What is changed in the diagnosis of osteoporosis: the role of radiologists

Osteoporosis (OP) is a very common condition with several repercussions on patients’ quality of life and health systems (1). OP is secondary to changes in normal bone turnover for decreased activity of osteoblasts (which produce bone matrix) or increased osteoclastic activity (2,3). These changes determine variation in bone mineral content (BMC) and then bone mineral density (BMD); thus, quantification of BMD correlate to changes in bone matrix.

These metabolic alterations induce reduction in the bone strength which in turn determines increased the risk of future fractures, to even low energy traumas; the most frequent sites are hip, forearm and the thoracolumbar spine (4).

Diagnosis of OP, even can be suspected on standard radiograms, is generally achieved using quantitative methods, among which dual-energy X-ray absorptiometry (DXA) is the most validated; moreover, some other novel techniques also provide further information on bone changes (5,6).

DXA is still the referring method for the quantification of BMD: it is defined as the BMC per square centimeter (g/cm²)—as its values are calculated on a plane image—and according to the World Health Organization (WHO) values are normal if they are above −1 standard deviations (SD)—in comparison of values obtained from a referring population (T-score), values ranging from −1 to −2.5 SD are considered osteopenic; while OP is defined if BMD value is below −2.5 SD (7-9). DXA examination is performed on the lumbar spine (evaluating vertebrae from L1 to L4), at the hip (evaluating the femoral neck and the total hip) and the distal third of radius. DXA has still its importance for the low dose delivered to the patient, the time of acquisition and its reproducibility; some limits consist in the presence of degenerative bone changes (such as marginal osteophytes) which can influence BMD value (10).

Some of these limitations can be bypassed using quantitative computed tomography (QCT), which consists in a volumetric of an anatomical bone region, then the BMD is expressed in term of g/cm³; BMD values lower than 80 g/cm³ are considered osteoporotic (11). The advantage of QCT is its capability to distinguish cortical and trabecular bone, that can be separately evaluated; however, its main limit is the high radiation dose delivered to the patient (12).

Quantitative ultrasound (QUS) is a radiation-free technique which exploits the variation of US wave while passing through the bone micro-architecture. QUS is usually performed at peripheral sites such as phalanges, distal radius, distal tibia and calcaneus; in particular, the evaluation of this latter has shown good correlation with risk fracture prediction (13-16).

Insufficiency vertebral fractures are a common complication of OP, their detection has been challenging in the past years, but has improved for the diffusion of vertebral morphometry, which can be applied on both conventional and DXA images (delivering only a small amount of radiation dose), but also using CT scouts; vertebral morphometry uses a semi-quantitative method to characterize vertebral fractures which helps the radiologist in the diagnosis (17-20).

The increased risk of future bone fractures, in course of OP, does not only depends on BMD, but also on the “quality” of bone: this characteristic is determined by several factors, such as the number and thickness of bone trabeculae and their micro-architectural organization, which are also related to bone turnover and matrix mineralization (21,22). Novel techniques have been developed in the recent years to investigate on bone quality (23). Among these, trabecular bone score (TBS) is applied to DXA images and provide a valued which is indirectly correlated to the trabecular network within the vertebral bone (24).

Other imaging methods consist of CT and magnetic resonance imaging (MRI). In the recent years, new kinds of CT technologies have been studied to evaluate bone micro-architecture (and then bone strength) to assess the risk of bone fractures; in particular finite element modeling (FEM) and multi-detector CT (MDCT) have shown their importance in the evaluation of BMD even in other regions besides lumbar spine, such as the hip; the quantification of BMD with this technique has been correlated to the increased risk of fracture in osteoporotic patients, showing a good correlation (25-31).

Another CT technique which has been developed in the last years and has the advantage of delivering low radiation dose to patients is the high-resolution peripheral QCT (HR-pQCT): this method allows the quantification of cortical and trabecular BMD in peripheral sites (radius, tibia, calcaneus?) and the obtained values have been correlated to the risk of bone fracture (32,33).

Advantages in MRI and the development of new sequences have been experimented to evaluate bone micro-architecture and metabolism in several sites. MRI findings may correlate to the clinical aspects of OP and predict the risk of bone fracture (34-41).

In conclusion, with the fast development of new technologies and their application to the diagnostic imaging, the radiologist plays a central for the correct interpretation of imaging data, which can be further correlated to the clinical scenario; for this reason, an adequate updating on the most recent methods is recommended, to seek the correct diagnosis of OP and eventually predict the risk of bone fracture.

Acknowledgements

None.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

References

1. Guglielmi G, Muscarella S, Bazzocchi A. RadioGraphics Integrated Imaging Approach to Osteoporosis: State-of-the-Art Review and Update. Radiographics 2011;31:1343-64. [Crossref] [PubMed]
2. Rachner TD, Khosla S, Hofbauer LC. New Horizons in Osteoporosis. Lancet 2011;377:1276-87. [Crossref] [PubMed]
3. Khosla S. Pathogenesis of Age-Related Bone Loss in Humans. J Gerontol A Biol Sci Med Sci 2013;68:1226-35. [Crossref] [PubMed]
4. Hernlund E, Svedbom A, Ivergård M, Compston J, Cooper C, Stenmark J, McCloskey EV, Jönsson B, Kanis JA. Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 2013;8:136. [Crossref] [PubMed]
5. Griffith JF, Genant HK. New Imaging Modalities in Bone. Curr Rheumatol Rep 2011;13:241-50. [Crossref] [PubMed]
6. Gong B, Mandair GS, Wehrli FW, Morris MD. Novel assessment tools for osteoporosis diagnosis and treatment. Curr Osteoporos Rep 2014;12:357-65. [Crossref] [PubMed]
7. Griffith JF, Genant HK. New advances in imaging osteoporosis and its complications. Endocrine 2012;42:39-51. [Crossref] [PubMed]
8. Honig S, Chang G. Osteoporosis: an update. Bull NYU Hosp Jt Dis 2012;70:140-4. [PubMed]
9. Karjalainen JP, Riekkinen O, Töyräs J, Jurvelin JS, Kröger H. New method for point-of-care osteoporosis screening and diagnostics. Osteoporos Int 2016;27:971-7. [Crossref] [PubMed]
10. Guglielmi G, Nasuto M, Avery LY, Cheng X. Bone densitometry: current status and future trends. J Genet Genomics 2016;64:97-103.
11. Engelke K, Libanati C, Fuerst T, Zysset P, Genant HK. Advanced CT based in vivo methods for the assessment of bone density, structure, and strength. Curr Osteoporos Rep 2013;11:246-55. [Crossref] [PubMed]
12. Oei L, Koromani F, Rivadeneira F, Zillikens MC, Oei EH. Quantitative imaging methods in osteoporosis. Quant Imaging Med Surg 2016;6:680-98. [Crossref] [PubMed]
13. McLeod KM, Johnson S, Rasali D, Verma A. Discriminatory Performance of the Calcaneal Quantitative Ultrasound and Osteoporosis Self-Assessment Tool to Select Older Women for Dual-Energy X-ray Absorptiometry. J Clin Densitom 2015;18:157-64. [Crossref] [PubMed]
14. Zha XY, Hu Y, Pang XN, Chang GL, Li L. Diagnostic value of osteoporosis self-assessment tool for Asians (OSTA) and quantitative bone ultrasound (QUS) in detecting high-risk populations for osteoporosis among elderly Chinese men. J Bone Miner Metab 2015;33:230-8. [Crossref] [PubMed]
15. Thomsen K, Jepsen DB, Matzen L, Hermann AP, Masud T, Ryg J. Is calcaneal quantitative ultrasound useful as a prescreen stratification tool for osteoporosis? Osteoporos Int 2015;26:1459-75. [Crossref] [PubMed]
16. Thomsen K, Ryg J, Hermann AP, Matzen L, Masud T. Calcaneal quantitative ultrasound and phalangeal radiographic absorptiometry alone or in combination in a triage approach for assessment of osteoporosis:a study of older women with a high prevalence of falls. BMC Geriatr 2014;14:143. [Crossref] [PubMed]
17. Oei L, Rivadeneira F, Ly F, Breda SJ, Zillikens MC, Hofman A, Uitterlinden AG, Krestin GP, Oei EH. Review of radiological scoring methods of osteoporotic vertebral fractures for clinical and research settings. Eur Radiol 2013;23:476-86. [Crossref] [PubMed]
18. Muszkat P, Camargo MB, Peters BS, Kunii LS, Lazaretti-Castro M. Digital vertebral morphometry performed by DXA: a valuable opportunity for identifying fractures during bone mass assessment. Arch Endocrinol Metab 2015;59:98-104. [Crossref] [PubMed]
19. Guglielmi G, di Chio F, Vergini MR, La Porta M, Nasuto M, Di Primio LA. Early diagnosis of vertebral fractures. Clin Cases Miner Bone Metab 2013;10:15-8. [PubMed]
20. Kim YM, Demissie S, Eisenberg R, Samelson EJ, Kiel DP, Bouxsein ML. Intra-and inter-reader reliability of semi-automated quantitative morphometry measurements and vertebral fracture assessment using lateral scout views from computed tomography. Osteoporos Int 2011;22:2677-88. [Crossref] [PubMed]
21. Fonseca H, Moreira-Gonçalves D, Coriolano HJ, Duarte JA. Bone quality:the determinants of bone strength and fragility. Sports Med 2014;44:37-53. [Crossref] [PubMed]
22. Alliston T. Biological regulation of bone quality. Curr Osteoporos Rep 2014;12:366-75. [Crossref] [PubMed]
23. Donnelly E. Methods for assessing bone quality: a review. Clin Orthop Relat Res 2011;469:2128-38. [Crossref] [PubMed]
24. Andreopoulou P, Bockman RS. Management of postmenopausal osteoporosis. Annu Rev Med 2015;66:329-42. [Crossref] [PubMed]
25. Link TM, Lang TF. Axial QCT: clinical applications and new developments. J Clin Densitom 2014;17:438-48. [Crossref] [PubMed]
26. Engelke K, Lang T, Khosla S, Qin L, Zysset P, Leslie WD, Shepherd JA, Schousboe JT. Clinical Use of Quantitative Computed Tomography (QCT) of the Hip in the Management of Osteoporosis in Adults:the 2015 ISCD Official Positions-Part I. J Clin Densitom 2015;18:338-58. [Crossref] [PubMed]
27. Zysset P, Qin L, Lang T, Khosla S, Leslie WD, Shepherd JA, Schousboe JT, Engelke K. Clinical Use of Quantitative Computed Tomography-Based Finite Element Analysis of the Hip and Spine in the Management of Osteoporosis in Adults: the 2015 ISCD Official Positions-Part II. J Clin Densitom 2015;18:359-92. [Crossref] [PubMed]
28. Engelke K, Lang T, Khosla S, Qin L, Zysset P, Leslie WD, Shepherd JA, Shousboe JT. Clinical Use of Quantitative Computed Tomography-Based Advanced Techniques in the Management of Osteoporosis in Adults: the 2015 ISCD Official Positions-Part III. J Clin Densitom 2015;18:393-407. [Crossref] [PubMed]
29. Nazemi SM, Cooper DM, Johnston JD. Quantifying trabecular bone material anisotropy and orientation using low resolution clinical CT images:A feasibility study. Med Eng Phys 2016;38:978-87. [Crossref] [PubMed]
30. Nazemi SM, Kalajahi SM, Cooper DM, Kontulainen SA, Holdsworth DW, Masri BA, Wilson DR, Johnston JD. Accounting for spatial variation of trabecular anisotropy with subject-specific finite element modeling moderately improves predictions of local subchondral bone stiffness at the proximal tibia. J Biomech 2017;59:101-8. [Crossref] [PubMed]
31. Pearson RA, Treece GM. Measurement of the bone endocortical region using clinical CT. Med Image Anal 2018;44:28-40. [Crossref] [PubMed]
32. Kroker A, Plett R, Nishiyama KK, McErlain DD, Sandino C, Boyd SK. Distal skeletal tibia assessed by HR-pQCT is highly correlated with femoral and lumbar vertebra failure loads. J Biomech 2017;59:43-9. [Crossref] [PubMed]
33. Mussawy H, Ferrari G, Schmidt FN, Schmidt T, Rolvien T, Hischke S, Rüther W, Amling M. Changes in cortical microarchitecture are independent of areal bone mineral density in patients with fragility fractures. Injury 2017;48:2461-5. [Crossref] [PubMed]
34. Capuani S. Water diffusion in cancellous bone. Microporous Mesoporous Mater 2013;178:34-8. [Crossref]
35. Koyama H, Yoshihara H, Kotera M, Tamura T, Sugimura K. The quantitative diagnostic capability of routine MR imaging and diffusion-weighted imaging in osteoporosis patients. Clin Imaging 2013;37:925-9. [Crossref] [PubMed]
36. Li GW, Xu Z, Chen QW, Tian YN, Wang XY, Zhou L, Chang SX. Quantitative evaluation of vertebral marrow adipose tissue in postmenopausal female using MRI chemical shift-based water-fat separation. Clin Radiol 2014;69:254-62. [Crossref] [PubMed]
37. Liu Y, Cao L, Hillengass J, Delorme S, Schlewitz G, Govindarajan P, Schnettler R, Heiss C, Bäuerle T. Quantitative assessment of microcirculation and diffusion in the bone marrow of osteoporotic rats using VCT, DCE-MRI, DW-MRI, and histology. Acta Radiol 2013;54:205-13. [Crossref] [PubMed]
38. Shen Y, Zhang YH, Shen L. Postmenopausal women with osteoporosis and osteoarthritis show different microstructural characteristics of trabecular bone in proximal tibia using high-resolution magnetic resonance imaging at 3 tesla. BMC Musculoskelet Disord 2013;14:136. [Crossref] [PubMed]
39. Manenti G, Capuani S, Fanucci E, Assako EP, Masala S, Sorge R, Iundusi R, Tarantino U, Simonetti G. Diffusion tensor imaging and magnetic resonance spectroscopy assessment of cancellous bone quality in femoral neck of healthy, osteopenic and osteoporotic subjects at 3T: Preliminary experience. Bone 2013;55:7-15. [Crossref] [PubMed]
40. Manenti G, Capuani S, Fusco A, Fanucci E, Tarantino U, Simonetti G. Osteoporosis detection by 3T diffusion tensor imaging and MRI spectroscopy in women older than 60 years. Aging Clin Exp Res 2013;25 Suppl 1:S31-4. [Crossref] [PubMed]
41. Chang G, Boone S, Martel D, Rajapakse CS, Hallyburton RS, Valko M, Honig S, Regatte RR. MRI assessment of bone structure and microarchitecture. J Magn Reson Imaging 2017;46:323-37. [Crossref] [PubMed]