Each month during the coming year, OrthoBuzz will bring you a current commentary on a “classic” article from The Journal of Bone & Joint Surgery. These articles have been selected by the Editor-in-Chief and Deputy Editors of The Journal because of their long-standing significance to the orthopaedic community and the many citations they receive in the literature. Our OrthoBuzz commentators will highlight the impact that these JBJS articles have had on the practice of orthopaedics. Please feel free to join the conversation about these classics by clicking on the “Leave a Comment” button in the box to the left.
Based in part on clinical observations of persistent stiffness, pain, and cartilage damage after prolonged immobilization, in a 1960 JBJS paper, Robert B. Salter described degenerative changes in cartilage of rabbit knee joints that had been immobilized. He suggested that this “obliterative degeneration” might be related to adherence of synovium to the articular surface, and he wondered elsewhere in the orthopaedic literature, “If intermittent motion is good for articular cartilage, would continuous motion be even better?”
This background led to the classic December 1980 JBJS publication in which Salter and his colleagues hypothesized that “continuous passive motion of a synovial joint in vivo would have a beneficial biological effect on the healing of full-thickness defects in articular cartilage.”
To test the hypothesis, Salter et al. made full-thickness cartilage defects at four sites in the knees of 147 rabbits. The rabbits were subjected postoperatively to either immobilization, intermittent active motion (normal cage activity), or continuous passive motion (CPM) created by a custom-made apparatus. Outcome measures included clinical observation of the animals, joint stiffness, and histology.
The extent of ultimate postoperative stiffness, adhesions, and cartilage healing all varied with the degree of immobilization, leading the authors to conclude that CPM
- Was well tolerated by the animals without causing harm detectable by gross or histologic evaluation
- Was associated with fewer adhesions than immobilization, and
- Stimulated more rapid and complete cartilage restoration than either immobilization or intermittent active motion.
Subsequent work by Salter and co-workers evaluated the effect of CPM on other animal models of full-thickness cartilage defects, intra-articular fractures, acute septic arthritis, patellar tendon injury, ligament repair, autogenous and allogenic periosteal and osteoperiosteal grafts, and other conditions. Based in part on the favorable results of these pre-clinical studies as well as preliminary clinical trials, Salter suggested in CORR in1989 that CPM might be indicated after a host of other orthopaedic procedures, including open reduction and internal fixation of intra-articular or selected diaphyseal and metaphyseal fractures, capsulotomy and arthrolysis for post-traumatic arthritis, synovectomy for rheumatoid arthritis or hemophilic arthropathy, arthrotomy and drainage of septic arthritis, release of contractures or adhesions, metaphyseal osteotomy with internal fixation, and reconstruction of a medial collateral ligament.
A Google Scholar search in October 2014 indicated that the 1980 Salter at al. JBJS publication has been cited approximately 1,096 times. Many of the articles that cite the 1980 JBJS study appropriately focus on the effect of CPM on either the histology of cartilage repair, or the effect of CPM on adhesions and joint stiffness.
However, Salter’s observation of decreased stiffness in animals treated with CPM has been extrapolated to clinical applications that were not included in his original work, most notably total knee arthroplasty (TKA).Today the clinical use of CPM after arthroplasty is controversial. A 2010 Cochrane review, for example, identified 20 randomized controlled trials of 1,335 patients in which CPM had been evaluated after TKA. The review concluded that there is evidence that CPM increases knee flexion range of motion, but “the effects are too small to be clinically worthwhile.” A more recent 2014 Cochrane review of 11 randomized clinical trials involving 808 patients concluded that there is not enough evidence to conclude that CPM reduces venous thromboembolism after total knee arthroplasty.
With respect to CPM after cartilage-repair procedures, many other investigators have confirmed the findings Salter reported in 1980 in animal models. Indeed, the basic-science support is strong enough that CPM has been commonly used in humans after cartilage repair, yet its actual efficacy in people remains controversial. For example, in a 2010 systematic review, Fazalare and co-workers reviewed 1,087 human clinical studies in which CPM had been used after cartilage repair procedures. In spite of that large number of studies, Fazalare was unable to find any randomized, controlled studies related to CPM, and heterogeneity among procedures and outcome measures in those articles precluded performing a meta-analysis.
Authors of today may be envious of the more than 6,900 words and 52 photographs, photomicrographs, and graphs (totaling 20 printed pages) that JBJS devoted to Salter et al. in 1980, and one can’t help but wonder what this classic JBJS paper would look like if modified to fit today’s standards. But the main message is this: in spite of high-quality basic science studies using animal models, there remains a need for well-controlled studies in humans to test the efficacy of CPM after cartilage repair and other procedures.
Thomas W. Bauer, MD, PhD
JBJS Deputy Editor for Research
A randomized study of 80 postmenopausal women with mild knee osteoarthritis found that those assigned to a supervised progressive-impact exercise program (including jumping and change-of-movement exercises) thrice weekly for a year experienced more biochemical improvements in their patellar cartilage, as determined by MRI T2 relaxation time, than those in a non-intervention control group. The exercise group also saw greater improvement in muscle strength and aerobic capacity, while patient-reported KOOS-score changes were similar in both groups.
Although many clinicians deem high-impact activity to be contraindicated in this population, this study suggests that postmenopausal women with mild knee OA can, under the supervision of a physical therapist, be encouraged to include high-impact exercises in their fitness regimen.
Some pediatricians have been hesitant to prescribe fluoroquinolone antibiotics such as levofloxacin for children because animal studies have found a risk of cartilage injury. A 5-year follow-up safety study of levofloxacin published recently in Pediatrics compared the safety of levofloxacin with a comparator antibiotic in more than 200 children. The number of musculoskeletal adverse events that were “possibly” related to the drugs was very low and essentially the same in both groups. This led the researchers to conclude that “the risks of cartilage injury with levofloxacin appear to be uncommon, are clinically undetectable during 5 years, or are reversible.” In a NEJM Journal Watch commentary on the study, Deborah Lehman, MD said these findings provide at most “a lack of endorsement of the fluoroquinolone-associated musculoskeletal problems seen in preclinical studies.” She adds that the study was limited by the fact that only half of the patients completed the planned 5-year follow up.