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Risk for developing osteoporosis in untreated premature menopause.

The bone mineral density (BMD) of the lumbar spine and proximal femur was determined by dual photon absorptiometry in 32 women with untreated premature menopause (cessation of menses before 45 years of age). The BMD of the spine and proximal femur in four obese patients was not different from the BMD of the age-matched controls. On the contrary, the BMD of the nonobese females with premature menopause was significantly lower with respect to the average values found in healthy young women, in age-matched and menopause-matched controls. The BMD deficit was greater over the lumbar spine than in the proximal femur. Forty three percent of nonobese patients were already under the vertebral fracture threshold and 25% of nonobese patients were below the hip fracture threshold. The BMD deficit in the lumbar spine was correlated to the loss observed in the femoral neck (r = 0.59, P less than 0.001), in the trochanter (r = 0.65, P less than 0.001) and in the Ward's triangle (r = 0.73, P less than 0.001). A negative correlation was observed between years of menopause and the BMD of the lumbar spine (r = -0.39, P less than 0.05). The results indicate the high individual risk for osteoporotic fractures in nonobese females with untreated premature menopause. The BMD loss was greater over the skeletal areas that are predominantly composed of trabecular bone compared with cortical bone.

Absorptiometry, Photon↗

Discriminatory ability of bone mass measurements (SPA and DEXA) for fractures in elderly postmenopausal women.

We investigated the discriminatory ability of forearm bone mineral content (BMCarm) measured by single photon absorptiometry (SPA) and spinal bone mineral density (BMDspine) measured by dual-energy X-ray absorptiometry (DEXA) in 387 elderly postmenopausal women. Of these, 22 had never sustained a fracture (normal), 91 had had less than three vertebral wedge fractures (mild), 51 had experienced a peripheral fracture (moderate), and 24 had had more than three vertebral wedge or compression fractures (severe). BMCarm exceeded BMDspine slightly in the ability to discriminate the mild and moderate groups (P less than 0.01-0.001), whether calculations were performed on raw values or the Z-scores compared with premenopausal women. Receiver operating (ROC) analysis showed that at every cutoff level BMCarm had a similar ability as BMDspine to discriminate between the vertebral fracture (mild and severe) groups and healthy premenopausal and nonfractured postmenopausal women (normal), whereas BMCarm had a significantly higher discriminatory ability of peripheral fractures (P less than 0.05) (moderate) group compared with premenopausal women. We conclude that SPA and DEXA are equally capable as diagnostic procedures in women with established osteoporosis.

Absorptiometry, Photon↗

Osteonal remodeling and mechanical properties of the femoral cortex in rabbits treated with 24R,25(OH)2D3.

The increase of bone mass by therapeutics does not always mean the enhancement of bone quality. The purpose of this study is to clarify the changes of osteonal remodeling and the mechanical properties of femoral cortex in rabbits treated with 24R,25(OH)2D3. Fifteen NZW rabbits (3 kg B.W.) were divided into three groups of 5 animals each. Groups 1, 2, and 3 were given vehicle, 10 micrograms/kg, and 100 micrograms/kg 24R,25(OH)2D3, respectively, daily for 8 weeks. At the end of the experiment, the left femur was removed and bone mineral content (BMC) was measured with single photon absorptiometry. Serum 24,25(OH)2D concentrations reached levels of approximately 15 and 200 times that of the controls in groups 2 and 3, respectively. Neither 25(OH)D nor 1,25(OH)2D level showed any significant change in either group. Group 3 showed significant increase in mineral content and density in the epimetaphyseal regions, but the increase at the diaphyseal region did not reach a statistically significant level. Mechanical test for torsion was conducted for mid-cortical regions. After the test, bone pieces were bonded together with adhesive to reconstruct the original form, and undecalcified cross-sectional sections were made at the diaphyses. Fluorescent microscopy disclosed a marked reduction of remodeling in secondary osteonal bone area. The numbers for double-labeled osteons for groups 1, 2, and 3 were 2.47 +/- 0.819, 1.14 +/- 1.02* and 0.137 +/- 0.307* N/mm2, respectively, and the numbers for osteons with resorption lacunae were 1.37 +/- 0.721, 0.412 +/- 0.370* and 0.268 +/- 0.339** N/mm2, respectively. However, neither structural stiffness nor strength correlated with the indices of osteonal remodeling; instead, they were significantly correlated with bone mineral contents.(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3↗

Evolution of spinal bone loss and biochemical markers of bone remodeling after menopause in normal women.

The main objective of this study was to describe longitudinal patterns of spinal bone loss in normal women who undergo a natural menopause. The second objective was to determine if a proportion of women suffer excessively rapid postmenopausal bone loss from the spine. If this was the case it was the aim to devise a means of predicting the woman at excess risk; but if all women lost bone at similar rates, the aim was to document changing loss rates over the first 5-8 postmenopausal years. Responding women in six suburban general practices recalled for cervical smears who had their last menstrual period 9- 36 months previously were invited to participate in a longitudinal study of bone loss and the biochemical markers plasma osteocalcin and urinary hydroxyproline. Sixty-four subjects agreed to participate, a response rate of 80%. In the ensuing 5 years, six received hormone replacement therapy and are not reported on. The main outcome measures were rates of spinal bone loss over 5 years, measured by dual photon absorptiometry, and radial bone loss over the first 2 years measured to quantitative computed tomography. Spinal bone loss was similar between individuals, with 94% of the variability in the data being accounted for by a statistical model that assumed parallel rates of bone loss. A less restrictive model allowing women to have different rates of spinal bone loss accounted for 12% more of the remaining variance in the data than the previous model. However, rates of radial bone loss were more dissimilar between women than rates of spinal loss. The results of the biochemical data collected serially showed that the plasma osteocalcin rose slowly to a plateau at 5 years postmenopause; in contrast, the hydroxyproline fell progressively with time over the whole period of study. These results were interpreted as being consistent with diminishing rates of bone destruction which gradually reequilibrated with bone formation as time passed after menopause.

Absorptiometry, Photon↗

Vertebral fractures and osteopenia in chronic alcoholic patients.

To assess whether vertebral fractures are associated with osteopenia in chronic alcoholic patients, a transversal study was carried out in 76 chronic alcoholic males and 62 age-matched healthy males. Lumbar bone mineral density (BMD) by dual photon absorptiometry and spinal chest X-ray films were done in all patients. Twenty-seven patients (36%) had vertebral fractures, but only 5 of them had a BMD below the fracture threshold. Twenty-two patients (29%) had osteoporosis by densitometric criteria. There were no significant differences in lumbar BMD between alcoholic patients with and without vertebral fractures (1.11 +/- 0.2 versus 1.13 +/- 0.2, P = ns). Previous trauma was recorded in 24 of the 27 patients with vertebral fractures and in 28 of the 49 patients without vertebral fractures (P < 0.001). Moreover, patients with vertebral fractures had more peripheral fractures than patients without vertebral fractures (81% versus 49%, P = 0.01). Only one patient was aware of a previous episode of traumatic vertebral fracture. In conclusion, chronic alcoholics frequently have traumas and vertebral fractures, the latter despite having a lumbar BMD above the fracture threshold, suggesting a frequent but unrecognized association between both processes. These results suggest that both spine films and BMD measurements should be obtained for diagnosis of osteoporosis in alcoholic patients.

Absorptiometry, Photon↗

Phosphorus-31 in vivo magnetic resonance spectroscopy of bone fails to diagnose osteoporosis.

The values of in vivo T1 relaxation time (T1) of phosphorus atoms of wrist bone have been measured by phosphorus-31 magnetic resonance spectroscopy (MRS) in 65 menopausal women separated into three groups: (1) age-matched women without any paraclinical or clinical osteoporosis; (2) patients with paraclinical osteoporosis detected only by dual photonic absorptiometry; and (3) women with clinical osteoporosis with vertebral fractures. No significant differences were found in T1 values in the presence of paraclinical or clinical osteoporosis as compared to control values. No relationships were found among the T1, the value of the Z-score, the value of bone mineral content, the age of patients, the number of their children, and the age of menopause. Phosphorus-31 magnetic resonance spectroscopy of the wrist fails to separate osteoporotic from nonosteoporotic women and cannot be clinically used at this time to perform a noninvasive diagnosis of osteoporosis.

Absorptiometry, Photon↗

Sex-related changes in the bone mineral content of atrophic mandibles.

In 25 edentulous anatomical mandible specimens (15 female, age range 69-90 years; 10 male, age range 68-88 years), the bone mineral content (BMC) was measured by dual-photon absorptiometry (DPA) and analyzed in a standardized area of the mandibular body. The results of our BMC examinations showed that there was a significant difference (P = 0.05) between the two sexes. Another notable fact was that, with advancing age, the values measured in the male mandibles tended to increase slightly but in a statistically significant way. Those of the female mandibles tended to decrease with age. A possible explanation for this observation may be derived from the fact that a reduction of the mandibular height leads to a reduction of the moment of resistance. As functional adaptation in order to preserve the stability of the atrophic body of the mandible, the amount of inner cortical bone of the male mandibles increases, leading to a reduction of the cancellous portion. In the mandibles of women, postmenopausal osteoporosis seems to prevent an analogous compensation mechanism.

Absorptiometry, Photon↗

Estimation of the effect of salmon calcitonin in established osteoporosis by biochemical bone markers.

We reviewed data on 42 postmenopausal women with established osteoporosis (forearm fracture or a low bone mass) who had been randomly treated for 1 year with either rectal salmon calcitonin (sCT), 100 IU daily (n = 25) or nasal sCT, 200 IU daily (n = 17) applying an estimation algorithm for bone loss rates. Both groups received a daily calcium supplement of 500 mg. A group of 18 age-matched women who received no treatment served as controls. The bone mineral content of the distal forearm (BMCarm) was measured every 3 months by single photon absorptiometry. The individual rates of change during the 1-year period were calculated by linear regression analysis (alpha BMCarm). Bone loss rates were estimated initially and after 1 year of therapy by measurements of serum alkaline phosphatase, plasma bone Gla protein, and fasting urinary hydroxyproline and calcium (both corrected for creatinine excretion) according to the estimation algorithm. Both administration forms revealed significant control group-corrected decreases in serum and urine markers of bone turnover of 15-40% (P < 0.05-0.01) and positive outcomes of 2% in alpha BMCarm (P < 0.01). The estimated effect on bone mass was expressed as the difference between the bone loss estimated after 1 year and initially (delta ESTBIO). A significant correlation was seen between alpha BMCarm and delta ESTBIO (r = 0.5, P < 0.0001). We conclude that the effect of sCT on bone can be followed up by biochemical markers for bone turnover, i.e., by an annual blood and fasting urine sample, applying an estimation algorithm for the rate of bone loss.

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↗

Bone mineral density and bone histomorphometric assessments of postpregnancy osteoporosis: a report of five patients.

Reports of five young women who developed vertebral fractures associated with pregnancy and lactation are presented (Fig. 1). Ages ranged from 24 to 37 (mean 30) years. All five patients have osteoporosis with two to nine vertebral fractures at presentation postpartum. Bone mineral density (BMD) was measured by single-photon absorptiometry, quantitative computer tomography, and dual-energy X-ray absorptiometry. BMD of the trabecular bone was less than normal values and it remained apparently low even several years after pregnancy. Histological findings of bone biopsy identified the bone loss with increasing bone resorption. Our present findings suggest that postpregnancy osteoporosis affects mainly the trabecular bone site, and the patients might have low peak bone mass and poor reversibility probably due to a low rate of remodeling.

Absorptiometry, Photon↗

Menopausal bone loss is partially regulated by dietary intake of vitamin D.

Five years ago we reported results from a cross-sectional study of the effect of nutritional factors on calcium-regulating hormones and bone loss in perimenopausal women. We found an inverse correlation between serum 25-hydroxyvitamin D (25OHD) and immunoreactive parathyroid hormone (PTH), and we postulated that over time, women with lower 25OHD would lose more bone because of increased bone remodeling induced by secondary hyperparathyroidism. We have followed 38 of these women for 5 years. Twenty-two have gone through menopause and we are reporting observations on these 22 subjects. Bone mineral analysis was performed twice a year at the distal and mid-radius using single-photon absorptiometry. The slope of the bone mineral content curve was calculated by least squares. Bone loss increased within 6 months of the rise in serum follicle stimulating hormone (FSH) to greater than 40 mIU/ml. We continued to see a negative correlation between 25OHD and PTH (r = -0.450, P = 0.03). Premenopause, PTH was negatively correlated with the proximal bone mineral content (PBMC) slope (-0.604, P = 0.002). The distal bone mineral content (DBMC) 5-year slope was correlated with dietary vitamin D (r = 0.509, P = 0.02), the higher the intake, the less negative the slope. The 5-year PBMC slope was negatively correlated with serum osteocalcin (OC) levels (r = -0.382, P = 0.08). Before menopause, the change in PBMC was positively correlated with OC (r = 0.450, P = 0.03). Postmenopause, the correlation with DBMC slope was negative (r = -0.506, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

25-Hydroxyvitamin D 2↗

The effect of overlying calcification on lumbar bone densitometry.

We studied bone mineral density (BMD) of the spine using dual photon absorptiometry, as well as standard anterior-posterior and lateral lumbar spine X-ray film in 113 ambulatory elderly male volunteers with a mean age of 72 years (range 66-91 years). Each subject had three measurements taken for lumbar vertebrae 1 through 4: BMD, length of aortic calcification (AC), and degenerative facet sclerosis graded 0-3. A separate statistical model was fit to BMD for each vertebra using analysis of covariance. AC did not contribute significantly to BMD. BMD was increased by 0.28-0.03 g/cm2 (L1-L4) with a sclerosis score of 2, and by 0.47-0.25 g/cm2 with a sclerosis score of 3, P less than 0.001. The association between increased BMD and overlying facet sclerosis may be related to the bone density within the sclerosis itself or to an association between degenerative joint disease and a generalized increase in subchondral bone.

Absorptiometry, Photon↗

Differential effects of glucocorticoids on cortical appendicular and cortical vertebral bone mineral content.

The susceptibility to glucocorticoid-induced bone loss may vary in different parts of the skeleton. We studied 62 patients with rheumatoid arthritis, 26 of whom were on low-dose glucocorticoid treatment. Bone mineral content (BMC) in the forearm was measured by single photon absorptiometry at a cortical, diaphyseal, and at a mixed cortical and trabecular, metaphyseal site. Lumbar BMC was measured by dual energy computed tomography in a trabecular and a cortical region of interest. The presence of vertebral deformities was evaluated on lateral spine radiographs. After correction for possibly confounding variables, prednisone therapy significantly influenced BMC at both the trabecular (-22.0%, 95% confidence interval -36.0% to -8.1%) and cortical (-24.8%, 95% confidence interval -39.3% to -10.3%) lumbar site. A significant effect was also seen at the metaphyseal (-15.7%, 95% confidence interval -27.1% to -4.2%), but not the diaphyseal (-3.9%, 95% confidence interval -14.1% to 6.4%) site in the forearm. Correlations between peripheral and vertebral BMC were moderate at best. The diaphyseal to metaphyseal BMC ratio did not identify patients with vertebral osteoporosis. It is concluded that the anterior cortical rim of the vertebral body is more susceptible to the effects of glucocorticoids than the cortical bone in the forearm, and that measurements of trabecular and anterior cortical vertebral BMC are essential in the management of patients with possible glucocorticoid-associated osteoporosis.

Absorptiometry, Photon↗

Lack of association between free testosterone and bone density separate from age in elderly males.

It is unclear what proportion of the variance in bone density in elderly males is accounted for by testosterone status. We studied 112 ambulatory, elderly volunteers (mean age 71.7 years) and determined free testosterone (FT), as well as bone density measurements by photon absorptiometry at multiple sites. Our studies of 35 of these subjects 4 years later included morning FT and dual energy X-ray absorptiometry. There were no significant correlations between FT and bone density at multiple scanning sites with the effects of age partialed out. We suspect that our inability to detect a significant effect of FT on bone density was related to the relative strength of other determinants of bone density, as well as to the fact that FT values are far more dynamic than bone density.

Absorptiometry, Photon↗

Comparative study of the performances of X-ray and gadolinium 153 bone densitometers at the level of the spine, femoral neck and femoral shaft.

We investigated the precision of gadolinium 153 dual photon absorptiometry (DPA) and quantitative digital radiography (QDR) bone densitometers by determining in vitro and in vivo coefficients of variation (CV) of bone mineral density (BMD). In vitro, the long-term CV of spine phantom BMD measured weekly for 40 weeks was 1.2% and 0.7% for DPA and QDR, respectively. Stimulating soft-tissue thickness with water, the CV of 6 repeat measurements of spine phantom at depths from 0 to 27 cm in 1 cm steps (a total of 168 measurements) increased from 0.1% at 0 cm of water to 2.5% at 27 cm for DPA, and from 0.2% at 0 cm to 1.4% at 27 cm for QDR; mean CV of the 28 series (0-27 cm) was higher for DPA (1.2% +/- 0.8%, mean +/- SD) than for QDR (0.7% +/- 0.6%; P less than 0.001). With the hip phantom, femoral neck BMD was determined, and the CV was also dependent on water thickness; mean CV of the 20 series (0-10 cm) was 2.1% +/- 1.2% for DPA and 1.3% +/- 0.9% for QDR (not significant). In vivo, at the spine level, with DPA, mean CV of BMD measured 6 times after repositioning in 6 healthy volunteers was 3.8% +/- 1.9% and 2.1% +/- 0.7% with 153 Gd activity of 0.46 Ci and 1 Ci, respectively (BMD range: 0.796-1.247 g/cm2, no significant difference between the two groups).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Comparison of dual photon and dual energy X-ray bone densitometers in a clinic setting.

In clinical practice, decisions must be made about whether and how to convert to newer technologies. To address this issue, two separate studies were conducted. We evaluated the relationships between results of lumbar spine measurements using two dual photon absorptiometry (DPA1 and DPA2) instruments and one dual energy X-ray (DXA) instrument with the same subjects (49 volunteers), and also in 65 patients who were measured on the DPA1 and DXA machines. Second, we measured the lumbar spine and the proximal femur in three groups of 12 female volunteers three times on one instrument within 1 week. We purposely simulated a busy clinic setting with different technologists, older radioactive sources, and a heterogeneous patient group. The comparison study indicated a significant difference between the mean bone density values reported by the machines, but the results were highly correlated (R2 = 0.89-0.96). The short-term precision errors (coefficients of variation) differed among the instruments, ranging from 1.3% (DXA of the spine) to 5.1% (DPA1 of the spine), and in the femoral neck, 2.3% and 2.4% (DXA and DPA1, respectively) versus 3.5% by DPA2. This study emphasizes the differences between instruments, the potential for greater error in busy clinic environments, and the apparent superiority of dual energy X-ray absorptiometry under these less than ideal conditions.

Absorptiometry, Photon↗

Serum osteocalcin and fracture susceptibility in elderly women.

The purpose of this investigation was to evaluate the bone turnover by using bone metabolic markers in relation to previous fracture history and independent of bone mass. Patients and controls were recruited from a population-based study of 193 women, all living in the same city and aged 60, 70, and 80 years. The bone mineral content (BMC) was measured bilaterally in the distal forearm by single-photon absorptiometry (SPA). At the same time, serum samples were obtained for biochemical analysis. Of the 193 women, we identified 26 with at least one major fracture during the past few years. Each of these 26 women with a certified recent previous fracture was individually matched with a woman from the same study group of equal BMC and age but without a fracture history. In the two groups, the serum samples were analyzed for osteocalcin, C-terminal procollagen peptide (P1CP), alkaline phosphatase, bone-specific alkaline phosphatase, calcium, phosphate, and albumin. The serum concentration of osteocalcin was 20% lower in the women with a previous fracture than in the controls (P = 0.03). The other markers of bone formation gave similar values in the two groups. There was a significant correlation between the osteocalcin and P1CP concentrations (P = 0.001). Our findings indicate that the susceptibility to fractures independent of factors such as age and BMC may be related to a decreased bone turnover.

Absorptiometry, Photon↗

Effect of weight manipulation on bone loss due to ovariectomy and the protective effects of estrogen in the rat.

While characterizing the effects of estrogen on an ovariectomized (OVX) rat model of bone loss, we examined several weight-matching regimens [e.g., ad libitum (feed bins continually full), weight matched (rate of weight gain for OVX and Sham-OVX groups was equalized), and weight restricted (weight gain rates for all groups were equalized to that of estrogen-treated OVX rats)] for possible effects. Bone loss following ovariectomy is primarily the result of an increase in bone resorption and is extremely sensitive to the effects of estrogens. Thus, in all of our analyses, treatment with 17 beta-estradiol served as a positive control for the prevention of bone loss. Each weight-matching study had three groups: control (Sham-OVX), OVX, and OVX + 17 beta-estradiol (0.1 mg/kg/day), and lasted for either 2, 4, or 6 weeks. Throughout the study, each Sprague Dawley rat was weighed every other day, and following sacrifice, a femur was removed for bone mineral density (BMD) analysis at the distal metaphysis by single photon absorptiometry. Following 2 weeks of dietary modifications, no significant differences were detected in BMD among the ad lib or weight matched groups. However, an estradiol-preventable reduction in BMD in restricted OVX rats was detected at 2 weeks postovariectomy. Additionally, OVX rats in all three dietary regimens displayed an estrogen-preventable reduction in proximal femur BMD at 4 and 6 weeks postovariectomy. These results indicate that a 4-week rat ovariectomized model of bone loss, under conditions of ad libitum feeding, shows great potential for pharmacologic manipulation.

Absorptiometry, Photon↗