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P J Meunier

Publications and source records attributed to P J Meunier.

At least 19 recordsLinked to original sources
PubMed2000

Activity increase after extraction of alkaline phosphatase from human osteoblastic membranes by nonionic detergents: influence of age and sex.

The solubilization of alkaline phosphatase (AP) from osteoblastic cell membranes obtained from human primary bone cell cultures was studied according to the age and sex of the donors (17 females, 11 males; age range: 2-77 years). Cell membranes were treated by non-ionic (n-octyl beta-D-glucopyranoside, OG), ionic or zwitterionic detergents, then centrifuged. When OG was used almost all the AP was solubilized. AP activity in supernatant of solubilization was compared to the activity of the suspension before centrifugation. The activity ratio (AR) increased in function of age for subjects between 65 and 74. Neither total nor specific AP activities were influenced by age or sex. Electrophoresis studies showed that the AP released was a GPI (glycosyl phosphatidylinositol)-anchored protein, amphipathic form, with 140 kDa as apparent molecular mass. The activity change of AP in the presence of OG may result from age-related modifications either in the AP structure or in the constituents of the plasma membranes (proteins or phospholipids).

Adolescent↗
PubMed2000

Alendronate and estrogen effects in postmenopausal women with low bone mineral density. Alendronate/Estrogen Study Group.

The bisphosphonate alendronate and conjugated equine estrogens are both widely used for the treatment of postmenopausal osteoporosis. Acting by different mechanisms, these two agents decrease bone resorption and thereby increase or preserve bone mineral density (BMD). The comparative and combined effects of these medications have not been rigorously studied. This prospective, double blind, placebo-controlled, randomized clinical trial examined the effects of oral alendronate and conjugated estrogen, in combination and separately, on BMD, biochemical markers of bone turnover, safety, and tolerability in 425 hysterectomized postmenopausal women with low bone mass. In addition, bone biopsy with histomorphometry was performed in a subset of subjects. Treatment included placebo, alendronate (10 mg daily), conjugated equine estrogen (CEE; 0.625 mg daily), or alendronate (10 mg daily) plus CEE (0.625 mg daily) for 2 yr. All of the women received a supplement of 500 mg calcium daily. At 2 yr, placebo-treated patients showed a mean 0.6% loss in lumbar spine BMD, compared with mean increases in women receiving alendronate, CEE, and alendronate plus CEE of 6.0% (P < 0.001 vs. placebo), 6.0% (P < 0.001 vs. placebo), and 8.3% (P < 0.001 vs. placebo and CEE; P = 0.022 vs. alendronate), respectively. The corresponding changes in total proximal femur bone mineral density were +4.0%, +3.4%, +4.7%, and +0.3% for the alendronate, estrogen, alendronate plus estrogen, and placebo groups, respectively. Both alendronate and CEE significantly decreased biochemical markers of bone turnover, specifically urinary N-telopeptide of type I collagen and serum bone-specific alkaline phosphatase. The alendronate plus CEE combination produced slightly greater decreases in these markers than either treatment alone, but the mean absolute values remained within the normal premenopausal range. Alendronate, alone or in combination with CEE, was well tolerated. In the subset of patients who underwent bone biopsies, histomorphometry showed normal bone histology with the expected decrease in bone turnover, which was somewhat more pronounced in the combination group. Thus, alendronate and estrogen produced favorable effects on BMD. Combined use of alendronate and estrogen produced somewhat larger increases in BMD than either agent alone and was well tolerated.

Adult↗
PubMed1999

Separate and combined value of bone mass and gait speed measurements in screening for hip fracture risk: results from the EPIDOS study. Epidémiologie de l'Ostéoporose.

Based on data from the EPIDOS prospective study, we have shown that femoral bone mineral density (BMD), calcaneal ultrasound measurements and fall-related factors are significant predictors of the risk of hip fracture. The goal of the present investigation, in the same cohort of elderly women, was (1) to assess and compare the value of femoral BMD, calcaneal broadband ultrasound attenuation (BUA), gait speed and age for identifying elderly women at high risk of hip fracture and (2) to determine whether combining two or more of these measurements would improve predictive ability over single measures. A total of 5895 elderly women had baseline measurements of femoral neck BMD by dual-energy X-ray absorptiometry, calcaneal BUA and gait speed. During an average of 33 months of follow-up, 170 women suffered a hip fracture. We compared the sensitivity and specificity of single and combined measures for three specific cutoff levels to define high risk, i.e., the median, the top quartile and the top decile of risk. We found that femoral BMD, calcaneal BUA, gait speed and age have approximatively the same discriminant value to identify women at high risk of hip fracture even though certain measures and combinations of measures have a significantly higher sensitivity for certain cutoff levels. The sensitivity of the available screening tools is low, even when they are combined: to obtain a sensitivity of about 80%, approximately 50% of the population must be considered to be at high risk.

Aged↗
PubMed1999

Treatment of postmenopausal women with osteoporosis or low bone density with raloxifene. Raloxifene Study Group.

Raloxifene, a selective estrogen receptor modulator (SERM), has been shown to improved bone mineral density (BMD) and serum lipid profiles in healthy postmenopausal women. The objective of this study was to examine the effects of raloxifene on BMD, biochemical markers of bone metabolism and serum lipids in postmenopausal women with low bone density or osteoporosis. This Phase II, multicenter, 24-month, double-masked study assessed the efficacy and safety of raloxifene in 129 postmenopausal women (mean age +/- SD: 60.2 +/- 6.7 years) with osteoporosis or low bone density (baseline mean lumbar spine BMD T-score: -2.8). Women were randomly assigned to one of three treatment groups: placebo, 60 mg/day raloxifene-HCl (RLX 60) or 150 mg/day raloxifene-HCL (RLX 150) and concomitantly received 1000 mg/day calcium and 300 U/day vitamin D3. At 24 months, BMD was significantly increased in the lumbar spine (+3.2%), femoral neck (+2.1%), trochanter (+2.7%) and total hip (+1.6%) in the RLX 60 group compared with the placebo group (p < 0.05). The RLX 150 group had increases in BMD similar to those observed with RLX 60. A greater percentage of raloxifene-treated patients, compared with those receiving placebo, had increased BMD (p < 0.05). Serum bone-specific alkaline phosphatase activity, serum osteocalcin, and urinary type I collagen:creatinine ratio were significantly decreased in the RLX-treated groups, compared with the placebo group (p < 0.01). RLX 60 treatment significantly decreased serum levels of triglycerides, and total- and LDL-cholesterol levels (p < 0.01). The rates of patient discontinuation and adverse events were not significantly different among groups. In this study, raloxifene increased bone density, decreased bone turnover, and improved the serum lipid profile with minimal adverse events, and may be a safe and effective treatment for postmenopausal women with osteoporosis or low bone density.

Aged↗
PubMed1999

High-resolution computed tomography for architectural characterization of human lumbar cancellous bone: relationships with histomorphometry and biomechanics.

The aim of the present study on human vertebral cancellous bone was to validate structural parameters measured with high-resolution (150 microm) computed tomography (HRCT) by referring to histomorphometry and to try to predict mechanical properties of bone using HRCT. Two adjacent vertical cores were removed from the central part of human L2 vertebral body taken after necropsy in 22 subjects aged 47-95 years (10 women, 12 men; mean age 79 +/- 14 years). The right core was used for structural analysis performed by both HRCT and histomorphometry. Two cancellous bone specimens were extracted from the left core: a cube for HRCT and a compression test, and a cylinder for a shear test. Significant correlations were found between HRCT and histomorphometric measurements (BV/TV, trabecular thickness, separation and number, and node-strut analysis), but with higher values for most of the tomographic parameters (BV/TV and trabecular thickness determined by HRCT were overestimated by a factor 3.5 and 2.5 respectively, as compared with histomorphometry). The maximum compressive strength and Young's modulus were highly correlated (rho = 0.99, p<0.0005). Significant correlation was obtained between bone mineral density (determined using dual-energy X-ray absorptiometry) and the maximum compressive strength (rho = 0. 64, p = 0.002). In addition the maximum compressive strength and architectural parameters determined by HRCT or histomorphometry showed significant correlations (e.g., for HRCT, BV/TV: rho = 0.88, p<0.0005, N.Nd/TV: rho = 0.73, p<0.001). The shear strength was significantly correlated with BV/TV (rho = 0.62, p = 0.002), Tb.Sp (rho = -0.58, p = 0.004) and TSL (rho = 0.55, p = 0.006) measured by HRCT. In conclusion, an HRCT system with 150 microm resolution is not sufficient to predict the true values of the structural parameters measured by histomorphometry, although high correlations were found between the two methods. However, we showed that a resolution of 150 microm allowed us to predict the mechanical properties of human cancellous bone. In vivo peripheral systems with such a resolution should be of interest and would deliver an acceptable radiation dose to the patient.

Aged↗
PubMed1999

Diagnosis and management of osteoporosis in postmenopausal women: clinical guidelines. International Committee for Osteoporosis Clinical Guidelines.

The authors, all physicians involved in clinical research on bone and practicing clinicians, propose practical guidelines for identifying persons with osteoporosis or those at high risk of developing the disease and for managing patients who may benefit from therapy. These guidelines are based on an analysis of peer-reviewed articles published before November 1998. A flowchart of women who might benefit from treatment is provided, including clinical presentation (recent fracture of the spine, hip, or other bone or no fracture; risk factors for osteoporosis); relevant investigations (bone mineral density measurement and laboratory tests required for the differential diagnosis); and therapeutic management (general measures such as calcium and vitamin D supplementation and specific pharmacologic interventions such as estrogen, bisphosphonates, intranasal calcitonin, raloxifene, fluoride salts, and other compounds that have been assessed in randomized clinical trials). The strongest evidence for antifracture efficacy (reduction of vertebral and nonvertebral fracture risk) was observed with alendronate.

Adult↗
PubMed1999

Influence of strontium on bone mineral density and bone mineral content measurements by dual X-ray absorptiometry.

The presence of Sr in bone influences bone mineral density (BMD) and content (BMC) measurements by dual-energy X-ray absorptiometry (DXA). This interaction is of interest, since strontium ranelate (S12911) demonstrated positive effects on bone metabolism in various animal models of osteoporosis, and is currently being evaluated for treatment of postmenopausal osteoporosis. The present in vitro study aimed to determine adjustment factors for DXA measurements of BMC and BMD at different Sr concentrations in order to estimate the corresponding values that would have been measured without Sr. A series of mixtures of Ca and Sr hydroxyapatites were prepared, with biologically relevant Sr/Ca ratios ranging from 0 to 3.5 mol/mol%, and a constant total concentration of divalent cations (145 mmol). The mixtures were conditioned in plastic dishes 4.5 cm in diameter, to obtain an areal density close to the human vertebral mineral density of 0.7-1.1 g/cm(2). DXA measurements of the mixtures were made with a wide range of different instruments and various acquisition modes. A direct linear relationship (r(2) > 0.99) was found between strontium content and overestimation of BMD and BMC. There were no significant differences in adjustment factors for BMC or BMD between the different machines or acquisition modes, and the presence of Sr in the water bath used to mimic soft tissues did not affect the accuracy and precision of the method. This demonstrates that reliable DXA determinations of BMD may be carried out in the presence of Sr, and may be interpreted in terms of calcium hydroxyapatite equivalent if the bone Sr content of the measured bone is known. The same adjustment factor (10% overestimation for 1 mol/mol% Sr) can be used for all presently available types of instrument and acquisition modes.

Absorptiometry, Photon↗
PubMed1999

Bone metastases from bronchial carcinoid tumors. Two case-reports.

Two case-reports of metastatic bone disease in patients with bronchial carcinoid tumors illustrate the diagnostic challenges raised by these slowly-growing malignancies of which the primary frequently escapes early identification. The first patient had the typical picture of a primary with a single bone metastasis. Unusual features in the second patient were the large number of bone metastases, involvement of distal skeletal sites, and elevation of serotonin and 5-hydroxyindoleacetic acid levels.

Aged↗
PubMed1999

Evidence-based medicine and osteoporosis: a comparison of fracture risk reduction data from osteoporosis randomised clinical trials.

The goal of osteoporosis therapy is to prevent fractures, and many therapies are available for this disease. Regarding proven fracture benefit, however, the quality of the randomised clinical trial evidence varies substantially among therapies. The purpose of this paper is, therefore, to review the published osteoporosis randomised clinical trial literature and to assess the quality of the evidence. Although more than 35 randomised trials for different therapies were reviewed, only alendronate and vitamin D plus calcium have clearly demonstrated a fracture benefit, with alendronate providing the greatest relative risk reduction. Quality clinical trial fracture data for calcitonin, etidronate, fluoride, hormone replacement therapy, parathyroid hormone, calcitriol (and other vitamin D preparations), vitamin D and calcium monotherapy, and selective oestrogen receptor modulators are either lacking or inconclusive or published only as abstracts.

Alendronate↗
PubMed1999

Effect of multiple intravenous pamidronate courses in Paget's disease of bone.

BACKGROUND: Pamidronate is a bisphosphonate whose short-term biological efficacy in Paget's disease of bone was convincingly established many years ago. A less well studied area is the efficacy of pamidronate in slowing disease progression and in preventing and treating complications. MATERIAL AND METHODS: We conducted an uncontrolled retrospective study of 79 Paget's disease patients given multiple intravenous pamidronate courses over a mean period of 45 +/- 19 months. The pamidronate dose per course was 180 mg, usually given over three days. The disease was severe and in some cases had proved refractory to other medications. Reasons for pamidronate therapy were pain or other subjective symptoms; established bone, joint, or nervous system complications; or prevention or these complications in patients with involvement of high-risk sites. RESULTS: Bone and joint pain improved under therapy, and in 78% of cases the outcome in terms of complication treatment and/or prevention was favorable. An important finding was waning of the clinical and biological effects of pamidronate as the number of courses increased. Fourteen percent of patients developed resistance to pamidronate, which seemed more closely related to disease extension than to focal lesion activity. CONCLUSION: These data suggest that a prompt return to normal of laboratory markers, most notably total alkaline phosphatase, should be sought, if needed by using higher doses than in our study.

Adult↗
PubMed1999

[Effects of raloxifene on bone loss and fracture risk in the menopausal woman].

The relevance and efficacy of long-term estrogen therapy is well established, though some undesirable side effects and contraindications persist. Raloxifene, the first selective estrogen receptive modulator (SERM) tested in phase III trials, offers a choice alternative. It increases bone mineral density, lowers serum lipid concentrations and reduces vertebral fractures.

Aged↗