Hyaluronic Acid in the Treatment of Hyposalivation

Dry mouth is one of the most common complaints among patients, in both dental and general medicine practices, especially among the older population. Xerostomia (or dry mouth) is a medical term used to describe the subjective sensation of dry mouth that commonly occurs because of decreased salivary flow (hyposalivation). Although the two terms do not correspond to the same conditions and should not be used interchangeably, many physicians do so, since most patients with xerostomia also have hyposalivation.

Approximately 30% of the population complains on some degree of dry mouth. When it happens occasionally, during dehydration or stress, it is not a cause for concern. The situation is more serious if it happens more often, such as every day. It could also point to an underlying health condition. In untreated patients, hyposalivation increase their vulnerability to tooth decay, gingivitis and oral mucosa sensation. Dry mouth is related to pain, sometimes insomnia and psychological problems and results in deterioration of life well-being.

Saliva is produced by major salivary glands (MaSGs), the parotid, submandibular and sublingual glands and by circa 600 to 1,000 minor salivary glands (MiSGs) located in the submucosa layer in the oral cavity. MaSG contributed to 90% of total saliva secretions, whereas MiSG contributed to the remaining 10%. MiSGs are important for preventing the subjective sensation of dry mouth, since the saliva produced by these glands creates a lubricating micron-thick film that protects the oral mucosae. Furthermore, MiSGs play a key role in saliva production during sleep; therefore, reduced MiSG flow appears to be a cause of nocturnal dry mouth.

Saliva is a hypotonic solution composed of 98.5% water with 1% organic and 0.5% inorganic components. The organic and inorganic components of saliva are present in low concentrations, with some proteins synthetized in the gland (such as α-amylase) present in relatively high concentrations. Other organic components detected in saliva are vitamin C, maltase, urea, uric acid, lactase, hormones (testosterone, cortisol), albumin, creatinine, amino acids, mucin and immunoglobulins (IgA, IgG, IgM). Saliva α-amylase and lipase play a role in starch digestion and triglyceride decomposition. Salivary mucins lubricate intraoral structures and help to form a barrier against microbial invasion. Salivary immunoglobulins, especially secretory IgA (SIgA), play a key role in neutralizing toxins, agglutinating bacteria, and preventing their adhesion to mucosal surfaces.

By moistening the oral mucosa, saliva facilitates chewing, swallowing, and speech. Furthermore, a constant flow of saliva facilitates the mechanical removal of food debris and microorganisms and regulates the oral pH, protecting against acidic byproducts of bacterial metabolism. This buffering capacity is essential for maintaining a healthy oral microbiome and preventing demineralization of tooth enamel. Saliva also serves as a protective factor against infections because of its numerous organic components. People with dry mouth not only have trouble chewing and swallowing food but also have difficulty with tasting, speaking, and a reduced tolerance for dentures. Furthermore, xerostomia increases the risk of caries, periodontal disease, candidiasis, oral ulcers, and dysphagia, which can negatively impact nutritional status and quality of life.

There is wide variability in individual salivary flow rates. The average daily flow of whole saliva varies between 0.5 and 1.5 L. The accepted range for normal unstimulated salivary flow is above 0.1 ml/min. Any unstimulated flow rate below 0.1 ml/min is considered hypofunction. Stimulated saliva represents 80 to 90 % of daily salivary production, and the stimulated flow rate varies from 1 to 3 mL/minute.

Several studies have considered changes in saliva quantity and quality throughout the lifetime. No consensus has been reached on the decrease in the salivary flow rate with age. Despite this, recent research by Vandenberghe-Descamps et al revealed a 38.5% reduction in the resting salivary flow rate and 38.0% reduction of stimulated salivary flow rate in elderly subjects compared with young subjects. The cause of salivary flow decline has been connected to the loss of acinar cells; loss of secretory tissue and adiposity increase, as well as neurophysiological deterioration. Additionally, changes in saliva composition with age have been reported in some studies. Most notably, the mucin concentration decreases, which promotes the development of diseases of the oral mucosa and dry mouth.

Given the impact of reduced salivary flow on quality of life and oral health, assessing salivary function should be part of routine dental examinations, especially since saliva sampling is easy and noninvasive. The most advocated clinical method for diagnosing salivary gland dysfunction is to quantify unstimulated and stimulated whole saliva flow rates (sialometry). Recently, the Clinical Dry Mouth Score (CODS) was developed to objectively quantify clinical signs of decreased salivary flow. The CODS aims to provide a quick, easy, and objective method for assessing salivary gland function in a clinical setting. The CODS assesses dry mouth through clinical and visual examination of the oral cavity on the basis of several signs of dryness, such as frothy saliva, dry oral mucosa, and sticking of the mouth mirror to the tongue or cheek fold.

Despite the various etiological factors underlying xerostomia, the available treatment options do not differ on the basis of the cause and are predominantly symptomatic-except in cases of drug-induced xerostomia, where therapy involves discontinuation of the systemic medication.

Therapeutic strategies implemented to manage xerostomia, regardless of its etiology, have thus far failed to yield definitive or consistently effective outcomes.

• Changes in unstimulated saliva before HA and AAs injections - mirror test [Time frame: Baseline]
• Changes in unstimulated saliva after HA and AAs injections - mirror test. [Time frame: 8 weeks following the baseline]
• Consistency changes in unstimulated saliva before HA and AAs injections. [Time frame: Baseline]
• Consistency changes in unstimulated saliva after HA and AAs injections. [Time frame: 8 weeks following the baseline]
• pH changes in unstimulated saliva before HA and AAs injections. [Time frame: Baseline]
• pH changes in unstimulated saliva after HA and AAs injections. [Time frame: 8 weeks following the baseline]
• Quantity of saliva changes in stimulated saliva before HA and AAs injections. [Time frame: Baseline]
• Quantity of saliva changes in stimulated saliva after HA and AAs injections. [Time frame: 8 weeks following the baseline]
• Buffering capacity changes in stimulated saliva before HA and AAs injections. [Time frame: Baseline]
• Buffering capacity changes in stimulated saliva after HA and AAs injections. [Time frame: 8 weeks following the baseline]