PAST LETTERS FROM THE PRESIDENT
Double-blind,
Randomized, Controlled 4-week Study of Oral Iloprost in Patients with
Painful Bone Marrow Edema of the Knee
N
Aigner1, A Vakil-Adli2, S Hofmann3, J Kramer4, M Mayerhöfer5,
R Meizer1, M Breitenseher5, J Hochreiter2, F Landsiedl1, C Norden6
1Orthopedic Hospital Vienna - Speising, Vienna, Austria, 2Krankenhaus
der Barmherzigen Schwestern, Linz, Austria, 3Landeskrankenhaus, Stolzalpe,
Austria, 4Institut fur CT & MRT-Diagnostik am Schillerpark, Linz,
Austria, 5Department of Radiodiagnostics - University Hospital of
Vienna, Vienna, Austria, and 6Schering AG, Specialized Therapeutics
Europe, Clinical Development Cardiovascular, Berlin, Germany
Bone marrow edema (BME) is a common cause of pain in the knee with restricted treatment options. We performed a double-blind, randomized, active-controlled study in order to explore the clinical effects of the prostacyclin analog iloprost (Schering AG, Germany) in 41 patients with painful bone marrow edema associated with osteonecrosis, osteoarthritis, bone bruise or axis deformity. Patients were randomized either to iloprost (n=21, 15 male, 6 female; mean age 53.2) or to Tramadol (n=20, 12 male, 8 female; mean age 50.8). An individual dose adjustment was allowed within the range of 100-300 µg of iloprost, and 100-300 mg of Tramadol. The treatment duration was 4 weeks. The treatment period was followed by an 8?week treatment-free follow-up. During and after treatment full weight bearing was allowed as tolerated. Efficacy of treatment was assessed by 100 mm visual analog scales for pain at rest and on exertion, Larson's knee score and MRI. The results are presented below.
|
Baseline
|
End
of treatment
|
|||||
|
Pain
at rest
|
Pain
on exertion
|
Larson
score
|
Pain
at rest
|
Pain
on exertion
|
Larson
score
|
|
|
Iloprost
|
41.2
± 4.8
|
62.5
± 4.5
|
58.6
± 2.9
|
13.5
± 4.9
|
26.1
± 5.6
|
81.3
± 3.3
|
|
Tramadol
|
33.9
± 4.5
|
60.1
± 4.6
|
59.6
± 2.3
|
9.2
± 2.7
|
24.4
± 6.3
|
82.4
± 2.5
|
These clinical effects were sustained over the follow-up. At the end of study, 53% of iloprost patients showed healing of at least one BME affected bone as compared to only 19% of Tramadol patients. Regression of subchondral lesions occurred in 4 iloprost patients. No serious adverse events occurred, however three Tramadol patients discontinued the treatment prematurely due to adverse events. We conclude that the oral application of the vasoactive drug iloprost results in substantial treatment effects on pain relief and joint function improvement. These effects were similar for iloprost and Tramadol. Iloprost treatment was associated more often with BME regression than Tramadol. Oral iloprost may offer a new and safe treatment option for patients with painful BME.