At age 56, Charlie’s shoulder arthritis was so advanced he could no longer lift 4×8 sheets of plywood or swing his hammer as a home remodeling contractor, let alone fish the Wilson River rowing his beloved McKenzie drift boat. He was told his only option was bilateral total shoulder replacement. Facing a long and uncertain surgical recovery, he was skeptical that total arthroplasty was his best and only option.
When I first examined Charlie, even I was skeptical that adipose tissue graft would provide him much relief at all, let alone get him back to rowing his drift boat and performing major home remodeling. Both of his shoulders literally ratcheted through a limited range of motion, with loud audible crepitation.
Our musculoskeletal ultrasound examination mirrored his x-rays: advanced osteoarthritis (OA) with bone spurring of the glenohumeral and acromioclavicular joints. I gave him a discouraging PARQ (procedures, alternatives, risks, questions). However, he’d heard of great results from two of his friends whom I had previously treated for knee and hip osteoarthritis. Both had avoided joint replacement surgery. With realistically low expectations, we agreed to perform adipose tissue graft on both of his shoulders.
The glenohumeral (GH) joint ranks third on the list of the large joints that are most commonly affected by osteoarthritis, after the knee and the hip.
General nonsurgical modalities, including physical therapy, NSAIDs, and corticosteroid injections are the mainstay of conventional treatment and have at best shown minimal short-term effectiveness. None of these treatments yield improvement in joint health or biomechanics.
Arthroplasty (total joint replacement) techniques have proven to be successful for the elderly. However, replacement options are not optimal for younger patients due to their higher functional demands and the finite life span of prostheses.
Orthobiologic therapies, including platelet-rich plasma (PRP) and adipose cell therapies, present great promise and opportunity for the treatment of GH osteoarthritis.
Shoulder arthritis is a complex multifactorial condition associated with progressive degeneration of cartilage, subchondral bone, and synovium. Subchondral bone changes are associated with a loss of shock absorption, brought on by articular cartilage degeneration. Bone reacts to the mechanical shock by hardening and bone spurs develop as cartilage degeneration progresses. The bone becomes stiffer, with reduced ability to absorb impact loads, thus causing more cartilage stress.1,2
Type-II collagen is the main structural protein of cartilage and constitutes a meshwork that is stabilized by other collagen types, glycosaminoglycans (GAGs) and non-collagenous proteins. Under the microscope, proteoglycans have a bottle-brush like structure, with water molecules attached to the individual bristles, essentially creating a flexible water cushion in cartilage, providing compressive resistance, and accounting for the fact that over 94% of the volume of human cartilage is water.
Cartilage destruction is only partially caused by mechanical wear and tear. Various proteases are secreted by the synovium itself, and these proteases essentially break down the structural proteins that hold cartilage together, accelerating cartilage loss. When combined with joint instability from ligamentous laxity, cartilage loss is accelerated.3,4
ORTHOBIOLOGICS instead of surgery?
Platelet-derived growth factors
Platelet Rich Plasma is considered minimally manipulated and falls under the FDA’s scope of section 361 (Public Health Service Act, 21 Code of Federal Regulation 1271) as a minimally manipulated human tissue and cell therapy. Platelet concentrates possess biologically active growth factors and tissue repair upregulating proteins inside tiny vesicles called alpha granules. These growth factors have the potential to reduce joint inflammation, decrease cartilage breakdown, and promote tissue repair.4 These factors include TGF-1, insulin-like growth factor, PDGF, basic fibroblast growth factor, and vascular endothelial growth factor. Chondrogenesis and stem cell proliferation have been shown to be positively affected by PRP through various growth factors. Because PRP has the ability to substantially reduce the cartilage damaging MMP-3 and MMP-13 activity, research has shown that cartilage matrix formation can be improved and cartilage healing can be facilitated. As a result of these combined effects, PRP constitutes a viable injectable alternative for treating shoulder arthritis.5,6
Adipose tissue grafts and ADSCs
Adipose tissue is generally accepted as the preferred source of regenerative cells. It is readily accessed and harvested, and few complications have been reported with the procedure. Mesenchymal stem cells (MSCs) that are derived from adipose tissue are known as adipose derived stem cells-ADSCs. ADSC therapies that can be divided into 2 types: minimally manipulated (micronized and microfragmented fat) and more than minimally manipulated (adipose-derived stromal vascular fraction [ADSVFs]). Currently, only minimally manipulated adipose tissues meet the FDA’s section 361 (Public Health Service Act, 21 Code of Federal Regulation 1271.) ADSCs have gained popularity during the last decade because they have a more specific cartilage regenerative capability compared with bone marrow-derived mesenchymal stem cells.6 The harvest site for ADSCs is the mid abdominal or posterior fat pads.
Burrow et al. demonstrated that, compared to bone marrow cells, adipose cells possess an enhanced proliferative capacity and are capable of retaining multipotency longer than donor-matched marrow MSCs during expansion.7 ADSCs exert anti-inflammatory effects, and secrete various critical molecules involved in tissue regeneration. These include collagens and collagen maturation enzymes, matricellular proteins, MMPs. Macrophage-colony stimulating factor, also involved, may affect the metabolism of the extracellular matrix in osteoarthritic cartilage. This may constitute an advantage for osteoarthritic cartilage since homeostasis is restored between MMPs and the tissue inhibitors of metalloproteinases (TIMPs).8,9
ADSCs for Shoulder Arthritis
Striano et al. conducted a study of shoulder arthritis and pain that was unresponsive to conventional treatments. 18 patients were treated with microfragmented adipose tissue.10 Significant improvement was observed at the 1-year follow-up in the numerical pain score (NPS) and the combined physician and patient-reported pain and function scores (ASES score): the average improvement that was registered in the NPS went from 7.5 to 3.6 (p < 0.001). The average improvement in the ASES score went from 33.7 to 69.2 at 1 year (p < 0.001). There were no reports indicating any postprocedural complications or serious adverse events. 75% of the patients had a concomitant partial or full-thickness rotator cuff tear, which also resolved with the microfragmented adipose treatment. Therefore, it is impossible to know if the treatment’s pain and functional improvements were due to improvement in osteoarthritis, rotator cuff healing, or both.
Catching his limit
Within 8 months of his initial adipose graft, Charlie brought me photos of his beautiful Wilson River salmon drift boat catch. And he had just completed a client’s remodel, having hung large picture windows while high up on scaffolding. Since his first treatment, over the last 4-years, he has been rowing his drift boat and working 40+ hours a week in his construction business. Last year, Charlie saw me for one additional ADSC adipose graft to his shoulders, and he continues to receive quarterly shoulder “tune-ups” with PRP. His improved shoulder has allowed him to work hard as a sought-after remodeling contractor and enjoy his river drifting passion for wild-caught Oregon salmon.
1. Li B, Aspden RM. Composition and mechanical properties of cancellous bone from the femoral head of patients with osteoporosis or osteoarthritis. J Bone Miner Res. 1997;12(4):641-651. doi:10.1359/jbmr.1918.104.22.1681
2. Bobinac D, Spanjol J, Zoricic S, Maric I. Changes in articular cartilage and subchondral bone histomorphometry in osteoarthritic knee joints in humans. Bone. 2003;32(3):284-290. doi:10.1016/s8756-3282(02)00982-1
3. Yang CY, Chanalaris A, Troeberg L. ADAMTS and ADAM metalloproteinases in osteoarthritis – looking beyond the ‘usual suspects’. Osteoarthritis Cartilage. 2017;25(7):1000-1009. doi:10.1016/j.joca.2017.02.791
4. Malemud CJ. Inhibition of MMPs and ADAM/ADAMTS. Biochem Pharmacol. 2019;165:33-40. doi:10.1016/j.bcp.2019.02.033
5. Kabiri A, Esfandiari E, Esmaeili A, Hashemibeni B, Pourazar A, Mardani M. Platelet-rich plasma application in chondrogenesis. Adv Biomed Res. 2014;3:138. Published 2014 Jun 25. doi:10.4103/2277-9175.135156
6. Francis, Sam L et al. “Adipose-Derived Mesenchymal Stem Cells in the Use of Cartilage Tissue Engineering: The Need for a Rapid Isolation Procedure.” Stem cells international vol. 2018 8947548. 3 Apr. 2018, doi:10.1155/2018/8947548
7. Burrow KL, Hoyland JA, Richardson SM. Human Adipose-Derived Stem Cells Exhibit Enhanced Proliferative Capacity and Retain Multipotency Longer than Donor-Matched Bone Marrow Mesenchymal Stem Cells during Expansion In Vitro. Stem Cells Int. 2017;2017:2541275.
8. Denkovskij J, Bagdonas E, Kusleviciute I, et al. Paracrine Potential of the Human Adipose Tissue-Derived Stem Cells to Modulate Balance between Matrix Metalloproteinases and Their Inhibitors in the Osteoarthritic Cartilage In Vitro. Stem Cells Int. 2017;2017:9542702. doi:10.1155/2017/9542702
9. Kalinina, Natalia & Kharlampieva, Daria & Loguinova, Marina & Butenko, Ivan & Pobeguts, Olga & Efimenko, Anastasia & Ageeva, Luidmila & Sharonov, George & Ischenko, Dmitry & Alexeev, Dmitry & Grigorieva, Olga & Sysoeva, Veronika & Rubina, Kseniya & Lazarev, Vassili & Govorun, Vadim. (2015). Characterization of secretomes provides evidence for adipose-derived mesenchymal stromal cells subtypes. Stem Cell Research & Therapy. 6. 10.1186/s13287-015-0209-8.
10. Han, Chang, and Xi-Sheng Weng. “Microfragmented adipose tissue and its initial application in articular disease.” Chinese medical journal vol. 132,22 (2019): 2745-2748. doi:10.1097/CM9.0000000000000518
Photos by Cagatay Demir on Unsplash, and by Matt Hardy and Tobi on Pexels.