Adherence, preference, and satisfaction of postmenopausal women taking denosumab or alendronate.

UNLABELLED: In this study, 250 women with osteoporosis were randomized to 12 months with subcutaneous denosumab 60 mg every 6 months or oral alendronate 70 mg once weekly, then crossed over to the other treatment. The primary endpoint, treatment adherence at 12 months, was 76.6% for alendronate and 87.3% for denosumab. INTRODUCTION: The purpose of this study is to evaluate treatment adherence with subcutaneous denosumab 60 mg every 6 months or oral alendronate 70 mg once weekly. METHODS: In this multicenter, randomized, open-label, 2-year, crossover study, 250 postmenopausal women with low bone mineral density received denosumab or alendronate for 12 months, then the other treatment for 12 months. The alendronate bottle had a medication event monitoring system cap to monitor administration dates. Definitions were as follows: compliance, receiving both denosumab doses 6 (± 1) months apart or 80-100% of alendronate doses; persistence, receiving both denosumab doses and completing the month 12 visit within the visit window or ≥ 2 alendronate doses in the final month; adherence, achieving both compliance and persistence. This report includes data from the first 12 months. RESULTS: The primary study endpoint, adherence in the first 12 months, was 76.6% (95/124) for alendronate and 87.3% (110/126) for denosumab. Risk ratios for denosumab compared with alendronate at 12 months were 0.58 (p = 0.043) for non-adherence, 0.48 (p = 0.014) for non-compliance, and 0.54 (p = 0.049) for non-persistence. Subject ratings for treatment necessity, preference, and satisfaction were significantly greater for denosumab and ratings for treatment bother were significantly greater for alendronate. Adverse events were reported by 64.1% of alendronate-treated subjects and 72.0% of denosumab-treated subjects (p = 0.403). The most common adverse events were arthralgia, back pain, pain in extremity, cough, and headache (each in <10% of subjects in each group). CONCLUSIONS: Significantly greater treatment adherence was observed for subcutaneous administration of denosumab every 6 months than for oral alendronate once weekly.

Effect of combined risedronate and hormone replacement therapies on bone mineral density in postmenopausal women.

Both hormone replacement therapy (HRT) and bisphosphonates are efficacious in the prevention and treatment of postmenopausal osteoporosis. Combined therapy with bisphosphonate and HRT is likely to be used in clinical practice, and limited data are available regarding its efficacy and safety. This was a 1-yr, double blind, placebo-controlled study in which 524 postmenopausal women received daily treatment with conjugated equine estrogens (0.625 mg) alone or in combination with risedronate (5 mg). Women who had not undergone hysterectomy received medroxyprogesterone acetate (up to 5 mg, daily or cyclically) at the discretion of the investigator. The primary efficacy end point was the percent change from baseline in mean lumbar spine bone mineral density (BMD) at 1 yr. Changes in BMD at the proximal femur and forearm, bone turnover markers, and histology and histomorphometry were also assessed. At 12 months, significant (P < 0.05) increases from baseline in lumbar spine BMD were observed in both treatment groups (HRT-only, 4.6%; combined risedronate-HRT, 5.2%); the difference between the two groups was not statistically significant. Both therapies led to significant increases in BMD at 12 months at the femoral neck (1.8% and 2.7%, respectively), femoral trochanter (3.2% and 3.7%), distal radius (1.7% and 1.6%), and midshaft radius (0.4% and 0.7%). The differences between groups were statistically significant (P < 0.05) at the femoral neck and midshaft radius. Both combined risedronate-HRT and HRT-only produced significant decreases in the biochemical markers of bone turnover, with somewhat greater decreases in the combined treatment group. Bone biopsy data showed normal bone structure and normal mineralization with either treatment. Expected decreases in bone turnover were observed and were greater in the combined treatment group (68-79% reduction relative to baseline values, P < 0.005). Overall, combined treatment had a safety profile similar to that of HRT-only, including bone and gastrointestinal safety profiles. In conclusion, the combined treatment with risedronate and HRT had a favorable effect on BMD similar to that of HRT alone at the lumbar spine and slightly, but significantly, greater than that of HRT alone at the femoral neck and midshaft radius. The combined treatment was well tolerated, and there were no adverse effects on the skeleton.