Hyaluronans: is clinical effectiveness dependent on molecular weight?

The original rationale for viscosupplementation with hyaluronans was fluid replacement, suggesting that the most viscous materials (eg, those of highest molecular weight [MW]) would provide the most clinical benefits. However, it has become clear that mechanisms of action for osteoarthritis pain management are not only mechanical but also biological. After intra-articular injection, hyaluronans exert a range of biological actions within the joint. Although high- and low- to mid-MW hyaluronans (but not hyaluronans <500 kDa MW) are more or less active (depending on the specific effect examined), it is not known which actions are clinically meaningful. There is no evidence for a difference between hyaluronan products in clinical efficacy measured as pain relief, but investigators in several preclinical studies evaluating joint-structure modification in osteoarthritis models have reported advantages to using low- to mid-MW hyaluronans.