Comparison of the short-term effects of three oral calcium vitamin D formulations and placebo on calcium metabolism

in Current Therapeutic Research (1998), 59(6), 370-378

Parathyroid hormone plasma concentrations in response to low 25-OH vitamin D circulating levels increases with age in elderly women.

in Osteoporosis International (1998), 8(4), 390-2

Plasma Estradiol Concentrations and Pharmacokinetics Following Transdermal Application of Menorest 50 or Systen (Evorel) 50

in Maturitas (1997), 27(2), 179-86

OBJECTIVES: In order to compare the pharmacokinetics of two transdermal estrogen replacement therapy (ERT) systems designed to release 50 micrograms 17 beta-estradiol/day, two studies were performed in ... [more ▼]

OBJECTIVES: In order to compare the pharmacokinetics of two transdermal estrogen replacement therapy (ERT) systems designed to release 50 micrograms 17 beta-estradiol/day, two studies were performed in healthy postmenopausal volunteers. METHODS: Both studies had a cross-over design and incorporated a 1-week wash-out period between treatments. In the first study, Menorest 50 and Systen 50 (Evorel 50) were compared over four days of application in 30 women. In the second, 13 women wore each of the two systems for a total of 12 days each (three patches each for 4 days), and comparison was made during the third patch period (steady state, between days 8 and 12). Plasma 17 beta-estradiol levels were assayed using specific direct radioimmunoassays, and pharmacokinetic parameters were calculated by standard methods. All the samples of the first study were re-analysed using a different radioimmunoassay and the results of both assays were compared. RESULTS: In both studies, plasma 17 beta-estradiol levels rose at a comparable rate and reached similar peak levels with each of the two formulations. Levels then remained relatively constant throughout both evaluation periods with Menorest 50, but began to decline after 12 hours in the first study and after 30 h under steady state conditions in the second study with Systen 50. The difference between the two products was statistically significant in both studies. Analysis of pharmacokinetic parameters confirmed the greater bioavailability of Menorest 50. In addition, 17 beta-estradiol levels remained within the suggested therapeutic ranges for relief of acute symptoms and protection against osteoporosis for longer periods of time with Menorest 50 than with Systen 50. CONCLUSION: Since the acute efficacy, long-term protective effects, side effects and risks associated with ERT may depend on critical threshold plasma levels, much attention should be paid to the pharmacokinetic profiles of different formulations. The comparison of these two different radioimmunoassays demonstrates the comparability of their results. [less ▲]

Prediction of Bone Loss Rate in Healthy Postmenopausal Women

in Calcified Tissue International (1997), 60(3), 261-4

Prevention of fractures is the only way to drastically reduce osteoporosis-related health expenditures. In order to optimize the cost/benefit ratio of a strategy of prevention, it is essential to identify ... [more ▼]

Prevention of fractures is the only way to drastically reduce osteoporosis-related health expenditures. In order to optimize the cost/benefit ratio of a strategy of prevention, it is essential to identify, as early as possible, women who will develop fractures later in their life. Therefore, and since postmenopausal bone loss is an asymptomatic process, screening procedures should detect, at the time of the menopause, women whose postmenopausal bone loss is higher than the mean, and will, a couple of years later, exhibit a low mineral content and a subsequent high risk for fractures. For 3 years we have followed a cohort of 92 healthy women who had undergone menopause less than 36 months previously. By a multivariate discriminant analysis based on the differences in lumbar bone density, assessed by dual photon absorptiometry, and in a few routine biochemical parameters (serum phosphorus, estrone, androstenedione, and urine calcium) observed during the first 6 months of the study, we have been able to correctly predict the rate of spinal bone loss, observed at the end of the 3 years, in 76% of the subjects. All of the women who presented a bone loss higher than 10% over the 3 years were correctly isolated by our discriminant functions after 6 months of follow-up. We conclude that a measurement of lumbar bone mineral density coupled with a few routine biochemical determinations, repeated twice at a 6-month interval in healthy postmenopausal women, can isolate 100% of postmenopausal "fast bone losers" with an overall specificity of 76%. [less ▲]

The role of bisphosphonates in the treatment of osteoporosis

in Drugs of Today (Barcelona, Spain : 1998) (1997), 33

Femoral osteoporosis in community-dwelling elderly females and controls living in retirement or nursing homes

in Osteoporosis International (1996), 6(S1), 118

25-OH vitamin D levels in healthy ambulatory postmenopausal women

in Osteoporosis International (1996), 6(S1), 119

Plasma Concentration of Estradiol Following Transdermal Administration of Systen 50 or Menorest 50

in Scandinavian Journal of Rheumatology. Supplement (1996), 103

Circulating levels of 17 beta estradiol (E2) following the administration of fixed doses of E2, show a great variability in kinetics depending upon the product administrated, the routes of administration ... [more ▼]

Circulating levels of 17 beta estradiol (E2) following the administration of fixed doses of E2, show a great variability in kinetics depending upon the product administrated, the routes of administration, and the interindividual variations in absorption and metabolism. This might have important implications both in terms of tolerance and effectiveness. Two new forms of transdermal E2 (SYSTEN Cilag and MENOREST Rhone-Poulenc Rorer) have been recently accepted in Europe for the treatment of climacteric symptoms. The present study was undertaken to compare the pharmacokinetic characteristics of plasma E2 profile under these two drugs. It was carried out in 30 healthy postmenopausal volunteers according to good clinical practice after informed consent, as a single blind, randomised, cross-over study during the classical wearing period of 4 days. Plasma E2 concentration was determined 24 hours before, 1/2 hour before and then 2, 4, 8, 12, 24, 48, 72, 84, 96 hours after the first patch administration. E2 measurement was performed using a specific direct radioimmunoassay developed in the FRH laboratories. The main criteria for this method were an intraassay coefficient of variation (CV) less than 6%, an interassay CV less than 8% in a concentration range of 15-140 pg/ml and a quantitative detection limit (LOQ) of 2.7 pg/ml with a 20% CV. The following kinetic parameters were analysed: C(max), C(mean), C96 and MRT. The bioequivalence was assessed by analysis of variance of C(max), C(mean), C96 and AuC after logarithmic transformation, complemented by Westlake test (95%). Data show that these two products are identical in terms of C(max) but C(mean), C96 and AuC are statistically greater when MENOREST 50(R) is administered; furthermore, E2 levels decrease more rapidly and more deeply with SYSTEN 50 than MENOREST 50. The differences of pharmacokinetic profiles after administration of two different forms of the same dose of 50 micrograms transdermal 17 beta estradiol might have important medical consequences. [less ▲]

A Double-Blind, Placebo-Controlled, Dose-Finding Trial of Intermittent Nasal Salmon Calcitonin for Prevention of Postmenopausal Lumbar Spine Bone Loss

in American Journal of Medicine (1995), 98(5), 452-8

PURPOSE: Nasal administration of salmon calcitonin (SCT) has been suggested for preventing trabecular bone loss during the first years following the menopause, but no conclusive evidence has appeared ... [more ▼]

PURPOSE: Nasal administration of salmon calcitonin (SCT) has been suggested for preventing trabecular bone loss during the first years following the menopause, but no conclusive evidence has appeared about the minimal effective dose. Since nasal calcitonin is highly expensive, it makes sense to define this dose. PATIENTS AND METHODS: We performed a double-blind, placebo-controlled, randomized, single-center study with a 3-arm parallel-group design. The subjects were 251 healthy women who had experienced natural menopause within the past 6 to 72 months and were not affected by any diseases or treatments that interfere with calcium metabolism. They were randomly allocated in groups of 6 to receive intranasal SCT 50 IU (n = 84), SCT 200 IU (n = 84), or placebo (n = 83). All treatments were given on 5 consecutive days per week. Statistical analysis was based on two populations: intention-to-treat (IT) and valid completers (VC). The main assessments performed were bone mineral density of the lumbar spine (LSBMD) and biochemical parameters reflecting bone turnover (serum alkaline phosphatase, urinary calcium/creatinine, and hydroxyproline/creatinine ratios). RESULTS: Changes over the treatment period were comparable in the IT and VC populations. In the group receiving the placebo, LSBMD decreased from baseline to end point by a mean of 6.28% (95% confidence interval [CI] -7.69 to -4.89) in the IT population and 6.98% (95% CI -8.86 to -5.11) in the VC population (P = 0.0001, end LSBMD versus baseline LSBMD). LSBMD increased slightly with the 50-IU/d dose of SCT, by 0.82% (95% CI -0.26 to 1.89) in the IT population, and 0.51% (95% CI -0.69 to 1.72) in the VC (P = NS, versus baseline). Subjects who received SCT 200 IU/d experienced significant increases of 2.03% (95% CI 0.92 to 3.15) in the IT population and 2.26% (95% CI 1.01 to 3.51) in the VC (both P = 0.001). The difference between the evolution of the combined groups receiving nasal SCT and the group treated with the placebo was highly significant (P = 0.0001). No significant changes were recorded in biochemical parameters reflecting bone turnover. CONCLUSIONS: SCT 50 IU/d administered nasally and intermittently appears to prevent lumbar bone loss in nonobese early postmenopausal women. [less ▲]

Bone mineral density of the spine and the hip measured with dual energy X-ray absorptiometry: normal range and fracture threshold for western European (Belgian) postmenopausal females.

in Clinical Rheumatology (1995), 14(1), 68-75

Bone mineral density (BMD) of the spine and the different regions of interest (ROI) of the hip were measured by dual energy X-ray absorptiometry in 278 healthy Belgian postmenopausal women and 93 ... [more ▼]

Bone mineral density (BMD) of the spine and the different regions of interest (ROI) of the hip were measured by dual energy X-ray absorptiometry in 278 healthy Belgian postmenopausal women and 93 postmenopausal type I osteoporotic females in order to: a) determine the normal range for lumbar and hip BMD values; b) define an "hypothetical" fracture threshold in this population; c) determine the preferential region to be considered for clinical use in type I osteoporosis. In the normal subjects, there is a negative relationship (< 0.001) between age or time elapsed since menopause (Tm) and BMD measured at the level of the spine or at the ROI of the hip. For the spine, evidence of a curvilinear relationship was assessed. Regressions of BMD at the hip as a function of age or time elapsed since menopause, were best fitted by a linear relationship. In the population of postmenopausal women who have experienced a vertebral crush fracture, no relationships were observed between spine BMD and age or Tm but the osteoporotic women had a spine BMD significantly lower compared to age-matched normal controls: Z-score = -1.2 +/- 0.6 (mean +/- SD) (p < 0.0001). Fracture threshold calculated as the 90th percentile of spine BMD measured in osteoporotic patients was 0.840 g/cm2, corresponding to the mean value -1 SD for a population of women aged 51 years. [less ▲]