Senile osteoporosis is associated with disc degeneration

Osteoporosis and disc degeneration of the spine are common conditions that primarily affect the elderly with significant impact on the quality of life. A number of studies reported that higher lumbar spine bone mineral density (BMD) was associated with disc degeneration (1-5). However, other studies reported that osteoporotic patients have more severe disc degeneration (6,7). Some authors suggest that osteoporosis would possibly delay disc degeneration because of an increase in intradiscal nutrient diffusion and a decreased endplate resistance and decreased intradiscal strain due to the low quality of the bone (8,9). On the other hand, it is also proposed that osteoporosis may be an etiological factor in the development of lumbar disc degeneration with osteoporosis inducing loss of vertebral height, leading to instability, facet arthrosis, and disc degeneration (7). After many years’ research, whether osteoporosis promotes or protects disc against degeneration still remains debated in the literature (8-12). Hereby we argue that current evidences suggest senile osteoporosis promotes disc degeneration.

Earlier studies reported osteoporosis protects against lumbar disc degeneration which was assessed by radiograph (1-5). Radiographic signs of disc degeneration typically include the presence and severity of anterior osteophytes, end plate sclerosis, and disc space narrowing. With visual MRI based approaches such as the commonly used Pfirrmann’s 5-level grading and the detailed Griffith’s 8-level grading, disc space narrowing is again incorporated as an integral sign of disc degeneration (13,14). However, osteoporosis is associated vertebral height loss, particularly vertebral middle height loss, which allows the expansion of the disc vertically (15). Thus the osteoporotic spine may less likely be graded as having disc space narrowing, and thereof, less likely be graded as having disc degeneration.

Another methodological issue is where and how to measure BMD. The prevalence of disc degeneration and facet arthrosis increases with aging, such that by 60 years of age, 60–80% of people have osteophytosis, disc narrowing, and/or facet joint arthrosis (16). Degenerative changes lead to artificially higher DAX-based areal lumbar BMD measurement due to marginal osteophytosis, trabecular thickening, subchondral sclerosis, and facet joint arthrosis (17,18). Narrowed disc spaces can lead to a higher areal BMD reading (19). In the elderly population, lumbar disc spaces are more likely to be narrower when vertebral areal BMD is higher (20). Osteoporosis in its most common form is a systemic disease. In this regard, hip densitometry can be a more reliable and better representative systemic BMD. However, it can also be argued that it is the local lumbar BMD that really matters when investigating the inter-play whether the higher lumbar BMD associated biomechanical alterations may contribute to disc degeneration. Quantitative computerized tomography (QCT)-measured vertebral body trabecular BMD may overcome the areal BMD measurement artefacts caused by spinal degeneration. However, with Griffith’s visual 8-level MRI grading, a small study of 48 elderly males with QCT measurement of lumbar spine BMD (L1L2) show a trend of more severe disc degeneration being weakly associated with higher trabecular BMD value (20). Muraki et al. (19) analyzed 630 women aged ≥60 years and found that the scores for degenerative spinal diseases were correlated with lumbar spine areal BMD, but not correlated with femoral neck BMD. Pye et al. (21) analyzed a sample of 500 men and women and examined osteophytes, disc space narrowing and endplate sclerosis at 4 lumbar discs with radiographs, showed that lumbar BMD increased with increasing grades for all radiographic features in both sexes. When they adjusted disc space narrowing score for age and body mass index it remained significantly correlated with BMD at the spine, but not at the femoral neck. Similar results have also been reported by Salo et al. (22).

With Griffith’s visual 8-level MRI grading, in elderly female (73.2±4.1 years, n=196) and male (73.5±4.3 years, n=163) subjects and according to lumbar areal BMD, we initially reported that disc degeneration tended to be less severe in osteoporotic subjects compared to osteopenic subjects and in osteopenic subjects compared to normal bone mineral density subjects (20). However, there was no significant relation between hip BMD and lumbar disc degeneration or disc space narrowing both for males and females (23). Furthermore, when the disc dimension and disc volume were quantitatively measured (15), we demonstrated that lower lumbar BMD (osteopenia and osteoporosis) is associated with a decrease in lumbar disc anterior height and posterior height, as well as a decrease in anterior-posterior diameter; however, the middle height of the discs was increased (therefore the disc biconvexity index was increased). The net result is that lower BMD is associated with a decrease of the disc volume (15). On the other hand, for the vertebral bodies, lower BMD was associated with a decrease of vertebral anterior/middle/posterior height, but not vertebral anterior-posterior diameter; lower BMD was associated with a decrease in vertebral volume, and an increased biconcavity index (15). Our 4-year longitudinal follow-up study with radiographs shows osteopenia and osteoporosis are associated with faster disc area decrease in both thoracic spine and lumbar spine, and both for both males and females (24). We can naturally assume that a decreased disc volume (as measured with MRI) and decreased disc lateral area (as measured with radiograph) are biomarkers of disc degeneration. One point worthy noting is that while elderly females overall had faster radiographic disc area loss during the 4-year follow-up than elderly males, for the subgroups of osteoporotic subjects in this study, elderly men and elderly women had similar extent of disc area loss during the 4-year follow-up period. This observation may tentatively suggest that factors associated with osteoporosis and osteoporosis themselves are important drivers for disc area loss and thus disc degeneration. An increase in central disc height without compensatory increase in disc width may potentially have a destabilizing effect on the spine contributing to altered spinal kinematics.

From a pathophysiological perspective, osteoporosis may negatively impact endplate and thereof contribute to disc degeneration. Although disc degeneration has a multifactorial etiology involving age, mechanical, and genetic factors, a final common pathway of decreased nutrition has been proposed (25). Failure to adequately supply nutrients to the disc cells is a major event in the initiation and progression of disc degeneration (26). Osteoporosis can cause endplate thinning and microfracture, which in turn lead to compromised endplate healing, and add calcification and decrease the vascularization in the endplates adjacent to the degenerated discs, which subsequently exacerbates degeneration of the associated discs (27,28). Experimental studies with aging sand rats show that in the osteoporotic spine, endplate sclerosis occurs with aging, which in turn inhibits nutrition supply to the intervertebral discs (29). In bilateral ovariectomy (OVX) rats, osteoporosis and disc degeneration occurs simultaneously, while the increase of calcification and decrease of vascularization of the endplate further contribute to disc degeneration (30-32). In a rat osteoporosis model induced by a combination of OVX and cervical muscle section, osteoporosis was associated with cartilage endplate lesion and greater disc degeneration in cervical spine (33). In a study using female rhesus monkeys, Zhong et al. (34) used intra-vertebral injection of pingyangmycin solution to induce slowly progressive disc degeneration. Endplate vascular channel decrease and shrinking, which were more obvious when combined with OVX, was observed. Zhong et al. (34) suggested that osteoporosis could promote endplate calcification and further decrease the vascularization of the endplates adjacent to the degenerated discs. Interestingly, in rat studies, alendronate (an antiresorptive agent to treat osteoporosis) administration initiated pre-OVX or three months post-OVX, or salmon calcitonin (a 32-amino acid linear polypeptide hormone used for postmenopausal osteoporosis treatment) administration initiated pre-OVX, not only alleviate vertebral osteoporosis but also protect disc against degeneration (30-32).

On the other hand, two studies related to this topic involving middle-aged subjects have been published (35,36). In a cadaveric lumbar spine specimen study, Wang et al. (35) used micro-CT to measure vertebral BMD, and disc degeneration was assessed by discography which was independent of disc height evaluation. They found that no significant association was found between the BMD of the whole vertebra and adjacent disc degeneration. However, when only the vertebral body was considered (with the posterior elements, such as lamina, facet joints, spinous process, transverse process, excluded), there was a significant association between greater vertebral body BMD and more severe degeneration in the disc cranial to the vertebra. This association remained after further excluding osteophytes and endplates from the vertebral body BMD measurement. It was suggested that the association between higher vertebral body BMD and severer disc degeneration may be a collaborative effect of general factors and local interaction. However, their samples were from 48 white men aged 21 to 64 years with a mean age of 50. In a twins study, Livshits et al. (36) studied a total of 908 subjects from a volunteer-based group of healthy Caucasian women (age range 32–77 years, median age: 53.02 years). The four MRI main traits of disc degeneration were scored: disc signal intensity within the nucleus pulposus, disc height measured in the middle of the disc, lumbar disc extension into the spinal canal and anterior osteophytes. They found that the individuals with more advanced degenerative changes in lumbar spine tended to have higher BMD in spine and hip. The association persists after taking other covariates into account and is true for the all four MRI traits studied. Some common genes, for example, polymorphisms of the vitamin D receptor gene, have double-edged effects that contribute to better BMD in the vertebra but also more degeneration in the intervertebral disk (37-40). In middle-aged subjects, when levels of peak spinal loading and bone strength is high, dense vertebral bone can possibly threaten the adjacent discs by increasing pressure in the disc nucleus (11). However, disc degeneration in an elderly population may behave rather differently compared with discs in middle-aged subjects.

To conclude, current evidences suggest senile osteopenia/osteoporosis in both elderly males and females is associated with disc degeneration. This is probably at least partially mediated by endplate degeneration and the associated decrease in nutrient supply to the disc, as well as the altered biomechanical stress. On the other hand, while more evidence is required, in young-middle aged subjects high physiological BMD may be associated disc degeneration (35,36). Due to the confounding effects that low vertebral BMD is associated with a decrease of vertebral middle height and an increase of disc middle height, and degenerative spines have an artificially elevated lumbar areal BMD measurement, and the difficulties in interpreting MRI results, for assessing the association between BMD and disc degeneration meticulous cares should be taken. We suggest the following points to be carefully considered when designing an in vivo study or interpreting results:

• Is the study addressing (i) young subjects (such as investigating genetic traits)? (ii) middle aged subjects? or elderly subjects? While in younger subjects disc degeneration is often associated with physical injury in males (41), signs of disc degeneration in the elderly can be associated with natural aging (42).
• Men and women should be analyzed separately. Menopause both contribute to rapid loss of bone mass as well as accelerated disc generation, and osteoarthritis (43-51).
• QCT-based vertebral trabecular BMD or hip BMD is preferred over areal lumbar BMD (52,53).
• To define disc degeneration in vivo, we recommend MRI based methods which provide quantification of biochemical composition of disc tissues, such as T2/T1rho/CEST (54-61). However, it should be noted that accurate measurement of disc tissues can be challenging (57,62-64), and a standard approach for segmenting annuls fibrosis and nucleus pulposus should be considered (64).
• Ideally, study subjects sample size should be sufficiently large (57) and lumbar disc levels are analyzed individually, as lumbar discs at different levels are under different biomechanical stress (65). It has been noted that, in elderly subject within a defined period of follow-up, caudal lumbar discs had greater lateral area decrease rate than cephalad lumbar discs (23). Adams and Dolan (66) suggested that there are two types of disc degeneration. ‘‘Endplate-driven’’ disc degeneration involves endplate defects and inwards collapse of the annulus, mostly affecting discs in the upper lumbar and thoracic spine, usually associated with compressive injuries. ‘‘Annulus-driven’’ disc degeneration involves a radial fissure and/or a disc prolapse, mostly affecting discs in the lower lumbar spine, and is associated with repetitive bending and lifting. Lower lumbar discs are subjected to greater loading in bending, and so are more susceptible to degenerative changes (including disc prolapse) which arises from bending injuries to the annulus.

Acknowledgements

The author thanks Professor Steven Boyd and Dr Ying Zhu, both at the University of Calgary, Canada, for helpful discussions.

Footnote

Conflicts of Interest: The author has no conflicts of interest to declare.

References

1. Harada A, Okuizumi H, Miyagi N, Genda E. Correlation between bone mineral density and intervertebral disc degeneration. Spine (Phila Pa 1976) 1998;23:857-61. [Crossref] [PubMed]
2. Dequeker J, Aerssens J, Luyten FP. Osteoarthritis and osteoporosis: clinical and research evidence of inverse relationship. Aging Clin Exp Res 2003;15:426-39. [Crossref] [PubMed]
3. Miyakoshi N, Itoi E, Murai H, Wakabayashi I, Ito H, Minato T. Inverse relation between osteoporosis and spondylosis in postmenopausal women as evaluated by bone mineral density and semiquantitative scoring of spinal degeneration. Spine (Phila Pa 1976) 2003;28:492-5. [Crossref] [PubMed]
4. Weintroub S, Papo J, Ashkenazi M, Tardiman R, Weissman SL, Salama R. Osteoarthritis of hip and fractures of the proximal end of the femur. Acta Orthop Scand 1982;53:261-4. [Crossref] [PubMed]
5. Marcelli C, Favier F, Kotzki PO, Ferrazzi V, Picot MC, Simon L. The relationship between osteoarthritis of the hands, bone mineral density, and osteoporotic fractures in elderly women. Osteoporos Int 1995;5:382-8. [Crossref] [PubMed]
6. Verstraeten A, Van Ermen H, Haghebaert G, Nijs J, Geusens P, Dequeker J. Osteoarthrosis retards the development of osteoporosis: observation of the coexistence of Osteoarthrosis and osteoporosis. Clin Orthop 1991.169-77. [PubMed]
7. Margulies JY, Payzer A, Nyska M, Neuwirth MG, Floman Y, Robin GC. The relationship between degenerative changes and osteoporosis in the lumbar spine. Clin Orthop 1996.145-52. [Crossref] [PubMed]
8. Mattei TA. Degenerative disc disease and osteoporosis. J Neurosurg Spine 2014;20:471-2. [Crossref] [PubMed]
9. Mattei TA. Osteoporosis delays intervertebral disc degeneration by increasing intradiscal diffusive transport of nutrients through both mechanical and vascular pathophysiological pathways. Med Hypotheses 2013;80:582-6. [Crossref] [PubMed]
10. Pan J, Tong X, Han Y, Chen J, Feng Z, Liu Y, Wang Y. The association between lumbar spine bone mineral density and lumbar disc degeneration: a study in Han Chinese. Chin J Osteoporos 2016;22:1156-60.
11. Adams M, Dolan P. Vertebral fracture and intervertebral discs. J Bone Miner Res 2012;27:1432. [Crossref] [PubMed]
12. Wei F, Zhong R, Wang L, Cui S, Liu S, Zou X, Zhou Z, Liang Z. Relationship between bone mineral density and lumbar intervertebral disc degeneration in rhesus macaques. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2014;28:718-22. [PubMed]
13. Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J, Boos N. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine (Phila Pa 1976) 2001;26:1873-8. [Crossref] [PubMed]
14. Griffith JF, Wang YX, Antonio GE, Choi KC, Yu A, Ahuja AT, Leung PC. Modified Pfirrmann grading system for lumbar intervertebral disc degeneration. Spine (Phila Pa 1976) 2007;32:E708-12. [Crossref] [PubMed]
15. Kwok AW, Wang YX, Griffith JF, Deng M, Leung JC, Ahuja AT, Leung PC. Morphological changes of lumbar vertebral bodies and intervertebral discs associated with decrease in bone mineral density of the spine: a cross-sectional study in elderly subjects. Spine (Phila Pa 1976) 2012;37:E1415-21. [Crossref] [PubMed]
16. Kellgren JH, Lawrence JS. Osteoarthrosis and disc degeneration in an urban population. Ann Rheum Dis 1958;17:388-97. [Crossref] [PubMed]
17. Masud T, Langley S, Wiltshire P, Doyle DV, Spector TD. Effect of spinal osteophytosis on bone mineral density measurements in vertebral osteoporosis. BMJ 1993;307:172-3. [Crossref] [PubMed]
18. Oxland TR, Lund T, Jost B, Cripton P, Lippuner K, Jaeger P, Nolte LP. The relative importance of vertebral bone density and disc degeneration in spinal flexibility and interbody in implant performance. An in vitro study. Spine (Phila Pa 1976) 1996;21:2558-69. [Crossref] [PubMed]
19. Muraki S, Yamamoto S, Ishibashi H, Horiuchi T, Hosoi T, Orimo H, Nakamura K. Impact of degenerative spinal diseases on bone mineral density of the lumbar spine in elderly women. Osteoporos Int 2004;15:724-8. [Crossref] [PubMed]
20. Wang YX, Griffith JF, Ma HT, Kwok AW, Leung JC, Yeung DK, Ahuja AT, Leung PC. Relationship between gender, bone mineral density, and disc degeneration in the lumbar spine: a study in elderly subjects using an eight-level MRI-based disc degeneration grading system. Osteoporos Int 2011;22:91-6. [Crossref] [PubMed]
21. Pye SR, Reid DM, Adams JE, Silman AJ, O’Neill TW. Radiographic features of lumbar disc degeneration and bone mineral density in men and women. Ann Rheum Dis 2006;65:234-8. [Crossref] [PubMed]
22. Salo S, Leinonen V, Rikkonen T, Vainio P, Marttila J, Honkanen R, Tuppurainen M, Kröger H, Sirola J. Association between bone mineral density and lumbar disc degeneration. Maturitas 2014;79:449-55. [Crossref] [PubMed]
23. Wang YX, Kwok AW, Griffith JF, Leung JC, Ma HT, Ahuja AT, Leung PC. Relationship between hip bone mineral density and lumbar disc degeneration: a study in elderly subjects using an eight-level MRI-based disc degeneration grading system. J Magn Reson Imaging 2011;33:916-20. [Crossref] [PubMed]
24. Wáng JQ, Káplár Z, Deng M, Griffith JF, Leung JCS, Kwok AWL, Kwok T, Leung PC, Wáng YX. Thoracolumbar Intervertebral Disc Area Morphometry in Elderly Chinese Men and Women: Radiographic Quantifications at Baseline and Changes at Year-4 Follow-up. Spine (Phila Pa 1976) 2018;43:E607-14. [Crossref] [PubMed]
25. Buckwalter JA. Spine update: aging and degeneration of the human intervertebral disc. Spine (Phila Pa 1976) 1995;20:1307-14. [Crossref] [PubMed]
26. Nachemson A, Lewin T, Maroudas A, Freeman MAF. In vitro diffusion of dye through the end-plates and annulus fibrosus of human lumbar intervertebral discs. Acta Orthop Scand 1970;41:589-607. [Crossref] [PubMed]
27. Wang YX, Griffith JF. Menopause causes vertebral endplate degeneration and decrease in nutrient diffusion to the intervertebral discs. Med Hypotheses 2011;77:18-20. [Crossref] [PubMed]
28. Moore RJ. The vertebral endplate: disc degeneration, disc regeneration. Eur Spine J 2006;15:S333-7. [Crossref] [PubMed]
29. Gruber HE, Gordon B, Williams C, Norton HJ, Hanley EN Jr. Vertebral endplate and disc changes in the aging sand rat lumbar spine: cross-sectional analyses of a large male and female population. Spine (Phila Pa 1976) 2007;32:2529-36. [Crossref] [PubMed]
30. Tian FM, Yang K, Wang WY, Luo Y, Li SY, Song HP, Zhang YZ, Shen Y, Zhang L. Calcitonin suppresses intervertebral disk degeneration and preserves lumbar vertebral bone mineral density and bone strength in ovariectomized rats. Osteoporos Int 2015;26:2853-61. [Crossref] [PubMed]
31. Song H, Luo Y, Wang W, Li S. Yang K1, Dai M, Shen Y, Zhang Y, Zhang L. Effects of alendronate on lumbar intervertebral disc degeneration with bone loss in ovariectomized rats. Spine J 2017;17:995-1003. [Crossref] [PubMed]
32. Luo Y, Zhang L, Wang WY, Hu QF, Song HP, Su YL, Zhang YZ. Alendronate retards the progression of lumbar intervertebral disc degeneration in ovariectomized rats. Bone 2013;55:439-48. [Crossref] [PubMed]
33. Ding Y, Jiang J, Zhou J, Wu X, Huang Z, Chen J, Zhu Q. The effects of osteoporosis and disc degeneration on vertebral cartilage endplate lesions in rats. Eur Spine J 2014;23:1848-55. [Crossref] [PubMed]
34. Zhong R, Wei F, Wang L, Cui S, Chen N, Liu S, Zou X. The effects of intervertebral disc degeneration combined with osteoporosis on vascularization and microarchitecture of the endplate in rhesus monkeys. Eur Spine J 2016;25:2705-15. [Crossref] [PubMed]
35. Wang Y, Boyd SK, Battié MC, Yasui Y, Videman T. Is greater lumbar vertebral BMD associated with more disk degeneration? A study using µCT and discography. J Bone Miner Res 2011;26:2785-91. [Crossref] [PubMed]
36. Livshits G, Ermakov S, Popham M, MacGregor AJ, Sambrook PN, Spector TD, Williams FM. Evidence that bone mineral density plays a role in degenerative disc disease: the UK Twin Spine study. Ann Rheum Dis 2010;69:2102-6. [Crossref] [PubMed]
37. Videman T, Gibbons LE, Battie MC, Maravilla K, Vanninen E, Leppavuori J, Kaprio J, Peltonen L. The relative roles of intragenic polymorphisms of the vitamin d receptor gene in lumbar spine degeneration and bone density. Spine (Phila Pa 1976) 2001;26:E7-12. [Crossref] [PubMed]
38. Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, Sambrook PN, Eisman JA. Prediction of bone density from vitamin D receptor alleles. Nature 1994;367:284-7. [Crossref] [PubMed]
39. Thakkinstian A, D’Este C, Eisman J, Nguyen T, Attia J. Meta-analysis of molecular association studies: vitamin D receptor gene polymorphisms and BMD as a case study. J Bone Miner Res 2004;19:419-28. [Crossref] [PubMed]
40. Videman T, Leppavuori J, Kaprio J, Battie MC, Gibbons LE, Peltonen L, Koskenvuo M. Intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration. Spine (Phila Pa 1976) 1998;23:2477-85. [Crossref] [PubMed]
41. Takatalo J, Karppinen J, Niinimäki J, Taimela S, Näyhä S, Järvelin MR, Kyllönen E, Tervonen O. Prevalence of degenerative imaging findings in lumbar magnetic resonance imaging among young adults. Spine (Phila Pa 1976) 2009;34:1716-21. [Crossref] [PubMed]
42. Adams MA, Roughley PJ. What is intervertebral disc degeneration, and what causes it? Spine (Phila Pa 1976) 2006;31:2151-61. [Crossref] [PubMed]
43. Wang YX, Griffith JF. Effect of menopause on lumbar disc degeneration: potential etiology. Radiology 2010;257:318-20. [Crossref] [PubMed]
44. Wang YX. Postmenopausal Chinese women show accelerated lumbar disc degeneration compared with Chinese men. J Orthop Translat 2015;3:205-11. [Crossref]
45. Gambacciani M, Pepe A, Cappagli B, Palmieri E, Genazzani AR. The relative contributions of menopause and aging to postmenopausal reduction in intervertebral disk height. Climacteric 2007;10:298-305. [Crossref] [PubMed]
46. Wáng YX, Griffith JF, Deng M, Yeung DK, Yuan J. Rapid increase in marrow fat content and decrease in marrow perfusion in lumbar vertebra following bilateral oophorectomy: an MR imaging-based prospective longitudinal study. Korean J Radiol 2015;16:154-9. [Crossref] [PubMed]
47. Wáng YX, Wáng JQ, Káplár Z. Increased low back pain prevalence in females than in males after menopause age: evidences based on synthetic literature review. Quant Imaging Med Surg 2016;6:199-206. [Crossref] [PubMed]
48. Wang YX, Káplár Z, Deng M, Leung JCS. Lumbar degenerative spondylolisthesis epidemiology: A systematic review with a focus on gender-specific and age-specific prevalence. J Orthop Translat 2016;11:39-52. [Crossref] [PubMed]
49. Imada K, Matsui H, Tsuji H. Oophorectomy predisposes to degenerative spondylolisthesis. J Bone Joint Surg Br 1995;77:126-30. [Crossref] [PubMed]
50. Dodge HJ, Mikkelsen WM, Duff IF. Age-sex specific prevalence of radiographic abnormalities of the joints of the hands, wrists and cervical spine of adult residents of the Tecumseh, Michigan, Community Health Study area, 1962-1965. J Chronic Dis 1970;23:151-9. [Crossref] [PubMed]
51. Srikanth VK, Fryer JL, Zhai G, Winzenberg TM, Hosmer D, Jones G. A meta-analysis of sex differences prevalence, incidence and severity of osteoarthritis. Osteoarthritis Cartilage 2005;13:769-81. [Crossref] [PubMed]
52. Adams JE. Quantitative computed tomography. Eur J Radiol 2009;71:415-24. [Crossref] [PubMed]
53. Troy KL, Edwards WB. Practical considerations for obtaining high quality quantitative computed tomography data of the skeletal system. Bone 2018;110:58-65. [Crossref] [PubMed]
54. Gübitz R, Lange T, Gosheger G, Heindel W, Allkemper T, Stehling C, Gerss J, Kanthak C, Schulte TL. Influence of Age, BMI, Gender and Lumbar Level on T1ρ Magnetic Resonance Imaging of Lumbar Discs in Healthy Asymptomatic Adults. Rofo 2018;190:144-51. [Crossref] [PubMed]
55. Müller-Lutz A, Schleich C, Schmitt B, Antoch G, Matuschke F, Quentin M, Wittsack HJ, Miese F. Gender, BMI and T2 dependencies of glycosaminoglycan chemical exchange saturation transfer in intervertebral discs. Magn Reson Imaging 2016;34:271-5. [Crossref] [PubMed]
56. Wang YX, Griffith JF, Leung JC, Yuan J. Age related reduction of T1rho and T2 magnetic resonance relaxation times of lumbar intervertebral disc. Quant Imaging Med Surg 2014;4:259-64. [PubMed]
57. Wáng YX, Zhang Q, Li X, Chen W, Ahuja A, Yuan J. T1ρ magnetic resonance: basic physics principles and applications in knee and intervertebral disc imaging. Quant Imaging Med Surg 2015;5:858-85. [PubMed]
58. Yoo YH, Yoon CS, Eun NL, Hwang MJ, Yoo H, Peters RD, Chung TS, Lee YH, Suh JS, Kim S. Interobserver and Test-Retest Reproducibility of T1ρ and T2 Measurements of Lumbar Intervertebral Discs by 3T Magnetic Resonance Imaging. Korean J Radiol. 2016;17:903-11. [Crossref] [PubMed]
59. Menezes-Reis R, Salmon CE, Bonugli GP, Mazoroski D, Tamashiro MH, Savarese LG, Nogueira-Barbosa MH. Lumbar intervertebral discs T2 relaxometry and T1ρ relaxometry correlation with age in asymptomatic young adults. Quant Imaging Med Surg 2016;6:402-12. [Crossref] [PubMed]
60. Wáng YX. Appropriate Normal Range of Lumbar Disc T1rho of Men and Women with Respect to Physiological Aging. Rofo 2018;190:560. [Crossref] [PubMed]
61. Deng M, Yuan J, Chen WT, Chan Q, Griffith JF, Wang YX. Evaluation of Glycosaminoglycan in the Lumbar Disc Using Chemical Exchange Saturation Transfer MR at 3.0 Tesla: Reproducibility and Correlation with Disc Degeneration. Biomed Environ Sci 2016;29:47-55. [PubMed]
62. Wáng YX. On Magnetic Resonance Imaging of Intervertebral Disc Aging. Sports Med 2017;47:187-8. [Crossref] [PubMed]
63. Mok GS, Zhang D, Chen SZ, Yuan J, Griffith JF, Wang YX. Comparison of three approaches for defining nucleus pulposus and annulus fibrosus on sagittal magnetic resonance images of the lumbar spine. J Orthop Translat 2016;6:34-41. [Crossref]
64. Wáng YX. Towards consistency for magnetic resonance (MR) relaxometry of lumbar intervertebral discs. Quant Imaging Med Surg 2016;6:474-7. [Crossref] [PubMed]
65. Adams MA, Lama P, Zehra U, Dolan P. Why do some intervertebral discs degenerate, when others (in the same spine) do not? Clin Anat 2015;28:195-204. [Crossref] [PubMed]
66. Adams MA, Dolan P. Intervertebral disc degeneration: evidence for two distinct phenotypes. J Anat 2012;221:497-506. [Crossref] [PubMed]