ABSTRACT
Chinese herbal medicines (CHMs) have been widely used during pregnancy, but feto-embryo safety tests are lacking. Here we evaluated in vitro embryotoxicity tests (IVTs) as alternative methods in assessing developmental toxicity of CHMs. Ten CHMs were selected and classified as strongly, weakly and non-embryotoxic. Three well validated IVTs and prediction models (PMs), including embryonic stem cell test (EST), micromass (MM) and whole embryo culture (WEC), were compared. All strongly embryotoxic CHMs were predicted by MM and WEC PM2. While all weakly embryotoxic CHMs were predicted by MM and WEC PM1. All non-embryotoxic CHMs were classified by EST, MM, but over-classified as weakly embryotoxic by WEC PM1. Overall predictivity, precision and accuracy of WEC determined by PM2 were better than EST and MM tests. Compared with validated chemicals, performance of IVTs for CHMs was comparable. So IVTs are adequate to identify and exclude embryotoxic potential of CHMs in this training set.
Subject(s)
Drugs, Chinese Herbal/toxicity , Embryo, Mammalian/drug effects , Embryonic Stem Cells/drug effects , Teratogens/toxicity , Toxicity Tests/methods , Animals , Blastocyst Inner Cell Mass/drug effects , Blastocyst Inner Cell Mass/metabolism , Blastocyst Inner Cell Mass/pathology , Cell Differentiation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/classification , Embryo, Mammalian/metabolism , Embryo, Mammalian/pathology , Embryonic Development/drug effects , Embryonic Stem Cells/metabolism , Embryonic Stem Cells/pathology , In Vitro Techniques , Mice, Inbred ICR , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/pathology , Predictive Value of Tests , Rats, Sprague-Dawley , Sensitivity and Specificity , Teratogens/classificationABSTRACT
Strontium ranelate is a new effective anti-osteoporotic treatment having a unique mode of action, reducing bone resorption while promoting continued bone formation, with a broad range of anti-fracture efficacy at vertebral as well as peripheral sites. In Phase III studies, it has proven its early and sustained efficacy against vertebral fractures in Caucasians along with a significant increase in lumbar bone mineral density (BMD). The aim of this randomized double-blind study was to demonstrate the efficacy of strontium ranelate (2 g/day) on lumbar spine bone mineral density and the clinical and biological safety in Asian postmenopausal osteoporotic patients compared to placebo over 1 year. Three hundred and twenty-nine eligible women from mainland China, Hong Kong and Malaysia were randomized into the study. The baseline characteristics were similar in the treatment and placebo groups: mean age of 66.2+/-6.5 years, time since menopause 17.6+/-7.2 years. In the Full Analysis Set (FAS, N=302), the mean baseline lumbar L2-L4 BMD was 0.715+/-0.106 g/cm(2) in the strontium ranelate group and 0.708 +/- 0.109 g/cm2 in the placebo group. The mean baseline femoral neck BMD was 0.575+/-0.074 g/cm2 and 0.566+/-0.069 g/cm2 respectively and mean total hip BMD was 0.642+/-0.080 g/cm2 and 0.631 +/-0.088 g/cm2 respectively. The overall compliance was 91.4% in the study drug group, and 97.4% in the placebo group. After 1 year of treatment, the lumbar spine, femoral neck and total hip BMD in the treated group was significantly increased by 3-5% as compared to placebo. Strontium ranelate was well tolerated. The most frequently reported emergent adverse events were comparable in both groups (60.4% versus 60.0%), with majority of them being mild gastrointestinal disorders. There were no clinically relevant changes in laboratory tests, such as blood routine, hepatic and renal function. It is thus concluded that the effects of 2 g/day strontium ranelate on BMD and its safety profile in this cohort of postmenopausal osteoporotic Asian women were consistent with results obtained from Caucasian women in which the efficacy on the reduction in risk of fracture has been proven.
Subject(s)
Bone Density Conservation Agents/therapeutic use , Organometallic Compounds/therapeutic use , Osteoporosis, Postmenopausal/drug therapy , Thiophenes/therapeutic use , Aged , Asian People , Bone Density , Bone Density Conservation Agents/adverse effects , Double-Blind Method , Female , Humans , Middle Aged , Organometallic Compounds/adverse effects , Osteoporosis, Postmenopausal/ethnology , Osteoporosis, Postmenopausal/physiopathology , Thiophenes/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: Famines have occurred in all areas of the world in every period of history. Many studies have shown that poor growth and development and adverse environmental conditions in childhood are associated with osteoporosis in later life. However, little information is available on the relation between famine and bone health. METHODS: This study examines the hypothesis that past experience of famine has an adverse impact on bone health, using data from Ms Os (Hong Kong), a large cohort study on osteoporosis in Asian women. There were 1,826 Hong Kong women aged 65 years or older recruited from the community. A standardized, structured interview and DXA were performed. Subjects who had experienced famine tended to have lower levels of education, social status and current daily calcium intake. They also have higher rates of cigarette consumption, depression and coronary heart disease. RESULTS: After adjustment for confounders, we found that subjects who had experienced famine have a significantly higher rate of developing osteoporosis than those who had not. CONCLUSIONS: We conclude that past exposure to famine, especially in childhood, is associated with osteoporosis.
