Detecting microdamage in bone Lee, T. C.; Mohsin, S.; Taylor, D. ...
Journal of anatomy,
August 2003, Letnik:
203, Številka:
2
Journal Article
Recenzirano
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Fatigue‐induced microdamage in bone contributes to stress and fragility fractures and acts as a stimulus for bone remodelling. Detecting such microdamage is difficult as pre‐existing microdamage ...sustained in vivo must be differentiated from artefactual damage incurred during specimen preparation. This was addressed by bulk staining specimens in alcohol‐soluble basic fuchsin dye, but cutting and grinding them in an aqueous medium. Nonetheless, some artefactual cracks are partially stained and careful observation under transmitted light, or epifluorescence microscopy, is required. Fuchsin lodges in cracks, but is not site‐specific. Cracks are discontinuities in the calcium‐rich bone matrix and chelating agents, which bind calcium, can selectively label them. Oxytetracycline, alizarin complexone, calcein, calcein blue and xylenol orange all selectively bind microcracks and, as they fluoresce at different wavelengths and colours, can be used in sequence to label microcrack growth. New agents that only fluoresce when involved in a chelate are currently being developed – fluorescent photoinduced electron transfer (PET) sensors. Such agents enable microdamage to be quantified and crack growth to be measured and are useful histological tools in providing data for modelling the material behaviour of bone. However, a non‐invasive method is needed to measure microdamage in patients. Micro‐CT is being studied and initial work with iodine dyes linked to a chelating group has shown some promise. In the long term, it is hoped that repeated measurements can be made at critical sites and microdamage accumulation monitored. Quantification of microdamage, together with bone mass measurements, will help in predicting and preventing bone fracture failure in patients with osteoporosis.
Summary
Stereology applied on histological sections is the ‘gold standard’ for obtaining quantitative information on cancellous bone structure. Recent advances in micro computed tomography (µCT) have ...made it possible to acquire three‐dimensional (3D) data non‐destructively. However, before the 3D methods can be used as a substitute for the current ‘gold standard’ they have to be verified against the existing standard. The aim of this study was to compare bone structural measures obtained from 3D µCT data sets with those obtained by stereology performed on conventional histological sections using human tibial bone biopsies. Furthermore, this study forms the first step in introducing the proximal tibia as a potential bone examination location by peripheral quantitative CT and CT. Twenty‐nine trabecular bone biopsies were obtained from autopsy material at the medial side of the proximal tibial metaphysis. The biopsies were embedded in methylmetacrylate before µCT scanning in a Scanco µCT 40 scanner at a resolution of 20 × 20 × 20 µm3, and the 3D data sets were analysed with a computer program. After µCT scanning, 16 sections were cut from the central 2 mm of each biopsy and analysed with a computerized method. Trabecular bone volume (BV/TV) and connectivity density (CD) were estimated in both modalities, whereas trabecular bone pattern factor (TBPf) was estimated on the histological sections only. Trabecular thickness (Tb.Th), number (Tb.N) and separation (Tb.Sp), and structure model index (SMI) were estimated with the µCT method only. Excellent correlations were found between the two techniques for BV/TV (r = 0.95) and CD (r = 0.95). Additionally, an excellent relationship (r = 0.95) was ascertained between TBPf and SMI. The study revealed high correlations between measures of bone structure obtained from conventional 2D sections and 3D µCT data. This indicates that 3D µCT data sets can be used as a substitute for conventional histological sections for bone structural evaluations.
Vertebral fracture is one of the major adverse clinical consequences of osteoporosis; however, there are few data concerning the incidence of vertebral fracture in population samples of men and ...women. The aim of this study was to determine the incidence of vertebral fracture in European men and women. A total of 14,011 men and women aged 50 years and over were recruited from population‐based registers in 29 European centers and had an interviewer‐administered questionnaire and lateral spinal radiographs performed. The response rate for participation in the study was approximately 50%. Repeat spinal radiographs were performed a mean of 3.8 years following the baseline film. All films were evaluated morphometrically. The definition of a morphometric fracture was a vertebra in which there was evidence of a 20% (+4 mm) or more reduction in anterior, middle, or posterior vertebral height between films—plus the additional requirement that a vertebra satisfy criteria for a prevalent deformity (using the McCloskey‐Kanis method) in the follow‐up film. There were 3174 men, mean age 63.1 years, and 3614 women, mean age 62.2 years, with paired duplicate spinal radiographs (48% of those originally recruited to the baseline survey). The age standardized incidence of morphometric fracture was 10.7/1000 person years (pyr) in women and 5.7/1000 pyr in men. The age‐standardized incidence of vertebral fracture as assessed qualitatively by the radiologist was broadly similar—12.1/1000 pyr and 6.8/1000 pyr, respectively. The incidence increased markedly with age in both men and women. There was some evidence of geographic variation in fracture occurrence; rates were higher in Sweden than elsewhere in Europe. This is the first large population‐based study to ascertain the incidence of vertebral fracture in men and women over 50 years of age across Europe. The data confirm the frequent occurrence of the disorder in men as well as in women and the rise in incidence with age.
The aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50-79 years. ...Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR = 1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR = 0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.
The presence of a vertebral deformity increases the risk of subsequent spinal deformities. The aim of this analysis was to determine whether the presence of vertebral deformity predicts incident hip ...and other limb fractures. Six thousand three hundred and forty-four men and 6788 women aged 50 years and over were recruited from population registers in 31 European centers and followed prospectively for a median of 3 years. All subjects had radiographs performed at baseline and the presence of vertebral deformity was assessed using established morphometric methods. Incident limb fractures which occurred during the follow- up period were ascertained by annual postal questionnaire and confirmed by radiographs, review of medical records and personal interview. During a total of 40348 person-years of follow-up, 138 men and 391 women sustained a limb fracture. Amongst the women, after adjustment for age, prevalent vertebral deformity was a strong predictor of incident hip fracture, (rate ratio (RR) = 4.5; 95% CI 2.1-9.4) and a weak predictor of 'other' limb fractures (RR = 1.6; 95% CI 1.1-2.4), though not distal forearm fracture (RR = 1.0; 95% CI 0.6-1.6). The predictive risk increased with increasing number of prevalent deformities, particularly for subsequent hip fracture: for two or more deformities, RR = 7.2 (95% CI 3.0-17.3). Amongst men, vertebral deformity was not associated with an increased risk of incident limb fracture though there was a nonsignificant trend toward an increased risk of hip fracture with increasing number of deformities. In summary, prevalent radiographic vertebral deformities in women are a strong predictor of hip fracture, and to a lesser extent humerus and 'other' limb fractures; however, they do not predict distal forearm fractures.
More severe vertebral fractures have more personal impact. In the European Prospective Osteoporosis Study, more severe vertebral collapse was predictable from prior fracture characteristics. Subjects ...with bi‐concave or crush fractures at baseline had a 2‐fold increase in incident fracture size and thus increased risk of a disabling future fracture.
Introduction: According to Euler's buckling theory, loss of horizontal trabeculae in vertebrae increases the risk of fracture and suggests that the extent of vertebral collapse will be increased in proportion. We tested the hypothesis that the characteristics of a baseline deformity would influence the size of a subsequent deformity.
Methods: In 207 subjects participating in the European Prospective Osteoporosis Study who suffered an incident spine fracture in a previously normal vertebra, we estimated loss of volume (fracture size) from plane film images of all vertebral bodies that were classified as having a new fracture. The sum of the three vertebral heights (anterior, mid‐body, and posterior) obtained at follow‐up was subtracted from the sum of the same measures at baseline. Each of the summed height loss for vertebrae with a McCloskey‐Kanis deformity on the second film was expressed as a percentage.
Results and Conclusions: In univariate models, the numbers of baseline deformities and the clinical category of the most severe baseline deformity were each significantly associated with the size of the most severe incident fracture and with the cumulated sum of all vertebral height losses. In multivariate modeling, age and the clinical category of the baseline deformity (crush > bi‐concave > uni‐concave > wedge) were the strongest determinants of both more severe and cumulative height loss. Baseline biconcave and crush fractures were associated at follow‐up with new fractures that were approximately twice as large as those seen with other types of deformity or who previously had undeformed spines. In conclusion, the characteristics of a baseline vertebral deformity determines statistically the magnitude of vertebral body volume lost when a subsequent fracture occurs. Because severity of fracture and number of fractures are determinants of impact, the results should improve prediction of the future personal impact of osteoporosis once a baseline prevalent deformity has been identified.
Incident vertebral deformities are commonly defined by observed changes in height between measurements on two consecutive radiographs. However, conventional radiographs are subject to magnification, ...and this magnification may differ between films, leading to artifactual changes in height. In order to minimize this effect, it is common practice to record the spine-film and film-focus distances, and from this to calculate a magnification factor for each film. We present a simple statistical method for correcting for differences in magnification between two films if the spine-film and film-focus distances are unknown. This method is shown to reduce the variance of the magnification differences in vertebral heights by 14%, considerably more than is possible using the spine-film distance. Using the statistical method, the number of vertebrae that showed not only a reduction in one or more height of 15%, but were also judged clinically to be free from any incident deformity by an expert radiologist, was reduced from 100 to 46. The number showing a reduction of 20% that were judged fracture-free was reduced from 15 to 9. In the subset of subjects for whom the spine-film distance was known, the reduction in false positives was similar, whichever method was used to correct for magnification. There was no difference in the number of confirmed incident fractures detected when magnification correction by either method was employed. It is concluded that correcting for magnification differences using the statistical method outlined here reduces the number of false positive deformities very substantially and by a similar extent as correcting the magnification using reliable, measured spine-film and film-focus distances. A further advantage of this method is that it can be used retrospectively.
A finite-element study to investigate the amount of trabecular bone at risk of fracture and the distribution of load between trabecular core and cortical shell, for healthy, osteopenic, and ...osteoporotic vertebrae.
To determine differences between healthy, osteopenic, and osteoporotic vertebrae with regard to the risk of fracture and the load distribution.
The literature contains no reports on the effects of osteopenia and osteoporosis on load distribution in vertebral bodies, nor any reports on the amount of trabecular bone at risk of fracture.
Computed tomography data of vertebral bodies were used to construct patient-specific finite-element models. These models were then used in finite-element analyses to determine the physiologic stresses and strains in the vertebrae.
For all three classes of vertebrae the contribution of the trabecular core to the total load transfer decreased from about 70% near the endplates to about 50% in the midtransverse region. The amount of trabecular bone that is at risk of fracture was about 1% for healthy vertebrae, about 3% for osteopenic vertebrae, and about 16% for osteoporotic vertebrae.
Our finite-element models indicated that neither osteopenia nor osteoporosis had any effect on the contribution of the trabecular core to the total load placed on the vertebra. The trabecular core carried about half the load. Our finite-element models indicated that osteoporosis had a significant effect on the amount of trabecular bone at risk of fracture, which increased from about 1% in healthy vertebrae to about 16% for osteoporotic vertebrae.
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