A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX

McCloskey, Eugene V.; Odén, Anders; Harvey, Nicholas C.; Leslie, William D.; Hans, Didier; Johansson, Helena; Barkmann, Reinhard; Boutroy, Stephanie; Brown, Jacques; Chapurlat, Roland; Elders, Petra J. M.; Fujita, Yuki; Glüer, Claus-C; Goltzman, David; Iki, Masayuki; Karlsson, Magnus; Kindmark, Andreas; Kotowicz, Mark; Kurumatani, Norio; Kwok, Timothy; Lamy, Oliver; Leung, Jason; Lippuner, Kurt; Ljunggren, Östen; Lorentzon, Mattias; Mellström, Dan; Merlijn, Thomas; Oei, Ling; Ohlsson, Claes; Pasco, Julie A.; Rivadeneira, Fernando; Rosengren, Björn; Sornay-Rendu, Elisabeth; Szulc, Pawel; Tamaki, Junko; Kanis, John A.

Affiliations

¹Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK

²MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK

³University of Manitoba, Winnipeg, Canada

⁴Lausanne University Hospital, Center of Bone Diseases, Lausanne, Switzerland

⁵Sektion Biomedizinische Bildgebung Klinik für Diagnostische Radiologie, Kiel, Germany

⁶INSERM UMR 1033 and Lyon University, E Herriot Hospital (HEH), Lyon, France

⁷Department of Rheumatology, Laval University, Quebec, Canada

⁸Department of General Practice and Elderly Care Medicine, VU University Medical Center, Amsterdam, The Netherlands

⁹Department of Public Health, Kinki University Faculty of Medicine, Osaka, Japan

¹⁰Department of Medicine, McGill University Health Centre and McGill University, Montreal, Canada

¹¹Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Malmö, and Department of Orthopaedics, Skåne University Hospital, Malmo, Sweden

¹²Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden

¹³Epi-Centre for Healthy Ageing, School of Medicine, Deakin University, Geelong, Australia

¹⁴Department of Community Health and Epidemiology, Nara Medical University School of Medicine, Nara, Japan

¹⁵Jockey Club Centre for Osteoporosis Care and Control, the Chinese University of Hong Kong, Hong-Kong, China

¹⁶Department of Osteoporosis, Inselspital, Berne University Hospital, Bern, Switzerland

¹⁷Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenberg, Sweden

¹⁸Center for Bone Research at the Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

¹⁹Department of Internal Medicine and Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands

²⁰Department of Hygiene and Public Health, Osaka Medical College, Osaka, Japan

Abstract and keywords

Trabecular bone score (TBS) is a gray-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a bone mineral density (BMD)-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual-level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables, and outcomes during follow-up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities, and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1 SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% confidence interval [CI] 1.35–1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR = 1.32, 95% CI 1.24–1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95% CI 1.65–1.87 versus 1.70, 95% CI 1.60–1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines.

Keywords: TRABECULAR BONE STRUCTURE; TBS; FRACTURE; RISK; FRAX; META-ANALYSIS

Links

DOI: 10.1002/jbmr.2734

PubMed: 26498132

WoS: 000377270400004

History

Received: 2015-02-26

Revised: 2015-10-08

Accepted: 2015-10-23

Online: 2015-10-24

Cited Works (20)

Year	Entry
1993	Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med. June 1993;94(6):646-650.
2004	Johansson H, Oden A, Johnell O, Jonsson B, de Laet C, Oglesby A, McCloskey EV, Kayan K, Jalava T, Kanis JA. Optimization of BMD measurements to identify high risk groups for treatment: a test analysis. J Bone Miner Res. June 2004;19(6):906-913.
2004	Schuit SCE, van der Klift M, Weel AEAM, de Laet CEDH, Burger H, Seeman E, Hofman A, Uitterlinden AG, van Leeuwen JPTM, Pols HAP. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone. January 2004;34(1):195-202.
2011	Hans D, Goertzen AL, Krieg M-A, Leslie WD. Bone microarchitecture assessed by TBS predicts osteoporotic fractures independent of bone density: the Manitoba study. J Bone Miner Res. November 2011;26(11):2762-2769.
2014	Iki M, Tamaki J, Kadowaki E, Sato Y, Dongmei N, Winzenrieth R, Kagamimori S, Kagawa Y, Yoneshima H. Trabecular bone score (TBS) predicts vertebral fractures in Japanese women over 10 years independently of bone density and prevalent vertebral deformity: the Japanese population-based osteoporosis (JPOS) cohort study. J Bone Miner Res. February 2014;29(2):399-407.
2011	Szulc P, Boutroy S, Vilayphiou N, Chaitou A, Delmas PD, Chapurlat R. Cross-sectional analysis of the association between fragility fractures and bone microarchitecture in older men: the STRAMBO study. J Bone Miner Res. June 2011;26(6):1358-1367.
2014	Silva BC, Leslie WD, Resch H, Lamy O, Lesnyak O, Binkley N, McCloskey EV, Kanis JA, Bilezikian JP. Trabecular bone score: a noninvasive analytical method based upon the dxa image. J Bone Miner Res. March 2014;29(3):518-530.
1993	Faulkner KG, Cummings SR, Black D, Palermo L, Glüer C, Genant HK. Simple measurement of femoral geometry predicts hip fracture: the study of osteoporotic fractures. J Bone Miner Res. September 1993;8(10):1211-1217.
2003	Albrand G, Munoz F, Sornay-Rendu E, DuBoeuf F, Delmas P. Independent predictors of all osteoporosis-related fractures in healthy postmenopausal women: the OFELY study. Bone. January 2003;32(1):78-85.
2006	Pasco JA, Seeman E, Henry MJ, Merriman EN, Nicholson GC, Kotowicz MA. The population burden of fractures originates in women with osteopenia, not osteoporosis. Osteoporos Int. September 2006;17(9):1404-1409.
2003	Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. September 6, 2003;327(7414):557-560.
1998	Looker AC, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP, Johnston CC Jr, Lindsay R. Updated data on proximal femur bone mineral levels of US adults. Osteoporos Int. 1998;8(5):468-489.
2005	Johnell O, Kanis JA, Oden A, Johansson H, De Laet C, Delmas P, Eisman JA, Fujiwara S, Kroger H, Mellstrom D, Meunier PJ, Melton LJ III, O'Neill T, Pols H, Reeve J, Silman A, Tenenhouse A. Predictive value of BMD for hip and other fractures. J Bone Miner Res. July 2005;20(7):1185-1194.
2008	Kanis JA, McCloskey EV, Johansson H, Strom O, Borgstrom F, Oden A. Case finding for the management of osteoporosis with FRAX^®: assessment and intervention thresholds for the UK. Osteoporos Int. October 2008;19(10):1395-1408.
2010	Keaveny TM, Kopperdahl DL, Melton LJ III, Hoffmann PF, Amin S, Riggs BL, Khosla S. Age‐dependence of femoral strength in white women and men. J Bone Miner Res. May 2010;25(5):994-1001.
2010	Papaioannou A, Morin S, Cheung AM, Atkinson S, Brown JP, Feldman S, Hanley DA, Hodsman A, Jamal SA, Kaiser SM, Kvern B, Siminoski K, Leslie WD; Scientific Advisory Council of Osteoporosis Canada. 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. Can Med Assoc J. November 23, 2010;182(17):1864-1873.
2004	Kanis J, Johnell O, De Laet C, Johansson H, Oden A, Delmas P, Eisman J, Fujiwara S, Garnero P, Kroger H, McCloskey E, Mellstrom D, Melton L, Pols H, Reeve J, Silman A, Tenenhouse A. A meta-analysis of previous fracture and subsequent fracture risk. Bone. August 2004;35(2):375-382.
1999	Kreiger N, Tenenhouse A, Joseph L, Mackenzie T, Poliquin S, Brown JP, Prior JC, Rittmaster RS. The Canadian Multicentre Osteoporosis study (CaMos): background, rationale, methods. Can J Aging. 1999;18(3):376-387.
1988	Hui SL, Slemenda CW, Johnston CC Jr. Age and bone mass as predictors of fracture in a prospective study. J Clin Invest. June 1988;81(6):1804-1809.
2007	Kanis JA, Oden A, Johnell O, Johansson H, De Laet C, Brown J, Burckhardt P, Cooper C, Christiansen C, Cummings S, Eisman JA, Fujiwara S, Glüer C, Goltzman D, Hans D, Krieg M-A, La Croix A, McCloskey E, Mellstrom D, Melton LJ, Pols H, Reeve J, Sanders K, Schott A-M, Silman A, Torgerson D, van Staa T, Watts NB, Yoshimura N. The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int. August 2007;18(8):1033-1046.

Cited By (35)

Year	Entry
2016	Kanis JA, Harvey NC, Cooper C, Johansson H, Odén A, McCloskey EV; The Advisory Board of the National Osteoporosis Guideline Group. A systematic review of intervention thresholds based on FRAX: a report prepared for the National Osteoporosis Guideline Group and the International Osteoporosis Foundation. Arch Osteoporos. December 2016;11(1):25.
2017	Compston J, Cooper A, Cooper C, Gittoes N, Gregson C, Harvey N, Hope S, Kanis JA, McCloskey EV, Poole KES, Reid DM, Selby P, Thompson F, Thurston A, Vine N; The National Osteoporosis Guideline Group (NOGG). UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos. December 2017;12(1):1-24.
2020	Sfeir JG, Pena Guzman TD, Bedatsova L, Broski SM, Drake MT. Use of trabecular bone score for risk stratification of patients with monoclonal gammopathy of undetermined significance. Bone. August 2020;137:115394.
2020	van der Burgh AC, Oliai Araghi S, Zillikens MC, Koromani F, Rivadeneira F, van der Velde N, Hoorn EJ, Uitterlinden AG, Ikram MA, Stricker BH. The impact of thiazide diuretics on bone mineral density and the trabecular bone score: the Rotterdam Study. Bone. September 2020;138:115475.
2021	Pouillès J-M, Gosset A, Breteau A, Trémollieres FA. TBS in early postmenopausal women with severe vertebral osteoporosis. Bone. January 2021;142:115698.
2021	Kim HJ, Dash A, Cunningham M, Schwab F, Dowdell J, Harrison J, Zaworski C, Krez A, Lafage V, Agarwal S, Carlson B, McMahon DJ, Stein EM. Patients with abnormal microarchitecture have an increased risk of early complications after spinal fusion surgery. Bone. February 2021;143:115731.
2021	Nalevaiko JZ, Marques JVO, Oliveira MF, Raetsch AWP, Marques GL, Petterle RR, Moreira CA, Borba VZC. Bone density and quality in patients treated with direct-acting oral anticoagulants versus warfarin. Bone. September 2021;150:116000.
2022	Palomo T, Dreyer P, Muszkat P, Weiler FG, Bonansea TCP, Domingues FC, Vieira JGH, Silva BC, Brandão CMA. Effect of soft tissue noise on trabecular bone score in postmenopausal women with diabetes: a cross sectional study. Bone. April 2022;157:116339.
2022	Ni X, Guan W, Pang Q, Jin C, Gong Y, Liu W, Wang O, Li M, Xing X, Yu W, Jiang Y, Xia W. Bone microstructure evaluated by TBS and HR-pQCT in Chinese adults with X-linked hypophosphatemia. Bone. July 2022;160:116423.
2022	Hafizi S, Lix LM, Hans D, Bolton JM, Leslie WD. Association of mental disorders and psychotropic medications with bone texture as measured with trabecular bone score. Bone. December 2022;165:116565.
2021	Pimentel A, Ureña-Torres P, Bover J, Fernandez-Martín JL, Cohen-Solal M. Bone fragility fractures in CKD patients. Calcif Tiss Int. April 2021;108(4):539-550.
2018	Unal M, Creecy A, Nyman JS. The role of matrix composition in the mechanical behavior of bone. Curr Osteoporos Rep. June 2018;16(3):205-215.
2020	Link TM, Kazakia G. Update on imaging-based measurement of bone mineral density and quality. Curr Rheumatol Rep. April 9, 2020;22(5):5.
2020	Camacho PM, Petak SM, Binkley N, Diab DL, Eldeiry LS, Farooki A, Harris ST, Hurley DL, Kelly J, Lewiecki EM, Pessah-Pollack R, McClung M, Wimalawansa SJ, Watts NB. American Association of Clinical Endocrinologists/American College of Endocrinology Clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis: 2020 update. Endocr Pract. May 2020;26(suppl 1):1-46.
2018	Biver E, Durosier-Izart C, Chevalley T, van Rietbergen B, Rizzoli R, Ferrari S. Evaluation of radius microstructure and areal bone mineral density improves fracture prediction in postmenopausal women. J Bone Miner Res. February 2018;33(2):328-337.
2020	Li G, Leslie WD, Kovacs CS, Prior J, Josse RG, Towheed T, Davison KS, Thabane L, Papaioannou A, Levine MAH, Goltzman D, Zeng J, Qi Y, Tian J, Adachi JD; Canadian Multicentre Osteoporosis Study (CaMos) Research Group. Combining frailty and trabecular bone score did not improve predictive accuracy in risk of major osteoporotic fractures. J Bone Miner Res. June 2020;35(6):1058-1064.
2020	Johansson L, Sundh D, Magnusson P, Rukmangatharajan K, Mellström D, Nilsson AG, Lorentzon M. Grade 1 vertebral fractures identified by densitometric lateral spine imaging predict incident major osteoporotic fracture independently of clinical risk factors and bone mineral density in older women. J Bone Miner Res. October 2020;35(10):1942-1951.
2023	Cosman F, Hans D, Shevroja E, Wang Y, Mitlak B. Effect of abaloparatide on bone microarchitecture assessed by trabecular bone score in women with osteoporosis: post hoc analysis of ACTIVE and ACTIVExtend. J Bone Miner Res. April 2023;38(4):464-470.
2019	Compston JE, McClung MR, Leslie WD. Osteoporosis. Lancet. January 26, 2019;393(10169):364-376.
2019	Kanis JA, Cooper C, Rizzoli R, Reginster J-Y; Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO); Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. January 2019;30(1):3-44.
2020	Kanis JA, Harvey NC, McCloskey E, Bruyère O, Veronese N, Lorentzon M, Cooper C, Rizzoli R, Adib G, Al-Daghri N, Campusano C, Chandran M, Dawson-Hughes B, Javaid K, Jiwa F, Johansson H, Lee JK, Liu E, Messina D, Mkinsi O, Pinto D, Prieto-Alhambra D, Saag K, Xia W, Zakraoui L, Reginster J-Y. Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures. Osteoporos Int. January 2020;31(1):1-12.
2020	Borgen TT, Bjørnerem Å, Solberg LB, Andreasen C, Brunborg C, Stenbro M-B, Hübschle LM, Figved W, Apalset EM, Gjertsen J-E, Basso T, Lund I, Hansen AK, Stutzer J-M, Dahl C, Nordsletten L, Frihagen F, Eriksen EF. Determinants of trabecular bone score and prevalent vertebral fractures in women with fragility fractures: a cross-sectional sub-study of NoFRACT. Osteoporos Int. March 2020;31(3):505-514.
2020	Matsumoto H, Tanimura C, Kushida D, Osaka H, Kawabata Y, Hagino H. FRAX score and recent fall history predict the incidence for sarcopenia in community-dwelling older adults: a prospective cohort study. Osteoporos Int. October 2020;31(10):1985-1994.
2020	Binkley N, Morin SN, Martineau P, Lix LM, Hans D, Leslie WD. Frequency of normal bone measurement in postmenopausal women with fracture: a registry-based cohort study. Osteoporos Int. December 2020;31(12):2337-2344.
2021	Saito S, Koga E, Okada Y, Tsuburai T, Yoshikata H, Miyagi E, Sakakibara H. Effects of age at estrogen replacement therapy initiation on trabecular bone score in Japanese adults with Turner syndrome. Osteoporos Int. April 2021;32(4):671-680.
2021	Burden AM, Tanaka Y, Xu L, Ha Y-C, McCloskey E, Cummings SR, Glüer CC. Osteoporosis case ascertainment strategies in European and Asian countries: a comparative review. Osteoporos Int. May 2021;32(5):817-829.
2021	Hsu Y, Hsieh T-J, Ho C-H, Lin C-H, Chen CK-H. Effect of compression fracture on trabecular bone score at lumbar spine. Osteoporos Int. May 2021;32(5):961-970.
2016	Oei L. Epidemiological, Radiological and Genetic Aspects of Endocrine Bone Diseases [PhD thesis]. Erasmus University Rotterdam; December 14, 2016.
2020	Axelsson KF. Aspects of Fracture Prevention: The Role of Fracture Liaison Services and Alendronate [PhD thesis]. University of Gothenburg; 2020.
2021	Sfeir JG. Assessment of Skeletal Fragility: Beyond Areal Bone Mineral Density [Master's thesis]. Rochester, MN: Mayo Clinic College of Medicine and Science; June 2021.
2017	Kreipke TC. Structural, Mechanical, and Biological Relationships of Trabecular Bone in Osteoporosis [PhD thesis]. University of Notre Dame; April 2017.
2020	Dwyer MP. The Effect of Loss of Estrogen on Trabecular Bone Score in Women At Increased Risk of Breast Cancer [Master's thesis]. University of Toronto; 2020.
2022	Ponzano M. Risk Assessment and Interventions for Individuals At Risk of Osteoporotic Fractures [PhD thesis]. University of Waterloo; 2022.
2018	Creecy A. Age- and Diabetes-Related Changes in the Matrix and Fracture Resistance of Bone [PhD thesis]. Nashville, TN: Vanderbilt University; August 10, 2018.
2020	Long EB. The Effect of Staphylococcus Aureus* Exposure on White-Tailed Deer Trabecular Bone Stiffness and Yield* [Master's thesis]. Rock Hill, SC: Winthrop University; May 2020.