The quantitative in vivo measuring of bone mineral denseness and organic structure composing has been an country of involvement for both clinicians and research workers.
These values are utile for measuring diseases impacting both bone mineral denseness ( BMD ) and organic structure composing. BMD measuring is presently the most accurate method for foretelling hazard of osteoporotic breaks ( Grainger et al 2001 ) . The BMD measurings are besides utile in supervising response of interventions for bar of bone loss and breaks. Body composing measurings are used to quantify soft tissue to measure changed associated with growing, disease, exercising and etc. Today, these measurings are most normally taken by utilizing double energy X-ray absorptiometry ( DXA ) .
DXA is a type of double energy imaging technique based on working the difference in the fading of soft tissue and bone tissue at different energy degrees. Since the find of double energy imagination, its engineering has advanced really rapidly and its practical applications have expanded far beyond the original purpose, which was to quantify the bone mineral content. With minor accommodations and alterations to the DXA system, its utilizations are now beyond the field of bone wellness and tissue composing measurings.X-ray engineering has been involved in medical probes since the early 1900s. At first, radiogram were taken utilizing X-rays to analyze bone constructions in patients.
This was possible because castanetss being denser than other soft tissues, absorb X raies more readily, therefore bring forthing an image. With betterments in the technique, X ray is used to observe lung diseases, obstructors in the abdominal variety meats, designation of rocks in gall bladder and the urinary system. Today the usage of X ray in medical specialty has been expanded to existent clip imaging such as angiography and surgical intercessions.
Plain radiograms have been used to measure bone mineral denseness. This was done by analyzing the radiogram of sidelong position of thoracolumbar spinal column, the information can be used to find osteopaenic alterations or to set up osteoporosis. However, on a radiogram the bone would look normal until a shortage of bone mineral content ( BMC ) in the order of 20 % occurs ( Ardran 1951 ) . Besides, obviously radiogram can non be used to supervise the alteration of mineral content because the consequences are non easy repeated.
Single photon absorptiometry
In 1963, individual photon absorptiometry ( SPA ) was introduced ( Cameron and Sorenson 1963 ) . This allowed bone mineral denseness to be measured in vivo and a quantitative value is obtained. This methods works by mensurating the soaking up by bone of a monochromatic, low energy photon beam. This beam is produced by a radioactive isotope beginning, iodine-125 is normally used and emits photons at 27.
3 keV ( Cameron and Sorenson 1963 ) . This technique was used to quantify bone loss due to osteoporosis in the forearm. To counterbalance for changing thickness of soft tissues around the bone, the patient is required to put the arm in a H2O bath of known breadth, as the soaking up coefficients of H2O and soft tissue virtually the same, bone mineral content and areal denseness can be quantified accurately. The beam of photons is scanned across the H2O bath and forearm and the transmittal at each point is noted.
Double photon absorptiometry
Subsequently, double photon absorptiometry was developed ( Reed 1966 ) . This uses two photon beams of different energy to counterbalance for soft tissue thickness and extinguishing the demand of a H2O bath to mensurate BMC. Scanning of the axial skeleton became possible, more clinically relevant osteoporotic break sites such as the hip and the spinal column can be measured. Both photon absorptiometry techniques have a figure of draw dorsums.
The radioactive isotopes have short half-lives, they needed to be replaced frequently and the decay can besides do job in follow up measurings. The scanning clip can be up to 30 proceedingss, for certain groups of population for illustration the aged, it can be really hard to maintain comparatively still for this period of clip and can do uncomfortableness. The image quality of this method is comparatively hapless and resulted in a low preciseness, which is the ability to bring forth the same consequences under the same fortunes.
Dual energy X-ray absorptiometry
The rule of DXA engineering is really similar to that of DPA. DXA uses beams of X raies emitted from an X-ray tubing instead than radioactive isotope beginnings to supply the double energies. The energies produced can be quickly exchanging or by utilizing a changeless possible X ray tubing with rare Earth filters to bring forth different energy degrees. ( Felsenberg et al 1995, Wahner et al 1988, Truscott et al 1996 ) An X-ray beginning addition the figure of photon passing through the topic in a given clip period, therefore cut downing scanning period and running cost.Hologic introduced the first commercial DXA system in 1987 ( Truscott et al 1996 ) , and so closely followed by other companies.
The first coevals of DXA scanners used collimated pencil beam, cut downing unneeded radiation exposure to the topic. The topic lies on a bed, beneath the bed is the X-ray beginning and above the topic is the sensor. The beginning and the sensor are held on the can build up and the arm move these two parts synchronously and scan the topic in a rectilineal form in the part of involvement ( ROI ) .
The 2nd coevals of DXA systems uses a fan beam ( Figure 1 ) of X raies collimated by a slit-beam in concurrence with an array of sensors ( Kelly et al 1991 ) . This allows the scan to be completed with a individual expanse of the scan which reduced the scan clip to around 30 seconds. The image quality is near radiographic which gives a much improved preciseness and truth, which is the ability to give the true consequence compared to an accepted gold criterion method. The system can mensurate the BMD of lumbar spinal column, hip, entire organic structure and organic structure composing. With the new debut of revolving C-arm scanner, a sidelong lumbar spinal column BMD can be measured and spinal morphometry can besides be performed.Figure 1. Illustration of a modern fan-beam DXA scanner.
Depending on different systems, X-ray can be emitted from the top or the underside of the C-arm.
Comparison with other methods
Many of the advantages of DXA comparing to earlier double energy imaging techniques have been mentioned above. DXA has higher truth and preciseness, the scan clip and running clip are greatly reduced.DXA measuring of BMD in vivo is necessarily contaminated with false readings. DXA methodological analysis can merely return an accurate value of the areal bone mineral denseness merely if the “ two constituent ” status is met. The scan ROI can merely incorporate two X-ray absorptiometrically disparate stuffs. As we know, the ROI contains a figure of different types of soft tissues, for illustration: adipose tissue, musculus tissue, different variety meats such as bowels, blood vas and intraosseous soft tissues ( Bolotin 2007 ) .
Although modern systems provide algorithms in the package to counterbalance the different composing of soft tissue, DXA can non supply 100 % accurate BMD readings because of this built-in defect in the methodological analysis.Apart from double energy technique, there are other methods for mensurating bone mineral denseness. One of which is quantitative computed imaging ( QCT ) . QCT of the spinal column and the hip are available on standard CT units. The advantage of the QCT technique is its ability to measure the 3-dimensional bone denseness ( g/cm3 ) and DXA can merely measure the two dimensional denseness ( g/cm2 ) , which is affected by the size of the bone. Two castanetss of equal denseness with different size, the bigger bone will give a greater BMD reading utilizing DXA.
QCT besides allows the separate measurings of trabeculate bone denseness, which is more sensitive to effects of endocrines and drug interventions. The scan clip of QCT is instead long, 20 proceedingss comparing to 30 seconds of DXA. The radiation dosage of QCT could be up to 100 times higher than that of DXA, 2 I?Sv of radiation produced by DXA is tantamount of less than one twenty-four hours of background radiation ( harmonizing to Report of the United Nations Scientific Committee on the Effectss of Atomic Radiation to the General Assembly ) . Furthermore, CT scanners are in great demand for its many applications and they cost 10 times more than DXA scanners.
Accuracy ( % )Precision ( % )Effective Radiation Dose ( I?Sv )Scan Time ( min )DXA Pencil Beam4-81& lt ; 15-10DXA Fan Beam4-80.
5-1210-60sDPA5-102-4530QCT3-64-610020Table 1. Comparison of different BMD measuring techniques. Adapted from Grainger et al 2001 p186.
Current DXA systems
Presently there are two chief rivals in the market for DXA scanners: Hologic and GE-Lunar. Hologic systems employ a individual base on balls fisheye fan beam, while the GE-Lunar systems use a multi-pass narrow-angle fan beam with some convergence between base on ballss ( Fan et al 2009 ) .
Hologic claims that by utilizing fisheye beam, it eliminates overlap mistakes and image deformation found in rectilineal acquisition techniques and consequences in superior image quality and informations stableness with subsequent scans. GE-Lunar pointed out that the fisheye beam causes more magnification depending on the distance off from the sensor ( Boudousq et al 2005 ) .The two systems have different analysis algorithms, part of involvement definitions and standardization criterions so they present consistently different readings from the same patient. This causes troubles in follow up scans of the same patient and besides comparing of different surveies when different scanners are used. With equal standardization methods of BMD measurings, it is possible to do the consequences from two systems comparable ( Ozdemir et al 2007 ) .
DXA engineering was originally intended to mensurate the denseness of the bone in order to measure the hazard of break. Now, it has a broad scope of applications. Because its high preciseness, it is a really utile tool to supervise the advancement of drug intervention, which is critical in drug tests. The algorithm behind the rule of double energy imagination was designed to mensurate denseness of bone, but by altering the topic of the equation to soft tissue we can mensurate the composing of soft tissue. Many of the latest DXA scanners have a revolving C-arm, which can get a sidelong image of the lumbar spinal column. This allows a morphometric appraisal of the lumbar spinal column to place breaks and it can besides be used to place cardiovascular diseases by analyses of the abdominal aortal calcification.
Osteoporosis is defined as a progressive systemic skeletal disease characterised by a low bone mass and microarchitectural impairment of bone tissue, taking to an addition in bone breakability and susceptibleness to break ( Grainger et al 2001 ) . Clinical hazard factors entirely can non foretell low bone denseness and the hazard of osteoporotic breaks, and bone mineral denseness is extremely correlated to cram strength ( Turner 1991 ) . Work force have a higher BMD than adult females but it reduces for both sexes after the 4th decennary. In adult females, the rate of loss in BMD is accelerated at the clip of climacteric and continues do so for the following 10-15 old ages ( Mosekilde and Mosekilde 1990 ) . DXA is a non-invasive, accurate and precise method to mensurate bone mineral denseness in a assortment of anatomical sites.
Figure 2. Illustration of a DXA scanner in operation. Adapted from Hologic booklet.During scanning, the patient lays level on the motorized bed, to the full clothed ( Figure 2 ) . The operator should look into for any metallic points such as jewelry in the part of involvement that can interfere with the denseness readings. A aligning counsel optical maser crosshair is emitted down from the scanner and the operator can travel the patient into the right place by traveling the bed. For hip BMD measurement a place block is placed at the pess of the patient and the leg ( typically the left ) is secured into place.
This is of import because the leg can follow many places depending the place of the joint and this can alter the BMD readings for the hip somewhat. Similar attack is done when the lumbar spinal column BMD is measured, the patient rests his/her legs on a block to guarantee the spinal column is every bit consecutive as possible.When the patient is in place, the operator can originate the scan on the computing machine, the scanner so makes a individual expanse up the patient. This normally takes 30s and an image or ROI and BMD readings are produced outright. No shielding was required during the scan because the X-ray sprinkling is minimised by collimation, plus the radiation dosage is infinitesimal.
Although the radiation dosage is really little, pregnant adult female are non scanned due to possible harm to the foetus. A print out ( Figure 3 ) can be produced and this information can be passed on to the patient ‘s clinician or a specializer.Figure 3.
Sample DXA study print out, contains BMD value, T and Z tonss for both lumbar spinal column and hip.Hip BMD is considered the gilded criterion by many for measuring the hazard of break and doing diagnosing of osteoporosis. Hip BMD is a stronger forecaster of hip break than BMD of other sites and predicts the hazard of other break every bit good as other measurings ( Marshall et al 1996 ) . Furthermore, unlike BMD of the lumbar spinal column, the hip is non affected by the calcification of the abdominal aorta. The DXA scanner can mensurate the BMD of entire hip and its many subregions including the femoral cervix the trochanter and the Ward ‘s trigon ( which is non a true anatomic country but is considered to be the country holding the lowest BMD in the femoral caput ) .
The World Health Organisation defined osteoporosis as a T-score of -2.5 or lower at any site of measuring and osteopaenia ( low bone mass ) as a T-score between -1 and -2.5 ( Kanis et al 1994 ) . A T-score is the figure of standard divergences below or above the average BMD for immature grownups between the ages of 20 to 30. A T-score of 0 agencies the patient has a BMD value that is precisely the mean for immature grownups.
Another term normally mentioned in BMD measuring is the Z-scores. A Z-score is the figure of standard divergence below or above the average BMD adjusted for the patient ‘s age and sex. This cut off point off was originally designed to compare the prevalence of osteoporosis in different states, it was non intended as the exclusive make up one’s minding factor of the direction of patients. The WHO cut off points are besides instead arbitrary. If a patient has a T-score of -2.4 but has a figure of relevant clinical hazard factors ( age, old breaks, parent hip breaks, current smoke and imbibing wonts, glucocorticoids use and rheumatoid arthritis ) , should the patient non be considered to get down intervention? When having a diagnosing of osteopaenia, patients can be unnecessarily distressed. Osteopaenia is neither a cause for dismay nor a ground to get down intervention.
About half of all postmenopausal adult females have a bone denseness value in the osteopaenic scope and most normal adult females over 65 could be labelled as osteopaenic ( Cummings et al 2002 ) .While BMD is a good forecaster of break hazard, denseness combined with clinical hazard factors ( those mentioned above ) for break is a better method than either of those used entirely. The Fracture Risk Assessment Tool ( FRAX ) estimates the 10 twelvemonth chance of break on the footing of clinical hazard factors for break and the BMD of the femoral cervix. The FRAX theoretical account was developed through an analysis of about 60,000 work forces and adult females in 12 population-based cohorts with about 250,000 peron-years of observation, and externally validated in an extra 11 cohorts with 230,000 work forces and adult females and more than 1.2 million person-years of observation ( Lewiecki 2009 ) .
FRAX is available both electronically ( www.shef.ac.uk/FRAX/ ) and in paper signifier ( Figure 4 ) .
With a comparatively accurate break chance, it is much easy for clinicians to make up one’s mind an equal intervention program for the single patients.Figure 4. Section of the FRAX tabular array for the UK adult females. Numbers indicate the 10-year chance of an osteoporotic break.FRAX has non been validated in patients outside the specified age scope ( 40-90 ) or in kids. The seven hazard factors are entered as yes or no responses, but the really hazard of the patient may depend on the existent dosage of endocrine or the badness of other factors.
Other of import hazard factors such as falling, rate of bone loss and high bone bend over are non included in the algorithm. FRAX remains a work in advancement, with go oning updates expected as new information becomes available. Future FRAX may include more state specific break rates and bone denseness measurings with engineerings other than DXA.
The spinal column has more trabeculate bone than other sites, spinal column BMD is more sensitive to effects of endocrines and drugs. Spine BMD measures the lumbar vertebrae, L1 to L4. The spinal column BMD is the entire mineral content of the whole lumbar spinal column, including the vertebral organic structures, the posterior elements and the facet articulations. The spinal column BMD is besides artifactually increased by degenerative arthritis and aortal calcification, both of which become common after age of 65 ( Cummings et al 2002 ) . The spinal column DXA measuring can be affected if one of more of the vertebral organic structures included in the measuring is fractured or affected by alterations due to arthritis, hence good trained operators are needed to except those vertebrae from the consequences.
Once intervention has been initiated, an of import portion of osteoporosis direction is to supervise the efficaciousness of interventions. This will assist to place the patients who do non react to the current therapy and those who are non-compliant. When utilizing BMD for subsequent intervention followup, the measurings should be done on the same machine and if machine is changed a cross standardization is needed. ( International Society for Clinical Densitometry, 2007 ISCD Official Positions Brochure ) . Harmonizing to the International Society for Clinical Densitometry, measurings should be performed before and one twelvemonth after the induction of therapy, with longer intervals one time efficaciousness has been established.Reacting to intervention does non needfully intend a addition in BMD. A patient can lose BMD after intervention but without the intervention, the loss could be greater.
So a patient can be reacting to intervention despite a loss in BMD. Many clinicians believe that by supervising the therapy it can better conformity. Most jobs with attachment occur within the first 3 months of get downing intervention so BMD measurings done 1 or 2 old ages into intervention is non likely to act upon attachment. Other biochemical markers are used to find patient response to therapy.
Surveies shown antiresorptive agents cut down the degrees of biochemical markers of bone turnover 3 to 6 months after intervention induction and these markers can be utile in finding response to therapy ( Bonnick and Shulman 2006 ) . Bone reabsorption markers include: N-telopeptide of type 1 collagen, C-telopeptide of type 1 collagen, pyridinoline and deoxypyridinoline, should be measured at baseline and at 3 months and 6 months after induction. Bone formation markers ( bone alkaline phosphatase, osteocalcin and propeptides of type 1 montage ) should be assessed at baseline and at 6 month after get downing therapy ( Nishizawa et al 2005 ) . Changes in these markers are valid intermediate end point for the efficaciousness of intervention, these could supply early informations to bespeak the success of intervention peculiarly before alteration in BMD is evident.However, the degree of alteration of any given marker that indicates curative efficaciousness remains open between the major administrations. Therefore, in malice of their rapid appraisal of curative efficaciousness, biochemical markers presently have limited pertinence and for most patients DXA spinal column is still the most appropriate diagnostic tool for supervising intervention efficaciousness.
Measuring organic structure composing is used for supervising growing and to measure the consequence of nutrition and exercising. Currently available methods such as neutron activation analysis, isotope dilution, anthropomorphous measurings and submerged weighing present a figure of proficient, ethical, preciseness and handiness jobs ( Grainger et al 2001 ) .
DXA is now one of the most often used techniques for organic structure composing measurings as a consequence of the increasing world-wide handiness of the scanner. It is non-invasive, easy applied to both healthy people and patients, and the radiation dosage is highly low. Newer scanners have besides reduced its scanning clip and are capable of supplying regional organic structure composing analysis. This technique is progressively being viewed as a mention method for the appraisal of entire organic structure fat, and since its debut it has became the gilded criterion method for organic structure fat measuring ( Plank 2005 ) .The DXA organic structure composing attack assumes that the organic structure consists of three constituents: fat, thin soft tissue and bone.
Those are distinguishable by their X-ray fading belongingss. Within any pel the proportions of merely two constituents can be resolved by the differential soaking up of two energies. Soft tissues and bone are comparative easy to separate. In countries where bone is non present, standardization allows fat and thin fractions to be resolved from soft tissue and the composing of these countries is extrapolated to the soft tissue overlying bone to bring forth a entire organic structure fat and thin soft tissue.Figure 5. An illustration of composing read out.
DXA is capable of entire and regional fat and thin soft tissue measuring. Adapted from hypertext transfer protocol: //www.leanresearch.com/Most DXA machines are calibrated to mensurate over a thickness of 12-28cm, so any divergence from this scope may impact the truth of the measuring, for illustration for badly corpulent patients ( Laskey et al 1992 ) .The entire organic structure measuring read out ( Figure 5 ) gives a comparing with the normal age and sex matched equals together with regional appraisals and entire tissue mass. Body composing measuring has a scope of clinical applications from measuring the alteration in composing due to disease or therapy to the organic structure composing monitoring for athleticss professionals.
Morphometric X-ray absorptiometry
Vertebral breaks are frequently symptomless or non diagnosed.
The diagnosing of vertebral breaks requires sidelong radiogram of both the thoracic and lumbar spinal column. The quantitative measuring of vertebral size is known as vertebral morphometry. Vertebral breaks are associated with increased disablement and morbidity and they are the most common osteoporotic breaks ( Genant et al 2000 ) . Womans with vertebral breaks have been shown to hold a 2-fold addition in the likeliness of break and a 5-fold addition in their hazards for subsequent vertebral break. Plus, one out of five adult females who have an incident of vertebral breaks will endure a subsequent break within the following 12 months ( Lindsay et al 2001 ) .Measurements of the front tooth, in-between and posterior vertebral highs of the T4-L4 vertebrae are classically done on sidelong radiogram. The disadvantages of this technique include deformation associated with patient placement and the clip taken to mensurate the vertebrae ( Grainger et al 2001 ) .
With the new revolving C-arm DXA scanners ( Figure 6 ) , a sidelong scan of T4-L4 can be obtained while the patient remains in a supine place. The scanner takes a individual expanse ( about 15 seconds ) of the thoracic and lumbar spinal column, the package is designed to mensurate the vertebral highs automatically and a print out is provided ( Figure 7 ) .Figure 6. Illustration of a revolving C-arm in operation. The leg block is used to unbend the spinal column.
Adapted from Hologic booklet.Figure 7. Sample vertebral break appraisal print out. Anterior, center and posterior vertebral highs and per centum distortion are automatically calculated. From hypertext transfer protocol: //avoidboneloss.com/hologicDXA vertebral break appraisal provides a convenient, inexpensive and safe manner to measure vertebral break. In general it can observe all terrible breaks but it can lose some more moderate breaks that can be seen on radiogram ( Cummings et al 2002 ) .
Abdominal aortal calcification
The abdominal aorta is state of affairs closely anterior to the lumbar spinal column.
Calcification in the abdominal aortal wall has been a hinderance to accuracy step spinal column BMD by DXA, because it would do the lumbar vertebrae appear to hold a higher BMD. The close association of the lumbar spinal column and the abdominal has now been exploited by the sidelong vertebral imaging engineering provided by DXA.Similar to the coronary circulation, aortal calcification is likely to act upon subsequent cardiovascular events such as aortal occlusion, aneurism development and distal embolisation.
Calcification within the aorta can besides impact on medical and surgical intervention by impairing the result of aortal stenting and aneurismal fixs ( Tintut and Demer 2001 ) . One quick and simple method called AAC-8 graduated table is used to gauge the entire length of calcification of the anterior and posterior aortal walls in forepart of vertebrae L1-L4 ( Schousboe et al 2006 ) . The anterior and posterior aortal walls are assigned a mark between 0-4 depending on the figure of vertebra is spans. The amount of the two tonss for the anterior and posterior walls gives the AAC-8 mark, a mark greater than two is considered moderate on this graduated table.Figure 8. Image demoing terrible abdominal aortal calcification. From www.
hologic.comAbdominal aortal calcification ( AAC ) can be a peculiarly valuable measuring since it contributes independently of traditional clinical hazard factors such as cholesterin, blood force per unit area, diabetes, and age to the anticipation of bosom onslaught hazard. Detection of moderate to severe AAC is tantamount to hazard of an extra 160 mg/dL of entire cholesterin ( Wilson et al 2001 ) . With the new revolving C-arm DXA scanner, AAC can be viewed in the same scan used for a vertebral break appraisal.
AAC seems to be peculiarly strong hazard factor in postmenopausal adult females, which is the population besides in greatest demand of BMD scans.
Dual energy X-ray absorptiometry provides a really utile non-invasive clinical tool to measure and supervise bone mineral denseness. DXA measurings of BMD have become an built-in portion for naming osteoporosis and monitoring intervention efficaciousness. Its organic structure composing measuring map is much more capable of other available methods and it is accepted as the gilded criterion for mensurating organic structure fat. The new revolving C-arm scanners have opened a whole new field of applications. It can observe malformations of the lumbar vertebrae and abdominal aortal calcifications. A new development in the field is 3D DXA scans taking full advantage of the revolving C-arms.
It would be natural to see the bone structures as 3D objects, the following coevals DXA devices will take multiple projections and unite the informations to organize a tomographic representation of the constructions. This will give an even more accurate image of bone denseness, geometry and strength ( www.hologic.com ) . DXA system scan green goods consequences of an extremely high criterion, have low running cost, low radiation dosage to topics and easiness of usage, I think this engineering will stay in clinical pattern for many old ages to come.