Biologic therapies are becoming increasingly popular in orthopaedics due to their potential to regenerate tissue and enhance bone healing. However, questions still remain about their efficacy and indications for use.

During a combined Specialty Day session of the Arthroscopy Association of North America (AANA), the American Orthopaedic Society for Sports Medicine (AOSSM), and the American Shoulder and Elbow Surgeons (ASES), experts discussed the use of biologics in orthopaedic applications.

“Biologics is an evolving frontier,” said Allan K. Mishra, MD, of the Menlo Medical Clinic and Stanford University Medical Center. He compared biologics to arthroscopy in its infancy. “In the 1970s, 1980s, and the early 1990s, the techniques and instrumentation for arthroscopy dramatically improved, which allowed us to be much better advocates and surgeons. I believe a similar situation will occur with orthobiologics.”

PRP for tendinopathy, arthritis
Platelet-rich-plasma (PRP) is a biologic therapy that has been used clinically for many years. Recently, it has emerged as an effective treatment option for various musculoskeletal conditions, including tendinopathy.

According to Dr. Mishra, several Level 1 studies support the use of PRP for the treatment of chronic lateral epicondylar tendinopathy. He cited a blinded randomized control trial (RCT) of 230 patients with chronic tennis elbow. All had received conservative treatment, which failed to relieve symptoms. Blood was drawn from all patients, and patients received 2 mL to 3 mL of either the PRP preparation or bupivacaine. At 24-week follow-up, the patients who received PRP injections had an 82 percent success rate (showing more than a 50 percent reduction in pain scores compared to baseline) and no significant complications, versus a 60 percent success rate in the control group (Fig.1)

Dr. Mishra also cited findings from a recent study that showed that a leukocyte-enriched form of PRP enhanced Achilles tendon repair, improved fiber structure, and increased type 1 collagen. “Now we have human histology data as well as RCT data that suggest PRP is a useful treatment option for tendinopathy,” he said.

Interest in using PRP and other biologics for knee arthritis is growing, due in large part to a lack of other treatment options, according to Dr. Mishra. “We can’t afford to give every patient a total knee arthroplasty (TKA)—we should be able to use PRP or other types of biologics to intervene,” he said. “Although we are still in search of the ideal PRP formulation and indication or specific patient match, I believe that within 5 years, the use of biologic orthopaedics will flatten the TKA curve.”

For the time being, he concluded, “Chronic lateral epicondylar tendinopathy is a specific indication for PRP that is supported by multiple Level 1 studies. Consider using PRP to augment Achilles tendon repairs, and stay tuned on the use of PRP for knee osteoarthritis—we still need optimization.”

The new kid on the block
“The key to bone marrow aspirate concentrate (BMAC) is mesenchymal stem cells (MSCs),” said Kevin D. Plancher, MD, MS, clinical professor at the Albert Einstein College of Medicine in New York City. MSCs are progenitor cells that have both chondrogenic and osteogenic potential and can differentiate into other types of cells, such as chondrocytes, myoblasts, adipocytes, and osteoblasts.

The primary indications for BMAC, according to Dr. Plancher, include rotator cuff repair, cartilage regeneration, chronic tendinopathy of the elbow or patella, and osteonecrosis in the hip, knee, or elbow. After selecting the donor site—either the anterior or posterior iliac crest, which have the greatest concentration of MSCs—Dr. Plancher aspirates 60 mL of bone marrow, concentrates it through centrifugation, and then injects it into the affected area.

Although the research on BMAC is limited, with no long-term follow-up studies, recent data are encouraging. A 2014 study evaluated 45 symptomatic patients who received BMAC injections as an adjunct to rotator cuff repair. “Patients who received MSCs had a faster healing rate; at 6 months, 100 percent of patients who received MSCs demonstrated healing, compared to only 67 percent of those who had not received MSCs,” Dr. Plancher said.

Similarly, a recent double-blind RCT showed that patients who received BMAC injections for treatment of meniscal regeneration in the knee showed a significant increase in meniscal volume and a significant reduction in pain at one-year follow-up. Another study in 30 patients with lateral epicondylosis revealed a significant improvement in functional outcomes, with no adverse effects, in those who had received a single injection of BMAC.

Dr. Plancher added that a systematic review of BMAC studies showed that the procedure is associated with minimal pain and swelling and a very low infection rate. In his series, he reported “no morbidity at the harvest site and no infections or complications to date at the injection site. But data from long-term studies are absolutely needed,” he stressed.

Nevertheless, Dr. Plancher encouraged orthopaedic surgeons to consider using BMAC in their practices. “It is a one-step proce-dure with promising clinical evidence and minimal-to-no complications,” he said. “But keep in mind that it is a new treatment—results may be variable, it can be expensive, and you have to manage patient expectations.”

The AANA/AOSSM/ASES Specialty Day program “Orthobiologics 2015: The Evolving Frontier” was moderated by Augustus D. Mazzocca, MD, MS. Additional presenters included C. Thomas Vangsness Jr, MD, and Stephen C. Weber, MD.

The presenters’ disclosure information, including potential conflicts of interest, can be viewed at www.aaos.org/disclosure

Maureen Leahy is assistant managing editor of AAOS Now. She can be reached at leahy@aaos.org

Bottom Line

• Biologics, including PRP and BMAC, are emerging as popular treatment options in orthopaedics due to their regenerative properties.
• Studies have shown that PRP is an effective therapy for tendinopathy; it may also prove effective in managing osteoarthritis in the knee.
• Not as widely used as PRP, BMAC delivers MSCs from a patient’s own bone marrow directly to a defect to aid in healing.
• Although early clinical evidence is promising, long-term studies on the safety and effectiveness of BMAC are needed.

References

1. Mishra AK, Skrepnik NV, Edwards SG, et al: Efficacy of platelet-rich plasma for chronic tennis elbow: A double-blind, prospective, multicenter, controlled trial of 230 patients. Am J Sports Med 2014;42(2):463-471. doi: 10.1177/0363546513494359. Epub 2013 Jul 3. http://ajs.sagepub.com/content/early/2013/07/03/0363546513494359.full
2. Alsousou J, Thompson M, Harrison P, Willett K, Franklin S: Effect of platelet-rich plasma on healing tissues in acute ruptured Achilles tendon: A human immunohistochemistry study. Lancet 2015;385;S19. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60334-8/abstract
3. Hernigou P, Flouzat Lachaniette CH, Delambre J, et al: Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: A case-controlled study. Int Orthop 2014;38(9):1811-1818. doi: 10.1007/s00264-014-2391-1. Epub 2014 Jun 7.
4. Vangsness CT Jr, Farr J 2nd, Boyd J, Dellaero DT, Mills CR, LeRoux-Williams M: Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: A randomized, double-blind, controlled study. J Bone Joint Surg Am 2014;96(2):90-98. doi: 10.2106/JBJS.M.00058.
5. Singh A, Gangwar DS, Singh S: Bone marrow injection: A novel treatment for tennis elbow. J Nat Sci Biol Med 2014;5(2):389-391. doi: 10.4103/0976-9668.136198.