Continuous treatment with odanacatib for up to 8 years in postmenopausal women with low bone mineral density: a phase 2 study.

UNLABELLED: The efficacy and safety of weekly oral odanacatib (ODN) 50 mg for up to 8 years were assessed in postmenopausal women with low bone mineral density (BMD). Treatment with ODN for up to 8 years resulted in continued or maintained increases in BMD at multiple sites and was well tolerated. INTRODUCTION: ODN is a selective inhibitor of cathepsin K. In a 2-year phase 2b study (3/10/25/50 mg ODN once weekly [QW] or placebo) and extensions (50 mg ODN QW or placebo), ODN treatment for 5 years progressively increased BMD and decreased bone resorption markers in postmenopausal women with low BMD ( ClinicalTrials.gov NCT00112437). METHODS: In this prespecified interim analysis at year 8 of an additional 5-year extension (years 6 to 10), patients (n = 117) received open-label ODN 50 mg QW plus weekly vitamin D3 (5600 IU) and calcium supplementation as needed. Primary end points were lumbar spine BMD and safety. Patients were grouped by ODN exposure duration. RESULTS: Mean (95 % confidence interval [CI]) lumbar spine BMD changes from baseline were 4.6 % (2.4, 6.7; 3-year continuous ODN exposure), 12.9 % (8.1, 17.7; 5 years), 12.8 % (10.0, 15.7; 6 years), and 14.8 % (11.0, 18.6; 8 years). Similar patterns of results were observed for BMD of trochanter, femoral neck, and total hip versus baseline. Geometric mean changes from baseline to year 8 for bone resorption markers were approximately -50 % (uNTx/Cr) and -45 % (sCTx), respectively (all groups); bone formation markers remained near baseline levels. No osteonecrosis of the jaw, delayed fracture union, or morphea-like skin reactions were reported. CONCLUSIONS: Treatment with ODN for up to 8 years resulted in gains in BMD at multiple sites. Bone resorption markers remained reduced, with no significant change observed in bone formation markers. Treatment with ODN for up to 8 years was well tolerated.

Independent origin of mono-rifampin-resistant Mycobacterium tuberculosis in patients with AIDS.

Historically, infections caused by Mycobacterium tuberculosis have been treated simultaneously with isoniazid and rifampin. As a consequence of this combined therapy, strains resistant only to rifampin were rarely recovered. However, recently there has been an increasing number of reports describing HIV-positive patients infected with mono-rifampin-resistant M. tuberculosis strains. Organisms cultured from seven patients (including six with AIDS) with infections caused by mono-rifampin-resistant M. tuberculosis, and seen at one New York City hospital, were analyzed by molecular techniques to test the hypothesis that dissemination of a single clone had occurred. IS6110 DNA fingerprinting and automated DNA sequencing of a region of the RNA polymerase beta subunit structural gene (rpoB) containing mutations that confer rifampin resistance showed that all organisms independently acquired the mono-rifampin-resistant phenotype. Molecular analysis of mono-rifampin-resistant organisms cultured from 13 additional patients in New York City confirmed independent strain origin. The data rule out the possibility of person-to-person strain transmission among these patients, and they suggest that host factors such as poor compliance with antituberculosis medications or decreased absorption of rifampin have been a driving force in the origin of these strains.