Repeated vertebral augmentation for new vertebral compression fractures of postvertebral augmentation patients: a nationwide cohort study – how useful is the current clinical gold standard for fracture risk?

Dear editor

Further to the recent publication on the “Repeated vertebral augmentation for new vertebral compression fractures of postvertebral augmentation patients: a nationwide cohort study”,¹ current data highlight the limitations of dual-energy X-ray absorptiometry scans. In this context, at best, dual-energy X-ray absorptiometry scans (which measure bone mineral density) can account for no greater than 50% of overall bone strength (defined as the ability to resist fracture). This is because the resulting images are two-dimensional and therefore unable to capture skeletal micro-architecture, which also contributes to bone strength.²

A better clinical measure of overall bone strength that more accurately reflects the ability of that bone to resist fracture and hence fracture risk reflect an unmet need and is urgently required. Recent evidence suggests that micro-computed tomography scans, which enable three-dimensional imaging, might provide a solution but use so far has necessarily been limited to ex vivo assessment owing to radiation hazards as well as technical and accessibility issues.^3,4 However micro-computed tomography images have identified bone volume fraction (the volumetric distribution of bone mass) as a strong determinant of bone strength (r²>0.8).^5,6

Further, perhaps other potential tools, alone or in combination with imaging may also play a role. For example, serum biomarkers of bone metabolism^7,8 along with other imaging modalities such as magnetic resonance imaging could capture the complex factors that make up bone strength.⁹ Preexisting algorithms like the FRAX (a fracture risk assessment tool calculator)¹⁰ might help reduce the overprediction issue currently faced.

With regard to the aforementioned evidence, there is a pressing need to consider first how we use bone densitometry in the diagnosis of osteoporosis in prostate cancer patients, before the National Health Service itself becomes fractured.

Disclosure

The authors report no conflicts of interest in this communication.

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References

1.		Liang CL, Wang HK, Syu FK, Wang KW, Lu K, Liliang PC. Repeated vertebral augmentation for new vertebral compression fractures of postvertebral augmentation patients: a nationwide cohort study. Clin Interv Aging. 2015;10:635–642.
2.		Greenspan SL, Wagner J, Nelson JB, Perera S, Britton C, Resnick NM. Vertebral fractures and trabecular microstructure in men with prostate cancer on androgen deprivation therapy. J Bone Miner Res. 2013;28(2):325–332.
3.		Cooper D, Turinsky A, Sensen C, Hallgrimsson B. Effect of voxel size on 3D micro-CT analysis of cortical bone porosity. Calcified Tissue Int. 2007;80(3):211–219.
4.		Genant HK, Engelke K, Prevrhal S. Advanced CT bone imaging in osteoporosis. Rheumatology (Oxford). 2008;47 Suppl 4:iv9–iv16.
5.		Nazarian A, von Stechow D, Zurakowski D, Muller R, Snyder BD. Bone volume fraction explains the variation in strength and stiffness of cancellous bone affected by metastatic cancer and osteoporosis. Calcif Tissue Int. 2008;83(6):368–379.
6.		Van Hemelrijck M, Garmo H, Michaelsson K, et al. Mortality following hip fracture in men with prostate cancer. PloS One. 2013;8(9):e74492.
7.		Wilson HC, Shah SI, Abel PD, et al. Contemporary hormone therapy with LHRH agonists for prostate cancer: avoiding osteoporosis and fracture. Cent European J Urol. 2015;68(2):165–168.
8.		Dabaja A, Bryson C, Schlegel P, Paduch D. The effect of hypogonadism and testosterone-enhancing therapy on alkaline-phosphatase and bone mineral density. BJU Int. 2015;115(3):480–485.
9.		Kröger H, Vainio P, Nieminen J, Kotaniemi A. Comparison of different models for interpreting bone mineral density measurements using DXA and MRI technology. Bone. 1995;17(2):157–159.
10.		University of Sheffield [homepage on the Internet]. WHO Fracture Risk Assessment Tool. World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK. Available from: https://www.shef.ac.uk/FRAX/. Accessed October 2, 2015.

Authors’ reply

Cheng-Loong Liang,¹ Hao-Kwan Wang,¹ Fei-Kai Syu,² Kuo-Wei Wang,¹ Kang Lu,¹ Po-Chou Liliang¹

¹Department of Neurosurgery, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan; ²Department of Pharmacy, China Medical University Hospital, Taichung City, Taiwan

Correspondence: Po-Chou Liliang, Department of Neurosurgery, E-Da Hospital, I-Shou University, 1 Yi-Da Road, Yan-Chau Shiang, Kaohsiung City 824, Taiwan, Tel +866 7 615 0011, Fax +866 7 615 0982, Email [email protected]

Dear editor

We thank the authors for their interest and comments regarding our article.¹ The diagnosis of osteoporosis can be made using conventional radiography and by measuring the bone mineral density (BMD).² The most popular method of measuring BMD is dual-energy X-ray absorptiometry (DEXA) scans. DEXA scan is currently recommended by the World Health Organization; however, it maybe not a gold standard. The accuracy of this density estimate is affected by many factors. For example, smaller people with smaller bones will lower the scores, machines from different manufacturers use different algorithms and yield noncomparable results, and anatomic abnormalities, such as previous spine surgery or compression fractures, will also skew the measurement. DEXA calculates BMD using an area; it is not an accurate measurement of true BMD, which is mass divided by a volume. It is unable to represent the skeletal micro-architecture, which also contributes to bone strength.³ In one study, some other technologies such as peripheral quantitative computed tomography and micro-computed tomography were able to improve the ability to assess structural parameters of cancellous and cortical bone.⁴

Recently, some progress has been made in measuring biomarkers of bone metabolism. Biomarkers of bone metabolism are broadly divided into two categories:⁵ markers of bone resorption, which reflect osteoclast activity and are for the most part degradation products of type I collagen; markers of bone formation, which reflect osteoblast activity and are byproducts of collagen synthesis, matrix proteins, or osteoblastic enzymes. These biomarkers can be easily measured in serum or urine.

Biomarkers of bone resorption are significantly elevated in postmenopausal women with osteoporosis, but the biomarkers of bone formation are not elevated and may indeed be decreased.^6,7 Biomarkers seem to be promising for prediction of bone loss, fracture, and response to therapy. However, their use alone to predict fracture and for osteoporosis diagnosis has yet to be established.⁸

Disclosure

The authors report no conflicts of interest in this communication.

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References

1.		Liang CL, Wang HK, Syu FK, Wang KW, Lu K, Liliang PC. Repeated vertebral augmentation for new vertebral compression fractures of postvertebral augmentation patients: a nationwide cohort study. Clin Interv Aging. 2015;10:635–642.
2.		Guglielmi G, Scalzo G. Imaging tools transform diagnosis of osteoporosis. Diagnostic Imaging Europe. 2010;26(3):7–11.
3.		Greenspan SL, Wagner J, Nelson JB, Perera S, Britton C, Resnick NM. Vertebral fractures and trabecular microstructure in men with prostate cancer on androgen deprivation therapy. J Bone Miner Res. 2013;28(2):325–332.
4.		Bagi CM, Hanson N, Andresen C, et al. The use of micro-CT to evaluate cortical bone geometry and strength in nude rats: correlation with mechanical testing, pQCT and DXA. Bone. 2006;38(1):136–144.
5.		Eastell R, Hannon RA. Biomarkers of bone health and osteoporosis risk. Proc Nutr Soc. 2008;67(2):157–162.
6.		Valimaki MJ, Tahtela R, Jones JD, Peterson JM, Riggs BL. Bone resorption in healthy and osteoporotic postmenopausal women: comparison markers for serum carboxy-terminal telopeptide of type I collagen and urinary pyridinium cross-links. Eur J Endocrinol. 1994;131(3):258–262.
7.		Kushida K, Takahashi M, Kawana K, Inoue T. Comparison of markers for bone formation and resorption in premenopausal and postmenopausal subjects, and osteoporosis patients. J Clin Endocrinol Metab. 1995;80(8): 447–2450.
8.		Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD. Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res. 2000;15(8):1526–1536.
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