Tag Archive | cartilage

Meniscal Extrusions: Imaging and Repair

This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.

Loss of hoop stress by either medial or lateral menisci can cause meniscal extrusion, which results in increased forces on articular cartilage. The degree of meniscal extrusion is typically measured as a 2-dimensional distance with MRI. However, investigators recently used 3-D MRI to analyze the relationship between medial meniscal extrusion (MME) and femoral cartilage change in patients with these tears.1

Fifteen males (mean age of 56 years) with a medial meniscal degenerative tear (grade 3 by the Mink classification) based on MRI were included. The cartilage area was reconstructed in 3-D, and the femoral cartilage was projected in 2-D by 3-D MRI analysis. The femoral cartilage of the femorotibial joint was divided into 4 segments, and the cartilage area ratio was defined as the ratio of cartilage with thickness ≥1.0 mm in each segment. The tibial MME area (mm2) and volume (cm3), excluding osteophytes, were measured by 3-D MRI.

The projected cartilage area ratio (cartilage thickness ≥1.0 mm) at the posteromedial segment was lower than the ratio at the other 3 segments. The cartilage area ratio at the posteromedial segment was not correlated with the MME distance measured by the 2-D MRI, but it was negatively correlated with MME area (r=-0.53, p=0.045) and MME volume (r=-0.62, p=0.016) as measured by 3-D MRI. Overall, the 3-D imaging more accurately reflected cartilage damage.

Both radial tears and posterior horn degeneration can lead to meniscal extrusion. When this injury is seen acutely in younger persons, repairs are often attempted. Recently efforts have been made to do repairs in older individuals. The use of cell-seeded nanofibrous scaffolds to repair radial tears and resulting hoop-structure injuries has been studied for prevention of articular cartilage degeneration using a rabbit model.2

Synovial mesenchymal stem cells were isolated and expanded into sheets that were then wrapped onto poly(e-caprolactone) scaffolds to create stable cell/scaffold tissue-engineered constructs (TECs). Scaffold-alone or TEC + scaffold constructs were then sutured into created radial meniscal defects (12 rabbits in each group).

The TEC-scaffold group maintained the structure of the hyaline cartilage with matrix staining with Safranin O up to 12 weeks after surgery. Although the cartilage coverage decreased in both groups, the TEC-scaffold group did not become significantly worse over time, suggesting stabilization of hoop structure integrity. Only the TEC-scaffold group showed repair tissue that exhibited positive Safranin O staining in the inner zone of the meniscus.

Future studies will be required to determine the role of tissue engineering in the preservation of meniscal coverage in the face of radial tears.

References

  1. Suzuki S, Ozeki N, Kohno Y, Mizuno M, Otabe K, Katano H, Tsuji K, Suzuki K, Itai Y, Masumoto J, Koga H, Sekiya I. Medial meniscus extrusion (MME) area and MME volume determined by 3D-MRI are more sensitive than MME distance determined by 2D-MRI for evaluating cartilage loss in knees with medial meniscus degenerative tears. ORS 2019 Annual Meeting Poster No. 0514.
  2. Shimomura K, Rothrauff BB, Hart DA, Hamamoto S,  Kobayashi M,  Yoshikawa H, Tuan RS, Nakamura N. Enhanced Repair of Meniscal Hoop Structure Injuries Using An Aligned Electrospun Nanofibrous Scaffold Combined with a Mesenchymal Stem Cell-derived Tissue Engineered Construct. ORS 2019 Annual Meeting Poster No. 0519.

A Four-Legged Step Toward Preventing Elbow Contractures

Up to 50% of patients who sustain an elbow injury subsequently develop some type of contracture, making elbow contracture following trauma a common and vexing clinical scenario. While we do not completely understand the molecular basis or structural mechanisms underlying these contractures, we do know that active range-of-motion (ROM) exercises and gentle stretching are often helpful, whereas prolonged immobilization and forceful passive ROM exercises are often, if not always, detrimental.

In the March 6, 2019 issue of The Journal, Dunham and colleagues document with a rat model a better understanding about which specific tissues around the elbow account for this condition. They performed a surgical procedure on rat elbows to simulate a dislocation and then immobilized the injured extremity for 6 weeks. After the authors obtained ROM measurements at that point, some of the rats were allowed an additional 3 or 6 weeks of free active motion before a postmortem surgical dissection was performed to determine which soft tissues were most responsible for the subsequent contracture.

While the authors hypothesized that all soft tissues (muscles/tendons, anterior capsule, and ligaments/cartilage) would play a significant role in posttraumatic stiffness, they found in fact that the  ligaments and cartilage caused 52% of the lost motion after 21 days of free motion and 74% of the contracture after 42 days of free motion. With this information, clinical therapies such as pharmacologic infiltrations or biophysical energy delivered to the ligaments or cartilage could be investigated. In addition, refined surgical techniques focused on these structures could be proposed and analyzed. This study represents a small preclinical step in further understanding the mechanisms of joint contracture, but it provides a foundation on which further investigations can be built.

Marc Swiontkowski, MD
JBJS Editor-in-Chief

Comparing the Potential of Cartilage-Cell Therapies

This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs.Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson. 

Other than by using shell allografts, it is not possible to replant whole cartilage or cells that even come close to a biological construct matching original cartilage. The old adage that cartilage, unlike bone, cannot repair itself holds true, as the natural damage repair of cartilage leads to the formation of “scar” cartilage (fibrocartilage).

However, there are connective tissue progenitor cells that can be found in multiple different tissues, and chondrogenic connective-tissue progenitors (CTP-Cs) are found within articular cartilage, even if it is osteoarthritic. Investigators recently designed a study to quantitatively define the CTP-Cs resident in cartilage and to compare overall cartilage-cell concentration, CTP-C prevalence, and biological potential of cells in tissues taken from patients with different grades of osteoarthritis.

Investigators procured samples of osteoarthritic articular cartilage from 23 patients undergoing elective total knee arthroplasty. All patients had grade 3-4 osteoarthritis on the medial side and grade 1-2 on the lateral side. Each patient sample was assessed for mean cell concentration and CTP prevalence by subjecting cells from a unit measure of cartilage to specific conditions to promote colony formation. The biological potential of the CTPs was measured using sophisticated imaging analysis.

Cell concentration was significantly greater (p < 0.001) in grade 3-4 cartilage than in grade 1-2 cartilage. This matches findings from previous histologic reports. Although the prevalence of CTP-Cs varied widely, it trended lower in grade 3-4 than grade 1-2 cartilage samples (p = 0.078). The biological performance of CTP-Cs from grade 1-2 and grade 3-4 cartilage was comparable. Increased cell concentration was a significant predictor of decreased CTP-C prevalence (p = 0.002). Sex was not a predictor of cell concentration, but age correlated negatively with prevalence of CTP-Cs. The number of cells per colony varied widely across the 23 patients, implying a highly individualized capacity.

This research contributes to our understanding of what might constitute appropriate cell selection for combination with biochemical interventions that could lead to robust cartilage repair that has greater longevity.

JBJS 100: Massive Rotator Cuff Tears, Continuous Passive Motion

JBJS 100Under one name or another, The Journal of Bone & Joint Surgery has published quality orthopaedic content spanning three centuries. In 1919, our publication was called the Journal of Orthopaedic Surgery, and the first volume of that journal was Volume 1 of what we know today as JBJS.

Thus, the 24 issues we turn out in 2018 will constitute our 100th volume. To help celebrate this milestone, throughout the year we will be spotlighting 100 of the most influential JBJS articles on OrthoBuzz, making the original content openly accessible for a limited time.

Unlike the scientific rigor of Journal content, the selection of this list was not entirely scientific. About half we picked from “JBJS Classics,” which were chosen previously by current and past JBJS Editors-in-Chief and Deputy Editors. We also selected JBJS articles that have been cited more than 1,000 times in other publications, according to Google Scholar search results. Finally, we considered “activity” on the Web of Science and The Journal’s websites.

We hope you enjoy and benefit from reading these groundbreaking articles from JBJS, as we mark our 100th volume. Here are two more:

The Outcome and Repair Integrity of Completely Arthroscopically Repaired Large and Massive Rotator Cuff Tears
L M Galatz, C M Ball, S A Teefey, W D Middleton, K Yamaguchi: JBJS, 2004 February; 86 (2): 219
In one of the earliest studies to investigate the relationship between the anatomic integrity of arthroscopic rotator cuff repair and clinical outcome, these authors found that the rate of recurrent defects was high but that at 12 months after surgery, patients experienced excellent pain relief and functional improvement. However, at the 2-year follow-up, the clinical results had deteriorated substantially. Investigations into the relationship between cuff-repair integrity and clinical outcomes are ongoing.

The Biological Effect of Continuous Passive Motion on the Healing of Full-thickness Defects in Articular Cartilage: An Experimental Investigation in the Rabbit
R B Salter, D F Simmonds, B W Malcolm, E J Rumble, D Macmichael, N D Clements: JBJS, 1980 January; 62 (8): 1232
In this paper, Salter and colleagues hypothesized that “continuous passive motion [CPM] of a synovial joint in vivo would have a beneficial biological effect on the healing of full-thickness defects in articular cartilage.” They found that CPM stimulated more rapid and complete cartilage restoration than either immobilization or intermittent active motion, and since then CPM has been commonly used in humans after cartilage repair. However, CPM’s actual efficacy in people—after cartilage repair or total knee arthroplasty—remains controversial.

What’s New in Sports Medicine 2018

Anatomy of male knee pain in blueEvery month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all OrthoBuzz Specialty Update summaries.

This month, OrthoBuzz asked Albert Gee, MD, a co-author of the April 18, 2018 Specialty Update on Sports Medicine, to select the five most clinically compelling findings from among the 30 studies cited in the article.

Anterior Cruciate Ligament (ACL) Reconstruction
–The conversations about graft selection for ACL reconstruction go on. A meta-analysis of 19 Level-I studies comparing 4-strand hamstring autograft with patellar tendon grafts1 revealed no differences in terms of rupture rate, clinical outcome scores, or arthrometer side-to-side testing at >58 months of follow-up. The prevalence of anterior knee pain and kneeling pain was significantly less in the hamstring group, and that group also exhibited a lower rate of extension deficit.

Cartilage Repair
–Fourteen-year outcomes from a randomized controlled trial (n = 80 patients) comparing autologous chondrocyte implantation (ACI) with microfracture for treating large focal cartilage defects included the following:

  • No significant between-group difference in functional outcome scores
  • Fairly high treatment failure rates in both groups (42.5% in the ACI group; 32.5% in the microfracture group)
  • Radiographic evidence of grade 2 or higher osteoarthritis in about half of all patients

These findings raise doubts about the long-term efficacy of these two treatments.

Rehab after Rotator Cuff Repair
–A randomized trial comparing early and delayed initiation of range of motion after arthroscopic single-tendon rotator cuff repair in 73 patients2 found no major differences in clinical outcome, pain, range of motion, use of narcotics, or radiographic evidence of retear. The early motion group showed a small but significant decrease in disability. The findings indicate that early motion after this surgical procedure may do no harm.

Platelet-Rich Plasma (PRP)
–A systematic review of 105 human clinical trials that examined the use of PRP in musculoskeletal conditions revealed the following:

  • Only 10% of the studies clearly explained the PRP-preparation protocol.
  • Only 16% of the studies provided quantitative information about the compositi0on of the final PRP product.
  • Twenty-four different PRP processing systems were used across the studies.
  • Platelet composition in the PRP preparations ranged from 38 to 1,540 X 103/µL.

Consequently, care should be taken when drawing conclusions from such studies.

Meniscal Tear Treatment
–A follow-up to the MeTeOR trial (350 patients initially randomized to receive either a partial arthroscopic meniscectomy or physical therapy [PT]) found that crossover from the PT group to the partial meniscectomy group was significantly associated with higher baseline pain scores or more acute symptoms within 5 months of enrollment. Investigators also found identical 6-month WOMAC and KOOS scores between those who crossed over and those who had surgery initially. These findings suggest that an initial course of PT prior to meniscectomy does not compromise outcomes.

References

  1. Chee MY, Chen Y, Pearce CJ, Murphy DP, Krishna L, Hui JH, Wang WE, Tai BC,Salunke AA, Chen X, Chua ZK, Satkunanantham K. Outcome of patellar tendon versus 4-strand hamstring tendon autografts for anterior cruciate ligament reconstruction: a systematic review and meta-analysis of prospective randomized trials. Arthroscopy. 2017 Feb;33(2):450-63. Epub 2016 Dec 28.
  2. Mazzocca AD, Arciero RA, Shea KP, Apostolakos JM, Solovyova O, Gomlinski G, Wojcik KE, Tafuto V, Stock H, Cote MP. The effect of early range of motion on quality of life, clinical outcome, and repair integrity after arthroscopic rotator cuff repair. Athroscopy. 2017 Jun;33(6):1138-48. Epub 2017 Jan 19.

If We “Own the Bone,” How About “Owning the Joint”?

MRI of Knee OA 2.jpgThis basic science tip comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.

Early cartilage changes in early-stage osteoarthritis (OA) often exist before symptoms arise. Using MRI, researchers assessed a random sample of 73 subjects, aged 40 to 79 years and without knee pain, for cartilage changes.1 A self-reported BMI at age 25, a current measured BMI, and change in BMI were recorded. Knee cartilage was scored semi-quantitatively (grades 0 to 4) on MRI. In primary analysis, cartilage damage was defined as ≥2 (at least moderate), and in a secondary analysis as ≥3 (severe). Researchers also conducted a sensitivity analysis by dichotomizing current BMI as <25 vs. ≥25. Logistic regression was used to evaluate the association of each BMI variable with prevalent MRI-detected cartilage damage, adjusted for age and sex.

Their abstract states that among the 73 subjects, knee cartilage damage ≥2 and ≥3 was present in 65.4% and 28.7%, respectively. Note the high prevalence. The median current BMI was 26.1, while the median past BMI was 21.6. For cartilage damage ≥2, current BMI had a non-statistically significant odds ratio (OR) of 1.65 per 5-unit increase in BMI (95% CI 0.93-2.92). For cartilage damage ≥3, current BMI showed a trend towards statistical significance with an OR of 1.70 per 5 units (95% CI 0.99-2.92). Past BMI and change in BMI were not significantly associated with cartilage damage. Current BMI ≥ 25 was statistically significantly associated with cartilage damage ≥2 (OR 3.04 [95% CI 1.10-8.42]), but not with damage ≥3 (OR 2.63 [95% CI 0.86-8.03]).

The take-home is that MRI-detected knee cartilage damage is highly prevalent in asymptomatic populations aged 40 to 79 years. There is a trend towards significance in the relationship between rising BMI and cartilage damage severity.  (It should be added there are localities where a BMI of 26.1, which is technically in the “overweight” zone, would be considered relatively low.) Although this study lends some support to the relationship between BMI and the pathogenesis of knee cartilage damage in asymptomatic people, the role of BMI in symptomatic OA progression is clearer.

In another study, researchers showed that weight loss over 48 months among obese and overweight individuals is associated with slowed knee cartilage degeneration and improved knee symptoms.2 These results point to a promising approach to disease modification that carries little or no risk.

References

  1. Keng A, Sayre EC, Guermazi A, Nicolaou S, Esdaile JM, Thorne A, Singer J, Kopec JA, Cibere J. Association of body mass index with knee cartilage damage in an asymptomatic population-based study. BMC Musculoskelet Disord. 2017 Dec 8;18(1):517. doi: 10.1186/s12891-017-1884-7. PMID: 29221481 PMCID: PMC5723095
  2. Gersing AS, Solka M, Joseph GB, Schwaiger BJ, Heilmeier U, Feuerriegel G, Nevitt MC, McCulloch CE, Link TM. Progression of cartilage degeneration and clinical symptoms in obese and overweight individuals is dependent on the amount of weight loss: 48-month data from the Osteoarthritis Initiative. Osteoarthritis Cartilage. 2016 Jul;24(7):1126-34. doi: 10.1016/j.joca.2016.01.984. PMID: 26828356 PMCID: PMC4907808

What’s New in Musculoskeletal Basic Science 2017

Specialty Update Image for OBuzz

Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all OrthoBuzz Specialty Update summaries.

This month, Matthew J. Allen, VetMB, PhD, author of the December 6, 2017 Specialty Update on Musculoskeletal Basic Science, summarized the five most compelling findings from among the more than 60 noteworthy studies summarized in the article.

Cartilage Repair

–Deriving induced pluripotent stem cells (iPSCs) from peripheral blood cells1 rather than from dermal fibroblasts obviates the need for in vitro expansion. This method may also serve to boost interest in the use of commercial cell-based therapies with defined potency that are available off-the-shelf and don’t require separate cell-harvesting procedures.

–The FDA recommends that large-animal models be used to corroborate basic-science findings from small-animal models. Recent work has demonstrated the efficacy of insulin-like growth factor (IGF)-1 in supporting mechanically competent repair tissue following chondrocyte implantation in a pig model.2

Infection

–Infection, especially from organisms that have developed antimicrobial resistance and/or that produce biofilms, continues to pose a challenging problem for orthopaedic surgeons. To provide a more rational and stratified approach to managing these complex cases, Getzlaf et al. recommend the use of a multidisciplinary approach in which patient-specific information about individual microorganisms is combined with detailed understandings of the vulnerabilities of candidate bacterial species.3

Aseptic Loosening

–There is a resurgence of interest in the role of subclinical infection in the etiopathogenesis of aseptic loosening. At the same time, molecular diagnostic methods for microbial infection are moving forward.4 Such methods may serve to highlight the relevance of subclinical microbial contamination as a cause of aseptic loosening.

Cartilage Imaging

–While the goal of cartilage imaging is to develop tools that are fast, inexpensive, sensitive, accurate, and noninvasive, there is growing interest in the use of more direct, invasive techniques such as optical coherence tomography (OCT),5 which could be used in vivo at the time of surgery to analyze cartilage damage.

References

  1. Li Y, Liu T, Van Halm-Lutterodt N, Chen J, Su Q, Hai Y. Reprogramming of blood cells into induced pluripotent stem cells as a new cell source for cartilage repair. Stem Cell Res Ther.2016 Feb 17;7:31.
  2. Meppelink AM, Zhao X, Griffin DJ, Erali R, Gill TJ, Bonassar LJ, Redmond RW,Randolph MA. Hyaline articular matrix formed by dynamic self-regenerating cartilage and hydrogels. Tissue Eng Part A.2016 Jul;22(13-14):962-70. Epub 2016 Jul 7.
  3. Getzlaf MA, Lewallen EA, Kremers HM, Jones DL, Bonin CA, Dudakovic A,Thaler R, Cohen RC, Lewallen DG, van Wijnen AJ. Multi-disciplinary antimicrobial strategies for improving orthopaedic implants to prevent prosthetic joint infections in hip and knee. J Orthop Res.2016 Feb;34(2):177-86. Epub 2015 Dec 29.
  4. Palmer MP, Melton-Kreft R, Nistico L, Hiller NL, Kim LH, Altman GT, Altman DT, Sotereanos NG, Hu FZ, De Meo PJ, Ehrlich GD. Polymerase chain reaction-electrospray-time-of-flight mass spectrometry versus culture for bacterial detection in septic arthritis and osteoarthritis. Genet Test Mol Biomarkers.2016 Dec;20(12):721-31. Epub 2016 Oct 17.
  5. Novakofski KD, Pownder SL, Koff MF, Williams RM, Potter HG, Fortier LA. High-resolution methods for diagnosing cartilage damage in vivo. 2016 Jan;7(1):39-51.

With OCA, Don’t Fret About Condyle Matching

OCA for OBuzz

Osteochondral allograft transplantations (OCAs) are becoming a mainstay of treatment for knee-cartilage injuries. To help ensure that the allograft plug is transplanted with <1 mm of step-off from the surrounding recipient cartilage, many surgeons restrict themselves to orthotopic OCAs—matching the graft-recipient condyles in a lateral-to-lateral or medial-to-medial fashion.

However, in the October 4, 2017 issue of The Journal of Bone & Joint Surgery, Wang et al. demonstrated that both orthotopic and non-orthotopic (e.g., lateral condyle-to-medial condyle) OCA resulted in significantly improved outcomes in 77 cases followed for a mean of 4.3 years. The authors found that reoperation rates and pre- and postoperative scores in physical functioning and pain did not differ significantly between the orthotopic (n=50) and non-orthotopic (n=27) groups. These results suggest that condyle-specific matching may not be necessary.

One problem with orthotopic OCA is that 75% of the available allograft is supplied in the form of lateral condyles, while most full-thickness cartilage lesions presenting for treatment occur in the medial condyle. Consequently, surgeon preferences for orthotopic OCA limit the number of available matches and lead to an estimated 13% of available grafts being discarded.

Noting that many factors contribute to successful resurfacing of cartilage defects in the knee, the authors say that “it may be overly simplistic to assume that a conventionally matched orthotopic allograft will ensure a smooth surface contour at the recipient site.” They go on to conclude that “if surgeons forewent condyle-specific matching, more allografts would be readily available, which would shorten wait times, provide fresher grafts with increased chondrocyte viability, and lower procedure costs.”

Restoring Cartilage: The Holy Grail of Orthopaedics

For decades, researchers have been investigating different methods of cartilage repair, but no approach has yet risen to “gold standard” status. In the June 24, 2015 edition of JBJS Case Connector, “Case Connections” looks at three different restorative/replacement approaches to cartilage defects.

In the springboard case by Ramirez et al., a high school athlete’s full-thickness glenoid osteochondral defect was filled arthroscopically with particulated juvenile cartilage allograft (see image below).

F1.largeIn an earlier case report by Convery et al., the authors recommended placing additional autogenous bone beneath allografts to augment the host bed and enhance incorporation of the allograft’s osseous shell.

Welsch et al. alert surgeons to the possibility of hypertrophic cartilage opposite a defect that’s treated with a matrix-associated autologous chondrocyte transplant (MACT). And finally, Adachi et al. report on osteonecrosis of the femoral condyles that was treated with tissue-engineered cartilage combined with a hydroxyapatite scaffold enhanced with mesenchymal stem cells.

Although prospective studies with suitable control groups will be needed to prove the efficacy of these and other restorative techniques, early intervention with biologic restoration of the articular surface could eventually have a profound influence on patients with cartilage damage.

JBJS Classics: The Role of Continuous Passive Motion in Orthopaedics

EachJBJS-Classics-logo 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