NEW YORK (Reuters Health) – The extent to which doxycycline slows the progression of knee osteoarthritis (OA) is not the same in neutrally aligned (non-varus) and malaligned (varus, or “bowlegged”) knees, according to a post hoc analysis of a randomized controlled trial.
“Varus malalignment negated the slowing of structural progression of medial compartment OA by doxycycline”, researchers reported online May 19th in the journal Osteoarthritis and Cartilage.
“Doxycycline slowed the rate of loss of radiographic joint space (the accepted surrogate for articular cartilage thickness) by 50% in neutrally aligned knees, but had little effect in varus knees,” lead author Dr. Steven A. Mazzuca from Indiana University School of Medicine in Indianapolis told Reuters Health by e-mail.
In the original study, 379 obese middle-aged women with unilateral varus or non-varus knee OA received doxycycline (100 mg twice daily p.o.) or placebo. Knees with mechanical-axis angle < 178 degrees were classified as varus.
In the original overall comparison with placebo, doxycycline slowed the annual rate of medial joint space narrowing in OA knees by 38% at 16 months (p = 0.027) and by 33% at 30 months (p = 0.017), the researchers report.
However, a very different picture emerged in the post hoc subgroup analysis looking at varus and non-varus knees separately.
Dr. Mazzuca and colleagues say, to their knowledge, this is the first report documenting that static varus angulation can negate a pharmacologic structure-modifying effect.
Why might doxycycline not work as well in the malaligned (varus) knee compared to the neutrally aligned (non-varus) knee? According to Dr. Mazzuca, “the normal ground forces and other stresses that the neutrally aligned knee is designed to transmit and/or absorb become abnormally large and/or misdirected in the malaligned knee. Abnormal biomechanical forces are what drive progression of OA.”
Therefore, “any drug designed to protect or repair articular cartilage pharmacologically is likely to be less effective in knees with compromised biomechanics than in knees that have yet to undergo such deterioration,” he said.
Because malalignment appears to moderate pharmacologic approaches to disease modification in OA, Dr. Mazzuca suggested that clinicians consider options for prevention and treatment of malalignment itself.
“I think that weight loss and/or maintenance of normal body weight is the best option for prevention of knee malalignment,” he said. “With respect to secondary prevention of abnormal biomechanics due to malalignment, devices such as knee braces and wedged insoles can alter gait in ways that make it less harmful to the joint.”
Osteoarthritis Cartilage 2010.