Gene therapy for the treatment of hip prosthesis loosening: adverse events in a phase 1 clinical study.

Revision surgery for loosened hip prostheses is a heavy burden for elderly patients with comorbidity. As an alternative to surgery we performed a study to stabilize the prosthesis by percutaneous cement injection after removing inflammatory tissue with an intraarticular virus-directed enzyme prodrug approach. Twelve elderly patients with debilitating pain from a loosened hip prosthesis were included in a phase 1 dose-escalating clinical study. The patients were admitted to the hospital for 10 days for an intraarticular vector and prodrug injection, and subsequently for a percutaneous bone cement injection. This paper reports the adverse and serious adverse events of the study. After prodrug injection 9 of 12 patients had gastrointestinal adverse events (nausea, vomiting, and diarrhea), and 8 patients had hepatic adverse events (rise in aspartate aminotransferase and alanine aminotransferase). Five patients developed anemia (World Health Organization grade 1 or 2) from hematomas after cement injection. There were four serious adverse events in the first 6 months after vector injection, but these were not related to gene therapy as judged by an independent safety committee. There was no dose-limiting toxicity. However, the extensive comorbidity in these patients makes it difficult to fully establish the safety of the approach in this small and heterogeneous patient population.

Arthrography in loosened hip prostheses. Assessment of possibilities for intra-articular therapy.

BACKGROUND: Loosening is a major complication in prosthesis surgery. Less invasive alternatives to revision surgery are required to prevent and treat prosthesis loosening. Some experimental therapies investigating alternative treatments exploit the intra-articular space as a route of administration. For efficient, local delivery of therapeutic agents a contained joint space is required. Furthermore, the volume of the joint space determines the concentration of the therapeutic ingredient in the joint. METHODS: A retrospective analysis of 221 hip arthrograms performed between 1994 and 2004 for diagnosis of prosthesis loosening was performed. All arthrograms were studied for leakage of contrast medium and the volume of injected contrast medium. RESULTS: There was a contained joint in 164 arthrograms (74%). The volume in these hips was 31+/-12.7 ml. Male patients had a larger joint volume than female patients (P=0.019). There was no difference in containment and joint volume between hips with a primary and with a revised prosthesis. CONCLUSIONS: For successful intra-articular therapy it is necessary that the injected agent remains in the jointspace. As leakage of contrast medium was shown in about a quarter of hips, this study shows that an arthrogram may be useful in the inclusion procedure for intra-articular studies to determine containment of the joint and also the volume that can be injected.

Nontraumatic multidirectional instability of the scaphotrapeziotrapezoid joint: a cause of scaphotrapeziotrapezoid osteoarthritis and static distal intercalated segment instability.

We report a case of bilateral multidirectional instability of the scaphotrapeziotrapezoid joint associated with osteoarthritis of the same joint and static dorsal intercalated segment instability. Because there is no previous trauma it is likely that this is a case of nontraumatic instability at the scaphotrapeziotrapezoid joint causing a dorsal intercalated segment instability deformity of carpal malalignment and secondary scaphotrapeziotrapezoid osteoarthritis.