Injectable collagenase is an alternative to surgical treatment for Dupuytren’s disease. Previous studies have reported on the effectiveness of collagenase in finger contractures. This prospective study reports on the short-term safety and efficacy of collagenase treatment in five thumb and first web space Dupuytren’s contractures. The thumb and first web space contractures were treated with injectable collagenase in four consecutive patients (five hands) with experience of previous surgical digital fasciectomy. The thumb contracture was measured by angle and span in two planes of thumb extension and abduction before injection and after manipulation. Collagenase treatment resulted in release of the contracture with a mean increase in thumb to index angle from 23° (10° to 35°) to 56° (45° to 60°) in extension and from 30° (10° to 50°) to 58° (50° to 65°) in abduction and a mean increase in span from 1.9 cm (1 to 3.5) to 3.9 cm (3 to 5) in extension and from 2.4 cm (1.5 to 3.5) to 3.9 cm (3 to 4.5) in abduction. All patients reported an increased range of movement and function and described collagenase therapy as preferable to surgery. In the short-term collagenase is an effective, well-tolerated and safe alternative to surgery for Dupuytren’s disease of the thumb

Aims. The aim of this meta-analysis was to assess the safety and efficacy of collagenase clostridium histolyticum compared with fasciectomy and percutaneous needle fasciotomy (PNF) for Dupuytren’s disease. Materials and Methods. We systematically searched PubMed, EMBASE, LILACS, Web of Science, Cochrane, Teseo and the ClinicalTrials.gov registry for clinical trials and cohort or case-control studies which compared the clinical outcomes and adverse effects of collagenase with those of fasciectomy or PNF. Of 1345 articles retrieved, ten were selected. They described the outcomes of 425 patients treated with collagenase and 418 treated by fasciectomy or PNF. Complications were assessed using inverse-variance weighted odds ratios (ORs). Clinical efficacy was assessed by differences between the means for movement of the joint before and after treatment. Dose adjustment was applied in all cases. Results. Random-effects modelling showed that patients treated with collagenase had 3.24 increased odds of adverse effects compared with those treated by fasciectomy (OR 4.39) or PNF (OR 1.72,). The effect was lost when only major complications were assessed. Joint movement analysis revealed a difference between means of less than 10%, indicating equivalent clinical efficacy in the short and medium term for collagenase and fasciectomy. We were unable to analyse this for PNF due to a shortage of data. Conclusion. There were no significant differences in effect size between collagenase and fasciectomy. The use of collagenase was associated with a higher overall risk of adverse effects than both fasciectomy and PNF. Cite this article: Bone Joint J 2018;100-B:73–80

Bone samples from the iliac crest of patients with no signs of bone disorder were treated with collagenase to remove the collagen component and so allow detailed observation of the mineral hydroxyapatite. Both polished and unpolished surfaces were studied in the scanning electron microscope and they showed that the mineral component of bone is composed of small rounded units about 10 nm across which are fused together to form larger spheroidal units roughly 100 nm in diameter. In the unpolished surfaces these 100 nm units are seen to aggregate to form columns approximately parallel to their neighbours and with numerous interconnections forming a continuous mineral phase. The polished sections also show the hydroxyapatite as a continuous phase of contiguous spheroids and the holes from which the collagen fibres were removed are clearly revealed. Lamellations in the surface are interpreted as resulting from adjacent layers of collagen fibres having orientations approximately perpendicular to each other

Objectives

Injectable Bromelain Solution (IBS) is a modified investigational derivate of the medical grade bromelain-debriding pharmaceutical agent (NexoBrid) studied and approved for a rapid (four-hour single application), eschar-specific, deep burn debridement. We conducted an ex vivo study to determine the ability of IBS to dissolve-disrupt (enzymatic fasciotomy) Dupuytren’s cords.

The August 2024 Wrist & Hand Roundup. 360. looks at: Methotrexate shows potential in reducing pain for hand osteoarthritis with synovitis; Circumferential casting versus plaster splinting in adult distal radius fractures: the CAST study findings; Surgery shows superior long-term success for Dupuytren contracture compared to needle fasciotomy and collagenase injection; Evolving trends in surgical management of wrist arthritis: a decade-long national analysis; Mid-term outcomes of three commonly used surgical reconstructions for scapholunate instability; SLAC and SNAC: what is the evidence for treatment?; Steroids for trapeziometacarpal osteoarthritis?; When is it safe to return to driving after distal radius fracture fixation? A prospective study

The February 2024 Foot & Ankle Roundup. 360. looks at: Survival of revision ankle arthroplasty; Tibiotalocalcaneal nail for the management of open ankle fractures in the elderly patient; Accuracy of a patient-specific total ankle arthroplasty instrumentation; Fusion after failed primary ankle arthroplasty: can it work?; Treatment options for osteochondral lesions of the talus; Managing hair tourniquet syndrome of toe: a rare emergency; Ultrasound-guided collagenase therapy for recurrent plantar fibromatosis: a promising line of therapy?

Aims. Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application. Methods. In the present study, we investigated the characterizations of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in hypoxic (1%) and normoxic (21%) atmospheres with a long-term culture from primary to 30 generations, respectively. The comparison between both atmospheres systematically analyzed the biological functions of MSCs, mainly including stemness maintenance, immune regulation, and resistance to chondrocyte apoptosis, and studied their joint function and anti-inflammatory effects in osteoarthritis (OA) rats constructed by collagenase II. Results. We observed that long-term hypoxic culture surpassed normoxic atmosphere during hUC-MSCs culture in respect of promoting proliferation, anti-tumorigenicity, maintaining normal karyotype and stemness, inhibiting senescence, and improving immunoregulatory function and the role of anti-apoptosis in chondrocytes. Furthermore, we demonstrated that the transplantation of long-term hypoxic hUC-MSCs (Hy-MSCs) had a better therapeutic effect on OA rats compared with the hUC-MSCs cultured in the normoxic atmosphere (No-MSCs) in terms of the improved function and swelling recovery in the joints, and substantially inhibited the secretion of pro-inflammatory factors, which effectively alleviated cartilage damage by reducing the expression of matrix metallopeptidase 13 (MMP-13). Conclusion. Our results demonstrate that Hy-MSCs possess immense potential for clinical applications via promoting stemness maintenance and enhancing immunoregulatory function. Cite this article: Bone Joint Res 2024;13(12):763–777

In Canada, Dupuytren's contracture is managed with partial fasciectomy or percutaneous needle aponeurotomy (PNA). Injectable collagenase will soon be available. The optimal management of Dupuytren’s contracture is controversial and trade-offs exist between the different methods. Using a cost-utility analysis approach, our aim was to identify the most cost-effective form of treatment for managing Dupuytren’s contracture it and the threshold at which collagenase is cost-effective. We developed an expected-value decision analysis model for Dupuytren’s contracture affecting a single finger, comparing the cost-effectiveness of fasciectomy, aponeurotomy and collagenase from a societal perspective. Cost-effectiveness, one-way sensitivity and variability analyses were performed using standard thresholds for cost effective treatment ($50 000 to $100 000/QALY gained). Percutaneous needle aponeurotomy was the preferred strategy for managing contractures affecting a single finger. The cost-effectiveness of primary aponeurotomy improved when repeated to treat recurrence. Fasciectomy was not cost-effective. Collagenase was cost-effective relative to and preferred over aponeurotomy at $875 and $470 per course of treatment, respectively. . In summary, our model supports the trend towards non-surgical interventions for managing Dupuytren’s contracture affecting a single finger. Injectable collagenase will only be feasible in our publicly funded healthcare system if it costs significantly less than current United States pricing. Cite this article: Bone Joint J 2013;95-B:1094–1100

Objectives. Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1’s effects on experimental OA. Methods. Collagenase (type II) was injected twice into both knees of three-month-old rabbits to induce OA, combined with two intra–articular injections of Torin 1 (400 nM). Degeneration of articular cartilage was evaluated by histology using the Mankin scoring system at eight weeks after injection. Chondrocyte degeneration and autophagosomes were observed by transmission electron microscopy. Matrix metallopeptidase-13 (MMP-13) and vascular endothelial growth factor (VEGF) expression were analysed by quantitative RT-PCR (qPCR).Beclin-1 and light chain 3 (LC3) expression were examined by Western blotting. Results. Intra-articular injection of Torin 1 significantly reduced degeneration of the articular cartilage after induction of OA. Autophagosomes andBeclin-1 and LC3 expression were increased in the chondrocytes from Torin 1-treated rabbits. Torin 1 treatment also reduced MMP-13 and VEGF expression at eight weeks after collagenase injection. Conclusion. Our results demonstrate that intra-articular injection of Torin 1 reduces degeneration of articular cartilage in collagenase-induced OA, at least partially by autophagy activation, suggesting a novel therapeutic approach for preventing cartilage degeneration and treating OA. Cite this article: N-T. Cheng, A. Guo, Y-P. Cui. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model. Bone Joint Res 2016;5:218–224. DOI: 10.1302/2046-3758.56.BJR-2015-0001

Aims. In the context of tendon degenerative disorders, the need for innovative conservative treatments that can improve the intrinsic healing potential of tendon tissue is progressively increasing. In this study, the role of pulsed electromagnetic fields (PEMFs) in improving the tendon healing process was evaluated in a rat model of collagenase-induced Achilles tendinopathy. Methods. A total of 68 Sprague Dawley rats received a single injection of type I collagenase in Achilles tendons to induce the tendinopathy and then were daily exposed to PEMFs (1.5 mT and 75 Hz) for up to 14 days - starting 1, 7, or 15 days after the injection - to identify the best treatment option with respect to the phase of the disease. Then, 7 and 14 days of PEMF exposure were compared to identify the most effective protocol. Results. The daily exposure to PEMFs generally provided an improvement in the fibre organization, a decrease in cell density, vascularity, and fat deposition, and a restoration of the physiological cell morphology compared to untreated tendons. These improvements were more evident when the tendons were exposed to PEMFs during the mid-acute phase of the pathology (7 days after induction) rather than during the early (1 day after induction) or the late acute phase (15 days after induction). Moreover, the exposure to PEMFs for 14 days during the mid-acute phase was more effective than for 7 days. Conclusion. PEMFs exerted a positive role in the tendon healing process, thus representing a promising conservative treatment for tendinopathy, although further investigations regarding the clinical evaluation are needed. Cite this article: Bone Joint Res 2020;9(9):613–622

The June 2015 Wrist & Hand Roundup360 looks at: Collagenase and Dupuytren’s disease – a genuine alternative to surgery?; iPad PROMise?; Should we learn how to do endoscopic carpal tunnel release?; Two-week radiographs a relic of the past?; Bible? Aspirate or excise?; Patient expectations and trapeziometacarpal osteoarthritis; Splintage in the treatment of sagittal band incompetence and extensor tendon subluxation

The February 2014 Wrist & Hand Roundup. 360 . looks at: simple debridement and ulnar-sided wrist pain; needle fasciotomy or collagenase injection; joint replacement in osteoarthritic knuckles; the Mannerfelt arthrodesis; scaphoid union rates with conservative treatment; the benefits of atorvastatin for muscle re-innervation after sciatic nerve transection; and complications of trapeziectomy

The scarcity of mesenchymal stem cells (MSCs) in iliac crest bone marrow aspirate (ICBMA), and the expense and time in culturing cells, has led to the search for alternative harvest sites. The reamer-irrigation-aspirator (RIA) provides continuous irrigation and suction during reaming of long bones. The aspirated contents pass via a filter, trapping bony fragments, before moving into a ‘waste’ bag from which MSCs have been previously isolated. We examined the liquid and solid phases, performed a novel digestion of the solid phase, and made a comparative assessment in terms of number, phenotype and differentiation capacity with matched ICBMA. The solid fraction from the filtrate was digested for 60 minutes at 37°C with collagenase. Enumeration was performed via the colony-forming unit fibroblast (CFU-F) assay. Passage (P2) cells were differentiated towards osteogenic, adipogenic and chondrogenic lineages, and their phenotypes assessed using flow cytometry (CD33, CD34, CD45, CD73, CD90, and CD105). MSCs from the RIA phases were able to differentiate at least as well as those from ICBMA, and all fractions had phenotypes consistent with other established sources. The median number of colonies for the three groups was: ICBMA = 8.5 (2 to 86), RIA-liquid = 19.5 (4 to 90), RIA-solid = 109 (67 to 200) per 200 μl. The mean total yield of cells for the three groups was: ICBMA = 920 (0 to 4275), RIA-liquid = 114 983 (16 500 to 477 750), RIA-solid = 12 785 (7210 to 28 475). The RIA filtrate contains large numbers of MSCs that could potentially be extracted without enzymatic digestion and used for bone repair without prior cell expansion

The long flexor tendons of the second, third and fourth toes of 94 chickens were cut and sutured. After operation the birds were divided into three groups. To reduce peritendinous adhesions, an aqueous solution of beta-aminopropionitrile (BAPN) was added to a solution of enriched native collagen (ECS) and applied to the cut tendons of one group; untreated controls and controls treated with collagen solution alone comprised the other groups. Chickens from each group were killed one, two, three, four and five weeks after operation. The results were evaluated both biomechanically and biochemically. It was found that the collagen solution alone had the same effect as the treatment with BAPN. It is suggested that the exogenous collagen present at the site of injury binds the collagenase inhibitor released by tendon cells, thus providing enough active collagenase to control the formation of fibrous adhesions. The inefficiency of BAPN in these experiments might have been due to either inadequate dosage or wrong timing, or both

Aims

This study aimed to investigate the role and mechanism of meniscal cell lysate (MCL) in fibroblast-like synoviocytes (FLSs) and osteoarthritis (OA).

Aims

CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration.

Aims

Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration.

Aims

Osteoarthritis (OA) is a common degenerative disease. PA28γ is a member of the 11S proteasome activator and is involved in the regulation of several important cellular processes, including cell proliferation, apoptosis, and inflammation. This study aimed to explore the role of PA28γ in the occurrence and development of OA and its potential mechanism.

Aims

Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells.

Aims

This study aimed to determine the expression and clinical significance of a cartilage protein, cartilage oligomeric matrix protein (COMP), in knee osteoarthritis (OA) patients.