Table 4.
Adverse Effects of the Included Studies Stratified by Molecular Weight Group.
| Classification | Study | HA Type | Sample Size | Systemic Adverse Effects | Local Adverse Effects | ||
|---|---|---|---|---|---|---|---|
| Rate | Event | Rate | Event | ||||
| LMW group | Migliore et al. (2005) 26 | Hyalgan | 19 | 0% (0/19) | None | NA | NA |
| van den Bekerom et al. (2008) 28 | Adant | 91 | 0% (0/91) | None | NA | NA | |
| Richette et al. (2009) 31 | Adant | 42 | 2.3% (1/42) | Pruritis | 9.5% (4/42) | Local hematoma: 1 Pain flares: 3 |
|
| Abate and Salini (2017) 35 | Hybrid HA (1100-1400 kDa HA and 80-100 kDa HA) | 20 | 0% (0/20) | None | NA | Only slight discomfort | |
| HA (800-1200 kDa) | 20 | 0% (0/20) | None | NA | |||
| Subtotal | 192 | 0.5% (1/192) | 9.5% (4/42) | ||||
| MMW group | Tikiz et al. (2005) 27 | Ostenil | 32 | 0% (0/32) | none | 9.3% (3/32) | Pain or swelling |
| van den Bekerom et al. (2008) 28 | Synocrom | 20 | 0% (0/20) | NA | NA | ||
| Migliore et al. (2009) 30 | Hyalubrix | 17 | 0% (0/17) | 5.9% (1/17) | Moderate hip pain | ||
| Battaglia et al. (2013) 32 | Hyalubrix | 50 | 0% (0/50) | NA | Peri- or posttreatment pain Superficial hematoma: 1 |
||
| Di Sante et al. (2016) 33 | HA (1000-2900 kDa) | 22 | 0% (0/22) | NA | NA | ||
| Doria et al. (2017) 34 | Hyalubrix | 40 | 0% (0/40) | NA | Self-limited postinjection Pain reaction |
||
| Clementi et al. (2018) 36 | Hyalubrix 60 | 27 | 0% (0/27) | NA | NA | ||
| Subtotal | 208 | 0% (0/208) | 8.2% (4/49) | ||||
| HMW group | Brocq et al. (2002) 22 | Hylan G-F 20 | 22 | 4.5% (1/22) | Aseptic arthritis with fever up to 38.5 °C | 9.1% (2/22) | Transient local pain |
| Conrozier et al. (2003) 23 | Hylan G-F 20 | 56 | 0% (0/56) | None | NA | 1. Transient hip pain: 10.1% of injections 2. Mild synovial fluid aseptic effusions: 2 |
|
| Caglar-Yagci et al. (2005) 24 | Hylan G-F 20 | 14 | 0% (0/14) | None | 21.4% (3/14) | Transient local pain | |
| Migliore et al. (2005) 25 | Hylan G-F 20 | 30 | 0% (0/30) | None | 10.0% (3/30) | Transient local heaviness | |
| Tikiz et al. (2005) 27 | Hylan G-F 20 | 24 | 0% (0/24) | None | 12.5% (3/24) | Pain or swelling | |
| van den Bekerom et al. (2008) 28 | Hylan G-F 20 | 15 | 0% (0/15) | None | NA | NA | |
| Subtotal | 161 | 0.6% (1/161) | 12.2% (11/90) | ||||
| UHMW group | Conrozier et al. (2009) 23 | Durolane | 40 | 0% (0/40) | None | 37.5% (15/40) | Local pain Mild: 10/40 Moderate: 3/40 Severe: 2/40 |
| Clementi et al. (2018) 36 | Fermathron S | 23 | 0% (0/23) | None | NA | NA | |
| Subtotal | 63 | 0% (0/63) | 37.5% (15/40) | ||||
HA = hyaluronic acid; LMW = low-molecular-weight; MMW = moderate-molecular-weight; HMW = high-molecular-weight; UHMW = ultra-high-molecular-weight; NA = not available.