total food intake. Various data suggests that calcium and vitamin D intake by adult periodontal maintenance patients is associated with better periodontal health. It was documented that lower dietary intake of calcium increased the risk of periodontal disease in a doseresponse relationship [32]. Further on, Mostafa B et al. [19] concluded that BP along with calcium and vitamin D supplements showed higher percentage of improvement. Therefore, the postmenopausal females of this study were given calcium and vitamin D supplements. The patients with a history of any systemic disorder and drug therapy were excluded, as they may alter the treatment plan or affect the outcome of the treatment. Patients with a previous history of fluoride therapy and vitamin D therapy were excluded because vitamin D supplementation significantly reduces tooth loss and improves periodontal outcome and fluoride anion can substitute for hydroxyl in HAP crystals and thereby changes the crystalline structure of the bone tissue and increases BMD [33, 34]. The radiographic investigations included IOPA X-ray and CBCT. In an IOPA X-ray, two-dimensional mapping is highly

susceptible to angulation errors induced when the radiologist positions the film and the X-ray tube head to expose the film. The periapical view has been designed to minimize this distortion. In the present study, long-cone paralleling technique was used to expose IOPA films with standardized grid. Using such a grid provides an accurate way of assessing changes in bone height less than 1 mm [35]. In this technique, the relatively parallel rays minimize the distortion of the image that would be caused by divergence of the beam between the bone and teeth and the film. Radiographic parameters were recorded by measuring the distance from the CEJ to CAB in millimetres. Radiographs were taken at 6 and 12 months because when use of BP continued, the bone gradually becomes denser. There is no further new bone, but the existing bone matrix is packed more tightly with mineral crystals. The old bone is not resorbed. The bone density measured radiographically increases most rapidly during the first 6 months (while resorption pits are filling in) and more gradually over the next years (while bone is becoming more mineralized) [36]. CBCT allows precise three-dimensional evaluation of anatomic structures and direct measurement of bone density, expressed in HU, characteristics that provide important information about the bone [33–40]. CT is the only method that allows the components of trabecular and compact bone tissue to be investigated separately [41]. Of the several methods available for bone density, CT scan is relatively sensitive (three to four times that of single-photon absorptiometry and twice that of dual-photon absorptiometry) and has intermediate precision (2–5 %, better than that of single-photon absorptiometry) and variable accuracy of 5–20 % (spanning the range of other available methods) [38]. Decrease in Plaque Index (PI) and Gingival Index (GI) (Table 2) can be possibly attributed to mechanical disruption of the existing plaque as a result of scaling and root planing [41]. Also, it can be due to the improved oral hygiene behaviour showed by the subjects in accordance to the motivation and demonstration of appropriate brushing technique as a part of the study protocol. Removal of sub-gingival plaque and calculus deposits through sub-gingival debridement exposes the cementum, root dentine and pocket epithelium for novel colonization. Species which may have thrived in the subgingival environment of the diseased pocket may find the new habitat less hospitable. A decreased concentration of microbial products and tissue breakdown products and a decrease in the flow of gingival crevicular fluid were responsible for the decreased gingival inflammation [42]. Decrease in PD and gain in CAL are attributed to resolution of inflammation, decreased oedema and a re-adaptation of apical junctional epithelium. After treatment with scaling and root planing, the regeneration of the root epithelial interface as a long junctional epithelial attachment occurs. This precludes the formation of the new connective tissue attachment. Concomitant with regeneration of the attachment epithelium are gradual


reductions in clinical inflammation that, in turn, appears to correlate to reductions in inflammatory cell populations, crevicular fluid flow and repair of the connective tissue matrix [43]. BPs are group of host-modulating agents that are clinically effective at reducing bone resorption and have shown the ability to inhibit host degradation enzymes, specifically the MMPs. Although the precise mechanisms of effects of BPs on periodontal ligament (PDL) cells are unknown, it is possible that these compounds affect MMP released from resident cells in the periodontal attachment apparatus including the PDL. The accumulation of BPs in the bone tissue could potentially make them available to the surrounding tissue [44]. This results in a reduction in inflammation and soft tissue destruction, which leads to more reduction in Gingival Index score and PD as well as more gain in attachment level.

2. 3. 4.

5.

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Limitations Although the present study observed good results and was quite successful in achieving its aims, there were few limitations of the study which included the following:

9.

10.

This is a long-term study with a relatively small sample size and high propensity to dropouts. The treatment with BPs is a long-term modality for patients with periodontitis, in which non-compliance may be a factor in deciding successful treatment outcomes. Additional studies with double-blinded placebo control are required to obtain comparative evaluation of effect of scaling and root planing alone and in conjunction with BP therapy in postmenopausal women with chronic periodontitis.

11.

12.

13.

14.

Conclusion In this study, BP therapy as an adjunct to scaling and root planing in postmenopausal women with moderate to severe chronic periodontitis showed significant beneficial clinical effects.

15.

16.

17.

Compliance with ethical standards Conflicts of interest None.

18.

19.

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