Dupuytren’s disease and frozen shoulder induced by treatment with a matrix metalloproteinase inhibitor

Hutchinson, J. W.; Tierney, Gillian; Parsons, S. L.; Davis, T. R. C.

doi:10.1302/0301-620x.80b5.0800907

Cited by 97 publications

(34 citation statements)

References 11 publications

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“…The active fibroblastic process that occurs in adhesive capsulitis is similar to that which occurs in Dupuytren disease of the hand. 19 Interestingly, patients treated with a synthetic matrix metalloproteinase inhibitor for gastric carcinoma had high rates of frozen shoulder and Dupuytren disease, 51 suggesting that abnormal expression of matrix metalloproteinase inhibitors is involved in the pathogenesis of the disease. 21 The biochemical rationale for the high incidence of frozen shoulder in patients with diabetes is speculative.…”

Section: Anatomy and Pathogenesismentioning

confidence: 99%

Current review of adhesive capsulitis

Hsu

Anakwenze

Warrender

et al. 2011

Journal of Shoulder and Elbow Surgery

320

269

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Section: Anatomy and Pathogenesismentioning

confidence: 99%

Current review of adhesive capsulitis

Hsu

Anakwenze

Warrender

et al. 2011

Journal of Shoulder and Elbow Surgery

320

269

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“…The exact sequence of events may depend on the drug used and the dosing regimen. The plasma drug concentrations necessary to produce efficacy for batimastat, marimastat, CGS-27023A and prinomastat also produced MSS [25,26]. Clinical studies in which MMPi treatment was not efficacious may have resulted because the therapeutic index was not clearly defined, and too low a dose was employed so as to avoid MSS.…”

Section: The Musculoskeletal Syndromementioning

confidence: 99%

The importance of estimating the therapeutic index in the development of matrix metalloproteinase inhibitors

Peterson

2006

Cardiovascular Research

181

166

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At least 56 matrix metalloproteinase (MMP) inhibitors have been pursued as clinical candidates since the late 1970's when the first drug discovery program targeting this enzyme family began. Some of these clinical candidates were pursued for multiple indications. However, the two primary indications that have been targeted are cancer (24 drugs) and anti-arthritis (27 drugs). Cardiovascular disease was listed as an indication for 10 drugs. Forty-six MMP inhibitors have been discontinued, 7 remain in clinical development, and only 1 (Periostat for periodontal disease) has been approved. Recently, negative phase II results were reported for the MMP inhibitor PG-116800, which was being evaluated as a treatment for post-ischemic myocardial remodeling to prevent heart failure. One major factor leading to the failure of PG-116800 and many of the other MMP inhibitors is the inadequate assessment of the therapeutic index, the ratio of dose required for efficacy vs. that for toxicology. This review describes the dose-limiting side effect that has hampered MMP inhibitor development (the musculoskeletal syndrome), cardiovascular clinical MMP inhibitor studies, a model of the therapeutic index using marimastat, and progress towards more selective MMP inhibitors not limited by the musculoskeletal syndrome.

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“…The observation that use of broad-spectrum matrix metalloproteinase (MMP) inhibitors in clinical trials aimed at reducing local invasion and distant metastasis in certain malignancies was associated with a (fibrotic) musculoskeletal syndrome 6 resembling DD and frozen shoulder 7 kindled the concept that altered activity of MMPs might be important in the pathogenesis of DD. We have previously reported a case-control series detailing the extent of the alteration in gene expression of MMPs, ADAMTSs, and TIMPs in DD.…”

mentioning

confidence: 99%