Program Book and Abstracts - ISCD

175 — AN OBSERVATIONAL COHORT STUDY OF RISEDRONATE AND
ALENDRONATE WITH THE ADDITION OF IBANDRONATE:
EFFECTIVENESS OF BISPHOSPHONATE TREATMENT ON
NONVERTEBRAL FRACTURES
Deborah T. Gold, PhD, Duke University Medical Center, Duke Universtiy, D, Jeff Lange,
Procter & Gamble Pharmceuticals, Mason, OH, Johann D. Ringe, Medical Dept. IV,
Hospital Leverkusen, University of Cologne, Leverkusen, Germany, Abby G. Ableson,
Cleveland Clinic, Cleveland, OH
In a prior observational study of 33,830 women aged 65+ who initiated weekly
bisphosphonate dosing, patients on risedronate had a lower incidence of nonvertebral
fracture during the first year of therapy than patients on alendronate(REAL)1.
Monthly dosing of bisphosphonate became available in 2005. In this study we
compared nonvertebral fracture incidence during the first year of therapy among
patients on monthly ibandronate to patients in the REAL study. The study population
of REAL was identified from health services utilization records between 2002-2004
and included new users of risedronate or alendronate. The current study includes new
users of ibandronate from the same data source. Cox proportional modeling was used
to compare fracture incidence among the 3 patient groups, adjusting for baseline
fracture risk. All 3 patient groups, mean age 75, had similar prevalent fracture status. In
REAL, the nonvertebral fracture incidence in year one of therapy was 1.99% for
risedronate patients and 2.30% for alendronate patients. In comparison, nonvertebral
fracture incidence was 2.79% for ibandronate patients. Relative to ibandronate, the
adjusted relative rate of nonvertebral fracture for risedronate patients was 0.76
(95%CI 0.60-0.96) and for alendronate patients was 0.92 (95%CI 0.74-1.13). These
results do not appear to be explained by baseline differences in fracture risk between
cohorts. As with all cohort studies, interpretation of results is limited by the
nonrandomized study design. In this study, patients on risedronate had a lower
incidence of nonvertebral fractures during their first year of therapy than patients on
ibandronate. 1Silverman OI 2007 18:25
176 — BISPHOSPHONATE THERAPY AND HIP FRACTURES WITHIN THE
RISEDRONATE AND ALENDRONATE (REAL) COHORT STUDY: SUBGROUP
WITH PRIOR FRACTURE
Robert Lindsay, MD, PhD, Helen Hayes Hospital, West Haverstraw, NY, Stuart L.
Silverman, Cedars-Sinai Medical Center, Beverly Hills, CA, Nelson B. Watts, Bone Health
and Osteoporosis Center, Cincinnati, OH, Pierre D Delmas, INSERM Unit 403, Lyon,
France, Jeff L. Lange
In a prior obserservational study of 33,830 women (ages 65 and over) initiating oncea-week
dosing of bisphosphonate, the incidence of hip fracture during the first year of
therapy for patients on risedronate (0.37%) was lower (adjusted rate ratio = 0.57)
than patients on alendronate (0.58%).1 To further assess the homogeneity of this
observation across patients at different levels of fracture risk, we utilized a subgroup
within this study who had a diagnosed fracture in the one year prior to initiating
bisphosphonate therapy. The original study population was identified within records of
health services utilization and included new users of once-a-week dosing of risedronate
or alendronate. In the one year prior to initiating therapy for this population, 6.0%
had a diagnosed nonvertebral fracture, 3.1% had a diagnosed vertebral fracture, and
8.4% (n = 2845) had either fracture - which defined the subgroup for analyses. Cox
proportional hazard modeling was used to compare the incidence of hip fractures
during the first year of therapy. Compared to the original study population, the
subgroup with a fracture prior to initiating therapy was older and had more risk
factors for fracture (table). Within this subgroup, during the first year of therapy, the
incidence of hip fracture for patients on risedronate (0.73%) was lower (adjusted rate
ratio 0.34, 95% confidence interval 0.13 0.92) than patients on alendronate (1.93%).
Regardless of fracture history, patients receiving risedronate had lower rates of hip
fractures during their first year of therapy than patients receiving
alendronate.1Silverman et al. OI 2007
177 — A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED
STUDY OF ODANACATIB (MK-822) IN THE TREATMENT OF
POSTMENOPAUSAL WOMEN WITH LOW BMD: 18-MONTH RESULTS
Felicia Cosman, MD, Helen Hayes Hospital, West Haverstraw, NY, Michael McClung,
Oregon Osteoporosis Center, Henry Bone, Michigan Bone and Mineral Center, Nadia
Verbruggen, Merck & Co., Inc., Andrea Rybak-Feiglin, Carolyn daSilva, Arthur Santora,
Avery Ince
Objectives: Cathepsin K, a cysteine protease expressed in osteoclasts, is necessary for
bone collagen degradation. Odanacatib, a selective inhibitor of cathepsin K, has been
shown to rapidly and reversibly decrease bone resorption in both preclinical and
Phase I clinical studies. Materials and Methods: A 1+1 year dose-ranging trial is ongoing
in postmenopausal women with low BMD to evaluate the safety and efficacy of weekly
doses of placebo, 3, 10, 25 or 50 mg of odanacatib on BMD and biochemical indices of
bone turnover. The primary hypothesis for the 1-year extension study was that
odanacatib would increase lumbar spine BMD compared with placebo over 24
months. An interim analysis comparing BMD at 18 months of treatment with that at
baseline was performed. Patients and investigators remain blinded to treatment
allocation. Postmenopausal women (N=399) with BMD T-scores d-2.0 and e-3.5 at
lumbar spine (LS), femoral neck (FN), trochanter, or total proximal femur were
randomized to receive placebo or 1 of 4 doses of odanacatib. Mean age was 64.2 ±
7.8 years. Three hundred twenty women completed the 12-month base study and
entered the 1-year extension. Results: Eighteen months of treatment produced doserelated
increases in BMD from baseline. The 50-mg dose of odanacatib resulted in a
4.8% increase from baseline in lumber spine BMD vs. 0.15% for placebo and a 2.4%
increase from baseline in total hip BMD vs. a 1.2% decrease for placebo. The 50-mg
dose resulted in a 49% reduction in uNTx/Cr vs. 2.3% for placebo and a 9%
reduction in BSAP vs. a 4% increase for placebo. The safety profile of odanacatib was
generally favorable. There were no dose-related trends in any adverse experiences
(AEs). The number of patients who discontinued the study due to AEs was the same
for the placebo and 50-mg groups (9 patients), as was the number who discontinued
due to AEs considered drug-related (4 patients). Rash was reported in 3.8% of those
in the 50-mg arm and in 8.4% of those in the placebo arm. Conclusions: Eighteen
months of odanacatib treatment was generally well-tolerated and increased lumbar
spine and total hip BMD in postmenopausal women with low BMD.
178 — BONE MINERAL DENSITY OF POSTMENOPAUSAL WOMEN
PARTICIPATING IN REGULAR YOGA ACTIVITY
Millie Sweesy-Barger, Department of Kinesiology, CSU Long Beach, Ralph Rozenek,
Ph.D., Department of Kinesiology, CSU Long Beach, CA, Albert C. Russo, Ph.D.,
Department of Physical Therapy, CSU Long Beach, CA, Susan E. Sklar, M.D., Department
of Kinesiology, CSU Long Beach, CA, Alison Wrynn, Ph.D. Department of Kinesiology,
CSU Long Beach, CA
Yoga is a popular form of activity that incorporates various body postures and poses.
Many people who participate believe that yoga will have beneficial effects on bone
mineral density (BMD). However, there is little scientific evidence to substantiate this.
The purpose of this cross-sectional study was to compare measures of BMD in a group
of post-menopausal women who regularly participated in yoga for a minimum of 3
years (Y; n=31) to a group of age-matched non-yoga participants (NY; n=31). Sites
measured for BMD included the AP spine, dual femur, non-dominant wrist, and whole
body. All subjects completed health and activity questionnaires. Data were analyzed
using MANCOVA (p < 0.05). Results showed that body mass (mean +/- sd) in Y (65.4
+/- 10.4 kg) was significantly lower than NY (72.9 +/- 14.3 kg). Percent body fat and
fat mass were also lower in Y (34.3 +/- 7.0%; 22.1 +/- 7.3 kg) than in NY (42.3 +/-
6.6%; 30.3 +/- 10.4 kg). However there were no differences in lean body mass (Y =
40.9 +/- 4.7 kg; NY = 39.4 +/- 4.8 kg). No differences were found in BMD at the spine,
femur, or whole body. Initial analysis indicated that wrist BMD was significantly higher
in NY (0.68 +/- 0.07 g/cm^2) compared to Y (0.64 +/- 0.07 g/cm^2). When covariates
were included in the analysis, no difference in wrist BMD was observed. These
preliminary results suggest that yoga activity may not provide an adequate stimulus to
produce positive effects on BMD.
— 2008 Annual Meeting 33