An Taquet
University of Liège
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by An Taquet.
Annals of Internal Medicine | 1998
Jean-Yves Reginster; Laurence Meurmans; Brigitte Zegels; Lucio Claudio Rovati; Helmut W. Minne; Gianpaolo Giacovelli; An Taquet; Ivo Setnikar; Julien Collette; Christiane Gosset
During the past 30 years, fluoride salts have been studied as agents for the treatment of osteoporosis in postmenopausal women with the expectation that stimulation of osteoblastic proliferation and activity and the subsequent increase in bone formation would be followed by a significant decrease in fracture rates [1-3]. It is widely accepted that fluoride is effective in increasing trabecular bone mass in the spine [4]. However, discrepant results have been obtained from studies evaluating the effects of fluoride salts on cortical bone mass and, more important, on the quality of the newly synthesized bone and on vertebral and nonvertebral fracture rates [5-9]. These differences are probably related to differences in fluoride dose, formulation, and regimen; duration of therapy; and treated populations. Because bone-forming agents such as fluoride are expected to work mainly by increasing bone mineral content without restoring disrupted bone tissue integrity, they may be particularly useful in patients with mild to moderate osteoporosis in whom the microarchitecture of the skeleton is not excessively damaged. To test this hypothesis, we studied the effect of low-dose fluoride (sodium monofluorophosphate [MFP]) plus calcium in a 4-year, randomized, double-blind, controlled clinical trial in postmenopausal women with moderately low bone mineral density (BMD) of the spine. Methods Patients Our study included white postmenopausal women with lumbar (L2 to L4) BMD of the spine below the 90th percentile of the distribution of BMD of the spine seen in Belgian women with osteoporosis [10, 11]. This degree of bone loss corresponded to a T-score of 2.5,in accordance with the operational definition of osteoporosis recently proposed by a World Health Organization study group [12]. Patients were included in the study regardless of whether they had previously had vertebral or nonvertebral fractures; most of the patients were thought to be free of vertebral fractures at enrollment. Previous hip fracture was an exclusion criterion. All patients were free of other causes of osteoporosis, such as diseases or medications known to interfere with bone metabolism; none had been treated with any drug for postmenopausal osteoporosis; and no such treatment was allowed during the study. Hormone replacement therapy was continued, for ethical reasons, in women for whom it had been prescribed before enrollment for purposes other than bone therapy. Randomization was not stratified with respect to hormone replacement therapy. Patients with bone diseases other than osteoporosis, renal insufficiency, hypochlorhydria, or severe chronic disorders that could have interfered with the study were excluded. Study Design Patients were randomly assigned in a blinded manner to one of two therapeutic groups. Every day for 4 years, they received either two chewable tablets that each contained 76 mg of MFP (10 mg of equivalent fluoride [fluoride ion]) and 1250 mg of calcium carbonate (500 mg of equivalent calcium) or two chewable tablets that each contained 1250 mg of calcium carbonate alone and were similar in appearance to the MFP-plus-calcium tablets. Total daily dosages, therefore, were 20 mg of equivalent fluoride plus 1000 mg of calcium in the MFP-plus-calcium group and 1000 mg of calcium in the calcium-only group. The two tablets were taken at different meals. We determined compliance at each study visit by asking each patient for the number of days on which she had not taken the tablets and by counting the unused tablets. Compliance was expressed as the percentage of tablets taken (100% if the patient had taken all of the tablets). Patients received randomization numbers sequentially. Randomization was computer generated in blocks of four according to a strict standard operating procedure by persons who had no contact with the persons in the center who assigned patients to study groups. The randomization code was kept at the study sponsors facility under secure conditions that were detailed in writing. The clinical research center was given opaque, sealed envelopes, each of which contained the code for one patient. Treatment assignment and other relevant information were thus concealed and were to be revealed only in the case of a medical emergency. Blinding was achieved by using the following procedures. First, the persons who did the visual readings of the spine radiographs saw the codes only after the results were analyzed. Second, the data were analyzed under blinded conditions: that is, a first analysis was done with groups A and B; the analysts did not know which group had received which treatment. Efficacy Evaluation Criteria The primary end point was the number of patients with new vertebral fractures during the 4-year treatment period, in accordance with recently published guidelines for the evaluation of drugs to be registered in Europe for the prevention or treatment of osteoporosis [13]. Standardized lateral radiographs of the thoracic and lumbar spine were obtained at enrollment and at each year of follow-up, for up to 4 years, in a single radiology center. The radiographs were sent to an independent assessor. Films were digitized, and the anterior, middle, and posterior heights of each vertebral body from the fourth thoracic (T4) to the fifth lumbar (L5) were determined (accuracy of the digitizer, 0.025 mm) by a computer program. This was done by persons with no knowledge of treatment assignment or film sequence. A new vertebral fracture (incident fracture) was defined as a reduction of at least 20% and an absolute decrease of at least 4 mm in any height of at least one vertebral body between enrollment and the latest follow-up film. All fractures, including borderline cases, were confirmed by visual reading. This definition was applied to vertebrae that were not fractured at enrollment, whereas fractures present at enrollment were determined on the digitized enrollment radiographs by using the Melton-Riggs 25% unadjusted algorithm [14]. The possible progression of such baseline lesions was assessed with the Vertebral Deformity Index obtained for each vertebra (T5 through L5); these were then summed to obtain the Spine Deformity Index, a continuous measure of vertebral deformities [15]. The Spine Deformity Index was also used as a secondary variable in patients with incident or progressing vertebral deformities, in whom it was expressed as the mean change between the last observed value and baseline. Bone mineral density was measured by using dual-energy x-ray absorptiometry on the same densitometer (Hologic QDR 1000, Waltham, Massachusetts) at 6-month intervals at the lumbar spine (L2 to L4) and the nondominant hip (total hip) after previously described and validated procedures were performed [11, 16]. In our hands, the long-term coefficients of variation of dual-energy x-ray absorptiometry are 0.8% for BMD of the spine and 1.1% for BMD of the total hip [17]. Biochemical determinations of bone remodeling were made at 6-month intervals. Bone formation was assessed by radioimmunoassay of serum bone-specific alkaline phosphatase (Ostase, Hybritech, San Diego, California). For bone resorption, we measured the ratio of urinary hydroxyproline to creatinine on the second fasting urine spot (2-hour morning urine) (Hypronostikon kit, Organon Technika, Oss Boxtel, the Netherlands). All peripheral (nonvertebral) fractures that occurred during the study were recorded independently of the nature and severity of the trauma that may have determined them. Statistical Analysis All analyses were done according to the intention-to-treat approach: that is, all patients who had at least one valid measurement after randomization were considered in the analysis, whether they were still taking the study drug or not. In the case of drop-out and, thus, discontinuation of therapy with the study medication, the patient was invited to return to the clinic at annual intervals (for 4 years, if possible) so that the radiography necessary to record outcome could be done. An exact-significance chi-square test was done to compare the number of patients with new vertebral fractures in the two groups. We calculated 95% CIs for vertebral fracture rates in each study group and for the difference in rates between the two groups, along with the point estimates of these rates. These rates were also expressed in terms of the number needed to treat for 4 years to prevent one fracture, including values for the lower and upper bounds of the 95% CIs. Changes in the Spine Deformity Index in patients with incident or progressing vertebral deformities were compared by analysis of variance. Analysis of variance for repeated measurements was used to compare the absolute values for BMD of the spine over the course of the study in the two groups. Analysis of variance for repeated measurements was also done to compare BMD of the total hip and percentage changes in biochemical markers of bone remodeling throughout the study. All P values are two-tailed. All statistical analyses were done with the SPS/WIN 6.2 statistical package (SPS, Inc., Chicago, Illinois). Role of Study Sponsor The trial was approved by the Ethical Committee of Liege University (registration no. 90/43-1262 of 14 May 1990), and all patients gave full informed consent before inclusion. The Rotta Research Group, which markets MFP and calcium combinations in Germany, Italy, and other countries, provided the drugs and funding for the study. Scientists from the Rotta Research Group were directly involved in the design, monitoring, and data management of the study and agreed to be listed as authors. However, the Rotta Research Group as a corporate entity had no control over the decision to approve or submit the manuscript for publication. Results Two hundred patients were enrolled in the study. The characteristics of the entire patient sample (100 patients were assigned to each group) at enrollment are shown in Table 1. The
Osteoporosis International | 1997
B Clemmesen; Pernille Ravn; Brigitte Zegels; An Taquet; Claus Christiansen; Jean-Yves Reginster
Abstract: 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, bur 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.
Calcified Tissue International | 1993
Jean-Yves Reginster; Claus Christiansen; B. Dequinze; Rita Deroisy; Ulysse Gaspard; An Taquet; P. Franchimont
SummaryObjective: To evaluate and compare the effects or oral and transdermal estrogen replacement therapy on biochemical markers of bone resorption in early postmenopausal women Design: Controlled, randomized group comparison. Setting: Outpatient clinic for menopausal women and research into osteoporosis. Subjects: Sixty healthy women menopausal for less than 5 years and who had never received any medications interfering with bone metabolism. Interventions: The 60 women were randomly allocated to 3 months therapy with either oral conjugated estrogens (0.625 mg/day) (n = 28) or transdermal estradiol (50 jig/day) (n = 32) in cyclical combination with medroxyprogesterone acetate (5 mg/day). Main outcome measures: Traditional (urinary calcium/creatinine and hydroxyproline/creatinine) and the new specific (urinary pyridinoline/creatinine and deoxypyridinoline/creatinine) markers of bone resorption were determined before and after 3 months of treatment. Results: In both groups, circulating levels of estrone and estradiol were significantly (P < 0.001) increased during treatment. In women treated with oral conjugated equine estrogens, urinary calcium/creatinine and hydroxyproline/creatinine ratios were significantly (P < 0.05) reduced. Pyridinoline/creatinine ratio fell from 69.1 (4) [mean (SEM)] to 50 (4) μmol/μmol (P < 0.01) and deoxypyridinoline/creatinine ratio fell from 10.8 (1) [mean (SEM)] to 8.3 (0.8) μmol/μmol (P < 0.01). In the group treated with transdermal estradiol, urinary hydroxyproline/creatinine ratio was significantly (P < 0.05) reduced. Pyridinoline/creatinine ratio fell from 66.3 (4) [mean (SEM)] to 46.2 (3) μmol/μmol (P < 0.01) and deoxypyridinoline/creatinine ratio fell from 11.5 (1.5) [mean (SEM)] to 7.7 (0.6) μmol/μmol (P < 0.01). There were no differences between the evolution of the biochemical variables in the two groups. Conclusion: These results suggest that oral conjugated equine estrogens and transdermal estradiol, in the given doses, are equally effective in reducing postmenopausal bone resorption.
Gynecological Endocrinology | 2001
Jean-Yves Reginster; Brigitte Zegels; Emmanuelle Lejeune; M. C. Micheletti; An Taquet; Adelin Albert
Calcium and vitamin D supplementation has been shown to reduce secondary hyperparathyroidism and play a role in the management of senile osteoporosis. In order to define the optimal regimen of calcium and vitamin D supplementation to produce the maximal inhibition of parathyroid hormone secretion, we have compared the administration of a similar amount of Ca and vitamin D, either as a single morning dose or split in two doses, taken 6 hours apart. Twelve healthy volunteers were assigned to three investigational procedures, at weekly intervals. After a blank control procedure, when they were not exposed to any drug intake, they received two calcium-vitamin D supplement regimens including either two doses of Orocal D3 (500 mg Ca and 400 IU vitamin D) 6 hours apart or one water-soluble effervescent powder pack of Cacit D3 in a single morning dose (1000 mg Ca and 880 IU vitamin D). During the three procedures (control and the two calcium-vitamin D supplementations), venous blood was drawn every 60 minutes for up to 9 hours, for serum Ca and serum PTH measurements. The order of administration of the two Ca and vitamin D supplementation sequences was allocated by randomization. No significant changes in serum Ca were observed during the study. During the 6 hours following Ca and vitamin D supplementation, a statistically significant decrease in serum PTH was observed with both regimens, compared with baseline and with the control procedure. Over this period of time, no differences were observed between the two treatment regimens. However, between the sixth and the ninth hour, serum PTH levels were still significantly decreased compared with baseline with split dose Orocal D3 administration, while they returned to baseline value with the Cacit D3 preparation. During this period, the percentage decrease in serum PTH compared with baseline was significantly more pronounced with Orocal D3 than with Cacit D3 (P = 0.0021). We therefore conclude that the administration of two doses of 500 mg of calcium and 400 IU of vitamin D3 6 hours apart provides a more prolonged decrease in serum PTH levels than the administration of the same total amount of Ca and vitamin D as a single morning dose in young healthy volunteers. This might have implications in terms of protection of the skeleton against secondary hyperparathyroidism and increased bone resorption and turnover in elderly subjects.
Calcified Tissue International | 1995
L. M. Thiry-Blaise; An Taquet; Jean-Yves Reginster; Betty Nusgens; P. Franchimont; C. M. Lapiere
Osteoporosis is a slowly progressing disease resulting from an imbalance between bone accretion and degradation. As interstitial collagenase is a key enzyme in the degradatior 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.
Osteoporosis International | 1997
Jean-Yves Reginster; An Taquet; G. Fraikin; Christiane Gosset; Brigitte Zegels
Osteoporosis is a disease characterized by a decrease in bone mass and a deterioration in skeletal microarchitecture leading to an increased fragility and susceptibility to fracture [I]. It is now widely accepted that one of the major determinants of skeletal weakness results from the bone loss occurring after the menopause as a consequence of dramatically increased osteoclastic resorption, only partially compensated by a moderate rise in the rate of bone formation by the osteoblasts [2]. Prevention of early postmenopausal bone loss has been successfully achieved by the use of drugs specifically aimed at reducing or inhibiting bone resorption. Estrogen [3], calcitonins [4,5] and bisphosphonates [68] are now considered safe and effective ways of maintaining mineral density of trabecular and/or cortical bone at premenopausal levels by counteracting the exacerbated activity of osteoclasts induced by the sharp postmenopausal decrease in circulating endogenous estrogens. However, in many cultural backgrounds, secondary prevention of osteoporosis, initiated in the immediate postmenopause, is not yet considered a public health priority either by the specialists dealing with bone metabolic disorders or by the primary care physicians, stillless by the general population [9,10]. Subsequently, care takers frequently face much more complicated situations with women consulting for the first time at later stages of the disease, namely after the diagnosis of osteoporosis has already been made, on the basis of random radiographs, densitometry measurements or, even worse, after the first fracture event. Unfortunately, no single medication of those currently available has yet unequivocally demonstrated its ability to fully prevent the occurrence of new vertebral or peripheral osteoporotic fractures once the disease is established. Even though a few promising results have been reported with inhibitors of bone resorption [11-15], patients treated
Endocrinology and Metabolism Clinics of North America | 1998
Jean-Yves Reginster; An Taquet; Christiane Gosset
None of the currently available medications for osteoporosis have demonstrated an ability to fully prevent the occurrence of new vertebral or peripheral osteoporotic fractures once the disease is established. Several new therapies, therefore, are currently being developed to optimize the risk/benefit ratio of osteoporosis treatment. This article discusses a number of treatments currently being considered, including anabolic steroids, growth hormone or insulin-like growth factors, ipriflavone, parathyroid peptides, and strontium. Several other compounds have been suggested recently for treatment of osteoporosis and other are at very early stages of their development. In addition to pharmacologic approaches to the treatment of osteoporosis, hip protectors also may reduce hip fractures.
Osteoporosis International | 1996
Jean-Yves Reginster; Brigitte Zegels; L Meurmans; Lucio Claudio Rovati; An Taquet; Ivo Setnikar; Julien Collette
BONE MASS IN POSTMENOPAUSAL WOMEN Passed M., Int. Med. Inst., Universit. 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.
Journal of Bone and Mineral Research | 1997
Jean-Yves Reginster; L Meurmans; Brigitte Zegels; Lucio Claudio Rovati; Helmut W. Minne; Giampaolo Giacovelli; An Taquet; Ivo Setnikar; Julien Collette
Osteoporosis International | 1996
An Taquet; B Clemmensen; Brigitte Zegels; P Ravin; Claus Christiansen; I Roumagnac; Jean-Yves Reginster