Imbalance of bone homeostasis is associated with disorders in the of nuclear factor-κB RANK/RANKL/osteoprotegerin (OPG) activating system mediated by matrix metalloproteinases (MMPs). The aim of this work was to evaluate relative dynamics of (MMPs) and their tissue inhibitor (TIMP) in peripheral blood during development of tuberculous osteitis (TO) in rabbit experimental model (n = 32): non-treated infectious control (group 1), and two experimental (treated) groups in which necrectomy, anti-tuberculosis treatment and replacement plastic surgery was performed by means of autografting (group 2), or 3D-printed composite scaffolds (group 3). Serum levels of MMP-3 and MMP-9, their tissue inhibitor (TIMP-1), receptor activator of nuclear factor-κB ligand (RANKL), nonspecific alkaline phosphatase (ALPL), serum albumin (AL), ceruloplasmin (CP), neutrophil elastase (NE) and adenosine deaminase (ADA) were determined before infection and 18 days, 2, 4 and 6 months after the infection. Osteogenesis was evaluated on the basis of microcomputed tomography (micro-CT) and pathohistological examination of bone tissue in control and experimental groups. At the stage of verified tuberculosis osteitis, we have detected a decrease in RANKL (p = 0.017) and AL (p = 0.04), along with increase in TIMP-1 (p = 0.04), CP (p = 0.0004) and NE (p = 0.02), with no changes in ALPL, ADA, and MMP-3 and MMP-9. In group 1 (infection control), foci of specific damage persisted and no signs of bone regeneration were detectable. Both experimental groups exhibited a progressing bone regeneration with the lowest osteodestruction scores in group 2 treated by autografting. The level of inflammatory response increased with progressing infection and declined upon combined treatment. The RANKL levels did not change within 2-6 months. Based on the differences in ALPL and TIMP-1, the use of composite material for plastic surgery was characterized by slower osteointegration and reparative osteogenesis compared to the use of autograft.