Abstract
Objectives
To evaluate the usefulness of vertebral morphometry in identifying unreferred vertebral fractures and correlate potential risk factors.
Subjects and methods
Female patients above 45 years, postmenopausal for at least 2 years, diagnosed with osteoporosis and undergoing treatment for at least three months were considered eligible. All of them underwent bone densitometry and vertebral morphometry performed by concomitant DXA. The presence of fractures was defined between T7 and L4; only moderate and severe fractures were considered for analysis. All volunteers were submitted to laboratory tests, anthropometry and responded a questionnaire on their lifestyle habits and medical history.
Results
Thirty two (17%) out of the 188 female patients presented with at least one vertebral fracture, among whom only 4 (12.5%) were previously aware of the fracture. The fractures were mainly located on the thoracic spine. Nine patients had severe fractures (28.1%), whereas 23 had moderate fractures (71.9%). On average, patients with fractures were 5 years older and weighed 5 kilograms less than those without fractures. The creatinine clearance was on average 9 mL/min less in patients with vertebral fracture. The assessment of vertebral fractures by morphometry is a fast, accurate and complementary method associated with low radiation exposure for identifying moderate and severe vertebral fractures. Predisposition to vertebral fractures does not depend solely on BMD.
Postmenopausal women; Genant; vertebral fracture; vertebral fracture assessment
INTRODUCTION
Bone fractures are the main cause of morbidity and mortality associated with osteoporosis. Fractures of long bones, such as that of the proximal femur, are usually fall-related, causing severe pain and incapacity, which lead patients to seek for immediate medical care. Vertebral fractures, however, may occur without obvious trauma and be associated with nonspecific symptoms (11 Cooper C, Atkinson EJ, MichaelO’Fallon W, Melton III JL. Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985-1989. J Bone Min Res. 1992;7:221-7.). Most spinal fractures are not clinically recognized at the time they occur: two out of three radiographically detected vertebral fractures are asymptomatic findings (11 Cooper C, Atkinson EJ, MichaelO’Fallon W, Melton III JL. Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985-1989. J Bone Min Res. 1992;7:221-7.). A large proportion of symptomatic fractures are associated with mild pain that tends to disappear in two to three weeks. Even vertebral fractures associated with moderate to severe pain can remain undiagnosed, since there are several other conditions that cause back pain.
Vertebral fractures cause loss of stature; chronic pain; abuse and harmful use of
anti-inflammatory and analgesic drugs; increased risk of falls; reduced lung
capacity; sleep disorders; increased patient dependency on others; decreased
appetite (22 Silverman SL. The clinical consequences of vertebral compression
fracture. Bone. 1992;13(suppl. 2):S27-31.); which all markedly impair
patients’ medical condition and quality of life. Most vertebral fractures occur at
an earlier age than hip fractures (33 Riggs BL, Melton III LJ. The worldwide problem of osteoporosis:
Insights afforded by epidemiology. Bone. 1995;17(5):505s-11s.), which
is an important early indicator of disease severity. The mortality rate 5 years
after a vertebral fracture is 20% higher than expected for the same age (44 Cooper C, Atkinson EJ, Jacobsen SJ, O’Fallon WM, Melton III LJ.
Population-based study of survival after osteoporotic fractures. Am J Epidemiol.
1993;137:1001-5.). Additionally, vertebral fractures, even if
asymptomatic, are predictors of increased risk of new fractures (55 Klotzbuecher CM, Ross PD, Landsman PB, Abbott III TA, Berger M.
Patients with prior fractures have an increased risk of future fractures: a
summary of the literature and statistical synthesis. J Bone Miner Res.
2000;15:721-39.
6 Black DM, Arden NK, Palermo L, Pearson J, Cummings SR. Prevalent
vertebral deformities predict hip fractures and new vertebral deformities but
not wrist fractures. Study of Osteoporotic Fractures Research Group. J Bone
Miner Res. 1999;14:821-8.
7 Ferrar L, Roux C, Feisenberg D, Gluer CC, Eastell R. Association
between incident and baseline vertebral fractures in European women: vertebral
fracture assessment in the Osteoporosis and Ultrasound Study (OPUS). Osteoporos
Int. 2012;23:59-65.
8 Delmas PD, Genant HK, Crans GG, Stock JL, Wong M, Siris E, et al.
Severity of prevalent vertebral fractures and the risk of subsequent vertebral
and nonvertebral fractures: results from the MORE trial. Bone 2003;
33:522-32.
9 Melton III LJ, Atkinson EJ, Cooper C, O’Fallon WM, Riggs BL.
Vertebral fractures predict subsequent fractures. Osteoporos Int.
1999;10:214-21.
10 Siris ES, Genant HK, Laster AJ, Chen P, Misurski DA, Krege JH.
Enhanced prediction of fracture risk combining vertebral fracture status and
BMD. Osteoporosis Int. 2007;18:761-70.-1111 McCloskey EV, Vasireddy S, Threlkeld J, Eastaugh J, Parry A, Bonner
N, et al. Vertebral fracture assessment (VFA) with a densitometer predicts
future fractures in elderly women unselected for osteoporosis. J Bone Miner Res.
2008;23:1561-8.),
therefore their identification is important for designing the clinical
treatment.
Clinical studies have shown that the existing treatments for osteoporosis increase spinal BMD between 4-12% and decrease the rate of vertebral fractures by 40-70% (1212 Compston J. Clinical and therapeutic aspects of osteoporosis. Eur J Radiol. 2009;71(3):388-91.-1313 Boonen S, Kay R, Cooper C, Haentjens P, Vanderschueren D, Callewaert F, et al. Osteoporosis management: a perspective based on bisphosphonate data from randomized clinical trials and observational databases. Int J Clin Pract. 2009;63(12):1792-804.). An early radiologic diagnosis, followed by the appropriate treatment, aids in preventing new fractures (1414 Genant HK, Bouxsein ML, Pérez AD, Messina O ; Grupo de trabajo Bone Imagen Ósea del CSA de la Fundación Internacional de Osteoporosis. Iniciativa de Fractura Vertebral. Rev Metab Óseo y Min. 2011;9(3):94-7.). Therefore it is important to identify vertebral fractures as early as possible.
The vertebral fracture assessment (VFA) performed by digital morphometry during a dual-energy X-ray absorptiometry (DXA) bone densitometry scan is a great opportunity for detecting vertebral fractures, which, by and large, might remain clinically unrecognized, but that could have relevant clinical implications.
The aim of the current study is to assess the prevalence of moderate and severe vertebral fractures identified by vertebral morphometry performed during DXA bone densitometry scans and its relation to the possible risk factors for osteoporosis in a population of postmenopausal patients being treated for osteoporosis at the outpatient clinic of metabolic bone diseases at the Department of Endocrinology, Federal University of São Paulo.
PATIENTS AND METHODS
Two hundred and five women diagnosed with osteoporosis and registered in the database of patients being followed up at the outpatient clinic of metabolic bone diseases, at the school-hospital from Escola Paulista de Medicina (Unifesp), took part in this study. The patients were invited to participate in the study either by telephone or in-person contact during their appointments in 2009. Data collection took place between June and December 2009. Eligible patients were aged 45 years or older, postmenopausal for at least two years, diagnosed with osteoporosis at some point, and receiving treatment for at least three months. The criteria used for diagnosing osteoporosis were those proposed by the World Health Organization (WHO): the patients with a T-score less than or equal to -2.5 in their lumbar spine, femoral neck and/or total femur bone densitometry scans were classified as osteoporotic. The official guidelines of the Brazilian Society for Clinical Densitometry, as published on the official website of this entity, were followed.
The current study received approval from the Research Ethics Committee at Unifesp (ERB n. 0839/08). All of the participating patients signed a voluntary informed consent form.
All of the patients underwent bone densitometry scans in a Discovery A equipment (Hologic®, Bedford, MA, USA, software version 12.3) for assessing bone mass; body fat mass; lean body mass; and vertebral fractures (digital morphometry – Figure 1). The analyzed sites were lumbar spine, femur and whole body. Vertebral fracture assessment was performed in the same unit, immediately after the densitometry scans, with the patient in supine position and rotation of the unit arm for image acquisition. The assessment of vertebrae was conducted by placing 6 points on each vertebral body (on the anterior, medial and posterior portions of both the upper and lower parts of each vertebra). The software was used for calculating the anterior, medial and posterior heights of each vertebra, which allowed for the determination of the vertebra’s deformity type and degree according to the Genant method (Figure 2). Such method classifies a fracture according to its severity, each vertebra being assigned a score: 0, if there is no fracture; 1, 2 or 3, if the fracture is mild, moderate or severe, respectively. In mild fractures, the reduction in height of the anterior, medial and posterior portions is 20-25%; in moderate fracture; it is 25-40%; and in severe fractures, higher than 40%. Moderate to severe vertebral fractures between T7 and L4 vertebrae were considered for analysis. All of the 188 VFA images were also evaluated by the semi quantitative method, in which the vertebrae deformity is graded only by visual inspection. Furthermore, 20 VFA images (10 of each group) were randomly assigned for two blinded physicians for a semiquantitative analysis to evaluate the presence or absence of a moderate or severe fracture between T7 and L4.
Example analysis of morphometric assessments comparing a severe biconcave fracture at L1 (A) and normal morphometry (B).
Schematic diagram of the semi-quantitative grading system for vertebral fractures: reproduced from Genant and cols. (1515 Genant Hk, Wu CY, Kuijk CV, Nevitt MC. Vertebral fracture assessment using a semiquantitative technique. J Bone Min Res. 1993;8(9):1137-48.).
Analytical methods
Laboratory parameters
All patients had blood samples collected for measuring PTH; carboxy-terminal telopeptide of type 1 collagen (CTX); 25-hydroxyvitamin D (25OHD); creatinine; alkaline phosphatase activity (AP); total calcium (Ca); phosphorus (P); amino-terminal propeptide of type 1 collagen (P1NP). Additionally, urine was also collected for measuring calcium (UCa) and creatinine (UCr) in the isolated samples. Ca, P and UCa were measured by an automatized colorimetric method. Both UCr and serum creatinine were measured by a kinetic colorimetric method. Clearance of creatinine (CrClear) was estimated by applying the Cockcroft-Gault equation (1616 Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976:16:31-41.). The UCa/UCr ratio was calculated. AP was measured by an enzymatic method (Olympus AU640 analyzer, USA). CTX, P1NP and PTH were measured using commercially available kits (chemiluminescence, Roche, Elecsys 2010 analyzer, USA). For CTX, the intra- and inter-assay coefficients of variation (CV) were 4.6 and 4.7%, respectively; for P1NP, the CVs were 1.8 and 2.7%, respectively; and for PTH, the CVs were 3.0 and 3.5%, respectively. 25OHD was measured by chemiluminescence (DiaSorin, Liaison analyzer, USA), with intra- and inter-assay CVs at 1.62 and 5.61%, respectively.
Anthropometric data
Body mass and height were measured using a digital scale and a wall stadiometer. Body mass index (BMI) was calculated as the ratio between body mass (kg) and the square of height (m2).
Questionnaire
The patients responded questions on their age; lifestyle habits (smoking habits and alcohol consumption); comorbidities (diabetes mellitus, specifically); fracture history dating to any time in their life or specifically after age 45; and current medications. Patients were classified as smokers or non-smokers; those who denied current smoking habits were considered as non-smokers.
Statistical analysis
The Statistical Package for the Social Science (SPSS) version 19.0 (SPSS Inc., Chicago, Illinois, EUA) was used for conducting the statistical analysis. All variables were subjected to the Kolmogorov–Smirnov test to assess the normality of data distribution. Independent Student’s t-test was used for comparing the anthropometric, laboratory and densitometric data obtained for the two groups (with and without fractures). The associations among categorical variables were evaluated by using the chi-squared test and p < 0.05 was considered significant. Agreement between observers was calculated using percentage of agreement and the κ statistic: κ = (p0-pc)/(1-pc), where p0 = the proportion of units in which the judges agreed; and pc = the proportion of units for which agreement is expected by chance (1717 Cohen J. A coefficient of agreement for nominal scales. Educ Psych Meas. 1960;20:37-46.).
RESULTS
Among the 205 patients selected for taking part in the study, 3 were deceased and 14 were not interested. Thus, data were obtained from a total of 188 patients, of which 32 (17%) presented with at least one moderate or severe vertebral fracture, and among whom only 4 (12.5%) the fracture had been previously diagnosed. Most patients (87.5%) were not aware of the presence of fractures and no description of vertebral fractures was found in their medical records, so, such information was unknown even by their doctors. Six (18,7%) out of these 32 patients had more than one vertebral fracture, with one patient presenting with 4 fractures. Among the 4 patients who were previously aware of the existing fracture, 3 presented with more than one vertebral fracture.
The fractures were mainly located on the thoracic spine, with 56% of the cases occurring at the T11 and T12 vertebrae (9 involving each one of these), as can be seen in figure 3. As for fracture severity, we found 9 patients with severe fractures (28.1%) and 23 with moderate fractures (71.9%). The semiquantitative analysis showed the same results.
There was an agreement of 95% with the first blinded physician reading of the exams regarding the presence or absence of moderate or severe vertebral fracture and of 100% with the second one. The κ statistic showed a κ = 0,9 for the first blinded physician and a κ = 1,0 for the second one.
The results obtained from the anthropometric measurements, laboratory tests and densitometry scans from patients with and without vertebral fractures (VF) assessed by VFA are shown in tables 1 and 2. The only statistically significant data between groups were age; clearance of creatinine; body fat mass; and total body mass. There were no other statistically significant differences for any parameters evaluated.
Comparison of body composition and bone mineral density results between the two groups: patients with and without vertebral fractures, as detected by digital morphometry performed by DXA
Considering the 188 participants, patients age varied between 48 and 86 years (mean age of 68). In the group of patients with vertebral fractures (VF), the mean age was 5 years more than that in the group of patients without VF. On average, patients with VF weighted 5 kg less than those without fractures. CrClear was on average 9 mL/min less in patients with vertebral fracture. In the group of patients with VF, 16 (50%) patients had CrClear less than 60 mL/min, whereas in the group of patients without fractures that figure amounted to 52 (33.3%). Total body composition scans of patients with fractures showed on average 2,633 g fat and 3,992 g total mass less when compared to patients without fracture.
According to their questionnaires, no patient reported relevant alcohol consumption; 11.7% were current or past smokers, 42.5% of them presented with at least one fracture after age 45, diabetes was reported by 19%, but the distribution of these factors were not different between the groups with and without VF. Previous or current use of glucocorticoids were reported by 11 (5,8%), but none of them in the fractured group.
Considering patients’ current treatment, besides calcium and cholecalciferol supplementation (according to the diet), most of them (n = 142, 75.5%) were using bisphosphonates at the time the assessment was performed; 16 (8.5%) were receiving raloxifene; 2 (1.06%) were being treated with teriparatide; 28 (14.8%) were receiving only calcium and/or cholecalciferol supplementation, with no significant difference between the groups.
DISCUSSION
The aim of this study was to assess the applicability of digital morphometry performed by VFA in detecting previously undiagnosed vertebral fractures in a population comprised of osteoporosis patients receiving treatment on an outpatient basis. The results showed that morphometry was able to detect moderate or severe vertebral fractures in 17% of such patients, in 87.5% of whom the fracture was unknown. In other words, approximately 1 out 7 patients receiving regular specialized treatment on an outpatient basis presented with an unknown vertebral fracture. In a study by Jager and cols., in which VFA was performed prospectively on all patients referred for DXA for bone mass assessment, the prevalence of moderate or severe vertebral fractures in patients with osteoporosis was 22% (1818 Jager PL, Jonkman S, Koolhaas W, Stiekema A, Wolffenbuttel BHR, Slart RHJA. Combined vertebral fracture assessment and bone mineral density measurement: a new standard in the diagnosis of osteoporosis in academic populations. Osteoporos Int. 2011;22:1059-68.), very similar to the results observed by us.
Vertebral fracture assessment conducted by quantitative morphometry performed by
X-ray absorptiometry (DXA) allows us to detect prevalent vertebral fractures, which
are often not clinically recognized at the time they occur. Many studies had already
validated the reliability of VFA interpretation against radiographs, mainly in
detecting moderate to severe vertebral fractures (1919 Binkley N, Krueger D, Gangnon R, Genant HK, Drezner MK. Lateral
vertebral assessment: a valuable technique to detect clinically significant
vertebral fractures. Osteoporosis. 2005;16:1513-8.
20 Hospers IC, van der Laan JG, Zeebregts CJ, Nieboer P, Wolffenbuttel
BH, Dierckx RA, et al. Vertebral fracture assessment in supine position:
comparison by using conventional semiquantitative radiography and visual
radiography. Radiology. 2009;251:822-8.-2121 Schousboe JT, Debold Cr. Reliability and accuracy of vertebral
fracture assessment with densitometry compared to radiography in clinical
practice. Osteoporos Int. 2006;17:281-9.). As shown by others, using
VFA, clinicians correctly identified 94% of radiographically defined grade 2 and
grade 3 vertebral fractures and 96% of non-fractures vertebrae were correctly
identified as normal on VFA (1919 Binkley N, Krueger D, Gangnon R, Genant HK, Drezner MK. Lateral
vertebral assessment: a valuable technique to detect clinically significant
vertebral fractures. Osteoporosis. 2005;16:1513-8.).
The fact that VFA can be performed at the same time BMD is measured constitutes a valuable opportunity. The relative risk of new fractures is increased 4.4 times in the presence of a vertebral fracture. Additionally, it also increases the risk of fragility fractures at other sites as well (55 Klotzbuecher CM, Ross PD, Landsman PB, Abbott III TA, Berger M. Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res. 2000;15:721-39.). A vertebral fracture is associated with a 19% chance of new vertebral fractures within the next 12 months (2222 Lindsay R, Silverman SL, Cooper C, Hanley DA, Barton I, Broy SB, et al. Risk of new vertebral fracture in the year following a fracture. JAMA. 2001;285:320-3.).
An additional advantage is the simultaneous visualization of both thoracic and lumbar
spine on a single image, thus using low exposure. The radiation dose for VFA is 3
micro-Sieverts (µSv), whereas that for a simple radiograph of the lumbar spine is
600 µSv (2323 Vokes T, Bachman D, Baim S, Binkley N, Broy S, Ferrar L, et al.
Vertebral fracture assessment: the 2005 ISCD Official Positions. J Clin
Densitom. 2006;9:37-46.). A 3 µSv radiation dose is
considered extremely low and comparable to the exposure dose received during a
normal day (2323 Vokes T, Bachman D, Baim S, Binkley N, Broy S, Ferrar L, et al.
Vertebral fracture assessment: the 2005 ISCD Official Positions. J Clin
Densitom. 2006;9:37-46.). Since it is a digital
technique, VFA allows for image manipulation and, thus, visualization enhancement,
which leads to more accurate measurements. Besides, the parallel distortion caused
by the X-rays’ obliquity in relation to the vertebra is minimized, for the VFA
performed by DXA emits rays that are perpendicular to the vertebra, especially when
conducted at the supine position. VFA acquisition increases scan time in 10-15
seconds in addition to the time required for placing the patient in lateral
decubitus position. The quantitative analysis is laborious, as measurements are
performed individually on each vertebra. Nevertheless, it is possible to proceed in
a so-called semi-quantitative manner, in which the vertebrae are graded solely by
visual inspection without performing direct measurements on each vertebra, which
facilitates the work and, consequently, reduces the cost of test. Several studies
have already shown an excellent correlation between quantitative and
semi-quantitative analyses (1515 Genant Hk, Wu CY, Kuijk CV, Nevitt MC. Vertebral fracture assessment
using a semiquantitative technique. J Bone Min Res.
1993;8(9):1137-48.,2424 Wu CY, Li J, Jergas M, Genant HK. Comparison of SQ and quantitative
techniques for the assessment of prevalent and incident vertebral fractures.
Osteoporos Int. 1995;5:354-70.
25 Li J, Wu CY, Jergas M, Genant HK. Diagnosing prevalent vertebral
fractures: a comparison between quantitative morphometry and a standardized
visual (semiquantitative) approach. In: Genant HK, Jergas M, Van Kuijk C,
editors. Vertebral fracture in osteoporosis. University of California, San
Francisco. Radiology Research and Education Foundation. 1995; p.
271-9.-2626 Grados F, Roux C, Vernejoul MC, Utard G, Sebert JL, Fardellone P.
Comparison of four morphometric definitions and a semiquantitative consensus
reading for assessing prevalent vertebral fractures. Osteoporos Int.
2001;12:716-22.)
specially when referring to moderate and severe fractures.
One disadvantage of VFA is that the visualization of vertebrae above T7 is hindered by the juxtaposition of thoracic structures. On the other hand, osteoporotic vertebral fractures are uncommon in this region. As shown by others, severe and moderate fractures above T7 are less than 5% of prevalent vertebral fractures (1818 Jager PL, Jonkman S, Koolhaas W, Stiekema A, Wolffenbuttel BHR, Slart RHJA. Combined vertebral fracture assessment and bone mineral density measurement: a new standard in the diagnosis of osteoporosis in academic populations. Osteoporos Int. 2011;22:1059-68.). There are difficulties for assessing the vertebrae in this region even with the use of radiography, which is considered as the standard imaging method for assessing fractures (1818 Jager PL, Jonkman S, Koolhaas W, Stiekema A, Wolffenbuttel BHR, Slart RHJA. Combined vertebral fracture assessment and bone mineral density measurement: a new standard in the diagnosis of osteoporosis in academic populations. Osteoporos Int. 2011;22:1059-68.).
The detection of mild fractures, however, presents difficulties both for VFA as by conventional radiographs (2727 Delmas PD, van de Langerijt L, Watts NB, Eastell R, Genant H, Grauer A, et al.; IMPACT Study Group. Underdiagnosis of vertebral fractures is a worldwide problem: The IMPACT study. J Bone Miner Res. 2001;16(suppl 1):S139.). Such fact reflects the inherent difficulty that exists in determining minimal deformities in the vertebrae (grade 1 fractures), regardless of the method. Furthermore, mild fractures (grade 1) have been shown to have lesser clinical importance given their weaker association with new fractures, causing lesser loss of stature and less back pain (2828 Genant HK, Mitlak BH, Myers S, Wang O. Radiographic fracture grade is related to clinical disease severity. Results from the rhPTH (1-34) fracture prevention study. Arthritis Rheum. 2000;43:S383.). The severity of vertebral fractures has proven better at predicting a non-vertebral fracture than has BMD itself (88 Delmas PD, Genant HK, Crans GG, Stock JL, Wong M, Siris E, et al. Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial. Bone 2003; 33:522-32.). For this reason, only moderate and severe fractures between T7 and L4 were included in our analysis.
The exact cost of this diagnostic method has not been well established in several
countries yet. In 2006, the amount paid by Medicare in Los Angeles for a VFA was
$40.48 (US Dollars) versus $84.94 (US Dollars) for a radiograph of the thoracic and
lumbar spine (2929 Medicare Reimbursement Calculator. GE Healthcare 2006 Updated.
Available at:
http://www.gehealthcare.com/usen/community/reimbursement/index.htlm. Accessed
on: April 18, 2006.
http://www.gehealthcare.com/usen/communi...
).
This investigation corroborates previous studies that showed that predisposition to fracture is not dependent solely on BMD. In our population, there was no difference in BMD between the groups. Considering that all patients were receiving treatment, some of them showed densitometry scan results compatible with osteopenia at the test conducted for this study. Other risk factors played an important role in predicting the risk of vertebral fracture, such as age, total body mass and body fat mass.
Adipocytes and osteoblasts are derived from the same progenitor cells in the mesenchymal tissue, therefore there can potentially exist autocrine and paracrine effects of adiponectin on bone metabolism. Adiponectin is a hormone that is exclusively secreted by adipose tissue into the blood stream. Its blood plasma levels are inversely related to the percentage of body fat in adults. Some studies have already shown there exists a relation between serum adiponectin and risk of fractures in men, irrespectively of other factors like BMI and BMD. This relation, however, has not been established in women (3030 Johansson H, Odén A, Lerner UH, Jutberger H, Loretzon M, Barrett-Connor E, et al. High serum adiponectin predicts incident fractures in elderly men: Osteoporotic Fractures in Men (MrOS) Sweden. J Bone Miner Res. 2012;6:1390-6.).
The difference in renal function was probably due to older age and lower weight observed in the group with FV, since there was no difference in the serum creatinine levels in both groups. Nonetheless, that may have contributed to greater fragility, as renal dysfunction progresses with abnormalities of bone turnover and mineralization, leading to a loss of bone strength (3131 Miller PD. Diagnosis and treatment of osteoporosis in chronic renal disease. Semin Nephrol. 2009;29:144-55.).
Most patients were receiving treatment with bisphosphonates and cholecalciferol and, therefore, the correlation with bone remodeling markers, PTH and 25OHD was hindered.
In summary, vertebral fractures were diagnosed by VFA realized during DXA examination
in 17% of patients followed in an outpatient clinic for osteoporosis, and in more
than 80% of them this diagnosis was hitherto unknown. Despite the fact that all
patients in this study already had a diagnosis of osteoporosis, knowing whether or
not a vertebral fracture exists is of utmost importance, since such knowledge can
change their therapeutic approaches. Various studies have already shown that
treatment reduces not only the risk of new fractures but also the number of
hospitalizations (3232 Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, et
al. Effects of continuing or stopping alendronate after 5 years of treatment:
the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial.
JAMA. 2006;296:2927-38.
33 Quandt SA, Thompson DE, Schneider DL, Nevitt MC, Black DM. Effect of
alendronate on vertebral fracture risk in women with bone mineral density T
scores of -1.6 to -2.5 at the femoral neck: the Fracture Intervention Trial.
Mayo Clin Proc. 2005;80:343-9.
34 Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, et
al. Etidronate for the primary and secondary prevention of osteoporotic
fractures in postmenopausal women. Cochrane Database Sys Rev.
2008;CD003376.-3535 Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, et
al. Alendronate for the primary and secondary prevention of osteoporotic
fractures in postmenopausal women. Cochrane Database Syst Rev.
2008;CD001155.). Therefore, routine VFAs in addition to densitometry scans
might modify the evaluation of the risk of new fractures of such a patient, changing
the diagnosis from osteopenia or osteoporosis to “severe osteoporosis” in cases
where a VF is detected. To take the opportunity of the presence of the patient in
the diagnostic center and to use the full resources that modern DXA devices offer,
increasing the accuracy of assessing the risk of fractures, seems a quite
appropriate strategy.
Acknowledgments
Roche Diagnósticos do Brasil kindly provided PTH, CTX and PINP assay kits.
REFERENCES
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1Cooper C, Atkinson EJ, MichaelO’Fallon W, Melton III JL. Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985-1989. J Bone Min Res. 1992;7:221-7.
-
2Silverman SL. The clinical consequences of vertebral compression fracture. Bone. 1992;13(suppl. 2):S27-31.
-
3Riggs BL, Melton III LJ. The worldwide problem of osteoporosis: Insights afforded by epidemiology. Bone. 1995;17(5):505s-11s.
-
4Cooper C, Atkinson EJ, Jacobsen SJ, O’Fallon WM, Melton III LJ. Population-based study of survival after osteoporotic fractures. Am J Epidemiol. 1993;137:1001-5.
-
5Klotzbuecher CM, Ross PD, Landsman PB, Abbott III TA, Berger M. Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res. 2000;15:721-39.
-
6Black DM, Arden NK, Palermo L, Pearson J, Cummings SR. Prevalent vertebral deformities predict hip fractures and new vertebral deformities but not wrist fractures. Study of Osteoporotic Fractures Research Group. J Bone Miner Res. 1999;14:821-8.
-
7Ferrar L, Roux C, Feisenberg D, Gluer CC, Eastell R. Association between incident and baseline vertebral fractures in European women: vertebral fracture assessment in the Osteoporosis and Ultrasound Study (OPUS). Osteoporos Int. 2012;23:59-65.
-
8Delmas PD, Genant HK, Crans GG, Stock JL, Wong M, Siris E, et al. Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial. Bone 2003; 33:522-32.
-
9Melton III LJ, Atkinson EJ, Cooper C, O’Fallon WM, Riggs BL. Vertebral fractures predict subsequent fractures. Osteoporos Int. 1999;10:214-21.
-
10Siris ES, Genant HK, Laster AJ, Chen P, Misurski DA, Krege JH. Enhanced prediction of fracture risk combining vertebral fracture status and BMD. Osteoporosis Int. 2007;18:761-70.
-
11McCloskey EV, Vasireddy S, Threlkeld J, Eastaugh J, Parry A, Bonner N, et al. Vertebral fracture assessment (VFA) with a densitometer predicts future fractures in elderly women unselected for osteoporosis. J Bone Miner Res. 2008;23:1561-8.
-
12Compston J. Clinical and therapeutic aspects of osteoporosis. Eur J Radiol. 2009;71(3):388-91.
-
13Boonen S, Kay R, Cooper C, Haentjens P, Vanderschueren D, Callewaert F, et al. Osteoporosis management: a perspective based on bisphosphonate data from randomized clinical trials and observational databases. Int J Clin Pract. 2009;63(12):1792-804.
-
14Genant HK, Bouxsein ML, Pérez AD, Messina O ; Grupo de trabajo Bone Imagen Ósea del CSA de la Fundación Internacional de Osteoporosis. Iniciativa de Fractura Vertebral. Rev Metab Óseo y Min. 2011;9(3):94-7.
-
15Genant Hk, Wu CY, Kuijk CV, Nevitt MC. Vertebral fracture assessment using a semiquantitative technique. J Bone Min Res. 1993;8(9):1137-48.
-
16Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976:16:31-41.
-
17Cohen J. A coefficient of agreement for nominal scales. Educ Psych Meas. 1960;20:37-46.
-
18Jager PL, Jonkman S, Koolhaas W, Stiekema A, Wolffenbuttel BHR, Slart RHJA. Combined vertebral fracture assessment and bone mineral density measurement: a new standard in the diagnosis of osteoporosis in academic populations. Osteoporos Int. 2011;22:1059-68.
-
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Funding: this research was sponsored by the Fundação de Amparo à Pesquisa do Estado de São Paulo (Fapesp); Grant 08/55567-7. Patricia Muszkat received a scholarship from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Publication Dates
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Publication in this collection
Apr 2015
History
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Received
29 Apr 2014 -
Accepted
13 Jan 2015