Andrew S. Lee

A current review of molecular mechanisms regarding osteoarthritis and pain

Osteoarthritis afflicts millions of individuals across the world resulting in impaired quality of life and increased health costs. To understand this disease, physicians have been studying risk factors, such as genetic predisposition, aging, obesity, and joint malalignment; however have been unable to conclusively determine the direct etiology. Current treatment options are short-term or ineffective and fail to address pathophysiological and biochemical mechanisms involved with cartilage degeneration and the induction of pain in arthritic joints. OA pain involves a complex integration of sensory, affective, and cognitive processes that integrate a variety of abnormal cellular mechanisms at both peripheral and central (spinal and supraspinal) levels of the nervous system Through studies examined by investigators, the role of growth factors and cytokines has increasingly become more relevant in examining their effects on articular cartilage homeostasis and the development of osteoarthritis and osteoarthritis-associated pain. Catabolic factors involved in both cartilage degradation in vitro and nociceptive stimulation include IL-1, IL-6, TNF-α, PGE2, FGF-2 and PKCδ, and pharmacologic inhibitors to these mediators, as well as compounds such as RSV and LfcinB, may potentially be used as biological treatments in the future. This review explores several biochemical mediators involved in OA and pain, and provides a framework for the understanding of potential biologic therapies in the treatment of degenerative joint disease in the future.

An Evidenced-Based Examination of the Epidemiology and Outcomes of Traumatic Rotator Cuff Tears

PURPOSE The purpose of this study was to systematically review the literature to better define the epidemiology, mechanism of injury, tear characteristics, outcomes, and healing of traumatic rotator cuff tears. A secondary goal was to determine if sufficient evidence exists to recommend early surgical repair in traumatic rotator cuff tears. METHODS An independent systematic review was conducted of evidence Levels I to IV. A literature search of PubMed, Medline, Embase, and Cochrane Collaboration of Systematic Reviews was conducted, with 3 reviewers assessing studies for inclusion, methodology of individual study, and extracted data. RESULTS Nine studies met the inclusion and exclusion criteria. Average patient age was 54.7 (34 to 61) years, and reported mean time to surgical intervention, 66 days (3 to 48 weeks) from the time of injury. The most common mechanism of injury was fall onto an outstretched arm. Supraspinatus was involved in 84% of tears, and infraspinatus was torn in 39% of shoulders. Subscapularis tears were present in 78% of injuries. Tear size was <3 cm in 22%, 3 to 5 cm in 36%, and >5 cm in 42%. Average active forward elevation improved from 81° to 150° postoperatively. The weighted mean postoperative UCLA score was 30, and the Constant score was 77. CONCLUSIONS Traumatic rotator cuff tears are more likely to occur in relatively young (age 54.7), largely male patients who suffer a fall or trauma to an abducted, externally rotated arm. These tears are typically large and involve the subscapularis, and repair results in acceptable results. However, insufficient data prevent a firm recommendation for early surgical repair. LEVEL OF EVIDENCE Level IV, systematic review Levels III and IV studies.

Transosseous-Equivalent Rotator Cuff Repair: A Systematic Review on the Biomechanical Importance of Tying the Medial Row

PURPOSE Double-row and transosseous-equivalent repair techniques have shown greater strength and improved healing than single-row techniques. The purpose of this study was to determine whether tying of the medial-row sutures provides added stability during biomechanical testing of a transosseous-equivalent rotator cuff repair. METHODS We performed a systematic review of studies directly comparing biomechanical differences. RESULTS Five studies met the inclusion and exclusion criteria. Of the 5 studies, 4 showed improved biomechanical properties with tying the medial-row anchors before bringing the sutures laterally to the lateral-row anchors, whereas the remaining study showed no difference in contact pressure, mean failure load, or gap formation with a standard suture bridge with knots tied at the medial row compared with knotless repairs. CONCLUSIONS The results of this systematic review and quantitative synthesis indicate that the biomechanical factors ultimate load, stiffness, gap formation, and contact area are significantly improved when medial knots are tied as part of a transosseous-equivalent suture bridge construct compared with knotless constructs. Further studies comparing the clinical healing rates and functional outcomes between medial knotted and knotless repair techniques are needed. CLINICAL RELEVANCE This review indicates that biomechanical factors are improved when the medial row of a transosseous-equivalent rotator cuff is tied compared with a knotless repair. However, this has not been definitively proven to translate to improved healing rates clinically.

Allograft Meniscus Transplantation

Menisci function to manage load transmission, provide secondary mechanical stability as well as nutrition, and lubricate the joint. Meniscus transplantation techniques continue to evolve and include: free soft tissue allograft implantation; separate anterior and posterior bone plugs; and bone bridges including key hole, trough, dovetail, and bridge-in-slot variations. The senior author’s preference is for the bridge-in-slot technique for lateral and medial menisci, owing to its simplicity and secure bony fixation, flexibility in allowing concomitant procedures as osteotomy and ligament reconstruction, and the ability to maintain the native anterior and posterior meniscal horn attachments. Meniscal allograft transplantation yields fair to excellent results in almost 85% of patients. Patients demonstrate significant decrease in pain, as well as an increase in activity. Long-term success is encouraging in well-selected patients but is unknown whether transplantation is protective against the progression of degenerative changes.

The Biomechanical Effects of 1.0 to 1.2 Mrad of Gamma Irradiation on Human Bone–Patellar Tendon–Bone Allografts

Background: Recent data suggest that anterior cruciate ligament (ACL) reconstruction with irradiated allograft tissue may lead to increased failure rates. Hypothesis: Low-dose (1.0-1.2 Mrad) gamma irradiation does not significantly alter the preimplantation biomechanical properties of bone–patellar tendon–bone (BTB) allografts. Study Design: Controlled laboratory study. Methods: Cyclic and failure mechanical properties were evaluated for 20 paired central-third human BTB allografts, with and without 1.0 to 1.2 Mrad of gamma irradiation. Testing included cyclic loading at 0.5 Hz for 100 cycles from 50 to 200 N and failure testing at a strain rate of 10% per second. Results: Cyclic elongation did not change significantly (P = .151) with irradiation, increasing from a mean ± SD of 9.4 ± 2.1 mm to 11.3 ± 3.4 mm. Cyclic creep strain approached a significant increase with irradiation (1.3% ± 0.8% to 2.6% ± 1.5%; P = .076). Failure testing was not affected with irradiation with regard to maximum load (1680 ± 417 mm to 1494 ± 435 mm), maximum stress (40.8 ± 10.6 MPa to 37.5 ± 15.7 MPa), elongation (7.85 ± 1.35 mm to 8.67 ± 2.05 mm), or strain at maximum stress (0.158 ± 0.03 to 0.175 ± 0.03). Graft stiffness significantly decreased by 20% with irradiation (278 ± 67 N/mm to 221 ± 50 N/mm; P = .035). Conclusion: Low-dose (1.0-1.2 Mrad) gamma irradiation decreases BTB graft stiffness by 20%, but it does not affect other failure or cyclic parameters. Clinical Relevance: Aside from graft stiffness during load to failure testing, low-dose (1.0-1.2 Mrad) gamma irradiation of central-third human BTB allografts is not deleterious to preimplantation biomechanical properties.

Considerations for the Use of Platelet-Rich Plasma in Orthopedics

The use of platelet-rich plasma (PRP) is expanding to numerous medical fields, including orthopedic surgery and sports medicine. The popularity of this new treatment option has prompted a rapid increase in research endeavors; however, the differences in application technique and the composition of PRP have made it difficult to compare results or make any firm conclusions regarding efficacy. The purpose of this article is twofold. First, to recommend details that should be provided in basic science and clinical PRP studies to allow meaningful comparisons between studies which may lead to a better understanding of efficacy. Second, to provide an understanding of the different PRP preparations and their clinical relevance. There are biochemical rationales for the use of PRP because it addresses several aspects of the healing process, including cell proliferation and tissue matrix regeneration, inflammation, nociception, infection, and hemostasis, all of which will be addressed. Given the current understanding of the importance the composition of PRP plays in tissue regeneration, it is likely that our future understanding of PRP will dictate ‘customizing’ the PRP preparation to the specific pathology of interest. The potential complications following PRP use are minor, and thus it appears to be a safe treatment option with a variety of potentially beneficial effects to injured musculoskeletal tissues.

Central-third bone-patellar tendon-bone allografts demonstrate superior biomechanical failure characteristics compared with hemi-patellar tendon grafts.

Background: Reconstruction of the anterior cruciate ligament (ACL) is commonly performed with a bone–patellar tendon–bone (BTB) allograft. However, grafts may result from harvesting the central region of a whole graft (C-BTB), the medial 10 mm of a lateral hemi-BTB (L-BTB) graft, or the lateral 10 mm of a medial hemi-BTB (M-BTB) graft. Purpose: To quantify potential differences in graft biomechanical properties when comparing whole versus hemi-BTB grafts. Study Design: Controlled laboratory study. Methods: Ten pairs of human BTB allografts (irradiated with 1.0-1.2 Mrad) were randomized to preparation as whole grafts or hemigrafts. From these, 10-mm grafts were prepared from the center or the most central portion, respectively. After measurements of tendon thickness, width, and length, specimens underwent cyclic tensile testing, followed by load-to-failure analysis. Biomechanical outcomes included cyclic elongation and creep strain along with the following failure characteristics: maximum load, elongation at maximum load, maximum stress, strain at maximum stress, and linear stiffness. Results: Regionally, the mean thickness of the C-BTB (5.18 ± 0.75 mm), M-BTB (5.08 ± 0.56 mm), and L-BTB (5.32 ± 0.62 mm) grafts were comparable (P > .72). Similarly, the mean length of the C-BTB (47.4 ± 6.73 mm), M-BTB (47.0 ± 5.45 mm), and L-BTB (50.7 ± 6.42 mm) grafts were alike (P > .43). While differences in cyclic elongation and strain were not significant, the M-BTB graft tended to elongate more (0.204 ± 0.13 mm; P = .075) and experience greater strain (0.56% ± 0.32%; P = .054) compared with the C-BTB graft (0.09 ± 0.03 mm and 0.23% ± 0.07%, respectively). Load-to-failure testing demonstrated a higher maximum load (2293 ± 531 N) and stiffness (356 ± 46 N/mm) of the C-BTB graft as compared with the M-BTB graft (1575 ± 325 N [P < .007] and 275 ± 37 N/mm [P < .008], respectively) and L-BTB graft (1585 ± 452 N [P < .008] and 277 ± 65 N/mm [P < .009], respectively). No differences were noted with respect to elongation or stress at maximum load among the grafts. Maximum stress in the C-BTB graft (45.4 ± 11.5 MPa) was greater than in the L-BTB graft (29.7 ± 10.6 MPa) (P < .03) and tended to be greater than the M-BTB graft (34.1 ± 6.27 MPa) (P = .087). Conclusion: Biomechanical failure properties (maximum load, stress, and stiffness) of the central portion of a whole BTB graft are superior to those of the medial portion of a lateral hemi-BTB graft and the lateral portion of a medial hemi-BTB graft. However, cyclic loading characteristics did not differ between grafts. Clinical Relevance: Although the true central-third BTB graft is biomechanically superior to hemi-BTB grafts, future studies are necessary to determine if the use of hemigrafts leads to an increased incidence of clinical failure.

A Retrospective Review of Anterior Cruciate Ligament Reconstruction Using Patellar Tendon: 25 Years of Experience

Background: The comparative data in the literature regarding rates of reoperation, revision ligament surgery, and contralateral surgery following anterior cruciate ligament reconstruction (ACLR) are variable and are often derived from studies with multiple surgeons, multiple centers, different surgical techniques, and a wide variety of graft choices. Purpose: To describe and analyze a single surgeon’s experience with ACLR using bone–patellar tendon–bone (BPTB) as the primary graft choice over a 25-year period. Study Design: Retrospective case series. Methods: All patients who underwent ACLR from 1986 to 2012 were identified from a prospectively maintained database. Traditional follow-up was only for patients who sought subsequent surgery with the index surgeon or presented with contralateral ACL injury. Covariates of interest included age, sex, time, and graft selection. Outcomes of interest included reoperation rates after primary/revision ACLR, rate of revision ACLR, success of meniscal repair with concomitant ACLR, and the proportion of patients undergoing contralateral surgery. Results: A total of 1981 patients (mean age, 29 years; 49% male) were identified. Of patients undergoing primary ACLR (n = 1809), 74% had BPTB autograft and 26% had a central third BPTB allograft. The mean age of patients undergoing autograft and allograft ACLR was 26 and 36 years, respectively (P < .05). Allograft tissue usage increased over time (P < .05). The rate of personal ACLR revision surgery was 1.7% (n = 30) for primary cases and 3.5% (n = 6) for revision cases. There were no significant differences in revision rates between primary autograft (1.6%) and allograft (2.0%) ACLR. With allograft use, the method of sterilization did not affect revision rates. The overall reoperation rate following primary ACLR was 10%; the 5-year reoperation rate was 7.7%. The reoperation rate was lower for primary cases reconstructed with allograft versus autograft (5% vs 12%) (P < .0001). Among primary ACLR cases, 332 patients (18%) underwent concomitant meniscal repair; 14% required revision meniscal surgery. The rate of contralateral ACLR was 6%. Conclusion: This information is useful for patients in the informed consent process, for perioperative decision making regarding graft choice, and for identifying patients who are at risk for injuring the uninvolved knee. The observed results in this series also emphasize that allograft ACLR can produce sustainable results with low complication rates in appropriately selected patients.

Long-Term Evaluation of Autologous Chondrocyte Implantation: Minimum 7-Year Follow-Up

Purpose: The purpose of this study was to report the clinical outcomes of autologous chondrocyte implantation (ACI) procedures performed by a single orthopedic surgeon at a minimum of 7 years follow-up. Methods: A retrospective review of prospectively collected data was performed on 29 patients who underwent ACI of the knee between the years of 1998 and 2003. Prospective data were collected to assess changes in standardized outcome measures preoperatively and 2, 4, and 7 years postoperatively. All patients enrolled in the study were also recruited to undergo physical examination when possible. Results: The final cohort consisted of 29 patients with a mean final follow-up time of 8.40 years (range = 7.14-10.88 years). Comparing preoperative scores to 7-year postoperative values, the mean International Knee Documentation Committee (IKDC) score improved from 39.80 to 59.24 (P < 0.001), mean Tegner-Lysholm score increased from 48.07 to 74.17 (P < 0.001), SF-12 physical score improved from 40.38 to 48.66 (P < 0.001), and SF-12 mental score improved from 44.14 to 48.98 (P < 0.05). Significant improvement occurred in Knee Injury and Osteoarthritis Outcome Score (KOOS) pain (56.03 to 80.36), symptoms (54.19 to 74.75), activities of daily living (72.01 to 85.90), sports (23.34 to 55.34), and quality of life (24.56 to 56.03) (P < 0.001). In addition, 7-year postoperative scores were at or near levels seen at 2 years (mean = 2.16; range = 0.94-4.03 years) and 4 years (mean = 4.43; range = 2.16-5.88 years) postoperatively, reflecting durable improvement. Subjectively, on a scale of 1 to 10 (10 being completely satisfied), the mean postoperative satisfaction rate was 8.14. Additionally, 88.9% of the patients would elect to have this surgery again if the same problem was to occur in the contralateral joint. Conclusions: The results of ACI in patients who present with symptomatic, full-thickness chondral defects remain durable at a minimum of 7-year follow-up with persistent, high levels of patient satisfaction. Level of Evidence: Case series; Level of evidence, IV.

Assessment of glenoid chondral healing: comparison of microfracture to autologous matrix-induced chondrogenesis in a novel rabbit shoulder model.

BACKGROUND Management of glenohumeral arthrosis in young patients is a considerable challenge, with a growing need for non-arthroplasty alternatives. The objectives of this study were to develop an animal model to study glenoid cartilage repair and to compare surgical repair strategies to promote glenoid chondral healing. METHODS Forty-five rabbits underwent unilateral removal of the entire glenoid articular surface and were divided into 3 groups--untreated defect (UD), microfracture (MFx), and MFx plus type I/III collagen scaffold (autologous matrix-induced chondrogenesis [AMIC])--for the evaluation of healing at 8 weeks (12 rabbits) and 32 weeks (33 rabbits) after injury. Contralateral shoulders served as unoperated controls. Tissue assessments included 11.7-T magnetic resonance imaging (long-term healing group only), equilibrium partitioning of an ionic contrast agent via micro-computed tomography (EPIC-μCT), and histologic investigation (grades on International Cartilage Repair Society II scoring system). RESULTS At 8 weeks, x-ray attenuation, thickness, and volume did not differ by treatment group. At 32 weeks, the T2 index (ratio of T2 values of healing to intact glenoids) was significantly lower for the MFx group relative to the AMIC group (P = .01) whereas the T1ρ index was significantly lower for AMIC relative to MFx (P = .01). The micro-computed tomography-derived repair tissue volume was significantly higher for MFx than for UD. Histologic investigation generally suggested inferior healing in the AMIC and UD groups relative to the MFx group, which exhibited improvements in both integration of repair tissue with subchondral bone and tidemark formation over time. DISCUSSION Improvements conferred by AMIC were limited to magnetic resonance imaging outcomes, whereas MFx appeared to promote increased fibrous tissue deposition via micro-computed tomography and more hyaline-like repair histologically. The findings from this novel model suggest that MFx promotes biologic resurfacing of full-thickness glenoid articular injury.