Modulation of the intramedullary pressure responses by calcium dobesilate in a rabbit knee model of osteoarthritis

Abstract

Background and purpose The presence of bone marrow edema in patients with osteoarthritis is associated with pain and disease progression. Management of bone edema with the synthetic prostacyclin iloprost may be complicated by side effects. Calcium dobesilate, a treatment for chronic venous disease, shares some pharmacological actions with iloprost but appears to be better tolerated. Anecdotal reports have suggested that calcium dobesilate may be useful for medical management of osteoarthritis, possibly by reducing bone marrow edema, and this study was performed to investigate possible benefits of treatment.

Methods The effects of a 6-week period of oral calcium dobesilate administration on tibial intramedullary pressure dynamics and physical joint characteristics were evaluated in 20 rabbits with unilaterally induced knee osteoarthritis that were randomly allocated to either a treatment group or a placebo control group. Treatment or placebo started 8 weeks after induction of osteoarthritis, and was followed by a 4-week washout period.

Results Calcium dobesilate did not affect joint thickness or range of motion, nor individual pressure measurements, compared to placebo. Pressure ranges in the operated limb were greater than in the intact limb after 8 weeks, and approached those of the intact limb after 6 weeks of treatment with calcium dobesilate but not with placebo. Inter-limb differences were lower (p = 0.02) in the dobesilate group following the washout period.

Interpretation Calcium dobesilate had a detectable effect on pressure dynamics in the subchondral bone of osteoarthritic joints in this model. The significance of these effects for pain and function should be established.

JM, AW, ES, and CF designed the study. JM and AW performed the experiments and collected and analyzed the data. JM wrote the draft manuscript, which was revised by AW, CF, and ES.

The authors gratefully acknowledge the help of Professor Thomas Eriksen and Gerhard Stuker in reading the manuscript and offering suggestions for its improvement. Practical assistance was given and randomization of the trial was performed by the Laboratory Animal Department of LIFE.

Financial assistance for the housing and care of the rabbits was received from ScanVet Animal Health a/s, Denmark. The company was not involved in data collection, analysis, or interpretation—or in writing of the manuscript.

The authors declare there are no other interests.