Chemically modified tetracyclines act through multiple mechanisms directly on osteoclast precursors

Percutaneous Doxycycline Treatment of Aneurysmal Bone Cysts With Low Recurrence Rate: A Preliminary Report

“…Furthermore, the lack of need for posttreatment physical rehabilitation (once pathologic fractures heal) offers patients greater mobility and maintenance of normal activities of daily living (recreational and work activity within limits set by the patient's orthopaedic surgeon) during the therapeutic regimen. Although the exact mechanism of regression is not known, pathology results in three patients not completing the full protocol of percutaneous treatment suggest direct cytotoxic action on the mesenchymal tumoral ABC component in addition to known metabolic therapeutic targets of doxycycline that inhibit VEGF, MMP, and osteoclast function [4,5,7,12,13,15,18,19,24,27,43].…”

“…In addition to a radiographic demonstration of tumor involution and bony healing, a pathologic analysis of three operative tissue specimens at the authors' institution, after percutaneous doxycycline treatment, documented the direct cytotoxic effect of doxycycline on the mesenchymal ABC cells. Beyond simple cytotoxicity, doxycycline is antiangiogenic [18,37], a potent inhibitor of MMP [12,13,27], an inhibitor of osteoclastic activity [12,13], induces apoptosis in osteoclasts, and promotes osteoblastic activity [4,7,12,13,15,19]. These multiple sites of action serve well to target the neoplastic cell of an ABC, destructive osteoclasts, tumor vascularity ingrowth, and support osteoblastic healing after tumor ablation.…”

“…In bone and soft tissue malignancy cell cultures, doxycycline demonstrates antitumoral properties with inhibition of MMP and angiogenesis [12,13,15], inhibition of osteoclastic function, and induction of osteoclastic apoptosis [12,13,15,19]. Doxycycline enhances osteoblastic healing of bone defects in dogs [8].…”

Disease modification in osteoarthritis: Are drugs the answer?

“…Given the current emphasis on cartilage damage in OA, it is easy to conclude that the mode of action of the drug is via inhibition of cartilage damage by metalloproteinases and perhaps other cartilagerelated mechanisms. But doxycycline does many other things (11,12). It affects bone and other tissues and interferes with many enzyme systems.…”

O efeito da tetraciclina modificada e sinvastatina na recidiva da movimentação dentária no ligamento periodontal de ratos

“…The EB-1053 inhibits the osteoclastic function in normal doses, but in low dosage increases osteoclastic function 29 . This could explain the decrease in bone mineral density to simvastatin in the specimens studied.…”