Annie Kung
Department of Medicine, the University of Hong Kong, Hong Kong PRC.

Osteoporosis is a growing problem in Asian countries due to increasing ageing population and changing life style. Differences in genetic and environmental factors may account for the differences in fracture incidence between the East and West. The ma'jor risk factors for low bone mass among Asian women are small body size, previous history of fracture, and a family history ofosteoporcitic fracture. Other adverse risks include low calcium intake, physical inactivity, smoking and excess alcohol intake. The high intake of phytoestrogens in Chinese and Japanese may offer protection against bone loss. The difference in genetic constitution, e.g. absence of ss genotype of the collagen Type 1α gene and predominance of bb genotype of vitamin D receptor gene, may also contribute to the difference in fracture incidence between Asians and Caucasians. Data on population-specific bone mass and diagnostic thresholds across different anatomic sites and BMD techniques are not available in all Asian countries. Although there is mounting awareness of osteoporosis among Asian countries, the level of awareness and the acceptance of various forms of treatment is still considerably low. Local strategy based on scientific evidence is needed for optional prevention.

Thiebaud Daniel
MD, Ass. Prof. University of Lausanne, Switzerland, Global Medical Advisor, Bone Clinical Strategy, Eli Lilly Co, USA

Raloxifene a selective estrogen receptor modulator (SERM) acts as estrogen agonist on bone and lipid metabolism, and as estrogen antagonist in the uterus and breast. Raloxifene (RLX) therapy decreased the incidence of new vertebral fractures(VF) by about 40% over a 3-year period in the MORE (Multiple Outcomes of Raloxifene Evaluation) trial, which studied 7705 postmenopausal women with osteoporosis randomized to placebo or RLX (60 or 120 mg/day). Further analyses evaluated whether RLX has early onset of effects on clinical VF and if the decreased risk of incident VF persists into the 4th year of RLX therapy. In the first year, RLX60 significantly decreased the incidence of new clinical VF in total study population (RR 0.32), and among women with prevalent VF (RR 0.34). At 4 years, the cumulative relative risk (RR) of new VF was 0.61 (95% confidence interval 0.51, 0.73) with the pooled RLX doses. In the total MORE population, the RR for new VF with RLX60 was 0.65 (95%CI 0.53, 0.79) from baseline to year 3; this was sustained during the 4th year [RR 0.61 (95%Cl 0.43, 0.88)]. Regarding the effects of RLX on breast tissue, after completion of the 4 years of MORE, a total number of 77 new breast cancer were collected with a 62% reduction in overall new cancer (p<0.001) and 72% reduction in invasive breast cancer (p<0.001).

The largest randomized, double-blind placebo-control led Asian osteoporosis trial was recently completed to determine the effects of RLX versus placebo on biochemical markers of bone metabolism and lipids in healthy, postmenopausal Asian women. 1000 healthy, ambulatory post-menopausal women from 10 Asian countries were randomly assigned to receive either RLX 60 mg/day or placebo. A 6-month interim (n=345) report in women treated with RLX showed reductions from baseline in serum levels of osteocalcin (-25% vs -6% with placebo, p<0.001) and of N-telopeptide cross-links (-17% vs -2%, p<0.00 1). RLX also improved the serum lipid profiles in these women. The tolerance was excellent: there was no significant difference between the RLX and placebo groups in the incidence of hot flushes or vasodilatation (8.8% vs 9.8%) or leg cramps (4. 1 % vs 5.2%) and no case of venous thrombo-embolism was observed.

Together these results confirm that raloxifene, a new SERM has estrogen agonist effects on bone and lipid metabolism but estrogen antagonist effects in the breast and uterus. The results obtained in Asian women confirm those from previous studies.

Bruce Ettinger
MD, Division of Research, Kaiser Permanente Medical Care Program, Oakland, California, USA

We have used the Kaiser Permanente Medical Care Programìs pharmacy database to examine rates of osteoporosis drug continuation among women health plan members. Our studies indicate low rates of continuation, especially for women beginning estrogen therapy. To better understand why women start and stop osteoporosis drugs, we conducted a telephone survey of women who following a bone density test showing osteopenia or osteoporosis started using estrogen, alendronate, or raloxifene. The interviews were conducted, on average, 7 months after treatment was begun. We found important differences in continuation rates between the 3 treatments; estrogen clearly had the worst continuation. Discontinuation was related to side effects of treatment in about two-thirds of cases; among these 3 osteoporosis drugs, raloxifene had the lowest rate of troublesome side effects. Our survey also found that, even amang these women with low bone density, non-skeletal health benefits (e.g. coronary heart disease or breast cancer risk reduction) were extremely important.
Several cases will be presented to illustrate the choice of osteoporosis therapy among postmenopausal women with varying degrees of osteoporosis.