KNEE
Efficacy of intra-articular polynucleotides in the treatment of knee
osteoarthritis: a randomized, double-blind clinical trial
Roberto Vanelli
•
Pietro Costa
•
Stefano Marco Paolo Rossi
•
Francesco Benazzo
Received: 19 June 2009 / Accepted: 22 December 2009 / Published online: 29 January 2010
Ó Springer-Verlag 2010
Abstract This randomized, double-blind clinical trial
was conducted over 16 weeks to assess the efficacy and
safety profile of intra-articular polynucleotides gel injec-
tions in the treatment of knee osteoarthritis associated
with persistent knee pain. 60 patients were enrolled and
randomized to receive intra-articular polynucleotides
(n = 30) or hyaluronan (n = 30); patients received five
weekly intra-articular knee injections and the follow-up
period was 3 months after the end of treatment. Primary
endpoint was to determine polynucleotides (PN) efficacy in
reducing knee pain at the end of the study, over baseline
value and over standard hyaluronan viscosupplementation
(HA). Pain levels were measured using a 0–10 cm Visual
Analogue Scale (VAS). Secondary endpoints included
Knee Osteoarthritis Outcome Score (KOOS), NSAIDs
consumption, crackling during movement and articular
mobility limitation. The mean global VAS pain decreased
from 5.7 ± 1.9 cm (T0) to 1.9 ± 1.5 cm (T16) in poly-
nucleotide group and from 4.9 ± 2.0 cm (T0) to
2.1 ± 1.4 cm (T16) in hyaluronan group. The reduction in
pain was statistically significant for both groups. KOOS
increases from baseline values were statistically significant
in both groups. No significant adverse events were reported.
These findings suggest that intra-articular polynucleotides
can be a valid alternative to traditional hyaluronan supple-
mentation for the treatment of knee osteoarthritis.
Keywords Polynucleotides Á Condrotide Á
Turnover Joint Á Osteoarthritis Á Hyaluronic acid Á
Intra-articular
Introduction
Osteoarthritis (OA) is a chronic joint disease characterized
by degeneration of the articular cartilage, changes in the
physico-chemical properties of the synovial fluid and
macroscopical modifications of the joint. Scientific and
clinical data gathered so far have correlated the onset and the
progression of osteoarthritis to both mechanical and bio-
logical factors [22]. Among the different kinds of arthritic
diseases, OA is the most frequent: it is estimated that
25–30% of people over 45 years old are affected by it [9].
Many different therapies are available nowadays for the
treatment of OA and other osteochondral defects, ranging
from non-pharmacologic therapy to pharmacological
approaches (viscosupplementation, oral supplements or
topical treatments), but a flawless treatment is still to be
found.
Non-pharmacologic approaches for patients with knee
OA may include weight loss (if overweight), exercise
programs, appropriate footwears and assistive devices for
activities of daily living (ADL). Pharmacologic therapies
for relieving pain include oral acetaminophen, NSAIDs and
other analgesics like tramadol, intra-articular glucocorti-
coids and viscosupplementation with hyaluronic acid.
Other options are oral supplements (like glucosamine or
chondroitin) and topical treatments like capsaicin methyl-
salicylate [2].
Patients with severe symptomatic OA who have pain
that has failed to respond to medical therapy and who have
progressive limitation in ADL should be referred to an
orthopaedic surgeon for evaluation. Surgical options
include traditional arthroscopic debridement, total joint
arthroplasty and innovative techniques such as autologous
chondrocytes implantation (ACI) [21] or cartilage repair
using mesenchymal stem cells [13].
R. Vanelli Á P. Costa Á S. M. P. Rossi (&) Á F. Benazzo
IRCCS Foundation, Orthopaedic and Traumatology Department,
S. Matteo Hospital Institute, University of Pavia, Pavia, Italy
e-mail: rossi.smp@gmail.com
123
Knee Surg Sports Traumatol Arthrosc (2010) 18:901–907
DOI 10.1007/s00167-009-1039-y