Screening for osteoporosis.
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Estrogen Replacement Therapy↗
Biomedical subjects
S M Ott
Publications and source records attributed to S M Ott.
Serum markers of bone formation in parenteral nutrition patients.
Bone gamma-carboxyglutamic acid containing protein (BGP) has been utilized effectively as a serum marker of bone turnover in healthy normals and in individuals with a variety of metabolic bone disorders including postmenopausal osteoporosis and Paget's disease. The utility of this serum marker in other bone disorders, including that associated with the maintenance of patients on long-term parenteral nutrition, still requires definition. Because of our interest in this clinical syndrome and the availability of serum and of bone formation rates (BFR) measured directly from double tetracycline labeling in 11 long-term parenteral nutrition patients, we measured BGP levels in these patients and attempted to correlate this measure with BFR. Serum vitamin D metabolites, immunoreactive parathyroid hormone (PTH), and alkaline phosphatase (alk phos) were also measured. Serum BGP was only weakly and not significantly correlated (r = 0.24, p = NS) with bone formation rate for the group as a whole. However, in a subgroup of 10 patients without hyperparathyroidism, there was strong and significant correlation (r = 0.81, P less than 0.01) between BGP and BFR. There was also a strong correlation between bone formation rate and serum 1,25 dihydroxyvitamin D [1,25(OH)2D] levels (r = 0.89, P less than 0.01, n = 11). The mechanism of this association could not be established. A correlation of borderline significance was observed between bone formation rate and serum alk phos (r = 0.60, P = 0.05, n = 11). The current data suggest that additional studies may help to more fully define the utility of serum measurements in quantifying bone dynamics in parenteral nutrition patients, and that measures of vitamin D metabolites, BGP, and alk phos may prove useful.
1-Carboxyglutamic Acid↗
Relationships between mandibular and skeletal bone in a population of normal women.
In this study, we measured mandibular bone mass and density and cortical thickness at gonion in 50 normal women between the ages of 20 and 90. The subjects showed neither radiographic nor metabolic evidence of osteoporosis. Comparisons (by age) were made between mandibular measurements. Mandibular measurements were also compared with measurements of bone mass in the spine and the wrist. Mandibular bone mass was not significantly affected with age but mandibular bone mass was significantly correlated with skeletal bone mass. Cortical thickness at gonion decreased with age.
Absorptiometry, Photon↗
Calcitriol treatment is not effective in postmenopausal osteoporosis.
STUDY OBJECTIVE: To determine if calcitriol is an effective treatment in postmenopausal osteoporosis. DESIGN: Double-blind, randomized clinical trial of 2 years' duration. SETTING: University medical center with patients recruited by media announcements. PATIENTS: Eighty-six postmenopausal women with vertebral compression fractures. INTERVENTIONS: Patients were treated with calcitriol or placebo. Mean dose was 0.43 micrograms/d. Dietary calcium was 1000 mg/d (24.9 mmol/d). The medication dose and dietary calcium were adjusted for hypercalciuria or hypercalcemia. MEASUREMENTS AND MAIN RESULTS: No significant differences between placebo and control groups were seen in the percent change in total body calcium (0.4% +/- 1.0 compared with 0.0% +/- 0.9), single photon absorptiometry (-0.5% +/- 1.2 compared with -3.1% +/- 0.9) or dual photon absorptiometry (0.0% +/- 1.7 compared with -1.0% +/- 2.2). New fractures were seen in 16% of the placebo group and 26% of the calcitriol groups, so the difference in percent fractures was 10% (95% CI, -5.7% to 25.7%). Bone biopsies did not show changes in either group. The calcitriol group had significantly higher serum and urine calcium values, but renal function was not worse than in the placebo group. CONCLUSIONS: Calcitriol is not an effective treatment for established postmenopausal osteoporosis.
Aged↗
Relationships between mandibular and skeletal bone in an osteoporotic population.
This study attempted to determine relationships between bone mass in the mandible and skeletal bone mass in a group of 85 postmenopausal women with osteoporosis. Mandibular bone mass was determined by microdensitometry, cortical thickness at the gonion, the height of the alveolar ridge in subjects who were edentulous, and periodontal probings. Skeletal measures were made up of total body calcium, bone mass at the radius, and the two newer bone mass measures of dual photon and computed tomography of the vertebrae. The height of the edentulous ridge correlated with total body calcium and mandibular mass. Most of the edentulous patients had ridges that were extremely resorbed. Mandibular mass correlated with all skeletal measures.
Aged↗
Mineral loss in the parenteral nutrition patient.
The impact of parenteral nutrition on mineral loss was examined in 11 long-term (10-79 mo) and 6 short-term (1-8 mo) patients. In the long-term patients, there was a significant (p less than or equal to 0.02) urinary loss of calcium and magnesium during infusion compared with periods off infusion. The magnitude of urinary excretion of these minerals was much lower than in previously reported series and in short-term patients. Despite this, in long-term patients the mean bone mass at the spine was lower than normal (p less than 0.001) but mean bone mass at the wrist was not. Current data suggest that hypercalciuria is not a consistent feature of parenteral nutrition. Furthermore, osteopenia is a feature of some long-term parenteral nutrition patients.
Adult↗
Metabolic bone disease of total parenteral nutrition: course after changing from casein to amino acids in parenteral solutions with reduced aluminum content.
Bone disease with total parenteral nutrition (TPN) has been attributed to aluminum loading or vitamin D therapy. We studied 17 patients who first received TPN containing casein hydrolysate with high Al and ergocalciferol (25 micrograms/d) for 6-72 mo followed by TPN containing amino acids with reduced Al and ergocalciferol (5 micrograms/d) for 9-58 mo. We also did a cross-sectional study of 22 patients receiving casein and ergocalciferol (25 micrograms/d) compared with 46 patients receiving amino acids and ergocalciferol (5 micrograms/d) for 6-58 mo. Bone formation was higher and osteoid area, bone-surface stainable Al and total bone Al were lower with amino acid TPN than with casein TPN. Bone formation varied inversely with both plasma Al and bone-surface Al, suggesting that plasma or bone-surface Al, acquired during TPN, can reduce bone formation and lead to patchy osteomalacia. Serum levels of iPTH and 1,25-dihydroxyvitamin D were higher with amino acid TPN.
Aluminum↗
Comparisons among methods of measuring bone mass and relationship to severity of vertebral fractures in osteoporosis.
Several techniques are now available for quantitation of bone mass, including total body calcium by neutron activation analysis (TBC), single and dual photon absorptiometry at the radius and spine, respectively (SPA and DPA), quantitative computed tomography of the spine (QCT), and cancellous bone volume from iliac crest bone biopsies. The aims of this study were to assess the correlation among these techniques and to determine if bone mass correlated with height loss or the severity of vertebral fractures in osteoporotic women. These measurements were performed in the same group of women (n = 122) with postmenopausal osteoporosis. TBC, SPA, DPA, and QCT correlated significantly with each other (r = 0.33-0.76). The correlation between QCT and DPA improved significantly (r = 0.33-0.57; P = 0.02) when integral QCT was used instead of the usual QCT of the central vertebra. The correlation was not improved by expressing DPA in different dimensions, but was improved by including normal women. Multiple linear regression analysis showed that TBC was predicted better using SPA, DPA, and QCT than by any single variable. Cancellous bone volume correlated weakly (r = 0.10-0.26) to the other measurements. Height loss and fracture index correlated significantly with each other (r = 0.66; P less than 0.001), but the correlations with bone mass measurements were weak (r = -0.09 to -0.47). For each patient, a bone mass index was defined using z scores from the SPA, DPA, QCT, and TBC measurements; this index correlated inversely with the fracture index (r = -0.29; P = 0.009). This correlation was not significant when controlled for age. Thus, bone mass measurements correlate moderately well with each other, but poorly with severity of fracture. Other factors in addition to low bone mass may be important in determining whether bone will fracture.
Adult↗
Accuracy of dual photon absorptiometry in excised femurs.
We investigated the accuracy of assessment of bone mineral content (BMC) by dual photon absorptiometry (DPA). Measurements were compared between BMC and ashed weight using two related scanners. The BMC in different locations of the femur was determined. Twelve cadaver femurs were cleaned of all soft tissue, divided into four parts (head, neck, trochanteric region, and shaft), and measured for BMC in an ethanol/water solution. The bones were then ashed and weighed. Volumetric density was also determined. The correlation coefficient between ash weight and BMC was 0.99 with an s.e.e. of 0.51 g and relative error of 4.8%. Similar correlations were seen within each region. The correlation between the machines was 0.99. Differences in volumetric density were found, with the density of the shaft greater than other regions, and the neck greater than the head or trochanteric regions.
Female↗
Ability of four different techniques of measuring bone mass to diagnose vertebral fractures in postmenopausal women.
Since bone mass has been shown to be an important determining factor of fractures in vitro, we undertook a study to evaluate whether bone mass measurements could separate postmenopausal women with vertebral compression fractures from women of a similar age without fractures. We also wanted to see if methods of measuring bone mass at the spine would be more sensitive or specific than methods that measured bone at the wrist or the entire skeleton. The techniques used were: total body calcium by neutron activation analysis (TBC), single photon absorptiometry (SPA), dual photon absorptiometry (DPA), and quantitative computed tomography (QCT). Normal women aged 20-85 were measured, but only those greater than 50 yr were used in the analysis. Mean values for women with fractures were significantly lower than normals (p less than .001): TBC 642 +/- 103 g vs. 764 +/- 114; SPA .658 +/- .134 g/cm vs. .779 +/- .142; DPA 3.75 +/- .82 g/cm vs. 4.37 +/- .86; QCT 59.0 +/- 25.7 mg/cc vs. 92.6 +/- 36.0. However, each of the methods showed considerable overlap between women with and without fractures. At 90% specificity the sensitivities of the tests were: TBC 34%; SPA 29%; DPA 33%; QCT 36%. When values were expressed as the % expected (based on age and height) then the sensitivities were: TBC 52%; SPA 36%; DPA 35%; QCT 44%. Using Bayes' theorem, we constructed curves showing the posttest probability of these tests at a prevalence of 20%. None of these bone mass measuring techniques showed complete separation between normal and osteoporotic women with fractures; about one-half of the women with fractures were below the normal range. The risk of having a fracture increases as bone mass declines, but our data suggest that bone mass is not the only factor leading to vertebral fractures in postmenopausal women.
Adult↗
Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee.
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Animals↗
Bone histologic response to deferoxamine in aluminum-related bone disease.
We have examined the changes in bone histology in 28 uremic patients after long-term treatment with the aluminum chelator, deferoxamine. Marked declines in stainable bone-surface aluminum were associated with increases in bone formation rate and osteoblastic osteoid following deferoxamine. The increased bone formation resulted from increases in bone apposition and length of double-tetracycline labels, the latter being highly correlated with the increase in osteoblastic osteoid (r = 0.85). While bone surface aluminum was highly correlated with bone formation rate (r = .69, p less than .001), bone aluminum content did not correlate with bone formation (r = 0.13) and was often elevated after treatment despite an improvement in bone histology. Patients who had undergone prior parathyroidectomy were less likely to have improved bone histology than those with intact parathyroid glands. We conclude that aluminum chelation therapy with deferoxamine is effective in ameliorating the bone histology of patients with chronic renal failure and bone aluminum accumulation, and that the change in stainable bone-surface aluminum is a more sensitive indicator than the change in bone aluminum content in assessing adequacy of chelation therapy. Patients who need deferoxamine treatment but have undergone a prior parathyroidectomy will probably require a more intensive treatment schedule than those who have intact parathyroid glands.
Aluminum↗
Heterogeneity of bone histology in parenteral nutrition patients.
The characteristics of bone disease associated with parenteral nutrition are controversial. To further elucidate the contribution of aluminum deposition to this syndrome and the spectrum of pathology in patients supported by current regimens utilizing crystalline amino acids, quantitative histomorphometry and staining for Al were performed on iliac crest bone biopsies from 26 long-term parenteral nutrition patients and 16 normal volunteers. Compared with normal subjects, median trabecular bone area (TBA) for a group with positive Al staining (n = 14) who were exposed to casein hydrolysate was significantly less (12.9% vs 20.7, p less than 0.05) as was the median rate of bone formation (RBF) (29 micron2 X mm-2 X d-1 vs 360, p less than 0.05). A variety of abnormal histological findings were present in patients without positive aluminum stains (n = 12) who were supported solely by regimens utilizing crystalline amino acids. However, neither decreased TBA (median TBA = 15.3%) nor decreased RBF (median RBF = 126 micron2 X mm-2 X d-1) was uniformly characteristic of the latter patient group.
Adult↗
Development and reversibility of aluminum-induced bone lesion in the rat.
We studied the effect of aluminum injections on bones of rats after intervals of 3, 6, and 9 weeks. To study reversibility, we allowed one group to recover for 3 weeks. Both weanling and adult rats were examined to determine the influence of age. The calcium, phosphate, creatinine, and parathyroid hormone levels were similar in aluminum-treated rats and controls. Aluminum could be seen by histochemical stain after 6 weeks, but at that time the bone was otherwise normal. By 9 weeks the bone formation (as measured by tetracycline labeling) in aluminum-treated rats was severely decreased on trabecular and endosteal surfaces. The periosteal surfaces showed normal formation. After 3 weeks of recovery, the bone formation rate in the young aluminum-treated rats was similar to that in the controls, although the serum and bone aluminum values had not significantly decreased. A higher percentage of aluminum was seen in the cement lines. In the adult rats, the bones had more stainable aluminum, and increased osteoid was noted along trabecular and periosteal surfaces. The doses of aluminum used in these rats greatly exceeded those that cause toxicity in humans; thus these findings may not directly apply to clinical practice. We conclude that aluminum administration can lead to decreased rates of bone formation in the rat, despite normal calcium level and renal function, and without decreased parathyroid hormone levels. The peritoneal route of administration could also have contributed to bone lesions by causing peritonitis, malabsorption, or both. Adult rats showed signs of early osteomalacia.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
Longitudinal changes in bone mass after one year as measured by different techniques in patients with osteoporosis.
Bone mass was measured in 49 postmenopausal women by the following techniques: single photon absorptiometry at the radius (SPA), dual photon absorptiometry at the lumbar spine (DPA), quantitative computed tomography at the lumbar spine with an area of interest of only trabecular bone (QCT) or of an integrated cross-section of the vertebral body (QCTi), and total body calcium by neutron activation analysis (TBCa). Each women had two measurements with a one-year interval. Half of them were treated with calcium supplementation only; the other half also received calcitriol (1,25 dihydroxycholecalciferol). The aim of this report was to compare the changes of bone mass as measured by the different techniques. The DPA and QCTi values were significantly lower at one year than at baseline (by paired t-tests). The mean percent changes (+/- SD) for the measurements were: TBC, -0.4 +/- 4.6%; SPA-1, 1.2 +/- 7.1%; SPA-2, 0.7 +/- 6.0%; DPA, -2.5 +/- 11%; QCT, 6.5 +/- 23%; and QCTi, -6.0 +/- 9%. The percent changes by one technique did not show significant correlation to the percent changes by the other methods. We conclude that the precision of the methods in this clinical setting is not sufficient to show correlations after only one year; in addition, there may have been different rates of changes at different sites of the skeleton.
Calcitriol↗
Bone oxalate in a long-term hemodialysis patient who ingested high doses of vitamin C.
We performed a bone biopsy on a patient who had been receiving hemodialysis for 23 years. The bone had oxalate deposition. Previous bone biopsies had shown osteitis fibrosis without oxalate deposition. The osteoid area was increased (11% of bone area), as was the fibrosis (6.1% of tissue area) and aluminum deposition (38% of surface). Bone formation rate was normal (259 mu 2/mm2/d). We examined bone biopsies of 22 patients who had been receiving hemodialysis for over 10 years, and none had oxalate deposits. We discovered that our patient had been ingesting 2.6 g/d of vitamin C. The bone oxalate deposition may have been caused by the ingestion of high doses of vitamin C.
Ascorbic Acid↗
Changes in bone histology after treatment with desferrioxamine.
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Adolescent↗