Collagenase Clostridium histolyticum for the Treatment of Distal Interphalangeal Joint Contractures in Dupuytren Disease.

PURPOSE: To explore the efficacy of injectable collagenase Clostridium histolyticum (CCH) in distal interphalangeal (DIP) joint contractures in Dupuytren disease. METHODS: A retrospective review was conducted for patients with DIP joint contractures treated with CCH. Baseline contracture and posttreatment residual contracture were recorded. The primary end point was achievement of 0° to 5° of residual contracture 30 days postmanipulation. Recurrence and adverse events are also reported. RESULTS: Twenty-one patients were treated with collagenase for DIP joint contractures and had a mean follow-up of 2.6 months. Seventeen of 21 patients reached the primary end point of less than 5° residual flexion contracture. Eleven of 21 patients experienced an adverse event, most commonly bruising and edema. No serious complications such as neurovascular injuries or tendon ruptures were recorded. Two patients had recurrence of disease. CONCLUSIONS: Injection with CCH is an option for the treatment of DIP joint contractures in Dupuytren disease. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Methylphenidate regulation of osteoclasts in a dose- and sex-dependent manner adversely affects skeletal mechanical integrity.

Methylphenidate (MP) is the most prescribed psychostimulant for ADHD patients, with clinically demonstrated detrimental effects on bone quality, potentially leading to early onset osteoporosis and higher fracture risk. The underlying mechanism for the effects of MP on bone remains elusive. This study demonstrates that sex- and dose-dependent effects of MP on bone quality and quantity are mediated by osteoclast activity. Four-week-old male and female rats were treated with low and high dose MP for 13 weeks. Bone quality and quantity were analyzed using microCT, mechanical testing, histomorphometry, and TRAP staining. Male and female rat bone marrow-derived osteoclasts were treated in a dose-dependent manner (0-1000 ng/ml) and osteoclast activity was determined at days 5, 7, and 14 using TRAP staining, as well as a pit formation assay at day 18. Animal studies showed a dose- and a sex-dependent decrease in mechanical integrity in femora and increased TRAP staining in MP-treated rats. Primary cultures revealed that MP had direct dose- and sex-dependent effects on osteoclast activity, as seen by increased differentiation, activity, and resorption. This study demonstrates for the first time that osteoclasts are differentially regulated by MP in adolescent male and female rats, resulting in sex-dependent effects on the skeleton.