The prevalence of carotid atherosclerosis and of its risk factors was examined in 517 apparently healthy French women, aged 45-54 years. Early phases of carotid atherosclerosis were assessed by B-mode ultrasonography. An intimal-medial thickening was found in 30.4% of the women and atheromatous plaques in 8.7%. The prevalence rate of carotid atherosclerosis increased with age, smoking, and postmenopausal status. However, after adjustment for the effect of age, postmenopausal women did not have more atherosclerotic lesions than did premenopausal women. No significant associations were found between carotid atherosclerosis and triglyceride, apolipoprotein A-I, body mass index, blood glucose, fibrinogen, plasma viscosity, or hematocrit. The mean age-adjusted levels of total cholesterol, low density lipoprotein cholesterol, apolipoprotein B, and systolic and diastolic blood pressures significantly increased with the severity of carotid atherosclerosis, whereas high density lipoprotein cholesterol significantly decreased. Multiple regression analysis showed that age, smoking, high density lipoprotein cholesterol, low density lipoprotein cholesterol (or apolipoprotein B), and systolic (or diastolic) blood pressure were significantly and independently related to the severity of carotid atherosclerosis. In conclusion, the association of early carotid lesions with major cardiovascular risk factors suggests that carotid atherosclerosis may be used as a marker of the general atherosclerotic process. (Arteriosclerosis and Thrombosis 1991;ll:966-972)

Cross-sectional associations between aortic elasticity assessed by carotid to femoral pulse wave velocity (PWV) and cardiovascular risk factors were examined in 429 apparently healthy middle-aged women. PWV was strongly and positively related to blood pressure and hypertension. Weak but significant positive associations were also found between PWV and age, heart rate, some lipids and lipoproteins, blood glucose (either as a continuous or dichotomous variable), body mass index, haematocrit, leucocyte count and family history of diabetes. No associations were observed between PWV and high density lipoprotein cholesterol, apolipoprotein A1, fibrinogen, cigarette smoking, menopausal status and a family history of hypertension or myocardial infarction. After adjustment for systolic blood pressure, PWV remained significantly related to heart rate, leucocyte count, blood glucose (as a dichotomous variable) and a family history of diabetes. Multiple regression analysis showed that systolic blood pressure and, to a lesser extent, heart rate, leucocyte count and a family history of diabetes were all independent determinants of PWV. This pattern of associations suggests that arterial stiffness measured by PWV reflects the sclerotic rather than the atherotic component of atherosclerosis. The potential influence of a family history of diabetes on the elastic properties of the aorta needs to be ascertained in further studies.

This paper presents the results of a two-center, double-masked, placebo-controlled, randomized, oral-dose study of risedronate treatment in postmenopausal osteoporosis. Patients had at least one, but no more than four prevalent vertebral fractures at baseline. They received either 2.5 mg continuous risedronate, 2.5 mg cyclic risedronate, or placebo for 2 years. Both risedronate and placebo were formulated as hard gelatin capsules. All women furthermore received a daily calcium supplement of 1 g which was taken separately from the study drug. During the 1-year of follow-up, all women received only a daily calcium supplement of 1 g. A total of 132 patients were enrolled (44 in each treatment group), of which 73% completed the 2-year treatment period and 70% all 3 years. Generally the outcome of the study was negative. Lumbar spine bone mineral density (BMD) increased 1.2% (NS) and 0.8% (NS) and after 2 and 3 years in the group treated with continuous risedronate, 1.7% (NS) and 2.3% (p < 0.05) in the group treated with cyclic risedronate, and 0.6% (NS) and 1.7% (NS) in the placebo group. BMD in the femoral neck increased 2.9% (p < 0.05) and 0.9% (NS) after 2 and 3 years in the group treated with continuous risedronate, 1.3% (NS) and 2.4% (p < 0.01) in the group treated with cyclic risedronate, and 1.3% (NS) and 2.6% (p < 0.01) in the placebo group. The differences between all three groups in spinal and femoral BMD after 2 years were not statistically significant, but reached statistical significance after 3 years (p < 0.01) in the femoral neck. Only minor changes were observed in the measured markers of bone turnover. Both the incidence and rate of new vertebral fractures showed no overall differences between the groups. The distribution of adverse events was similar across treatment groups. None of the serious adverse events were considered causally related to risedronate. The lack of effect shown in the present study may be explained by insufficient dose regimen and/or impaired absorption from the intestinal tract. Further investigations (ongoing phase III trials) are needed to define future dose regimens in order to validate the effect on bone mass, fracture rate and biochemical markers. In these studies another formulation of the drug and other dosing instructions are used.

No abstract

These results suggest that oral conjugated equine estrogens and transdermal estradiol, in the given doses, are equally effective in reducing postmenopausal bone resorption.

within 48 hours of a myocardial infarction-does not improve survival. I cited the two earlier studies in my editorial.4' It may have escaped Dr Walker's notice that 13% of the patients in the conservatively treated group in TIMI II had for clinical reasons undergone coronary angioplasty within 14 days of the infarction. If this "conservative" policy were implemented in the United Kingdom it would greatly increase the number of coronary angioplasties. In patients not treated with thrombolysis and in whom the thrombosis has occluded the artery, leading to transmural infarction, angioplasty is rarely useful. In contrast, in the United Kingdom patients who have been treated with thrombolysis should be assessed clinically and by an exercise test. Many of those with symptoms or a strongly positive test result will be suitable for angioplasty and it is these patients, rather than those treated within 48 hours of the infarct, who will increase the angioplasty workload.

Osteoporosis is a slowly progressing disease resulting from an imbalance between bone accretion and degradation. As interstitial collagenase is a key enzyme in the degradation of bone matrix, we investigated a possible relationship between the collagenase gene and osteoporosis. Analysis of an amplified genomic DNA fragment from -524 to +52 by denaturing gradient gel electrophoresis and sequencing allowed us to detect three dimorphic sites upstream of base -300, one of them leading to a BanI restriction site. None of the sites could be directly associated with osteoporosis. The allele frequencies of the three dimorphic sites were estimated. The interallelic ratios were high, thus providing new useful genetic markers for linkage analysis. When comparing these ratios in osteoporotic and nonosteoporotic subjects, no significant differences could be observed.

Ipnfiavone (Ip) has been shown to affect bone metabolism mainly by inhibiting bone resorption. A multicentre study was aimed at evaluating the effects of a long-term (3 years) treatment with Ip in postmenopausal women (PMVV) with low bone mass. 141 PMW aged 50-65 years, having a baseline radial bone mineral density (BMD) value <1 SD compared to age-matched, healthy women, and giving their informed consent were randomly allocated to receive either oral Ip (3x200 mglday) or a matched placebo (PI) for 2 years according to a double-blind (db.), parallel group design. At the end of the 2-year d.b. period, all patients received in open fashion for 1 year Ip at the same dosage. A 1 gtday oral calcium supplementation was given during the whole 3-year period to all patients. Serial measurements (every 6 months) of radial BMD (DPA), urinary hydrexyproline/creatinine (HOP/c0 and haematology and blood chemistry parameters were performed. 93 women completed the 3-year treatment, 50 treated with Ip from baseline to month 36 (T36), of Parma, Italy (group A), and 43 receiving PI from baseline to T24, and then Ip from T24 to T36 (group B). Results on BMD are shown in the figure.Distal radius BMD (m~_SE) 9 = Group A o = Group B o 6 12 18 24 30 36 •onths 9 p<005 vs baseline in g~oup A # p<0.05 Vs 24 nlonths it~ group B HOP/cr was significantly reduced (p<0.05.vs baseline at T18 and T36) in group A. In group B, HOP/cr was increased (ns) during PI treatment, and decreased (ns) during Ip treatment. Adverse drug reactions were mainly gastrointestinal, with a similar distribution in the 2 groups. In conclusion, Ip was shown to be able to prevent peripheral bone mass loss dunng 3 years of treatment. Moreover, patients receiving PI for 2 years had a significant recovery of BMD when the PI was replaced by Ip for 1 additional year.Since both ostenclasts and macrophages belong to the mononuolear phagocytic system through their common origin from an undifferentiated hematopoietic precursor call, it is concdvable, that bisphosphonates not only affect bone metabolism but also immune and inflammatory responses. The migration of mononuclear cells into perivascular tissues is a central event in inflammatory reactions. Since the effects of bisphosphonates on the immune system are still incompletely understood, we studied the effects of the aminobisphosponate alendronate on the transeedothalial migration of human peripheral blood mononudear cells (PBMNC) in an in vitro model. PBMNC were cultivated overnight in the presence or absence of various concentrations of alendronate. For transr migration experimems, human umbilical vein endothelial cells (EC) were cultured to confluence on hydrated collagen gels. After a 4 hour incubation with PBMNC in the presence or absence of aleedronate, the fractions of cells nocadherent to the EC, those bound to the EC and those that had migrated through the EC monolayer and into the collagen were individually recovered and quentitated. Alendronate ill concentrations of 10 and 100 pM significantly increased the percen...