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Adjunctive use of modified Yunu-Jian in the non-surgical treatment of male smokers with chronic periodontitis: a randomized double-blind, placebo-controlled clinical trial


Periodontal disease is an infectious disease that affects the periodontium of susceptible hosts, and is characterized by the inflammation and destruction of the surrounding tooth-supporting tissues [1]. Approximately 20 % of the adult population of Hong Kong has a probing pocket depth (PPD) ?6 mm [2]. Although bacteria play a critical role in the life cycle of this disease, they are not solely responsible for the onset of this disease, with host factors playing an important role in the outcome of this disease [3]. Smoking is one of the greatest risk factors for periodontitis [4, 5], and is associated with an increased risk of periodontal attachment loss [2, 6]. Although routine non-surgical periodontal therapy has been shown to be effective for the treatment of chronic periodontitis in smokers, smokers tend to exhibit more residual periodontal pockets [79] than non-smokers. Smokers also show a greater tendency towards progressive radiographic alveolar bone loss despite post-treatment periodontal maintenance care [10].

In the conceptual context of Chinese medicine (CM), periodontal disease is mainly categorized as ya xuan (gaping gums), ya lou (leaking gums) and ya nu (bleeding gums) [11, 12]. The recommended treatment for this disease involves the mechanical removal of deposits from the affected teeth [13, 14]. The use of herbal medicine recipes has also been suggested to rectify the disease-associated imbalance in the human body along the four major philosophical frameworks, including attention to poor oral hygiene, wei huo (stomachheat, SH), shen yin xu (kidneyyin deficiency, KYD) and weakness in qi and xue (blood) [15]. The concept of CM dictates that the kidney dominates the gu (bone) and sheng sui (create marrow) and that the kidney therefore also dominates the teeth, whereas the pi (spleen) and stomach meridians pass through the teeth and gum. Accordingly, periodontal disease could therefore be a problem associated with unwanted changes to the homeostasis in the spleen and stomach or kidney [14]. From the perspective of CM, smoking would not only affect the lungs and airways, but would also fire up the qi, destroy blood and consume yin fluids [16].

Several CM formula have been used to treat ya xuan, ya lou and ya nu, including Radix Achyranthis bidentatae (Huai Ni Xi), Rhizoma Drynariae (Gu Su Bu), Radix Ophiopogonis (Mai Men Dong), Cortex Phellodendri (Huang Bai) and Radix et Rhizoma Rehmanniae (Sheng Di Huang). All of these recipes have been reported to attenuate in vivo inflammation, enhance immune function and/or modulate bone homeostasis [17, 18]. Rhizoma Drynariae and Rehmannia glutinosa (Shu Di Huang) has also been reported to exhibit therapeutic effects towards bone fracture healing, including the induction of proliferation and osteogenic differentiation of human bone mesenchymal stem cells [19, 20]. Rhizoma Drynariae, which contains naringin as its main effective component, is one of the most widely investigated of all of these herbal preparations [20].

YunuJian (YJ), which is also known as Jade maiden/women decoction, Fair maiden decoction or Rehmannia and gypsum combination, is a CM heat purging formula used to reduce stomachheat (SH) and enrich kidneyyin (KY) [13]. This formula is also commonly used to manage diabetes mellitus and gum/oral inflammation. In terms of the different concepts of CM, the regular smoking of cigarettes leads to the burning of the stomach and fei (lung) [21], placing the affected individual at a higher risk of experiencing ya xuan due to SH. The activity of YJ can be modified or refined by the addition of CM herbs and/or minor changes to one of its five key ingredients. The aim of this study was to explore the adjunctive effect of using a specifically modified YJ (mYJ) formulation (Table 1) to target SH and KYD in male smokers with chronic periodontitis. In terms of its modification, Rhizoma Drynariae, Cortex Phellodendri and Radix Puerariae (Ge Gen; to promote circulation and increase blood flow) were added to YJ, whereas Rehmannia glutinosa was replaced with Radix et Rhizoma Rehmanniae. Overall, this study applied the CM ya xuan treatment philosophy to achieve host modulation in contemporary periodontal therapy [18].

Table 1

Composition of modified YunuJian (mYJ) and placebo

Chinese name

Pharmaceutical name

g/daya

YunuJian

Rehmannia and gypsum combination

Shi Gao
b

Gypsum Fibrosum

25

Sheng Di Huang

Radix et Rhizoma Rehmanniae

20

Mai Men Dong
b

Radix Ophiopogonis

18

Zhi Mu
b

Rhizoma Anemarrhenae

15

Huai Niu Xi
b

Radix Achyranthis Bidentatae

15

Gu Sui Bu

Rhizoma Drynariae

15

Huang Bo

Cortex Phellodendri

10

Ge Gen

Radix Puerariae

15

Placebo

 Ku Gua

Momordica Charantia

20

aWeight equivalent of the raw ingredient per preparation

bTogether with Rehmannia glutinosa (Gaetn.) Libosch. Ex Fisch. Et Mey. (20 g raw ingredient per preparation) constituted the original YunuJian recipe

In recent years, over-the-counter CM preparations such as GuchiJianzhou granules, Guchi pills (or Guchi Wan), Guchi extract and Yazhou Baidu powders have been developed to aid in the management of chronic periodontitis [18]. Despite the increasing availability of potential adjunctive agents, there have been very few properly designed CM-periodontal clinical trials or reports pertaining to the correct clinical usage of these preparations or formulae.

Non-surgical mechanical therapy can be effective for the treatment of periodontitis [22]. Smokers, however, have been repeatedly shown to experience inferior healing responses following non-surgical periodontal therapy [7, 9]. Clinicians have attempted a variety of approaches, including adjunctive antibiotics [23], toothpastes containing triclosan/copolymers in an un-blinded fashion [24], and Er:YAG lasers, in place of regular mechanical therapy [25] to enhance or augment non-surgical periodontal healing in smokers. Unfortunately, however, none of these efforts have produced satisfactory results.

This study aimed to evaluate the adjunctive use of mYJ (Table 1) for the non-surgical periodontal treatment of male smokers with chronic periodontitis in a randomized, double blind, prospective, placebo-controlled study. Middle-aged male smokers who had been diagnosed with CM syndrome of SH and/or KYD, but were otherwise healthy, were recruited into this trial. Full-mouth clinical treatment responses were measured, together with radiographic treatment outcomes at selected sites, which were measured by computer-assisted densitometric image analysis (CADIA) and gingival crevicular fluid (GCF) volume. Digital subtraction radiography (DSR) was used to supplement the periodontal healing response assessment as described before [26], which is considered as a sensitive follow-up protocol for alveolar bone healing after periodontal treatment [27, 28]. General CM signs of SH and KYD were recorded over a 12-month study period. Standard clinical and radiographical periodontal parameters were followed throughout the clinical trial to provide an indication of the reduction in the periodontal inflammation (reduction of bleeding on probing or BOP), resolution/remodeling of the diseased periodontium (reduction of PPD) and bony repair (increase in radiographic periodontal bone density) [29]. As the monitoring of changes in the key CM syndrome of participants during a CM clinical trial was deemed necessary [30], and the current study was conducted accordingly.