1. Unloading joints to treat osteoarthritis, including joint distraction.

Lafeber FP, Intema F, Van Roermund PM, Marijnissen AC.

Current Opinion in Rheumatology. 2006; 18(5): 519-25. Review.

Purpose of review: Patients are increasingly becoming interested in non-pharmacologic approaches to manage their osteoarthritis. This review examines the recent literature on the potential beneficial effects of unloading joints in the treatment of osteoarthritis, with a focus on joint distraction.

Recent findings: Mechanical factors are involved in the development and progression of osteoarthritis. If ‘loading’ is a major cause in development and progression of osteoarthritis, then ‘unloading’ may be able to prevent progression. There is evidence that unloading may be effective in reducing pain and slowing down structural damage. This review describes unloading by footwear and bracing (nonsurgical), unloading by osteotomy (surgical), and has a focus on unloading by joint distraction. Excellent reviews in all these three fields have been published over the past few years. Recent studies argue for the usefulness of a biomechanical approach to improve function and possibly reduce disease progression in osteoarthritis.

Summary: To improve patient function and possibly reduce disease progression, a biomechanical approach should be considered in treating patients with osteoarthritis. Further research (appropriate high-quality clinical trials) and analysis (clinical as well as preclinical and fundamental) are still necessary, however, to understand, validate, and refine the different approaches of unloading to treat osteoarthritis.

  1. Functional articular cartilage repair: here, near, or is the best approach not yet clear?

Mastbergen SC, Saris DB, Lafeber FP.

Nature Reviews Rheumatology. 2013; 9(5): 277-90. Review.

In this Review we describe three approaches for cartilage tissue repair at the rheumatology–orthopaedics interface: disease-modifying osteoarthritis (OA) drug (DMOAD) treatment; cell-based therapies, and intrinsic cartilage repair by joint distraction. DMOADs can slow the progression of joint damage. Cell-based therapies have evolved to do the same, through selection of the most potent cell types (and combinations thereof), as well as identification of permissive boundary conditions for indications. Joint distraction techniques, meanwhile, have now demonstrated the capacity to stimulate actual intrinsic tissue repair. Although this progress is promising, true biological joint reconstruction remains distant on the developmental pathway of ‘regenerative medicine’. Prolonged functional repair—that is, cure of diseases such as OA—remains an unmet medical need and scientific challenge, for which comparative and constructive interaction between these physical, chemical and cellular approaches will be required. Careful selections of patients and combinations of approaches will need to be made and tested to demonstrate their cost-effectiveness. Only with such rational and integrated assessment of outcomes will the promising results of these approaches be consolidated in clinical practice.

  1. A 20 years of progress and future of quantitative magnetic resonance imaging (qMRI)

of cartilage and articular tissues—A personal perspective.

Eckstein F., Peterfy C.

Semin Arthritis Rheum. 2016; 45(6): 639-47. Review.

In 1994, the first article on quantitative magnetic resonance imaging (qMRI) of articular cartilage was published, and tremendous progress in image acquisition, image analysis, and applications has since been made. The objective of this personal perspective is to highlight milestones in the field of qMRI of cartilage and other articular tissues over these past 20 years.

Based on a Pubmed search of original articles, the authors selected 30 articles which they deemed to be among the first to provide an important technological step forward in qMRI of cartilage, provided a first application in a particular context, or provided mechanistic insight into articular cartilage physiology, pathology, or treatment.

This personal perspective summarizes results from these 30 articles. Further, the authors provide examples of how qMRI of cartilage has translated to quantitative analysis approaches of other articular tissues, including bone, meniscus, and synovium/edema. Eventually, the report provides a summary of how the lessons learned might be applied to future clinical trials and clinical practice.

Over the past 20 years, quantitative imaging of articular tissues has emerged from a method to a dynamic field of research by its own. Continuing the qMRI biomarker qualification process will be crucial in convincing regulatory agencies to accept these as primary outcomes in phase 3 intervention trials. Once successful structural intervention will actually become available in OA, qMRI biomarkers may play an essential role in monitoring response to therapy in the clinic, and in stratifying disease phenotypes that respond differently to treatment

“In the same year, however, a first treatment study was published that demonstrated that an increase in cartilage thickness could be achieved by a “mechanical” intervention, in the compartment affected by radiographic OA [36]. This “anabolic” response was achieved by 2-month joint distraction with an external fixation frame in patients with late stage disease (mostly KLG = 3 and 4) aged <60 (48 ± 7) years. qMRI revealed an 25% increase in cartilage thickness and a significant reduction in denuded bone areas 1 year later, accompanied by an increase in weight-bearing radiographic JSW. This study thus Provides an important “proof-of-concept” that reversal of cartilage loss is attainable. The patients treated by distraction also generally improved clinically, with the WOMAC increasing from 45 to 77 points, and the VAS decreasing from 73 to 31 mm over 1 year.”

  1. The effect of patient age at intervention on risk of implant revision after total replacement of the hip or knee: a population-based cohort study.

Bayliss LE, Culliford D, Monk AP, Glyn-Jones S, Prieto-Alhambra D, Judge A, Cooper C, Carr AJ, Arden NK, Beard DJ, Price AJ.

Lancet. 2017 Apr 8;389(10077):1424-1430.7. Review.

BACKGROUND: Total joint replacements for end-stage osteoarthritis of the hip and knee are cost-effective and demonstrate significant clinical improvement. However, robust population based lifetime-risk data for implant revision are not available to aid patient decision making, which is a particular problem in young patient groups deciding on best-timing for surgery.

METHODS: We did implant survival analysis on all patients within the Clinical Practice Research Datalink who had undergone total hip replacement or total knee replacement. These data were adjusted for all-cause mortality with data from the Office for National Statistics and used to generate lifetime risks of revision surgery based on increasing age at the time of primary surgery.

FINDINGS: We identified 63 158 patients who had undergone total hip replacement and 54 276 who had total knee replacement between Jan 1, 1991, and Aug 10, 2011, and followed up these patients to a maximum of 20 years. For total hip replacement, 10-year implant survival rate was 95·6% (95% CI 95·3-95·9) and 20-year rate was 85·0% (83·2-86·6). For total knee replacement, 10-year implant survival rate was 96·1% (95·8-96·4), and 20-year implant survival rate was 89·7% (87·5-91·5). The lifetime risk of requiring revision surgery in patients who had total hip replacement or total knee replacement over the age of 70 years was about 5% with no difference between sexes. For those who had surgery younger than 70 years, however, the lifetime risk of revision increased for younger patients, up to 35% (95% CI 30·9-39·1) for men in their early 50s, with large differences seen between male and female patients (15% lower for women in same age group). The median time to revision for patients who had surgery younger than age 60 was 4·4 years.

INTERPRETATION: Our study used novel methodology to investigate and offer new insight into the importance of young age and risk of revision after total hip or knee replacement. Our evidence challenges the increasing trend for more total hip replacements and total knee replacements to be done in the younger patient group, and these data should be offered to patients as part of the shared decision making process.