Unsuccessful attempt to demonstrate progesterone's bone formation actions.
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Bone Remodeling↗
Biomedical subjects
F Tremollieres
Publications and source records attributed to F Tremollieres.
Accuracy and precision of in vivo bone mineral measurements in sheep using dual-energy X-ray absorptiometry.
We evaluated the precision and accuracy of in vivo measurements of spine bone mineral density (BMD) and bone mineral content (BMC) in five ewes using dual-energy X-ray absorptiometry (DXA, Lunar DPX-L). The short-term in vivo reproducibility expressed as the coefficient of variation (CV) varied from 0.9 to 1.6% for spine BMD and from 1 to 3.1% for spine BMC. The ex vivo measurements, performed in 20 cm of water to simulate soft tissue thickness, correlated closely with the in vivo measurements, yielding an r value of 0.98 and 0.97 for spine BMD and BMC, respectively. The accuracy was determined by comparing the total BMC of each vertebra measured in vivo with the corresponding ash weight. The correlation coefficient between the two measurements was r = 0.98, with an accuracy error of 5.6%. We concluded that the DXA allows a precise and accurate measurement of spine bone mineral in live ewes using the methodology designed for humans.
Absorptiometry, Photon↗
[Estrogens and selective estrogen receptor modulators in the treatment of osteoporosis].
Estrogen deficiency is the major determinant of bone loss, not only in the first years postmenopause, but also throughout the entire life and in the elderly. Major progress in the knowledge of cellular actions of estrogens has been made leading to a better understanding of the underlying mechanisms of different estrogen-deficiency related diseases such as osteoporosis, atherosclerosis and also maybe cerebral aging. Estrogen replacement therapy remains the first choice treatment in the prevention of postmenopausal osteoporosis, but the continuous aging process of the female population raises the question of a better strategy of action in a more efficient prevention of hip fractures. Moreover, the potential gynecological effects of estrogens are likely to limit their indications or long-term use. The development of new compounds, called SERMs (selective estrogen receptor modulators), with both agonist and antagonist estrogen actions, in particular with no negative effects on the uterus and the breast opens new therapeutical insights into the prevention of postmenopausal osteoporosis.
Age Factors↗
Effects of cyclical etidronate therapy on bone loss in early postmenopausal women who are not undergoing hormonal replacement therapy.
This study was carried out to investigate the effectiveness and tolerability of cyclical etidronate therapy in the prevention of bone loss occurring in early postmenopausal women who are not undergoing hormone replacement therapy (HRT). A total of 109 Caucasian women aged 45-60 years were treated with etidronate 400 mg/day or placebo for 14 days followed by calcium supplementation 500 mg/day for 77 days. Ninety-one women completed the 2 years of the study. After 2 years, the estimated difference between the two groups as regards lumbar spine bone mineral density (BMD) was 2.53% (SEM 1.07%; p = 0.01); BMD of the hip and wrist were not significantly different between treatment groups. A clear reduction in bone turnover was obtained as evidenced by a significant decrease in serum alkaline phosphatase level and in urinary N-telopeptide/ creatinine ratio in the etidronate group; the difference between the two groups was -12% +/- 3.2% for serum alkaline phosphatase level (p = 0.019) and -22.9% +/- 13.7% for the urinary N-telopeptide/creatinine ratio (p = 0.047). There was no statistically significant difference between the two groups in terms of the serum osteocalcin levels and urinary hydroxyproline/ creatinine and calcium/creatinine ratios. Etidronate was generally well tolerated and its adverse event profile was similar to that of placebo. The results of this study indicate that cyclic etidronate therapy can prevent trabecular bone loss, with no deleterious effect on cortical bone, in the first 5 years of menopause and that it has a very high safety margin.
Alkaline Phosphatase↗
Can we detect women with low bone mass using clinical risk factors?
The magnitude of osteoporosis, the established relationship between low bone mass and the risk of fracture, and the availability of preventive treatment suggest that the early detection of women with low bone mass is justified. The feasibility of population screening using bone mass measurements remains controversial. Another approach is the use of clinical risk factors to detect women at high risk. However, several studies have demonstrated that the assessment of risk factor status does not appear to be an efficient tool for the identification of perimenopausal women with low bone mass. The poor performance of the prediction models might be explained in part by unmeasured factors, especially genetic factors, which are an important determinant of bone mass. On the other hand, the clinical usefulness of clinical risk factors needs to be more precisely evaluated, especially in the detection of women at high risk for hip fracture.
Bone Density↗
Effect of menopause on femoral and vertebral bone loss.
The aim of this study was to investigate the effect of menopause on bone loss in the proximal femur and the lumbar spine. The rates of change in bone mineral density (BMD) were measured longitudinally by dual X-ray absorptiometry (DXA) at the femoral neck (FN), Ward's triangle (WT), and trochanter (TR) together with the lumbar spine in 81 healthy postmenopausal women (45-65 years of age) who had passed a natural menopause, 6 months to 12 years before. A significant correlation between the rate of change and interval since menopause was evidenced. The best fit of the data was a binomial function of interval since menopause at the spine, FN, and WT and a simple linear regression at TR level. At each skeletal site, the rate of bone loss (mean +/- SD) was significantly different (p<0.05) and twice as high in women who were between 6 months and 2 years postmenopausal at enrollment (FN, -1.82 +/- 1.1%; WT, -2.43 +/- 1.7%; TR, -1.12 +/- 1.7%) than in those who were beyond 5 years of menopause (FN, -0.48 +/- 0.8%; WT, -0.68 +/- 2.1% TR, 0.41 +/- 1.2%). A poor correlation (r = 0.39 - 0.42, p<0.001) was found between the rate of vertebral and that of femoral postmenopausal bone loss. This study demonstrates that menopause is associated with a rapid and transient bone loss in BMD of the proximal femur, which declines with time after 3 years. These data suggest that therapy should be initiated as early as possible after menopause to prevent bone loss.
Absorptiometry, Photon↗
[Sex steroids and bone tissue].
The precise mechanism of action of sexual steroids in the regulation of bone tissue is still poorly understood. Besides the indirect action via the production of calciotropic hormones, the fact that receptors respond to oestrogens as well as to androgens and progesterone is evidence that sexual steroids have a direct action in regulating bone activity. The anti-osteoclastic action of oestrogens, via the modulation in osteoblastic production of different substances such as interleukin-1 and -6, TGF beta, GM-CSF which inhibit osteoclastogenesis and bone resorption activity, is well documented. More recently, the direct role in osteoclast inhibition was suggested by the observation that osteoclasts carry oestrogen receptors. Likewise, certain in vivo and in vitro data suggest that oestrogens could also have a positive effect on bone formation regulation. For androgens, currently available data show that in vitro stimulation of bone formation, with increased proliferation and cell differentiation, could be mediated by TGF beta. The role of progesterone is more recently known. In vivo, progesterone increases cell growth and IFGF-II secretion by non-transformed human osteoblasts. The number of potential mechanisms which have already been demonstrated suggest the complexity of sex hormone regulation which leads to the final situation of physiological calcium sparing in the skeleton while maintaining skeletal structure.
Bone and Bones↗
Should we define osteoporosis based on bone mineral density criteria?
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Absorptiometry, Photon↗
The effects of menopause on longitudinal bone loss from the spine.
Two hundred and thirty women aged 45-66 years were divided into three groups according to their menopausal status and were followed to assess the changes in vertebral bone mineral density (BMD). These included 71 premenopausal, 42 perimenopausal, and 117 postmenopausal women. Menopausal status was assessed through menstrual history and plasma concentrations of 17 beta estradiol and luteinizing hormone. BMD was measured by dual photon absorptiometry between 2 and 5 times over an average period of 27 months, and annual rates of changes were calculated by linear regression. BMD decreased significantly (P < 0.0001) in the three groups during the follow-up. Mean (+/- SD) annual rate of change was -0.79 +/- 1.5% for premenopausal, -2.35 +/- 1.5% for perimenopausal, and -1.24 +/- 1.5% for postmenopausal women. There was no difference in the rates of bone loss between the perimenopausal group and the postmenopausal group within 3 years after menopause (1-2 years: -2.34 +/- 2.1%; 2-3 years: -1.9 +/- 1.5%). Thereafter, rates decreased exponentially with time since menopause to fall out at the same level as the premenopausal level. These longitudinal data indicate that vertebral bone loss begins before menopause and accelerates sharply during menopause to decline exponentially with time after 3 years.
Absorptiometry, Photon↗
Spine and femur densitometry at the menopause: are both sites necessary in the assessment of the risk of osteoporosis?
The aim of our study was to compare the results provided by the measurement of vertebral and femoral bone mineral density (BMD) for assessing the individual risk of osteoporosis as defined by either low BMD and/or rapid bone loss. Vertebral and femoral BMD were measured twice at a mean interval of 21 months in 85 normal, early postmenopausal women who had passed a natural menopause 6 months to 3 years previously. According to the measurement site, 36% (spine), 29% (femoral neck), 35% (Ward's triangle), and 25% (trochanter) fall in the "at risk" category, defined by a BMD value of 1 SD or more below the normal values for premenopausal women. Based on vertebral BMD, 39-48% of the women at risk had a normal femoral BMD. On the other hand, 24-37% of the women classified at risk based on femoral BMD maintained a low risk at the vertebral level. The annual rate of bone loss was significantly greater for the Ward's triangle (-2.7 +/- 3.8%) and femoral neck (-2.1 +/- 2.5%) than for the spine (-1.5 +/- 2.1%) and trochanter (-1.5 +/- 3.4%). There was a significant relationship between the rate of loss measured at the spine and femoral levels (r = 0.34-0.58). Among the 21 women with a rapid vertebral bone loss, 48-67% had a low bone loss at the femoral level and vice versa. The ratio between mean rate of loss and the precision of the measurement sites was greater for the spine (1.6) compared with the femur (1.1-0.71).(ABSTRACT TRUNCATED AT 250 WORDS)
Absorptiometry, Photon↗
Risk factors for hip fracture. MEDOS study: results of the Toulouse Centre.
The development of preventive strategies for hip fractures requires better identification of risk factors. The MEDOS study was designed to study prospectively the incidence of hip fracture in 14 centres from six countries and characterise risk factors. At one centre (Toulouse), data were gathered from questionnaires completed by 386 cases of hip fracture aged over 50 years and 848 age- and sex-matched controls over a 12-month period. Of the 935 variables of the MEDOS questionnaire, 235, grouped into 56 items, were statistically analysed. Odds ratios (and 95% confidence intervals) were estimated for each variable from a multiple stepwise logistic regression model. The population comprised 19.2% men and 80.8% women, with a mean age of 80 +/- 8.8 years; 80% were living in an urban area and 76% with their family. Of the 17 significant variables, moderate excess weight and a high nutritional intake of calcium were associated with a decreased risk of hip fracture. Loss of autonomy, a higher height than normal (> 1SD), and a history of previous fractures significantly increased the risk of fracture. Interestingly, all these variables accounted for only 18% of the risk of hip fracture.
Aged↗
Prevention of post-menopausal bone loss with 1 alpha-hydroxy vitamin D3. A three-year prospective study.
An open and controlled prospective study was used to assess the preventive efficiency of 1 alpha-hydroxy vitamin D3 (1 alpha (OH) Vit. D3) on post-menopausal vertebral bone loss. Of the 36 patients included in the study, 25 completed two years of treatment with 1 microgram/day of 1 alpha (OH) Vit. D3 and 500 mg of calcium. The vertebral bone mineral density measured by dual photon absorptiometry did not vary in the treated group, whereas it decreased significantly in the control group at the end of the 2 years. At two years, withdrawal of treatment led to a significant bone loss, whereas bone mass remained stable in a subgroup of patients who underwent a third year of treatment with 1 alpha (OH) Vit. D3. Overall, tolerance was satisfactory. However, urinary calcium increased significantly during treatment and one third of the patients developed hypercalciuria > or = 7.5 mmoles/24 h. No variation in either serum calcium or creatinine levels was noted. These results indicate that 1 alpha (OH) Vit. D3 could be useful in preventing post-menopausal bone loss provided it was complemented by regular monitoring of urinary calcium excretion.
Aged↗
Effect of 17 beta-oestradiol and norethisterone acetate on vertebral bone mass and lipid metabolism in early postmenopausal women.
We studied the effects on vertebral bone density and lipid metabolism of long-term administration of 17 beta-oestradiol combined with norethisterone acetate in a 2-year prospective study carried out in 40 women, divided into 2 groups of 20 subjects. One group received treatment, while the other constituted the control group. In the untreated group, vertebral bone density was found to be decreased significantly by 1.1% at 12 months and by 4.4% at 24 months in relation to initial values (P < 0.001). Total cholesterol was significantly higher (P < 0.05) at the end of the 2-year period. By contrast, in the treated group, bone density showed significant increases of 5.6% at 12 months and 7% at 24 months (P < 0.001). Significant reductions in the biochemical markers of bone remodelling (osteocalcin and the urinary calcium/urinary creatinine ratio) were also observed. Total cholesterol, high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol and triglycerides did not change significantly during treatment. These results, as well as the good compliance with treatment (78%), suggest that this treatment regimen could be useful in the prevention of postmenopausal bone loss.
Bone Density↗
Assessment of the risk of post-menopausal osteoporosis using clinical factors.
OBJECTIVE: We wished to assess the predictive value of the main clinical risk factors for osteoporosis over a low vertebral bone mineral density. DESIGN: A cross-sectional study was made of a cohort of peri and post-menopausal women (mean age, 54 years). PATIENTS: One thousand, five hundred and sixty-five normal white women were selected from among the women referred to our menopause clinic for screening and prevention of osteoporosis. MEASUREMENTS: Each woman had replied to a detailed standardized questionnaire including the main clinical risk factors and had her bone density measured using dual photon absorptiometry. RESULTS: The predictive value for a low vertebral bone mineral density (2 SD below the normal young adult value) was assessed for 15 historical and anthropometric variables. Among these, age, age at menarche, weight, height, menopause and its duration, were independent predictors of a low bone mineral density, in a multiple logistic regression analysis. Odds ratios were calculated for each of these variables, weight, menopause and its duration being the three most influential variables. At best this model makes it possible to correctly classify 73% of women with a low bone mineral density and 66% of those with a normal bone mineral density. If this model is used for screening, it could possibly save 25% of bone densitometry examinations. CONCLUSIONS: Direct bone densitometry remains indispensable to assess osteoporosis risk, since risk factors alone are not sufficient for accurate delineation of either low or normal bone mineral density.
Adult↗
Studies on regulation of insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-4 production in human bone cells.
Previous studies have shown that the actions of IGF-II in bone are determined not only by its concentration, but also by the concentration of IGFBP-4 as well as other IGFBPs. In this study, we sought to determine by Western ligand blotting the effects of growth hormone, IGF-I and IGF-II on the production of IGFBP-3 and IGFBP-4 in TE89 human osteosarcoma cells and in untransformed normal human bone cells derived from rib. Human growth hormone at 10 micrograms/l decreased the amount of IGFBP-4 but had no effect on the IGFBP-3 level in the conditioned medium of low density cultures of TE89 cells and human bone cells derived from rib. Human growth hormone had no effect on IGFBP-3 or IGFBP-4 levels in the conditioned medium of high density human bone cell cultures. IGF-I and IGF-II, which increased human bone cell proliferation, decreased the level of IGFBP-4 (30% of control at 100 micrograms/l IGF-I and IGF-II) but increased the level of IGFBP-3 (3-10 fold at 100 micrograms/l IGF-I and IGF-II) after 48 h of treatment in the conditioned medium of both low and high density TE89 cell cultures. Similar changes in IGFBP-3 and IGFBP-4 levels were also seen in the conditioned medium of human bone cells derived from rib after treatment with IGF-I and IGF-II. Studies to determine the underlying molecular mechanisms by which IGF-II decreased the amount of IGFBP-4 in the conditioned medium revealed that IGF-II decreased the IGFBP-4 mRNA abundance and increased the IGFBP-3 mRNA abundance in human bone cells. Based on the above findings, we conclude that the production of both IGFBP-3 and IGFBP-4 is regulated in bone cells and that local and systemic agents may modulate the responsiveness of bone cells to IGFs by regulated secretion of IGFBP-3 and IGFBP-4.
Base Sequence↗
Precision and sensitivity of dual-energy x-ray absorptiometry in spinal osteoporosis.
This study evaluated the performance of dual-energy x-ray absorptiometry (DEXA) with regard to (1) the correlation with dual-photon absorptiometry (DPA), (2) the ability to discriminate between normal and osteoporotic patients, and (3) long-term reproducibility. The bone mineral density (BMD) of the spine in 112 subjects, both normal and osteoporotic, was measured with DPA and DEXA (Lunar Corporation, Madison, Wisconsin) of the spine. The femur BMD of 22 cases was also measured with both machines. The results for the two techniques were highly correlated (r greater than 0.9, SEM = 0.02 to 0.04 g/cm2). BMD was measured using DEXA in 80 women (mean age = 61 years) with established spinal osteoporosis and 110 normal age-matched controls. The osteoporotic patients had significantly reduced spine and femur BMDs compared to the controls: -23% for L2-4 BMD (Z score = 2.6) and -13 to -20% for femur BMD (Z score = 1.1-1.3). L2-4 BMD had the best discriminative value, with an area under the ROC curve of 94%; the Ward's triangle BMD had an area of 84%. The precision error in vitro in a phantom over a 1-year period was 0.7%. The measured precision in vivo with young adults was approximately 1% (SD = 0.012 g/cm2) for L2-4 BMD and 1.7-2.3% (SD = 0.015-0.022 g/cm2) for femur over the 1 year period. The reproducibility was not as good for osteoporotic patients (SD = 0.017 g/cm2).
Absorptiometry, Photon↗
Fluoride therapy in postmenopausal osteopenic women: effect on vertebral and femoral bone density and prediction of bone response.
Fifty-two postmenopausal women (mean age 60 +/- 5 years) with low BMD (less than -2SD of young adult values) but who had not experienced previous crush fracture were treated with 50 mg of sodium fluoride (NaF), 1 g of calcium and 400 IU of vitamin D2 per day for 2 years. Repeated vertebral and femoral BMD measurements were made and compared with those of a control group consisting of 16 untreated women. Serum alkaline phosphatase and osteocalcin, blood and urinary fluoride levels were measured regularly to determine their predictive value on bone response. 18 of 52 (35%) of the treated patients experienced side effects (29% gastric, 4% lower extremity pain syndrome) but only in 6 cases (12%) was it necessary to discontinue treatment. In neither of the two groups was any fracture recorded (vertebral or otherwise). Among the 43 women who were treated for at least 2 years, 21 (49%) were considered to have responded (i.e., with an increase of vertebral BMD greater than 0.043 g/cm2). There was a mean linear increase in BMD in this group of 0.0041 g/cm2 per month (i.e., 5.5% per year). On the other hand in the non-responder group and in the control group, vertebral BMD either remained stable or decreased. However no difference was detected between the two groups (treated and controls) at the femoral site after 2 years; both groups showed a significant decrease in BMD. The responders had a lower initial osteocalcin level and treatment led to a relatively greater increase in osteocalcin.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Bone mineral density and thyroid hormone therapy.
The purpose of this study was to evaluate prospectively the evolution of femoral and vertebral bone mineral density (BMD) in hypothyroid subjects treated with replacement doses (mean +/- SD dose of L-thyroxine = 135 +/- 32 micrograms/day) as compared to an untreated group. Vertebral bone density was also measured in other patients who had been treated for at least 2 years with either suppressive (mean dose = 154 +/- 36 micrograms/day, n = 28) or replacement doses (mean dose = 104 +/- 52 micrograms/day, n = 21) according to the thyrotrophin response (TSH) to the thyrotrophin releasing hormone (TRH) administration. In primary hypothyroid patients, a mean decrease of 5.4% (P less than 0.01) for vertebral BMD, 7.3% (P less than 0.01) for trochanter and 7% (P less than 0.001) for femoral neck was observed after 1 year of treatment. This loss was unrelated either to age or to menopausal status (ANOVA). A clinical and hormonal state of euthyroidism was reached since the 3rd month of treatment. Fasting urinary calcium/creatinine excretion was increased significantly (P less than 0.05) at the 3rd month, and plasma osteocalcin (OC) increased significantly from the 3rd month onwards (P less than 0.05) up to the 12th month (P less than 0.025). In the cross-sectional study, vertebral BMD was not significantly different from age-matched normal values in patients receiving either substitutive or suppressive doses of LT4. These results suggest that in the case of primary hypothyroidism even appropriate thyroid replacement therapy could lead during the first year of treatment to a significant reduction in vertebral and femoral BMD. However, the fact that an increased fracture rate has not been documented in long-term treated patients, and the results of our cross-sectional study, suggest that this bone mass reduction could be transient and reversible due to new bone formation at the end of the resorptive sequence.
Adult↗