Effect of recombinant human parathyroid hormone (1-84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial.

BACKGROUND: Recombinant human parathyroid hormone (1-84) (PTH) increases bone mass and strength and improves bone quality by stimulating new bone formation. OBJECTIVE: To determine the safety of PTH and its effect on the incidence of vertebral fractures in postmenopausal women with osteoporosis. DESIGN: 18-month, randomized, double-blind, placebo-controlled, parallel-group study. SETTING: 168 centers in 9 countries. PATIENTS: 2532 postmenopausal women with low bone mineral density at the hip or lumbar spine. INTERVENTIONS: Women received 100 mug of recombinant human PTH or placebo daily by subcutaneous injection. All received calcium, 700 mg/d, and vitamin D3, 400 U/d. MEASUREMENTS: New or worsened vertebral fractures (primary outcome) and changes in bone mineral density and safety (secondary outcomes). RESULTS: 67.2% of patients who received at least 1 dose of the study drug completed the study. Parathyroid hormone reduced the risk for new or worsened vertebral fractures, but in sensitivity analyses, the magnitude of the reduction was changed with assumptions about fracture incidence in patients who did not complete the study (relative risk assuming no fractures, 0.42 [95% CI, 0.24 to 0.72] [P = 0.001]; relative risk assuming fracture incidence observed in all patients who completed the trial, 0.60 [CI, 0.36 to 1.00] [P = 0.05]; relative risk assuming fracture incidence observed in the placebo group, 0.62 [CI, 0.37 to 1.04] [P = 0.07]). Compared with placebo, mean bone mineral density increased at the spine by 6.9% (CI, 6.4% to 7.4%) and at the hip by 2.1% (CI, 1.7% to 2.5%) but decreased at the forearm in the PTH-treated group. Parathyroid hormone treatment increased the percentage of participants with hypercalciuria, hypercalcemia, and nausea by 24% (CI, 20% to 27%), 23% (CI, 21% to 26%), and 14% (CI, 11% to 16%), respectively, compared with placebo. LIMITATIONS: Baseline serum PTH and vitamin D levels were not measured. Many patients discontinued the trial prematurely. CONCLUSIONS: Parathyroid hormone (1-84) reduced the overall risk for new or worsened vertebral fracture in postmenopausal women with osteoporosis. Hypercalciuria, hypercalcemia, and nausea were more common in women who took the drug. Although the magnitude of the reduction was sensitive to assumptions about fracture incidence in patients who did not complete the study, the findings suggest that PTH provides an alternative therapeutic option for fracture prevention.

Alcohol-containing mouthwash and oropharyngeal cancer: a review of the epidemiology.

BACKGROUND: There has been concern that the use of alcohol-containing mouthwash may increase the risk of developing oropharyngeal cancer, or OPC. The authors examine the epidemiologic literature relating to this issue. TYPES OF STUDIES REVIEWED: The authors identified all nine English-language epidemiologic studies of OPC that made reference to mouthwash. The findings and major strengths and limitations of each study are described. In addition, the authors reanalyzed data from one of the studies. RESULTS: The results of six of the studies reviewed are negative and provide no support for the hypothesis that use of alcohol-containing mouthwash increases the risk of OPC. One of the three studies with positive results was a case series and included a follow-up case-control study, the results of which were negative. The authors reanalyzed the study with the most positive results. This analysis found that the study results were just as positive for nonmucosal cancers developing in the mouth as they were for the usual type of OPC. The authors concluded that this study's positive finding resulted from recall bias. CLINICAL IMPLICATIONS: It is unlikely that the use of mouthwashes that contain alcohol increases the risk of developing OPC.