2001 - Basel - Switzerland

PAGE 2001: oral presentation
 

Auckland Bones and Summer Sun

NHG Holford1, S Bååthe 2, Mats Karlsson2

1) Dept of Pharmacology & Clinical Pharmacology, University of Auckland, New Zealand

Osteoporosis is common in post-menopausal women. A variety of drug treatments have been approved for treatment of osteoporosis and the prevention of fractures but there is little information about their comparative effectiveness. We undertook an analysis of data collected as part of clinical trials in postmenopausal women undertaken in Auckland (Prof Ian Reid). Bone mineral density (BMD) was used as a biomarker for the progression of osteoporosis. Treatments tested were pamidronate, calcium supplementation, hydrochlorothiazide and tamoxifen. Each trial had a placebo treatment group. The pamidronate trial included calcium supplementation in both pamidronate and placebo groups. Measurements of total body BMD (376 subjects; 1962 observations) were used to describe changes in bone. BMD was measured using a Lunar DPX-L dual energy x-ray absorptiometer (Lunar Radiation, Madison, WI). The within subject precision of measurement claimed by the manufacturer is 0.4%. Serial BMD measurements were made every 6 months for up to 4 years. Models for the time course of BMD progression and the time course of drug effects on BMD were developed using hierarchical mixed effect non-linear regression (NONMEM). The best model for BMD progression was linear but the slope of the line varied with the month of the year in a cyclical fashion. The average annual slope decreased with age while the baseline BMD increased with weight and decreased with age. Baseline total body BMD was 1.05 g/cm2 with average decrease (alpha) of 0.00808 g/cm2/y. Cyclical annual amplitude for alpha was 0.0086 g/cm2 with the acrophase in mid-January. Peak BMD was predicted to be in mid-March. Each of the drug treatments was best described by a slowly developing increase in BMD which approached an asymptote (beta). The equilibration half-life for all drug treatments was 9 months. The model suggested a symptomatic rather than protective benefit on BMD progression. The steady state increase (g/cm2) in BMD due to each treatment (beta) was 0.0213 for pamidronate, 0.0102 for calcium supplementation, 0.00521 for tamoxifen and 0.0143 for hydrochlorothiazide. Disease progression modelling has demonstrated the seasonal variation in BMD expected from exposure to sunlight in the Southern hemisphere and provides a direct estimate of the relative treatment benefits of 4 different therapies for increasing BMD.




Reference: PAGE 10 (2001) Abstr 231 [www.page-meeting.org/?abstract=231]
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