**3. The role of TNFα in patients with periodontal disease and osteoporosis**

The main mechanism by which TNFα contributes to the evolution of osteoporosis is by disturbing the balance between bone resorption and bone formation [17]. Previously, TNFα blockade was considered to be an effective method to suppress and prevent bone resorption [18]. TNFα blockade significantly stimulated bone formation in mice.

We conducted a study of 46 postmenopausal female subjects in which we assessed the levels of TNFα in crevicular fluid and serum [19]. Subjects were divided into two groups: the Study Group - patients with osteoporosis and periodontal disease (n = 24) and the Control Group - patients with periodically healthy periodically disease (n = 22).

Probing depth (PD), bleeding on probing (BOP), and clinical attachment loss (CAL) had significantly higher values in the study group than in the control group (p < 0.05) [19]. We could not observe any significant differences in the values of the plate index between the groups.

All samples showed detectable levels of TNFα. Significantly high levels of TNFα were detected in both serum and GCF for the study group compared to the control group. Serum TNFα was positively correlated with BOP (p < 0.01). There were no significant correlations between probing depth, clinical attachment loss, plaque index, and TNFα levels. Serum TNFα levels were correlated with TNFα levels in crevicular fluid.

Maintaining the balance of proinflammatory and anti-inflammatory cytokines in the body is one of the manifestations of self-regulation [20]. Over the past decade, considerable evidence suggests that oestrogen prevents bone loss by blocking the production of proinflammatory cytokines, such as interleukin-1 (IL-1), IL-6, IL-10, tumour necrosis factor (TNF) α in the spinal cord and bone cells.

Cytokines are soluble proteins that can initiate, mediate, and control immune and inflammatory responses. It has been proposed that pro and anti-inflammatory cytokines contribute to various bone metabolic diseases, including periodontitis and postmenopausal osteoporosis [21]. Among pro-inflammators, TNFα has been reported to play a key role in periodontal bone destruction [22].

In our study we demonstrated significant differences in TNFα values between the osteoporosis group and the control group. It can be suggested that increased

TNFα values in GCF and serum contribute to the large number of B cells and T cells present in inflammatory periodontal tissues, increasing the destruction of periodontal tissue [19].

The fact that the values in the crevicular fluid were correlated with the serum values clearly indicates the influence that the systemic status generates on the local status (periodontal, in the case of the present study).

Periodontal tissue destruction is closely related to the release of inflammatory mediators, such as TNFα. These mediators are able to aggravate the inflammatory response. It has been shown that the severity of periodontal disease is associated with their concentration in the crevicular fluid.

Some subjects may have a more pronounced inflammatory response to bacterial aggression, a response that depends on the quality and quantity of the bacterial flora, as well as systemic factors (heredity, certain infectious/inflammatory diseases, osteoporosis, etc.).

Inflammatory cytokines can influence this delicate balance by promoting osteoclast differentiation and activation. Bone loss is thus attributed more to increased bone resorption than to reduced bone neo-formation, with osteoclasts being the main culprits.
