*Metabolic Disorders in Patients with Chronic Osteomyelitis: Etiology and Pathogenesis DOI: http://dx.doi.org/10.5772/intechopen.92052*

several authors [14, 31, 32], capable of persisting in osteoblasts and that leads to additional stimulation of inflammatory process that stepwise turns into local hyperergic reaction. It is important to take into account that pathogens also play a role in matrix destruction—particularly *S. aureus* can adhere to matrix elements and destroy them [33].

The hyperergic reaction leads to excessive synthesis of matrix metalloproteases (MMPs). Among them, MMP-2 (gelatinase A) and MMP-9 (gelatinase B) [34] play the main role. Excessive synthesis of MMP is a key point in the process because it has two major effects:


**Figure 4.**

*Pathogenetic stages and processes associated particularly with bone matrix destruction.*

*Clinical Implementation of Bone Regeneration and Maintenance*

OPG is a soluble glycoprotein synthesized by different cell types, including osteoblasts [29]. This compound can be found in monomeric (50 kDa) or dimeric (120 kDa) form (the dimeric form contains disulfide bonds between monomers). Dimeric form has a higher affinity to RANKL than a monomeric one, and the

RANKL (RANK-ligand) is a compound synthesized by several cell types. It can be expressed in three different molecular forms: transmembrane trimer, primary (secreted) form, and cell ectodomain [30]. RANKL serves as a ligand for RANK receptor that activates osteoclasts. RANKL is a target for osteoprotegerin; if OPG is secreted in low amounts, more RANKL remains unbound and the intensity of

Therefore, a "pathogenetic chain" is as follows: infection-osteoblast cell death

The matrix destruction in infection can be explained by several factors. The "starting point" in pathogenesis is the infection itself. *S. aureus* is, as shown by

and proliferation rate decrease-OPG synthesis decrease-RANKL inhibition decrease-osteoclastogenesis activation-bone resorption increase-shift of bone remodeling toward a resorption prevalence-decrease in bone tissue quality and quantity in the infection site. The resulting clinical effect is slowing of the consoli-

dation of the bone tissue defects, pseudarthroses, and related conditions.

chemical analogues of OPG should have the features of dimeric form.

*Pathogenetic stages and processes associated particularly with bone turnover shift.*

**142**

resorption increases.

**Figure 3.**

**5. Matrix destruction**

The matrix destruction leads to increase in following resorption markers: B-cross-laps (С-terminal telopeptide) and desoxypyridinoline/creatinine ratio.


A clinician should note that the destruction of the matrix is combined with lowering of its synthesis by osteoblasts. Therefore, both processes act in a synergic way and occur at the same time, which negatively influences the treatment (**Figure 4**).
