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1.
Bone mineralization density distribution (BMDD) as assessed by quantitative backscattered electron imaging (qBEI) in iliac crest bone biopsies has become in the last years a powerful diagnostic tool to evaluate the effect of metabolic bone diseases and/or therapeutic interventions on the mineralization status of the bone material. However until now, normative reference data are only available for adults. The aim of the present study is to close this gap and establish normative data from children and compare them with reference BMDD data of adults.qBEI analyses were performed on bone samples from 54 individuals between 1.5 and 23 years without metabolic bone diseases, which were previously used as study population to establish normative histomorphometric standards.In the trabecular compartment, none of the BMDD parameters showed a significant correlation with age. The BMDD was shifted towards lower mineralization density (CaMean − 5.6%, p < 0.0001; CaPeak − 5.6%, p < 0.0001; CaLow + 39.0% p < 0.001; CaHigh − 80.7%, p < 0.001) and the inter-individual variation was higher compared to the adult population.The cortices appeared to be markedly less mineralized (CaMean − 3.1%, p < 0.0001) than cancellous bone due to higher amounts of low mineralized secondary bone. However, the cortical BMDD parameters showed a strong correlation (r = 0.38 to 0.85, with p < 0.001 to < 0.0001) with cancellous BMDD parameters.In conclusion, this study provides evidence that BMDD parameters in growing healthy subjects are relatively constant and that these data can be used as normative references in pediatrics osteology. The larger inter-individual variability compared to adults is most likely related to alterations of the bone turnover rate during growth.  相似文献   

2.
The effects of fluoride at concentrations of 2.0 and 4.5 mM in drinking water on growth rate, vitamin D, water and mineral metabolism, bone histomorphometry, and osteoinduction of demineralized allogenic bone matrix (DABM) were compared in the rat. Whereas fluoride did not influence fluid intake or growth rate at the lower concentration, it increased fluid intake and inhibited growth rate at the higher concentration. Fluoride produced dose-related increases in serum fluoride and alkaline phosphatase but did not alter serum 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D. Serum calcium and phosphate were reduced by fluoride at concentrations of 2.0 mM but not 4.5 mM. Cancellous bone fractional area was increased by fluoride at 2.0 mM and was reduced by fluoride at 4.5 mM. Fluoride had no effect on cancellous bone surface length or the percentage surface lined by osteoblasts and osteoclasts. Fluoride increased medullary area and decreased the endosteal bone formation rate. Fluoride increased periosteal bone formation and apposition rates at concentrations of 2.0 mM but not 4.5 mM. Fluoride inhibited mineralization in DABM implants, and at the higher concentration, fluoride increased the formation of new bone matrix. These results indicate that in the rat, fluoride increases cortical and trabecular bone at therapeutic doses and reduces trabecular bone at toxic doses. The serum concentration of fluoride at therapeutic doses in the rat is similar to that in patients with osteoporosis who are on treatment with fluoride. In the rat, there is a narrow range between toxic and therapeutic doses.  相似文献   

3.
The intermethod variation in the measurement of basic bone histomorphometric parameters was evaluated on 100 undecalcified transiliac bone biopsies. Two contiguous samples were taken from 50 patients (33 females; 17 males; mean age: 52 +/- 19 years) for diagnostic purposes. The diagnoses were osteoporosis (n = 38), renal osteodystrophy (n = 18), primary hyperparathyroidism (n = 16), osteomalacia (n = 12), metastatic bone disease (n = 2), thyrotoxic bone (n = 2), fluorosis (n = 2), and 10 biopsies were considered as "normal" bone. Trabecular bone volume (TBV) was measured with both a manual integrating eyepiece and an automatic (QUANTIMET 720-Cambridge Instruments, Cambridge, England) method. Trabecular resorption surfaces (TRS), trabecular osteoid surfaces (TOS), and volume (TOV) were measured with both a manual and a semiautomatic (VIDEOPLAN-Kontron, Munich, West Germany) method. The calcification rate (CR) was measured with both a manual and a semiautomatic method in eight cases after double labeling with tetracycline. Inter- and intraobserver variations were always lower with the automatic and semiautomatic methods than with the manual method, except for TOV. For all the parameters there was a highly significant correlation between manual and computerized methods (0.98 greater than r greater than 0.90). For TBV and CR no significant difference was noted, but for TBV the QUANTIMET appeared more sensitive, that is, better able to detect low values of the structure to be measured. For TRS, the manual method underestimated low values and appeared less sensitive than the semiautomatic method. For the 100 biopsies, the VIDEOPLAN underestimated the osteoid parameters by 13% for TOS and 26% for TOV.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

4.
Rauch F  Travers R  Parfitt AM  Glorieux FH 《BONE》2000,26(6):581-589
Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility and low bone mass. Four clinical types are commonly distinguished. Schematically, type I is the mildest phenotype, type II is usually lethal, type III is the most severe form compatible with postnatal survival, and type IV is moderately severe. Although mutations affecting collagen type I are responsible for the disease in most patients, the mechanisms by which the genetic defects cause abnormal bone development have not been well characterized. Therefore, we evaluated quantitative static and dynamic histomorphometric parameters in tetracycline-labeled iliac bone biopsies from 70 children, aged 1.5 to 13.5 years, with OI types I (n = 32), III (n = 11), and IV (n = 27). Results were compared with those of 27 age-matched controls without metabolic bone disease. Biopsy core width, cortical width, and cancellous bone volume were clearly decreased in all OI types. Decreased cancellous bone volume was due to a 41%–57% reduction in trabecular number and a 15%–27% lower trabecular thickness. Regression analyses revealed that trabecular number did not vary with age in either controls or OI patients, indicating that no trabecular loss occurred. The annual increase in trabecular thickness was 5.8 μm in controls and 3.6 μm in type I OI, whereas no trabecular thickening was evident in type III and IV OI. Wall thickness, which reflects the amount of bone formed during a remodeling cycle, was decreased by 14% in a subgroup of 17 type I OI patients, but was not determined in the other OI types. The remodeling balance was less positive in type I OI than in controls, and probably close to zero in types III and IV. Surface-based parameters of bone remodeling were increased in all OI types, indicating increased recruitment of remodeling units. No defect in matrix mineralization was found. In conclusion, there was evidence of defects in all three mechanisms, which normally lead to an increase in bone mass during childhood; that is, modeling of external bone size and shape, production of secondary trabeculae by endochondral ossification, and thickening of secondary trabeculae by remodeling. Thus, OI might be regarded as a disease in which a single genetic defect in the osteoblast interferes with multiple mechanisms that normally ensure adaptation of the skeleton to the increasing mechanical needs during growth.  相似文献   

5.
The effects of ovariectomy for four weeks and of 17 beta-estradiol for three weeks on histomorphometry of the tibial diaphysis were determined in young rats. The effects of ovariectomy on histomorphometry of subcutaneous implants of demineralized bone matrix were also examined. Groups of young female rats were either ovariectomized or sham operated. After surgery, the animals were weight matched and pair fed. Despite the same caloric intake, ovariectomized rats grew more rapidly than pair-fed, sham-operated controls but were significantly heavier at sacrifice in only one of three experiments. Ovariectomy did not change mean serum calcium, phosphate, 25-hydroxyvitamin D (25-OHD), or 1,25-dihydroxyvitamin D [1,25(OH)2D] but significantly lowered mean serum magnesium. Serum estradiol was not detectable in ovariectomized animals. 17 beta-Estradiol in ovariectomized animals significantly increased mean serum estradiol and lowered mean serum phosphate but did not change mean serum calcium, magnesium, 25-OHD, or 1,25(OH)2D, as compared to values in sham-operated controls. Bone formation rate was significantly enhanced in ovariectomized animals at both the endosteal and periosteal surfaces of the tibial diaphysis as compared to values in sham-operated controls. The increase in bone formation rate was reversed by 17 beta-estradiol at the periosteal but not endosteal surface. Ovariectomy increased the bone apposition rate, mineralization rate, and osteoid thickness of the tibial diaphysis. These increases were reversed by 17 beta-estradiol. In implants, ovariectomy increased the resorption of implant matrix and enhanced the formation of new matrix. Ovariectomy resulted in increases in forming surface and resorbing surface in the implants.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

6.
Bone mineral density (BMD) at the lumbar vertebrae (L(1)-L(4)) was assessed by dual-energy X-ray absorptiometry (DXA) in 20 children with chronic kidney disease (CKD) on dialysis, and its results were compared with bone biopsy and biochemical parameters. Biopsy specimens provided evidence of hyperparathyroid bone disease in eight cases (40%), and low bone turnover in 12 (60%). For BMD, expressed as Z-scores relative to normal, median Z-scores were -1.05 (range -2.36 to 1.06) for hyperparathyroid patients and -1.05 (range -4.40 to -0.03) for low bone turnover patients, with no statistical differences between groups (P = 0.512). In relation to BMD, of the whole sample, five (25%) had a Z-score under -2.0. When it was corrected for height, BMD was in the normal range. Additionally, there were no significant differences in single samples of serum calcium, alkaline phosphatase, phosphorus and intact parathyroid hormone (PTH) between groups with high or low bone turnover. Assessment of nutritional status, through height/age, showed that ten patients had Z-scores below -2.0 (median -2.12, range -7.13 to 0.73). In conclusion, renal osteodystrophy (ROD) seems to have a high prevalence among CKD pediatric patients, although only approximately a quarter of them developed changes in BMD. In children with CKD, measurements of bone mineral density may not be used for classification of various forms of ROD.  相似文献   

7.

Summary  

Children with inflammatory bowel disease (IBD) manifest low bone mass; the cause remains unclear. We performed transilial bone biopsies in 20 IBD children at diagnosis and found a mild cortical bone deficit and slow bone turnover. It is possible that low mechanical stimulation due to inadequate muscle mass contributes to the bone deficit.  相似文献   

8.
We recently developed a new, rapid method for conducting static histomorphometry on large histologic sections. This method has now been applied on both iliac crest and lumbar vertebral bone to compare the age-related changes at these two skeletal sites and to investigate the correlation between the histomorphometric measures at the iliac crest and the vertebral body. The material comprised matched sets of unilateral transiliac crest bone biopsies and lumbar vertebral bodies (L-2) from 24 women (19-96 years) and 24 men (23-95 years) selected from a larger autopsy material. Three female subjects (80, 88, and 90 years) had a known vertebral fracture of L-2. The iliac crest biopsies and 9-mm-thick mediolateral slices of half the entire vertebral bodies were embedded in methylmetacrylate, stained with aniline blue, and scanned into a computer with a flatbed image scanner at a high resolution. With a custom-made computer program the following static histomorphometric measures were determined: trabecular bone volume; marrow and bone space star volume; node-strut analysis; trabecular bone pattern factor; trabecular thickness; trabecular number; trabecular separation; and anisotropy of bone and marrow phase. In addition, connectivity density was measured (ConnEulor method). The results showed that the age-related changes in the static histomorphometric measures are generally similar in the iliac crest and the vertebral body, and that these age-related changes are independent of gender. An exception, however, is connectivity density, where the age-related changes are similar for women and men in the vertebral body but significantly different in the iliac crest. Furthermore, the results showed that the histomorphometric measures were weakly intercorrelated between the iliac crest and the vertebral body, despite the generally similar pattern in age-related changes at these two skeletal sites. The highest correlation coefficient was found for trabecular separation (Tb.Sp; r = 0.63). Trabecular bone volume showed a correlation coefficient of r = 0.59. It is concluded that static histomorphometry performed on one skeletal site does not automatically predict static histomorphometric measures at another skeletal site. Therefore, it is recommended that static histomorphometry be performed at the skeletal site of interest-if at all possible.  相似文献   

9.
This review reports on proceedings of a bone histomorphometry session conducted at the Fortieth International IBMS Sun Valley Skeletal Tissue Biology Workshop held on August 1, 2010. The session was prompted by recent technical problems encountered in conducting histomorphometry on bone biopsies from humans and animals treated with anti-remodeling agents such as bisphosphonates and RANKL antibodies. These agents reduce remodeling substantially, and thus cause problems in calculating bone remodeling dynamics using in vivo fluorochrome labeling. The tissue specimens often contain few or no fluorochrome labels, and thus create statistical and other problems in analyzing variables such as mineral apposition rates, mineralizing surface and bone formation rates. The conference attendees discussed these problems and their resolutions, and the proceedings reported here summarize their discussions and recommendations.  相似文献   

10.
Dynamic bone histomorphometry is the standard method for measuring bone remodeling at the level of individual events. Although dynamic bone histomorphometry is an invaluable tool for understanding osteoporosis and other metabolic bone diseases, the technique's two‐dimensional nature requires the use of stereology and prevents measures of individual remodeling event number and size. Here, we used a novel three‐dimensional fluorescence imaging technique to achieve measures of individual resorption cavities and formation events. We performed this three‐dimensional histomorphometry approach using a common model of postmenopausal osteoporosis, the ovariectomized rat. The three‐dimensional images demonstrated the spatial relationship between resorption cavities and formation events consistent with the hemiosteonal model of cancellous bone remodeling. Established ovariectomy was associated with significant increases in the number of resorption cavities per unit bone surface (2.38 ± 0.24 mm?2 sham surgery versus 3.86 ± 0.35 mm?2 bilateral ovariectomy [OVX], mean ± SD, p < 0.05) and total volume occupied by cavities per unit bone volume (0.38% ± 0.06% sham versus 1.12% ± 0.18% OVX, p < 0.001), but there was no difference in surface area per resorption cavity, maximum cavity depth, or cavity volume. In addition, we found that established ovariectomy is associated with increased size of bone formation events because of the merging of formation events (23,700 ± 6,890 µm2 sham verusus 33,300 ± 7,950 µm2 OVX). No differences in mineral apposition rate (determined in 3D) were associated with established ovariectomy. That established estrogen depletion is associated with increased number of remodeling events with only subtle changes in remodeling event size suggests that circulating estrogens may have their primary effect on the origination of new basic multicellular units with relatively little effect on the progression and termination of active remodeling events. © 2012 American Society for Bone and Mineral Research  相似文献   

11.
12.
Bone material characteristics are important contributors in the determination of bone strength. Raman spectroscopic analysis provides information on mineral/matrix ratio, mineral maturity/crystallinity, relative pyridinoline (Pyd) collagen cross-link content, relative proteoglycan content and relative lipid content. However, published reference data are available only for adults. The purpose of the present study was to establish reference data of Raman outcomes pertaining to bone quality in trabecular bone for children and young adults. To this end, tissue age defined Raman microspectroscopic analysis was performed on bone samples from 54 individuals between 1.5 and 23 years with no metabolic bone disease, which have been previously used to establish histomorphometric and bone mineralization density distribution reference values. Four distinct tissue ages, three well defined by the fluorescent double labels representing early stages of bone formation and tissue maturation (days 3, 12, 20 of tissue mineralization) and a fourth representing old mature tissue at the geometrical center of the trabeculae, were analyzed. In general, significant dependencies of the measured parameters on tissue age were found, while at any given tissue age, sex and subject age were not confounders. Specifically, mineral/matrix ratio, mineral maturity/crystallinity index and relative pyridinoline collagen cross-link content index increased by 485%, 20% and 14%, respectively between days 3 and 20. The relative proteoglycan content index was unchanged between days 3 and 20 but was elevated in the old tissue compared to young tissue by 121%. The relative lipid content decreased within days 3 to 20 by − 22%. Thus, the method allows not only the monitoring of material characteristics at a specific tissue age but also the kinetics of tissue maturation as well. The established reference Raman database will serve as sensitive tool to diagnose disturbances in material characteristics of pediatric bone biopsy samples.  相似文献   

13.
14.
15.
Summary Inter-observer variation has been examined for a number of histomorphometric indices in 20 normal human iliac crest biopsies. Quantitation was performed using an eye-piece graticule and eye-piece micrometer. The same sections were examined by two observers and the methodology was identical. Intra-observer variation was also assessed. Significant inter-observer differences were found for the measurement of total trabecular bone volume, osteoid volume and surface, double plus single and double tetracycline labeled surfaces, and the mean osteoid seam width. The percentage variance due to inter-observer variation was highest for osteoid surface and volume, total resorption surface, and mean osteoid seam width. Intra-observer variation in both observers was small. We conclude that a large inter-observer variation may occur in the measurement of a number of histomorphometric indices, even when section preparation and methodology are identical. Caution should be used in basing the diagnosis of metabolic bone disease on strictly defined control data from other observers, particularly when this has been obtained from centers where the effects of inter-observer variation may be magnified by differences in methodology.  相似文献   

16.
Bone formation and resorption have been measured in patients with idiopathic osteoporosis by histomorphometry of 7.5-mm trephine biopsies and in the whole body by 85Sr radiotracer methodology and calcium balances. The studies were synchronized and most were preceded by double in vivo tetracycline labeling. Correlations between histological and kinetic bone formation indices were better when better when based on the extent of double tetracycline labels than on measurements of osteoid by visible light microscopy. Correction of the kinetic data for long-term exchange, using 5 months' serial whole body counting of retained 85Sr, improved the fit of the kinetic to the histological data. A statistical analysis of the measurement uncertainties showed that the residual scatter in the best correlations (between exchange-corrected bone formation rates and double-labeled osteoid surface indices) could be attributed to measurement imprecision alone. The exchange-corrected resorption rate correlated fairly well with iliac trabecular resorption surfaces, and using a volume referent rather than a surface referent for the histological index improved the statistical fit when patients with therapeutically accelerated bone turnover were included. A much better correlation was obtained by including osteoid volume acting as an independent predictor of bone resorption in a bivariate regression with a resorption surface index. The residual errors could then be accounted for by known measurement uncertainties. Whereas osteoid taking a double label closely predicted the kinetic rate of bone formation, further analysis suggested that osteoid that took no label or a single label was more closely related to bone resorption, presumably as a secondary result of the coupling of bone formation to bone resorption. The idea that continued bone loss in some patients is associated with defective osteoblastic bone formation is supported by the low rates found in some patients by both techniques. Heuristically these studies validate both in vivo tetracycline labeling for dynamic histomorphometry and corrections for long-term exchange in kinetic studies of bone formation, providing a quantitative framework for the design and analysis of future studies of bone remodeling in the osteoporoses.  相似文献   

17.
Bonn Risk Index (BRI) is being used for the assessment of urinary calcium oxalate (CaOx) crystallization. There are no published data regarding BRI during growth. The objective of this study was to establish age- and sex-dependent BRI values in healthy children and adolescents. A total of 1,050 Caucasian subjects aged 3–18 years (525 males, 525 females) without a history of kidney stone disease were enrolled in the cross-sectional study. The study group was divided into 15 ranges according to age, each comprising 70 subjects. Urinary ionized calcium [Ca2+] was measured using a selective electrode while the onset of spontaneous crystallization was determined using a photometer and titrating with 40 mmol/L ammonium oxalate (Ox2−). The calculation of BRI value was based on the ratio of [Ca2+] to the required amount of ammonium oxalate added to 200 ml of urine to induce crystallization. The median BRI was 0.26 1/L and the values of the 5th and 95th percentiles were 0.06 1/L and 1.93 1/L, respectively. BRI correlated positively with body-area-related BRI (1/L × 1.73 m2) (R = 0.18; P < 0.05), whereas a negative correlation was found between BRI and body weight (1/L × kg) (R = −0.85; P < 0.05). Neither sex nor age differences were detected in BRI across studied children and adolescents. The values of Bonn Risk Index were constant during growth and there was a limited influence of age and sex on BRI in children over 3 years of age. The BRI may be valuable in the evaluation of pediatric patients at risk for kidney stones, particularly if the BRI from stone formers is demonstrated to be higher than in normal children.  相似文献   

18.

Summary

Age-related change in bone mineral density (BMD) varied according to skeletal site in Indian subjects. A larger proportion of subjects was classified as osteoporotic and osteopenic using the Caucasian database than newly derived peak BMD values at most skeletal sites. Results establish useful normative data for reliable interpretations of individual dual-energy X-ray absorptiometry (DEXA) values

Introduction

Osteoporosis is believed to occur at a relatively younger age in the Indian population. With increasing knowledge on significant differences in BMD between various racial groups, there is increased emphasis for the use of population-specific reference database.

Methods

BMD at multiple skeletal sites was measured using DEXA (Prodigy, Lunar) in 615 Indian women (20–86 years) and 489 Indian men (20–83 years). Best-fit models were drawn for each skeletal site. Osteopenia and osteoporosis diagnosis rates were calculated using Caucasian and derived Indian peak BMD values.

Results

Age-related change in BMD varied with skeletal site in both sexes. Peak BMD in women was observed between 31 and 40 years of age at the hip, spine, and radius 33% and between 20 and 30 years at the ultradistal radius. Peak BMD in men was attained between 20 and 30 years at the hip and radius 33% and between 31 and 40 years at the spine and ultradistal radius. A larger proportion of Indian subjects was classified as osteoporotic and osteopenic based on the Caucasian database than newly derived Indian peak BMD values at all skeletal sites except radius 33% and femoral neck in females above 40 years of age.

Conclusion

Results establish useful normative data for the Indian population for reliable interpretations of individual DEXA values.  相似文献   

19.
Skaggs DL  Samuelson MA  Hale JM  Kay RM  Tolo VT 《Spine》2000,25(18):2400-2402
STUDY DESIGN: The perioperative and postoperative complications associated with harvesting posterior iliac crest bone graft in children were reviewed. A retrospective study was performed and a questionnaire interview conducted. OBJECTIVES: To determine the morbidity associated with posterior iliac crest bone graft in children. SUMMARY OF BACKGROUND DATA: Iliac crest bone is commonly used as a source of bone graft in spine surgery. Although there are multiple reports of complications in adults, there are no reports in children. METHODS: A retrospective chart review was performed of 214 consecutive children who underwent spinal fusion with posterior iliac crest bone graft from 1990 through 1996. An interview was conducted of 87 patients with normal mental status, predominantly those with idiopathic scoliosis with a minimum of 2 years' follow-up (mean, 55 months). RESULTS: The review showed one (0.5%) instance of arterial injury in the sciatic notch. Two (1%) patients had infections, both of which resolved with a single irrigation and débridement. There was one documented instance of sacroiliac penetration that did not cause clinical problems. The chart review showed three (1.4%) instances of continued pain and one (0.5%) of numbness. By contrast to the few reports of pain in the chart review, responses to an interview of 87 patients showed 21 (24%) children reporting pain at the iliac crest site, with 13 (15%) reporting problems with daily activities. The self-reported pain, on a scale of 1 to 10, ranged from 1 to 10 with a mean of 4. Nonsteroidal anti-inflammatory drugs (NSAIDS) were taken by eight (9%) children for pain at the bone graft site. Five (6%) reported skin irritation, and 18 (20%) mentioned numbness surrounding the scar. CONCLUSION: The perioperative rate of complications in iliac crest bone grafting in children is low (2%). The complication of pain (24%) and pain that is severe enough to interfere with daily activity (15%) is significant at a mean follow-up of more than 4 years. The true extent of pain and numbness after posterior iliac crest bone grafting in children was severely underreported in the medical records and may be underrecognized.  相似文献   

20.
In a prospective study we compared bone mass measured independently by dual photon absorptiometry (DPA) on lumbar spine and by histomorphometry on transiliac biopsy. Measurements were done in 83 patients (23 males, 60 females) with various generalized bone diseases, including spinal osteoporosis, primary hyperparathyroidism and osteopetrosis. Iliac bone density was analyzed on bone biopsy with an automatic image analyzer and expressed as the trabecular bone volume (TBV), the cortical thickness (CT) and the total bone density (TBD) which includes the density of both spongy and cortical bone within the periosteal envelope. The bone mineral content (BMC) and density (BMD) were measured from L2 to L4 with a Novo Lab 22a device. For the 83 patients, there were significant correlations between values given by both methods, with r values ranging from 0.74 to 0.43, according to the bone mass parameters analyzed. In the 37 patients with untreated vertebral osteoporosis, the TBV--but not the CT nor the TBD--correlated significantly with the BMD of the spine (r = 0.53, p less than 0.001). In conclusion, there is a significant correlation between bone density of the iliac crest assessed histomorphometrically and spinal density measured by DPA. Despite the fact that DPA measures both trabecular and cortical bone of the spine, it correlates better with iliac trabecular bone mass than with the overall iliac bone density.  相似文献   

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