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Recommendations for the application of bone density measurement. What can you believe?

This study examined the conclusions of published reports that review the literature and make recommendations about appropriate applications of bone density measurement. It is based on a survey of 22 organizations producing such reports between 1986 and Spring 1995. Overall, the application of bone density measurement for the diagnosis of osteoporosis was supported by 65% of reports, by 44% for the monitoring and follow-up of patients with previously diagnosed disease, and by 59% for monitoring and follow-up of patients receiving treatment that may affect their bone density. A smaller proportion of reports from government and public organizations compared with other types of organizations and a smaller proportion of reports using more rigorous methods supported the applications for bone density measurement identified in the survey. A larger proportion of the reports published after 1990 compared with those published between 1986 and 1990 support the applications of bone density measurement, with the exception of population screening. The results of this survey suggest that there is considerable disagreement about the potential applications of bone density measurement. Publicly funded organisations and those using more rigorous methods tended to be more conservative in their conclusions.

Bone Density↗

Evaluation of bone density in the mandibles of young Australian adults of Mongoloid and Caucasoid descent.

OBJECTIVES: To evaluate the bone density in the mandibles of young Australian adults of Mongoloid and Caucasoid descent. METHODS: A panoramic radiograph (Orthophos C, Siemens AG, Bensheim, Germany) was obtained of 79 dental students from the School of Oral Health Sciences, The University of Western Australia. Exposure factors were varied for males and females. The films were automatically processed in a single batch and the optical density measured blindly at two locations by two examiners. The optical density was compared by race and sex to detect bone density differences. Individual lifestyle habits (exercise, alcohol consumption, smoking and diet) was recorded in a self-administered questionnaire. Multiple regression analysis was used to analyse the effects of physical, environmental and medical characteristics. RESULTS: The Mongoloid subjects were found to have approximately 20% higher bone density at the angle of mandible than Caucasoid subjects (P = 0.0094 for males, P = 0.0004 for females). CONCLUSION: Race is the most important variable associated with bone density. Mongoloid subjects should be given a higher exposure for panoramic radiography than that normally used for Caucasoid subjects.

Adolescent↗

Effect of sub-elite competitive running on bone density, body composition and sexual maturity of adolescent females.

The attainment of optimal peak bone mass during adolescence is important in the primary prevention of osteoporosis. Exercise may contribute to skeletal development and bone density during growth, although competitive exercise is suggested to have an adverse effect. This study assesses the effect of moderate exercise on the bone density of adolescent females. Additionally, other factors which significantly influence attainment of peak bone mass were identified. This was a cross-sectional study of 42 adolescent females, classified as runners (n=15) or non-runners (n=27). Nutrient intake, energy expenditure, menstrual history and pubertal stage were recorded. Bone age, skinfold thickness, body composition and bone mineral density (BMD) of total body, lumbar spine and proximal femur were measured. Statistical analyses used Student's t-test, Pearson correlation and multiple regression analyses. Runners had lower fat mass and higher lean mass, with a trend to higher BMD in all sites measured. There were no significant differences in menstrual cycle regularity, age at menarche or number who had attained menarche. Pubic hair development was similar in both groups. Breast development was delayed in runners, although this may have been a function of lower fat mass in this group. When subjects were categorized according to menarchal status, postmenarchal girls were significantly taller and heavier, with higher fat mass and significantly higher total body and lumbar spine BMD. There was no significant relationship between BMD at any site and dietary nutrient intake. Multiple regression analyses, using BMD as the dependent variable, identified running status, pubertal stage, fat mass and lean mass as significant determinants. When BMD/height was used, significant determinants in total body BMD were fat mass, pubertal stage and running status, while in the lumbar spine, only the latter two variables remained significant. In conclusion, body composition, physical activity and sexual maturity were identified as significant determinants of bone density during adolescence. Runners had significantly lower body fat than non-runners, but this did not interfere with hormonal cyclicity, and caused no detriment to their bone density. The results of this study are reassuring, since they indicate that sub-elite competitive athletics has no detrimental effect on bone mass accrual in adolescent females.

Adolescent↗

The association between estrogen status and alveolar bone density changes in postmenopausal women with a history of periodontitis.

While numerous studies have demonstrated a relationship between 17-beta-estradiol (E2) deficiencies and skeletal bone loss in postmenopausal females, the influence of E2 deficiency on alveolar bone resorption is poorly understood. The purpose of this study was to examine the association between the estrogen status of postmenopausal women and alveolar bone density changes in a 1-year longitudinal study. Twenty-four postmenopausal women, within 7 years of menopause, were divided into 2 groups, E2-sufficient (n = 10) and E2-deficient (n = 14). Venous blood samples were taken at baseline, 6 months, and 1 year for radioimmunoassay determination of serum E2 levels. At baseline and 1 year, 4 vertical bite-wing radiographs were taken for computer-assisted densitometric image analysis (CADIA). Areas of interest (AOIs) for CADIA were crestal and subcrestal regions of posterior interproximal alveolar bone. Serum E2 levels were significantly higher at all 3 time points in the E2-sufficient subjects (P < 0.002), repeated measures ANOVA). Overall, mean CADIA values (0.30 +/- 0.07 for the E2-sufficient women and -0.44 +/- 0.07 for the E2-deficient women) were statistically different between groups (P < 0.001, repeated measures ANOVA), indicating that the E2-sufficient women displayed a mean net gain in alveolar bone density and the E2-deficient women displayed a mean net loss in alveolar bone density. Furthermore, the E2-sufficient women exhibited a higher frequency of sites demonstrating a gain in alveolar bone density, while the E2-deficient women exhibited a higher frequency of sites demonstrating loss in alveolar bone density. These data suggest that estrogen status may influence alveolar bone density changes as demonstrated with CADIA.

Alveolar Bone Loss↗

Factors influencing vertebral bone density after renal transplantation.

In an effort to determine the influence of immunosuppressive therapy and other clinical variables on posttransplant osteopenia, vertebral bone density was measured at least 6 months after transplantation in 65 adult primary renal transplant recipients receiving a variety of immunosuppressive regimens. Fifteen of the 65 patients (23%) had vertebral bone densities below a fracture threshold of 1.0 g hydroxyapatite/cm2. Multivariate analyses indicated that cumulative steroid dose and female gender were the major independent predictors of low vertebral bone density. In women, postmenopausal status also was associated with osteopenia. There was no correlation between cumulative cyclosporine dose and bone density. Results of this study indicate that posttransplant osteopenia is common in renal transplant recipients, including those treated with CsA. Although CsA has allowed the use of lower cumulative doses of steroids, concomitant steroid therapy remains the preeminent factor accounting for loss of bone density.

Adult↗

Two year comparison of sevelamer and calcium carbonate effects on cardiovascular calcification and bone density.

BACKGROUND: Calcium-based phosphate binders may induce tissue calcification, and little is known about their effects on bone density. We compared the effects of a calcium with a non-calcium phosphate binder on both arterial calcification and bone density measured by computed tomography. METHODS: Seventy-two adult haemodialysis patients were randomized to treatment with calcium carbonate (CC) or sevelamer (SEV) for 2 years. Electron beam CT scans were performed at baseline and at 6, 12 and 24 months. Serum phosphorus, calcium, calcium x phosphorus product and intact parathyroid hormone (iPTH) were measured and other routine laboratory tests were also carried out. RESULTS: The average calcium x phosphorus product was similar in the two treatment groups. However, patients receiving CC had significantly lower average iPTH (P<0.01), were more likely to have hypercalcaemic episodes (P = 0.03) and had significantly greater increases in coronary artery (CC median 484, P<0.0001, SEV median 37, P = 0.3118, between-group P = 0.0178) and aortic (CC median 610, P = 0.0003, SEV median 0, P = 0.5966, between-group P = 0.0039) calcification scores. The CC group also had a significant decrease in trabecular bone density (CC median -6%, P = 0.0049, SEV median +3%, P = 0.0296, between-group P = 0.0025). However, there was no significant difference in cortical bone density between the two groups. CONCLUSIONS: This 2 year study shows that calcium carbonate use is continuously associated with progressive arterial calcification in haemodialysis patients. In addition, it suggests that it is also associated with decreased trabecular bone density. However, this latter finding requires confirmation by a study specifically devoted to this issue.

Adult↗

Calcaneal bone density reduction in patients with restricted mobility.

This cross-sectional study revealed a prevalence of reduced calcaneal bone density in a population of 49 chronic continuing care patients with restricted mobility. Calcaneal bone density was measured using the Compton gamma ray scattering technique, which permits examination of trabecular bone. Predicted densities were determined from the ages and weights of the subjects. Descriptive factors such as gender, diagnosis, duration of the condition, and muscle tone were correlated with bone density. Twenty-eight patients (57%) had indications of reduced calcaneal bone density. None of the descriptive factors was associated with the variability in bone density ratio (forward stepwise regression analysis, p = NS). The reduced calcaneal density found in these patients with restricted mobility is probably a result of their not bearing weight and the inevitable severe reduction in their physical activity.

Absorptiometry, Photon↗

The increase in spinal bone density that occurs in response to fluoride therapy for osteoporosis is not maintained after the therapy is discontinued.

In 44 osteoporotic subjects who had been treated with fluoride for 37 +/- 16 months, the fluoride was discontinued because they had shown fluoride-dependent increases in trabecular spinal bone densities from low initial levels (below the fracture threshold) to values that were equivalent to normal peak bone densities in the spines of young adults. During the subsequent period, after discontinuation of the fluoride therapy (i.e. 19 +/- 9 months), spinal bone density decreased in 73% of the subjects (i.e. 32 of 44, p < 0.03), at a rate that was comparable to the rate of the previous gain that had occurred during the treatment with fluoride (i.e. -3.23 +/- 2.39 mg/cm3 per month, compared with + 3.91 +/- 1.96 mg/cm3 per month in this, subgroup of patients, p < 0.001). Although 9 of the 44 subjects showed continuing increases in spinal bone density after discontinuation of the fluoride therapy, spinal bone density decreased in the entire group of 44 at an average rate of -1.02 +/- 4.72 mg/cm3 per month (p < 0.001, compared with the rate of the previous gain during the treatment with fluoride; i.e. +3.83 +/- 1.82 mg/cm3 per month). Surprisingly, our data showed that the rate of decrease in spinal bone density during the post-fluoride period was not affected by concurrent (undesigned) treatment with calcium, calcium plus estrogen, or calcium plus calcitriol. The cessation of fluoride therapy was also associated with a decrease in serum alkaline phosphatase activity (i.e. a decrease from the elevated levels that were observed during the period of fluoride therapy, back to the original, pre-treatment levels; p < 0.001), and that the rate of spinal bone loss after cessation of fluoride could be correlated with the prior rate of increase in serum alkaline phosphatase activity that had occurred during the treatment with fluoride (n = 44, r = 0.312, p = 0.039). Together, the observations from this retrospective analysis of data obtained from our clinical subjects suggest that fluoride-treated osteoporotic subjects who have exhibited increases in trabecular spinal bone density are at risk for bone loss after discontinuation of the fluoride therapy.

Adult↗

Osteoclast formation in bone marrow cultures from two inbred strains of mice with different bone densities.

For the purpose of identifying genes that affect bone volume, we previously identified two inbred mouse strains (C57BL/6J and C3H/HeJ) with large differences in femoral bone density and medullary cavity volume. The lower density and larger medullary cavity volume in C57BL/6J mice could result from either decreased formation or increased resorption or both. We recently reported evidence suggesting that bone formation was increased in vivo and that osteoblast progenitor cells are more numerous in the bone marrow of C3H/HeJ compared with C57BL/6J mice. In the present study, we determined whether osteoclast numbers in vivo and osteoclast formation from bone marrow cells in vitro might also differ between the two mouse strains. We have found that the number of osteoclasts on bone surfaces of distal humerus secondary spongiosa was 2-fold higher in 5.5-week-old C57BL/6J mice than in C3H/HeJ mice of the same age (p < 0.001). Bone marrow cells of C57BL/6J mice cocultured with Swiss/Webster mouse osteoblasts consistently produced more osteoclasts than did C3H/HeJ bone marrow cells at all ages tested from 3.5-14 weeks of age (p < 0.001). Osteoclast formation was also greater from spleen cells of 3.5-week-old C57BL/6J mice than C3H/HeJ mice. The distribution of nuclei per osteoclast and the 1, 25-dihydroxyvitamin D3 dose dependence of osteoclast production from bone marrow cells were similar. Osteoclasts that developed from both C57BL/6J and C3H/HeJ marrow cells formed pits in dentin slices. Cultures from C57BL/6J marrow cells formed 2.5-fold more pits than cultures from C3H/HeJ marrow cells (p < 0.02). We compared the abilities of C57BL/6J and C3H/HeJ osteoblasts to support osteoclast formation. When bone marrow cells from either C57BL/6J or C3H/HeJ mice were cocultured with osteoblasts from either C57BL/6J or C3H/HeJ newborn calvaria, the strain from which osteoblasts were derived did not affect the number of osteoclasts formed from marrow cells of either strain. Together, these observations suggest that genes affecting the bone marrow osteoclast precursor population may contribute to the relative differences in bone density that occur between C3H/HeJ and C57BL/6J mouse strains.

Animals↗

Bone density in myelomeningocele: the effects of ambulatory status and other factors.

Measurements were made of distal radius, mid-radius, tibia and metatarsal bone-density of 80 patients with myelomeningocele (17 thoracic, six L1/L2, 13 L3, 30 L4, 14 L5/sacral). For the upper extremity the bone density primarily was low in the thoracic patients, but in the tibia and metatarsal it showed a more linear correlation with neurological levels. The effect of age was highly significant at all sites; after controlling for this, the neurological level was a significant determinant of bone density at all sites, and this effect was greater in older children. Patients with impaired ambulation had decreased bone-density in the distal radius, tibia and metatarsal, but not in the mid-radius. Race had no significant effect on density after accounting for differences in neurological level. Weight for height and multiple fractures did not correlate with bone density. Although ambulatory status (weight-bearing stresses) and neurological status (muscle stresses) are both important factors in bone density, this study suggests that the latter is a more important determinant.

Adolescent↗

A 170Tm gamma scattering technique for the determination of absolute bone density.

A new technique for the determination of absolute bone density is described. The procedure is based on the measurement of both transmitted and scattered photons emitted from a 650 mCi radioisotope source of 170Tm in a narrow beam geometry. The method takes into consideration the change in the effective Z/A as a function of bone density which is due to the changing of the elementary composition of bone when bone material is resorbed. The experimental results show that the density of homogeneous materials can be measured with a reproducibility of 2 per cent. The bone density values for the 24 bone specimens measured by the new method show a good correlation (r=0 with 94) with results obtained by application of Archimedes' principle.

Acrylates↗

[Increased bone density in patients with multiple myeloma treated with clodronate].

The indication of bisphosphonates in hypercalcemia is fully accepted, the long term therapy with bisphosphonates is still controversial. The aim of our study was to evaluate the influence of clodronate on the bone density of myeloma patients. Twenty patients were included in the study. Clodronate is administered in the total dose of 3,000 mg, which is delivered in 4-6 hour infusions, 600 mg/day, once in tree 3 months. The effect of clodronate on bone density is evaluated by CT-densitometry in a period of 6 months. At the beginning of May 1994, 15 patients had completed at least two estimations of bone density. The amount of hydroxyapatite in these six months increased in 9 patients, in one of them there was no change and in 4 of them decreasing bone density was detected. The mean bone density before the administration of clodronate was -2.6 SD (standard deviation of European standard of bone density for age and sex). After 6 months of therapy the bone density increased to -2.3 SD. The mean amount of hydroxyapatite in spongiosa was raised from the mean value 32.71 mg/ml before clodronate administration to 38.91 mg/ml after the 6 month treatment period. The mean increase in calciumhydroxyapatite in trabecular bone mass was 6.2 mg. Clodronate contributed to the amelioration of bone pain in the majority of patients, but this effect is difficult to evaluate because of other treatment modalities administered concomitantly. The tolerance of clodronate was good. No impairments of renal function or other adverse effects were observed. Only in 2 patients the decrease in calcium concentration caused slight tetania. Therefore close monitoring of the calcium level is recommended and in the case of its decrease below the physiological level peroral substitution of calcium was started.

Bone Density↗

Iliac trabecular bone formation predicts radial trabecular bone density changes in type 1 osteoporosis.

In 28 patients with idiopathic or postmenopausal type 1 (spinal crush fracture) osteoporosis, resorption indices and dynamic measurements of trabecular bone formation based on in vivo tetracycline labeling in 7.5 mm transiliac biopsies have been compared with trends in radial cortical and trabecular bone density measured with computed tomography. Positive correlations were observed between trabecular bone density trends in the radius and indices of bone formation in the ilium. These were improved when one of the two resorption indices was included with a formation index in bivariate regressions. Marked interindividual variations in radial bone density trends were also seen in cortical bone. These correlated poorly with trends in trabecular bone. Weak negative relationships between cortical bone trends and indices relating to bone formation and resorption were observed, but a positive association was seen with single-labeled surfaces on iliac trabeculae. If, as has been suggested, there are periodic variations in bone formation, the results suggest that axial and peripheral trabecular bone density trends are synchronized in osteoporosis, perhaps in response to systemic factors, such as circulating hormones.

Aged↗

Radiographic assessment of bone density around integrated titanium implants after ovariectomy in rats.

OBJECTIVES: This study evaluated the influence of ovariectomy 8 weeks after implant placement on bone integrated to titanium implants. MATERIAL AND METHODS: Thirty-eight female rats were submitted to a titanium implant at the tibiae proximal methaphysis. After a healing period of 8 weeks the animals were randomly divided into three groups: control (CTL-10 animals), sham-operated (SHAM-14 animals) and ovariectomy (OVX-14 animals). The CTL group was then sacrificed in order to confirm integration of the implant. The SHAM group was submitted to fictitious surgery and the OVX group was submitted to bilateral ovariectomy. After 12 weeks post-implant placement, the SHAM and OVX groups were sacrificed. In order to confirm the systemic osteopenia in rats, a dual-energy X-ray absorptiometry (DXA) was performed. For the evaluation of bone density, digital radiographs were taken. The grey level of the bone adjacent to implant was measured using image software and the bone density was calculated at six points on both sides of the implant. RESULTS: Densitometry measurements of the femur confirmed systemic bone mass loss in the OVX group. Individualized bone analyses of different regions surrounding the implant showed a significantly lower radiographic bone density (P < 0.05) in the cancellous region of the OVX group (77.48 +/- 23.39 grey levels) when compared with the CTL and SHAM groups (91.61 +/- 32.10 and 102.57 +/- 32.50 grey levels, respectively). CONCLUSIONS: The present study showed a decrease of the radiographic bone density in the cancellous region of bone around titanium implants placed 8 weeks before ovariectomy in rats.

Absorptiometry, Photon↗

Bone density in osteopenic women: a modified distal radius density measurement procedure to develop an "at risk" value for use in screening women.

This study measured radial and lumbar spine bone density in postmenopausal white female patients with nontraumatic fractures and their age-matched controls. Bone density measurements were made with a single-beam densitometer. Distal radial bone density measurements were made at the site at which the radius and ulna are separated by 5 mm, which is approximately 5 mm from the distal radioulnar joint. Lumbar spine density was obtained using a dual-beam densitometer. Density at the commonly used "2/3" site near the midradius was also measured. Forty-six crush fracture osteoporotic patients, 35 hip fracture patients, and 20 osteopenic patients referred to the clinic for back pain or excessive bone loss but with no history of nontraumatic fracture were studied. Bone density values at all sites in the patient populations were statistically reduced from control values (p less than 0.01). At a mean age of 62 years, density of the midradius was 12% below the control value. However, both vertebral and distal radial densities ("5 mm" site) were 25% below control values. The spine/distal radius ratio remained constant. It was demonstrated that bone density at the modified distal radial site could be used to predict vertebral density in osteopenic patients. An "at risk" value useful in screening procedures was determined as that distal radius density value greater than or equal to 95% of all values from fracture patients--325 mg/cm2. It is concluded that distal radial density at the new "5 mm" site can be used in conjunction with midradius density as a preliminary test for both generalized and trabecular bone mass loss in women.

Absorptiometry, Photon↗

The OsteoQuant: an isotope-based CT scanner for precise measurement of bone density.

OBJECTIVE: We attempted to design and construct a computed tomography scanner with an in vivo precision of better than 0.5% for trabecular bone density of the radius. MATERIALS AND METHODS: A number of considerations involving physical limitations, stability of the system, and cost led to the development of the OsteoQuant, an isotope-based computed tomography scanner working on the translate-rotate principle. With 16 detectors providing a total of 128 projections and 256 data points per projection, the measurement time for one cross section is typically 90 s. Optimal for bone measurements in arms and legs, 125I was chosen as the photon source. The detectors are photomultipliers with Nal(TI) crystals employed in the counting mode. Usually, six to ten slices are measured at a given site, 2 mm apart from each other, and bone density is calculated for trabecular, subcompact, and compact bone. For repeat measurements, the evaluation sites are carefully matched, and the same volume of bone is analyzed at each measurement occasion. RESULTS: The long-term precision of the scanner, measured with a water cylinder, is 0.03%. This error includes the performance of the scanner hardware, calibration of the photon count rates, and reconstruction process. In vivo precision is influenced by additional factors such as slice positioning, patient cooperation, and bone contour detection. At the distal end of the tibia, trabecular bone density can be measured with a precision of 0.1%. The error for trabecular bone density in the radius is 0.3%. CONCLUSION: The OsteoQuant surpasses the design goals and represents an ideal instrument to assess small changes in bone density over time.

Bone Density↗

Osteoarthritis, bone density, postural stability, and osteoporotic fractures: a population based study.

OBJECTIVE: Osteoarthritis (OA) is associated with an increase in bone density both locally and at distant sites. Prospective data are limited on the relationship between OA and fracture. We studied the possible relationship between self-reported OA, bone density, postural stability measures, and atraumatic fractures as part of a study of men and women over 60 years of age. METHODS: Subjects were part of the Dubbo Osteoporosis Epidemiology Study (a longitudinal population based study of fracture risk factors). Bone density was measured by dual energy x-ray absorptiometry. Postural stability was assessed by the validated measures of quadriceps strength and sway. Medication use and self-reported arthritis were assessed by a structured personal interview. Fractures were ascertained retrospectively by interview and prospectively by viewing radiographic reports for fracture. RESULTS: Among a study population of 1101 women and 720 men (mean age 69) there were 462 subjects (25%) who reported a diagnosis of OA. In both sexes, subjects with OA had higher bone density (adjusted for age and body mass index) at both the femoral neck (men, p = 0.026; women, p = 0.048) and lumbar spine (men, p = 0.0007; women, p = 0.0007). However, in both sexes, those with self-reported OA also had higher body sway and lower quadriceps strength. The combination of these observed differences in fracture risk factors led to no predicted change in fracture risk overall when using established nomograms for this population [men, OR = 1.11 (95% CI 0.83-1.45); women, OR = 1.08 (95% CI 0.83-1.39)]. This paralleled our observational finding that self-reported OA was not associated with a decrease in fracture incidence compared to those not reporting OA in both men (RR 0.64, 95% CI 0.29-1.39) and women (RR 1.00, 95% CI 0.66-1.51). CONCLUSION: Individuals with self-reported OA, despite higher bone density, are not protected against nonvertebral osteoporotic fracture, apparently due to worsened postural stability and thus an increased tendency to fall.

Aged↗

Weight-bearing exercise, overexercise, and lumbar bone density over age 50 years.

This cross-sectional study of 78 healthy subjects older than age 50 years was designed to examine the association between weight-bearing exercise and lumbar bone mineral content as assessed by quantitative computed tomography. In women, a strong correlation existed between bone density and the amount of exercise for up to 300 min/wk. However, 5 of 28 women exercising 300 min/wk or more had surprisingly low bone density, not explained by other factors. In 50 men, we also found a strong positive correlation between exercise and bone density for those up to age 65 years. Over age 65, 3 men had low bone density despite extremely vigorous exercise. We conclude that moderate weight-bearing exercise may increase lumbar bone density, but we raise the hypothesis that extremely vigorous exercise actually may be detrimental to bone density in individuals after age 50.

Aged↗