1 Rheumatology Department, Princess Alexandra Hospital,
2 Department of Medicine, University of Queensland, and
3 Paediatric Respiratory Research Centre, Mater Children's Hospital, Brisbane, Australia
Correspondence to:
B. A. Hills, Paediatric Respiratory Research Centre, Mater Children's Hospital, South Brisbane, Queensland 4101, Australia.
SIR, Much scientific and clinical data have been collected [1, 2] to support the theory [3, 4] that the vital load-bearing boundary lubricant in the joint is surface-active phospholipid (SAPL). Oligolamellar layers of SAPL adsorbed to the articular surface have been observed by electron microscopy [4] to be the outermost hydrophobic layer which imparts superb lubrication, reducing wear and lowering friction to physiological levels that are extremely low by engineering criteria. SAPL is also an effective release agent capable of inhibiting articular gelling/fusion implicated in stiffness [5].
Articular surfaces from hips and knees removed at joint replacement surgery in patients with osteoarthritis (OA) were found to be appreciably deficient in SAPL [6], raising the possibility that the introduction of exogenous SAPL to osteoarthritic joints might arrest or even reverse joint degeneration. Administration of exogenous SAPL to the lungs (`surfactant rescue') of neonates with the respiratory distress syndrome (RDS) is now a well-established clinical modality [7].
Preliminary studies in vitro clearly demonstrated that oligolamellar layers of SAPL, very similar to those found on sliding surfaces in vivo [3, 4], could be formed on the surface of agar gel by administration of SAPL as a solution in propylene glycol (PG). PG is approved by the Food and Drug Administration (FDA) as a lipid vehicle for i.m. and i.v. injectates, and is miscible in all proportions with dipalmitoyl phosphatidylcholine (DPPC), which is the surface-active component of lung surfactant [7]. To investigate the possibility of an inflammatory reaction in vivo, various DPPC solutions in PG were injected intra-articularly (i.a.) and found to produce no overt symptoms in ovine or equine joints. Moreover, synovial fluid (SF) markers of inflammation, including alkaline phosphatase (ALP), neutrophil count, density and protein, changed less after DPPC than after prilocaine administration in five horses.
In this study, we report the effects of a single injection of SAPL into one knee of 10 patients (six male, four female) with bilateral moderatesevere OA. With permission from the ethics committee of the Princess Alexandra Hospital, Brisbane, each test joint was injected i.a. with an autoclaved solution of 400 mg of L--DPPC (Sigma, St Louis, MO, USA) dissolved in 2 ml of PG (clinical grade) via a sterile medial approach after aspiration of the joint to dryness. All patients underwent a clinical assessment pre-treatment and 1, 2, 4, 6, 10 and 14 weeks post-injection, in which the Lequesne index [8] and WOMAC scores for pain, stiffness and disability [9] were recorded.
Five patients experienced discomfort or transient pain upon injection, while one developed an effusion which resolved upon aspiration with no re-accumulation over 2 months, nor deterioration in clinical state. Synovial fluid analysis revealed an inflammatory cell count and non-wax, non-pyrophosphate crystalline debris. He was not assessed further. In each of the remaining nine patients, all four scores decreased within 24 weeks of treatment, lasting several weeks in all but one (#8 in Fig. 1). Mean values for all nine patients are plotted in Fig. 2
for pain, disability and stiffness. Using each patient as his/her own control, statistical analysis using the paired t-test shows significant improvement in all four scores for at least one assessment time. The reduction in pain was highly significant (P<0.0086) for the whole period of monitoring post-injection.
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Although this was an open study, the improvement, particularly in pain, indicates that a placebo-controlled evaluation of DPPC/PG injections is warranted. In addition, the dose response and the effect of multiple doses require study. In ongoing equine clinical trials, repeat doses at 2 monthly intervals are proving expedient and radiological evidence indicates improvement in the articular topography.
The scores and time course for improvement displayed in this study are comparable to those following i.a. injection of corticosteroids [10]. This is in keeping with the 3-fold elevation of synovial SAPL recorded in equine synovial fluid following an i.a. injection of corticosteroid commonly administered to degenerating joints [10].
Although administered ostensibly as a lubricant, SAPL could have other physiological benefits, including putative roles in the control of cartilage hydration [1] and scavenging of oxygen free radicals implicated in chondrocyte destruction [6]. Hence, exogenous SAPL may act as a `disease-modifying' drug in degenerative joint disease that offers potential clinical benefits.
References