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Treatment of osteoarthritis: systemic enzyme therapy
Last reviewed: 08.07.2025
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Systemic enzyme therapy was developed in 1954 by M. Wolf and K. Ransberger and is successfully used in Europe and the USA in the treatment of various diseases accompanied by inflammatory syndrome.
We are talking about gastric juice-resistant tablet forms of enzymes such as papain, bromelain (plant proteins), trypsin and chymotrypsin, obtained from the pancreas of animals.
The use of modern diagnostic methods has made it possible to objectify the effectiveness of systemic enzyme therapy and to approach the issue of enzyme resorption from the lumen of the small intestine into the blood.
After entering the blood, mainly the lymph, proteinases in a form associated with a2 - macroglobulin penetrate the liver and lungs, where they affect the macrophages and functional cells of these organs, changing their metabolism, which is manifested by an improvement in the antitoxic function of the liver or an increase in the barrier function of the lungs.
Exogenous proteinases, interacting in the blood with a 2 -macroglobulin, can affect the metabolism of biologically active substances released in the inflammation focus (bradykinins, leukokinins). Proteolytic enzymes are able to break down the above peptides, providing anti-edematous and anti-inflammatory effects, especially in chronic inflammatory diseases occurring with impaired microcirculation. Improvement of microcirculation is due to the fibrinogenolytic effect of systemic enzyme therapy drugs, as well as the ability to increase the activity of tissue plasminogen activator, which is suppressed due to the presence of a chronic inflammatory process.
Modulation of cytokine activity, growth factors (TGF-beta) using systemic enzyme therapy drugs is of particular interest in connection with the imbalance in the immune system observed in osteoarthrosis. It is known that excess IL-1 and TNF play a major role in the pathogenesis of synovitis and cartilage tissue damage in osteoarthrosis, so the ability of activated proteinase a 2 -macroglobulin to remove and inactivate them is very important.
Taking into account these properties of systemic enzyme therapy preparations and the peculiarities of pathogenesis, F. Singer was the first to use Wobenzym as an alternative to diclofenac treatment in 1990. During a randomized double-blind study of the effectiveness of Wobenzym in the treatment of osteoarthrosis, the drug was prescribed at 7 pills 3 times a day for 5 weeks. The clinical effectiveness of systemic enzyme therapy was comparable to the results of diclofenac treatment at a dose of 100 mg per day over a similar period.
Currently, the systemic enzyme therapy drug Phlogenzym is widely used in the treatment of patients with osteoarthrosis. Trypsin and bromelain, which are part of this drug, inactivate adhesion molecules, including PSAM-1, IKAM-2 and LFA-3, which play an important role in inducing inflammation. This action of the drug also helps to reduce the intensity of the inflammatory reaction and thus regulates its course.
Systemic enzyme therapy was first used in Ukraine by V.N. Kovalenko in 1995 in the treatment of patients with rheumatoid arthritis and osteoarthrosis. Later, it began to be successfully used in treatment regimens for other rheumatic diseases in various clinics and centers in Ukraine.
Clinical experience of treating patients with osteoarthrosis using systemic enzyme therapy drugs Phlogenzym and Wobenzym in combination with NSAIDs and chondroprotectors by V.N. Kovalenko, L.B. Sholokhova (2001), O.V. Pishak (2002) proved the effectiveness, safety and good long-term results of combined pharmacotherapy. Phlogenzym was prescribed 2 tablets 3 times a day during the course of treatment (3-4 weeks).
A course of systemic enzyme therapy increases the functional activity of phagocytic blood cells, which is accompanied by a decrease in the content of IgA, CIC and a 2 -macroglobulin in the blood serum. The use of systemic enzyme therapy in patients with osteoarthrosis with osteopenic changes prevents the loss of BMD. After the second course of treatment with Phlogenzym, a significant decrease in plasma proteolytic activity, the content of peroxide-modified proteins in the blood, medium-weight molecules is noted with normalization of the level of ceruloplasmin and the metabolism of carbohydrate-protein components of connective tissue.
Currently, systemic enzyme therapy is included in the standards of treatment of rheumatic diseases recommended by the Association of Rheumatologists of Ukraine.