Abstract
Summary
We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures.
Introduction
The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors.
Methods
A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible.
Results
Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed.
Conclusions
These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).
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References
Kanis JA on behalf of the World Health Organization Scientific Group (2007) Assessment of osteoporosis at the primary health care level. Technical Report. World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK Available at: https://www.sheffield.ac.uk/FRAX/pdfs/WHO_Technical_Report.pdf (Accessed December 23, 2020)
Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E (2008) FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 19:385–397
Kanis JA, Harvey NC, Cooper C, Johansson H, Oden A, McCloskey EV, Advisory Board of the National Osteoporosis Guideline G (2016) 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 11:25
Kanis JA, Harvey NC, Johansson H, Liu E, Vandenput L, Lorentzon M, Leslie WD, McCloskey EV (2020) A decade of FRAX: how has it changed the management of osteoporosis? Aging Clin Exp Res 32:187–196
Kanis JA, Johansson H, Harvey NC, Gudnason V, Sigurdsson G, Siggeirsdottir K, Lorentzon M, Liu E, Vandenput L, McCloskey EV (2020) Adjusting conventional FRAX estimates of fracture probability according to the recency of sentinel fractures. Osteoporos Int 31:1817–1828
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, Gluer C, Goltzman D, Hans D, Krieg MA, La Croix A, McCloskey E, Mellstrom D, Melton LJ 3rd, Pols H, Reeve J, Sanders K, Schott AM, Silman A, Torgerson D, van Staa T, Watts NB, Yoshimura N (2007) 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 18:1033–1046
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hrobjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71
Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A (2016) Rayyan-a web and mobile app for systematic reviews. Syst Rev 5:210
Sigurdsson G, Aspelund T, Chang M, Jonsdottir B, Sigurdsson S, Eiriksdottir G, Gudmundsson A, Harris TB, Gudnason V, Lang TF (2006) Increasing sex difference in bone strength in old age: the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-REYKJAVIK). Bone 39:644–651
Harris TB, Launer LJ, Eiriksdottir G, Kjartansson O, Jonsson PV, Sigurdsson G, Thorgeirsson G, Aspelund T, Garcia ME, Cotch MF, Hoffman HJ, Gudnason V (2007) Age, Gene/Environment Susceptibility-Reykjavik Study: multidisciplinary applied phenomics. Am J Epidemiol 165:1076–1087
Fujiwara S, Kasagi F, Yamada M, Kodama K (1997) Risk factors for hip fracture in a Japanese cohort. J Bone Miner Res 12:998–1004
Fujiwara S, Kasagi F, Masunari N, Naito K, Suzuki G, Fukunaga M (2003) Fracture prediction from bone mineral density in Japanese men and women. J Bone Miner Res 18:1547–1553
Macdonald HM, McGuigan FE, Stewart A, Black AJ, Fraser WD, Ralston S, Reid DM (2006) Large-scale population-based study shows no evidence of association between common polymorphism of the VDR gene and BMD in British women. J Bone Miner Res 21:151–162
Dobnig H, Piswanger-Solkner JC, Roth M, Obermayer-Pietsch B, Tiran A, Strele A, Maier E, Maritschnegg P, Sieberer C, Fahrleitner-Pammer A (2006) Type 2 diabetes mellitus in nursing home patients: effects on bone turnover, bone mass, and fracture risk. J Clin Endocrinol Metab 91:3355–3363
Ostovar A, Nabipour I, Larijani B, Heshmat R, Darabi H, Vahdat K, Ravanipour M, Mehrdad N, Raeisi A, Heidari G, Shafiee G, Haeri M, Pourbehi M, Sharifi F, Noroozi A, Tahmasebi R, Aghaei Meybodi H, Assadi M, Farrokhi S, Nemati R, Amini MR, Barekat M, Amini A, Salimipour H, Dobaradaran S, Moshtaghi D (2015) Bushehr Elderly Health (BEH) Programme, phase I (cardiovascular system). BMJ Open 5:e009597
Shafiee G, Ostovar A, Heshmat R, Darabi H, Sharifi F, Raeisi A, Mehrdad N, Shadman Z, Razi F, Amini MR, Arzaghi SM, Meybodi HA, Soltani A, Nabipour I, Larijani B (2017) Bushehr Elderly Health (BEH) programme: study protocol and design of musculoskeletal system and cognitive function (stage II). BMJ Open 7:e013606
Kreiger N, Tenenhouse A, Joseph L, Mackenzie T, Poliquin S, Brown JP, Prior JC, Rittmaster RS (1999) The Canadian Multicentre Osteoporosis Study (CaMos): background, rationale, methods. Can J Aging 18:376–387
Jones G, Nguyen T, Sambrook PN, Kelly PJ, Gilbert C, Eisman JA (1994) Symptomatic fracture incidence in elderly men and women: the Dubbo Osteoporosis Epidemiology Study (DOES). Osteoporos Int 4:277–282
Bischoff-Ferrari HA, Molino C, Rival S, Vellas B, Rizzoli R, Kressig RW, Kanis JA, Manson JE, Dawson-Hughes B, Orav EJ, da Silva JAP, Blauth M, Felsenberg D, Ferrari SM, Theiler R, Egli A, Group D-HR (2021) DO-HEALTH: Vitamin D3 - Omega3 - Home Exercise - Healthy Aging And Longevity Trial - design of a multinational clinical trial on healthy aging among European seniors. Contemp Clin Trials 100
Bischoff-Ferrari HA, Vellas B, Rizzoli R, Kressig RW, da Silva JAP, Blauth M, Felson DT, McCloskey EV, Watzl B, Hofbauer LC, Felsenberg D, Willett WC, Dawson-Hughes B, Manson JE, Siebert U, Theiler R, Staehelin HB, de GodoiRezende Costa Molino C, Chocano-Bedoya PO, Abderhalden LA, Egli A, Kanis JA, Orav EJ, Group D-HR (2020) Effect of vitamin D supplementation, omega-3 fatty acid supplementation, or a strength-training exercise program on clinical outcomes in older adults: the DO-HEALTH randomized clinical trial. JAMA 324:1855–1868
Hernandez JL, Marin F, Gonzalez-Macias J, Diez-Perez A, Vila J, Gimenez S, Galan B, Arenas MS, Suarez F, Gayola L, Guillen G, Sagredo T, Belenguer R, Moron A, Arriaza E, ECOSAP study investigators (2004) Discriminative capacity of calcaneal quantitative ultrasound and of osteoporosis and fracture risk factors in postmenopausal women with osteoporotic fractures. Calcif Tissue Int 74:357–365
Diez-Perez A, Gonzalez-Macias J, Marin F, Abizanda M, Alvarez R, Gimeno A, Pegenaute E, Vila J, Osea E, enAtencionPrimaria study i, (2007) Prediction of absolute risk of non-spinal fractures using clinical risk factors and heel quantitative ultrasound. Osteoporos Int 18:629–639
Day NOS, Luben R, Khaw KT, Bingham S, Welch A, Wareham N (1999) EPIC-Norfolk: study design and characteristics of the cohort. Br J Cancer 80(Suppl 1):95–103
Khaw KT, Reeve J, Luben R, Bingham S, Welch A, Wareham N, Oakes S, Day N (2004) Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus: EPIC-Norfolk prospective population study. Lancet 363:197–202
Dargent-Molina P, Favier F, Grandjean H, Baudoin C, Schott AM, Hausherr E, Meunier PJ, Breart G (1996) Fall-related factors and risk of hip fracture: the EPIDOS prospective study. Lancet 348:145–149
Schott AM, Cormier C, Hans D, Favier F, Hausherr E, Dargent-Molina P, Delmas PD, Ribot C, Sebert JL, Breart G, Meunier PJ (1998) How hip and whole-body bone mineral density predict hip fracture in elderly women: the EPIDOS prospective study. Osteoporos Int 8:247–254
Zwart M, Azagra R, Tranche S, Gil Y, Tudela N, Quiñones O, Alonso J, Alvarez G, Saez M, Aguye A, Martin C, Gabriel P (2021) Epidemiology of osteoporotic fractures and subsequent fractures in the Asturian Region of Spain. the EPIFROS cohort. Osteoporos Int 32:in press
Zwart M, Azagra R, Aguye A, Tranche S, Saez M, Alvarez G, Alonso J, Qui√±ones O, Tudela N, Gil Y, Martin C, Diaz-Herrera MA, Gabriel P (2021) FRAX® predictive ability to predict major osteoporotic fractures and hip fractures in the Spanish population. the EPIFROS Asturias cohort. Osteoporos Int 32:in press
O’Neill TW, Felsenberg D, Varlow J, Cooper C, Kanis JA, Silman AJ (1996) The prevalence of vertebral deformity in european men and women: the European Vertebral Osteoporosis Study. J Bone Miner Res 11:1010–1018
European Prospective Osteoporosis Study Group, Felsenberg D, Silman AJ, Lunt M, Armbrecht G, Ismail AA, Finn JD, Cockerill WC, Banzer D, Benevolenskaya LI, Bhalla A, Bruges Armas J, Cannata JB, Cooper C, Dequeker J, Eastell R, Felsch B, Gowin W, Havelka S, Hoszowski K, Jajic I, Janott J, Johnell O, Kanis JA, Kragl G, Lopes Vaz A, Lorenc R, Lyritis G, Masaryk P, Matthis C, Miazgowski T, Parisi G, Pols HA, Poor G, Raspe HH, Reid DM, Reisinger W, Schedit-Nave C, Stepan JJ, Todd CJ, Weber K, Woolf AD, Yershova OB, Reeve J, O’Neill TW (2002) Incidence of vertebral fracture in europe: results from the European Prospective Osteoporosis Study (EPOS). J Bone Miner Res 17:716–724
Ismail AA, Pye SR, Cockerill WC, Lunt M, Silman AJ, Reeve J, Banzer D, Benevolenskaya LI, Bhalla A, Bruges Armas J, Cannata JB, Cooper C, Delmas PD, Dequeker J, Dilsen G, Falch JA, Felsch B, Felsenberg D, Finn JD, Gennari C, Hoszowski K, Jajic I, Janott J, Johnell O, Kanis JA, Kragl G, Lopez Vaz A, Lorenc R, Lyritis G, Marchand F, Masaryk P, Matthis C, Miazgowski T, Naves-Diaz M, Pols HA, Poor G, Rapado A, Raspe HH, Reid DM, Reisinger W, Scheidt-Nave C, Stepan J, Todd C, Weber K, Woolf AD, O’Neill TW (2002) Incidence of limb fracture across Europe: results from the European Prospective Osteoporosis Study (EPOS). Osteoporos Int 13:565–571
Iki M, Fujita Y, Tamaki J, Kouda K, Yura A, Kadowaki E, Sato Y, Moon JS, Okamoto N, Kurumatani N, Study Group for Functioning C, Quality of Life in Elderly J (2009) Design and baseline characteristics of a prospective cohort study for determinants of osteoporotic fracture in community-dwelling elderly Japanese men: the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study. BMC Musculoskelet Disord 10:165
Fujita Y, Tamaki J, Kouda K, Yura A, Sato Y, Tachiki T, Hamada M, Kajita E, Kamiya K, Kaji K, Tsuda K, Ohara K, Moon JS, Kitagawa J, Iki M, group Fs, (2021) Determinants of bone health in elderly Japanese men: study design and key findings of the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) cohort study. Environ Health Prev Med 26:51
Berry SD, Samelson EJ, Pencina MJ, McLean RR, Cupples LA, Broe KE, Kiel DP (2013) Repeat bone mineral density screening and prediction of hip and major osteoporotic fracture. JAMA 310:1256–1262
Hannan MT, Weycker D, McLean RR, Sahni S, Bornheimer R, Barron R, Travison TG, Kiel DP (2019) Predictors of imminent risk of nonvertebral fracture in older, high-risk women: the Framingham Osteoporosis Study. JBMR Plus 3:e10129
Feinleib M, Kannel WB, Garrison RJ, McNamara PM, Castelli WP (1975) The Framingham Offspring Study. Design and preliminary data Prev Med 4:518–525
Azagra R, Roca G, Encabo G, Prieto D, Aguye A, Zwart M, Guell S, Puchol N, Gene E, Casado E, Sancho P, Sola S, Toran P, Iglesias M, Sabate V, Lopez-Exposito F, Ortiz S, Fernandez Y, Diez-Perez A (2011) Prediction of absolute risk of fragility fracture at 10 years in a Spanish population: validation of the WHO FRAX tool in Spain. BMC Musculoskelet Disord 12:30
Azagra R, Roca G, Encabo G, Aguye A, Zwart M, Guell S, Puchol N, Gene E, Casado E, Sancho P, Sola S, Toran P, Iglesias M, Gisbert MC, Lopez-Exposito F, Pujol-Salud J, Fernandez-Hermida Y, Puente A, Rosas M, Bou V, Anton JJ, Lansdberg G, Martin-Sanchez JC, Diez-Perez A, Prieto-Alhambra D (2012) FRAX(R) tool, the WHO algorithm to predict osteoporotic fractures: the first analysis of its discriminative and predictive ability in the Spanish FRIDEX cohort. BMC Musculoskelet Disord 13:204
Azagra R, Zwart M, Aguye A, Martin-Sanchez JC, Casado E, Diaz-Herrera MA, Morina D, Cooper C, Diez-Perez A, Dennison EM, Groimap,Group FS (2016) Fracture experience among participants from the FROCAT study: what thresholding is appropriate using the FRAX tool? Maturitas 83:65–71
Hars M, Biver E, Chevalley T, Herrmann F, Rizzoli R, Ferrari S, Trombetti A (2016) Low lean mass predicts incident fractures independently from FRAX: a prospective cohort study of recent retirees. J Bone Miner Res 31:2048–2056
Hooven FH, Adachi JD, Adami S, Boonen S, Compston J, Cooper C, Delmas P, Diez-Perez A, Gehlbach S, Greenspan SL, LaCroix A, Lindsay R, Netelenbos JC, Pfeilschifter J, Roux C, Saag KG, Sambrook P, Silverman S, Siris E, Watts NB, Anderson FA Jr (2009) The Global Longitudinal Study of Osteoporosis in Women (GLOW): rationale and study design. Osteoporos Int 20:1107–1116
Pasco JA, Nicholson GC, Kotowicz MA (2012) Cohort profile: Geelong Osteoporosis Study. Int J Epidemiol 41:1565–1575
Svanborg A (1977) Seventy-year-old people in Gothenburg a population study in an industrialized Swedish city. II. General presentation of social and medical conditions. Acta Med Scand Suppl 611:5–37
Johansson C, Black D, Johnell O, Oden A, Mellstrom D (1998) Bone mineral density is a predictor of survival. Calcif Tissue Int 63:190–196
Stenström M, Olsson J-O, Mellström D (2000) Thyroid hormone replacement is not related to increased risk of osteoporosis. Osteoporos Int 11:S114
Johansson J, Nordstrom A, Nordstrom P (2015) Objectively measured physical activity is associated with parameters of bone in 70-year-old men and women. Bone 81:72–79
Syddall HE, Aihie Sayer A, Dennison EM, Martin HJ, Barker DJ, Cooper C (2005) Cohort profile: the Hertfordshire Cohort Study. Int J Epidemiol 34:1234–1242
Visser M, Kritchevsky SB, Goodpaster BH, Newman AB, Nevitt M, Stamm E, Harris TB (2002) Leg muscle mass and composition in relation to lower extremity performance in men and women aged 70 to 79: the Health, Aging and Body Composition study. J Am Geriatr Soc 50:897–904
Krokstad S, Langhammer A, Hveem K, Holmen TL, Midthjell K, Stene TR, Bratberg G, Heggland J, Holmen J (2013) Cohort profile: the HUNT study, Norway. Int J Epidemiol 42:968–977
Gulati AM, Hoff M, Salvesen O, Dhainaut A, Semb AG, Kavanaugh A, Haugeberg G (2017) Bone mineral density in patients with psoriatic arthritis: data from the Nord-Trondelag Health Study 3. RMD Open 3:e000413
Iki M, Tamaki J, Sato Y, Morita A, Ikeda Y, Kajita E, Nishino H, Akiba T, Matsumoto T, Kagamimori S, Kagawa Y, Yoneshima H, Matsukura T, Yamagami T, Kitagawa J, Group JS (2015) Cohort profile: the Japanese Population-based Osteoporosis (JPOS) Cohort Study. Int J Epidemiol 44:405–414
Pluijm SM, Visser M, Smit JH, Popp-Snijders C, Roos JC, Lips P (2001) Determinants of bone mineral density in older men and women: body composition as mediator. J Bone Miner Res 16:2142–2151
Huisman M, Poppelaars J, van der Horst M, Beekman AT, Brug J, van Tilburg TG, Deeg DJ (2011) Cohort profile: the Longitudinal Aging Study Amsterdam. Int J Epidemiol 40:868–876
Hoogendijk EO, Deeg DJH, de Breij S, Klokgieters SS, Kok AAL, Stringa N, Timmermans EJ, van Schoor NM, van Zutphen EM, van der Horst M, Poppelaars J, Malhoe P, Huisman M (2020) The Longitudinal Aging Study Amsterdam: cohort update 2019 and additional data collections. Eur J Epidemiol 35:61–74
Goldshtein I, Gerber Y, Ish-Shalom S, Leshno M (2018) Fracture risk assessment with FRAX using real-world data in a population-based cohort from Israel. Am J Epidemiol 187:94–102
Leslie WD, MacWilliam L, Lix L, Caetano P, Finlayson GS (2005) A population-based study of osteoporosis testing and treatment following introduction of a new bone densitometry service. Osteoporos Int 16:773–782
Leslie WD, Caetano PA, Macwilliam LR, Finlayson GS (2005) Construction and validation of a population-based bone densitometry database. J Clin Densitom 8:25–30
Szulc P, Munoz F, Duboeuf F, Marchand F, Delmas PD (2005) Bone mineral density predicts osteoporotic fractures in elderly men: the MINOS study. Osteoporos Int 16:1184–1192
Yoshimura N, Kinoshita H, Danjoh S, Takijiri T, Morioka S, Kasamatsu T, Sakata K, Hashimoto T (2002) Bone loss at the lumbar spine and the proximal femur in a rural Japanese community, 1990–2000: the Miyama study. Osteoporos Int 13:803–808
Kwok T, Khoo CC, Leung J, Kwok A, Qin L, Woo J, Leung PC (2012) Predictive values of calcaneal quantitative ultrasound and dual energy X ray absorptiometry for non-vertebral fracture in older men: results from the MrOS study (Hong Kong). Osteoporos Int 23:1001–1006
Kwok AW, Gong JS, Wang YX, Leung JC, Kwok T, Griffith JF, Leung PC (2013) Prevalence and risk factors of radiographic vertebral fractures in elderly Chinese men and women: results of Mr. OS (Hong Kong) and Ms. OS (Hong Kong) studies. Osteoporos Int 24:877–885
Mellstrom D, Johnell O, Ljunggren O, Eriksson AL, Lorentzon M, Mallmin H, Holmberg A, Redlund-Johnell I, Orwoll E, Ohlsson C (2006) Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden. J Bone Miner Res 21:529–535
Jutberger H, Lorentzon M, Barrett-Connor E, Johansson H, Kanis JA, Ljunggren O, Karlsson MK, Rosengren BE, Redlund-Johnell I, Orwoll E, Ohlsson C, Mellstrom D (2010) Smoking predicts incident fractures in elderly men: Mr OS Sweden. J Bone Miner Res 25:1010–1016
Blank JB, Cawthon PM, Carrion-Petersen ML, Harper L, Johnson JP, Mitson E, Delay RR (2005) Overview of recruitment for the Osteoporotic Fractures in Men Study (MrOS). Contemp Clin Trials 26:557–568
Orwoll E, Blank JB, Barrett-Connor E, Cauley J, Cummings S, Ensrud K, Lewis C, Cawthon PM, Marcus R, Marshall LM, McGowan J, Phipps K, Sherman S, Stefanick ML, Stone K (2005) Design and baseline characteristics of the Osteoporotic Fractures in Men (MrOS) Study–a large observational study of the determinants of fracture in older men. Contemp Clin Trials 26:569–585
Wong SY, Kwok T, Woo J, Lynn H, Griffith JF, Leung J, Tang YY, Leung PC (2005) Bone mineral density and the risk of peripheral arterial disease in men and women: results from Mr. and Ms Os. Hong Kong Osteoporos Int 16:1933–1938
NHEFS The NHANES I Epidemiologic Follow-up Study. https://www.ncdc.gov/nchs/nhanes/nhefs/defaultaspx (Accessed January 30, 2021)
Garnero P, Sornay-Rendu E, Chapuy MC, Delmas PD (1996) Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 11:337–349
Gerdhem P, Ringsberg KA, Obrant KJ, Akesson K (2005) Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women. Osteoporos Int 16:1425–1431
Gluer CC, Eastell R, Reid DM, Felsenberg D, Roux C, Barkmann R, Timm W, Blenk T, Armbrecht G, Stewart A, Clowes J, Thomasius FE, Kolta S (2004) Association of five quantitative ultrasound devices and bone densitometry with osteoporotic vertebral fractures in a population-based sample: the OPUS study. J Bone Miner Res 19:782–793
Lamy O, Krieg M-A, Stoll D, Aubry-Rozier B, Metzger M, Hans D (2012) The OsteoLaus cohort study. Osteologie 21:77–82
Shevroja E, Marques-Vidal P, Aubry-Rozier B, Hans G, Rivadeneira F, Lamy O, Hans D (2019) Cohort profile: the OsteoLaus study. Int J Epidemiol 48:1046–1047g
Honkanen R, Kroger H, Tuppurainen M, Alhava E, Saarikoski S (1995) Fractures and low axial bone density in perimenopausal women. J Clin Epidemiol 48:881–888
Sund R, Honkanen R, Johansson H, Oden A, McCloskey E, Kanis J, Kroger H (2014) Evaluation of the FRAX model for hip fracture predictions in the population-based Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE). Calcif Tissue Int 95:39–45
Bagger YZ, Tanko LB, Alexandersen P, Hansen HB, Mollgaard A, Ravn P, Qvist P, Kanis JA, Christiansen C (2004) Two to three years of hormone replacement treatment in healthy women have long-term preventive effects on bone mass and osteoporotic fractures: the PERF study. Bone 34:728–735
Cockayne S, Adamson J, Clarke A, Corbacho B, Fairhurst C, Green L, Hewitt CE, Hicks K, Kenan AM, Lamb SE, McIntosh C, Menz HB, Redmond AC, Richardson Z, Rodgers S, Vernon W, Watson J, Torgerson DJ, study R, (2017) Cohort randomised controlled trial of a multifaceted podiatry intervention for the prevention of falls in older people (the REFORM trial). PLoS ONE 12:e0168712
Melton LJ 3rd, Crowson CS, O’Fallon WM, Wahner HW, Riggs BL (2003) Relative contributions of bone density, bone turnover, and clinical risk factors to long-term fracture prediction. J Bone Miner Res 18:312–318
Melton LJ 3rd, Atkinson EJ, O’Connor MK, O’Fallon WM, Riggs BL (1998) Bone density and fracture risk in men. J Bone Miner Res 13:1915–1923
Hofman A, Grobbee DE, de Jong PT, van den Ouweland FA (1991) Determinants of disease and disability in the elderly: the Rotterdam Elderly Study. Eur J Epidemiol 7:403–422
De Laet CE, Van Hout BA, Burger H, Weel AE, Hofman A, Pols HA (1998) Hip fracture prediction in elderly men and women: validation in the Rotterdam Study. J Bone Miner Res 13:1587–1593
Schuit SC, van der Klift M, Weel AE, de Laet CE, Burger H, Seeman E, Hofman A, Uitterlinden AG, van Leeuwen JP, Pols HA (2004) Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone 34:195–202
Ikram MA, Brusselle GGO, Murad SD, van Duijn CM, Franco OH, Goedegebure A, Klaver CCW, Nijsten TEC, Peeters RP, Stricker BH, Tiemeier H, Uitterlinden AG, Vernooij MW, Hofman A (2017) The Rotterdam Study: 2018 update on objectives, design and main results. Eur J Epidemiol 32:807–850
Ikram MA, Brusselle G, Ghanbari M, Goedegebure A, Ikram MK, Kavousi M, Kieboom BCT, Klaver CCW, de Knegt RJ, Luik AI, Nijsten TEC, Peeters RP, van Rooij FJA, Stricker BH, Uitterlinden AG, Vernooij MW, Voortman T (2020) Objectives, design and main findings until 2020 from the Rotterdam Study. Eur J Epidemiol 35:483–517
Marques A, Lucas R, Simoes E, Verstappen SMM, Jacobs JWG, da Silva JAP (2017) Do we need bone mineral density to estimate osteoporotic fracture risk? A 10-year prospective multicentre validation study. RMD Open 3:e000509
Beaudart C, Reginster JY, Petermans J, Gillain S, Quabron A, Locquet M, Slomian J, Buckinx F, Bruyere O (2015) Quality of life and physical components linked to sarcopenia: the SarcoPhAge study. Exp Gerontol 69:103–110
Koh WP, Wu AH, Wang R, Ang LW, Heng D, Yuan JM, Yu MC (2009) Gender-specific associations between soy and risk of hip fracture in the Singapore Chinese Health Study. Am J Epidemiol 170:901–909
Dai Z, Wang R, Ang LW, Low YL, Yuan JM, Koh WP (2014) Protective effects of dietary carotenoids on risk of hip fracture in men: the Singapore Chinese Health Study. J Bone Miner Res 29:408–417
Shepstone L, Fordham R, Lenaghan E, Harvey I, Cooper C, Gittoes N, Heawood A, Peters T, O’Neill T, Torgerson D, Holland R, Howe A, Marshall T, Kanis J, McCloskey E (2012) A pragmatic randomised controlled trial of the effectiveness and cost-effectiveness of screening older women for the prevention of fractures: rationale, design and methods for the SCOOP study. Osteoporos Int 23:2507–2515
Shepstone L, Lenaghan E, Cooper C, Clarke S, Fong-Soe-Khioe R, Fordham R, Gittoes N, Harvey I, Harvey N, Heawood A, Holland R, Howe A, Kanis J, Marshall T, O’Neill T, Peters T, Redmond N, Torgerson D, Turner D, McCloskey E, Team SS (2018) Screening in the community to reduce fractures in older women (SCOOP): a randomised controlled trial. Lancet 391:741–747
Popp AW, Senn C, Franta O, Krieg MA, Perrelet R, Lippuner K (2009) Tibial or hip BMD predict clinical fracture risk equally well: results from a prospective study in 700 elderly Swiss women. Osteoporos Int 20:1393–1399
Krieg MA, Cornuz J, Ruffieux C, Van Melle G, Buche D, Dambacher MA, Hans D, Hartl F, Hauselmann HJ, Kraenzlin M, Lippuner K, Neff M, Pancaldi P, Rizzoli R, Tanzi F, Theiler R, Tyndall A, Wimpfheimer C, Burckhardt P (2006) Prediction of hip fracture risk by quantitative ultrasound in more than 7000 Swiss women > or =70 years of age: comparison of three technologically different bone ultrasound devices in the SEMOF study. J Bone Miner Res 21:1457–1463
Johansson H, Oden A, Johnell O, Jonsson B, de Laet C, Oglesby A, McCloskey EV, Kayan K, Jalava T, Kanis JA (2004) Optimization of BMD measurements to identify high risk groups for treatment–a test analysis. J Bone Miner Res 19:906–913
McCloskey EV, Beneton M, Charlesworth D, Kayan K, deTakats D, Dey A, Orgee J, Ashford R, Forster M, Cliffe J, Kersh L, Brazier J, Nichol J, Aropuu S, Jalava T, Kanis JA (2007) Clodronate reduces the incidence of fractures in community-dwelling elderly women unselected for osteoporosis: results of a double-blind, placebo-controlled randomized study. J Bone Miner Res 22:135–141
Cummings SR, Black DM, Nevitt MC, Browner WS, Cauley JA, Genant HK, Mascioli SR, Scott JC, Seeley DG, Steiger P et al (1990) Appendicular bone density and age predict hip fracture in women. The Study of Osteoporotic Fractures Research Group. JAMA 263:665–668
Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, Cauley J, Black D, Vogt TM (1995) Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med 332:767–773
Elders PJM, Merlijn T, Swart KMA, van Hout W, van der Zwaard BC, Niemeijer C, Heymans MW, van der Heijden AA, Rutters F, van der Horst HE, Lips P, Netelenbos JC, van Schoor NM (2017) Design of the SALT Osteoporosis Study: a randomised pragmatic trial, to study a primary care screening and treatment program for the prevention of fractures in women aged 65 years or older. BMC Musculoskelet Disord 18:424
Merlijn T, Swart KM, van Schoor NM, Heymans MW, van der Zwaard BC, van der Heijden AA, Rutters F, Lips P, van der Horst HE, Niemeijer C, Netelenbos JC, Elders PJ (2019) The effect of a screening and treatment program for the prevention of fractures in older women: a randomized pragmatic trial. J Bone Miner Res 34:1993–2000
Dawson-Hughes B, Harris SS, Krall EA, Dallal GE (1997) Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 337:670–676
Szulc P, Boutroy S, Vilayphiou N, Chaitou A, Delmas PD, Chapurlat R (2011) Cross-sectional analysis of the association between fragility fractures and bone microarchitecture in older men: the STRAMBO study. J Bone Miner Res 26:1358–1367
Nilsson AG, Sundh D, Johansson L, Nilsson M, Mellstrom D, Rudang R, Zoulakis M, Wallander M, Darelid A, Lorentzon M (2017) Type 2 diabetes mellitus is associated with better bone microarchitecture but lower bone material strength and poorer physical function in elderly women: a population-based study. J Bone Miner Res 32:1062–1071
Lorentzon M, Nilsson AG, Johansson H, Kanis JA, Mellstrom D, Sundh D (2019) Extensive undertreatment of osteoporosis in older Swedish women. Osteoporos Int 30:1297–1305
Johansson L, Sundh D, Magnusson P, Rukmangatharajan K, Mellstrom D, Nilsson AG, Lorentzon M (2020) 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 35:1942–1951
Scott D, Blizzard L, Fell J, Giles G, Jones G (2010) Associations between dietary nutrient intake and muscle mass and strength in community-dwelling older adults: the Tasmanian Older Adult Cohort study. J Am Geriatr Soc 58:2129–2134
Cervo MM, Shivappa N, Hebert JR, Oddy WH, Winzenberg T, Balogun S, Wu F, Ebeling P, Aitken D, Jones G, Scott D (2020) Longitudinal associations between dietary inflammatory index and musculoskeletal health in community-dwelling older adults. Clin Nutr 39:516–523
Walley T, Mantgani A (1997) The UK general practice research database. Lancet 350:1097–1099
van Staa TP, Geusens P, Kanis JA, Leufkens HG, Gehlbach S, Cooper C (2006) A simple clinical score for estimating the long-term risk of fracture in post-menopausal women. QJM 99:673–682
Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, Downey P, Elliott P, Green J, Landray M, Liu B, Matthews P, Ong G, Pell J, Silman A, Young A, Sprosen T, Peakman T, Collins R (2015) UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med 12:e1001779
Littlejohns TJ, Holliday J, Gibson LM, Garratt S, Oesingmann N, Alfaro-Almagro F, Bell JD, Boultwood C, Collins R, Conroy MC, Crabtree N, Doherty N, Frangi AF, Harvey NC, Leeson P, Miller KL, Neubauer S, Petersen SE, Sellors J, Sheard S, Smith SM, Sudlow CLM, Matthews PM, Allen NE (2020) The UK Biobank imaging enhancement of 100,000 participants: rationale, data collection, management and future directions. Nat Commun 11:2624
WHI The Women’s Health Initiative Study Group (1998) Design of the Women’s Health Initiative clinical trial and observational study. Control Clin Trials 19:61–109
Hays J, Hunt JR, Hubbell FA, Anderson GL, Limacher M, Allen C, Rossouw JE (2003) The Women’s Health Initiative recruitment methods and results. Ann Epidemiol 13:S18-77
Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, LeBoff M, Lewis CE, McGowan J, Neuner J, Pettinger M, Stefanick ML, Wactawski-Wende J, Watts NB, Women’s Health Initiative I (2003) Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women’s Health Initiative randomized trial. JAMA 290:1729–1738
Birks YF, Porthouse J, Addie C, Loughney K, Saxon L, Baverstock M, Francis RM, Reid DM, Watt I, Torgerson DJ, Trial PCHP, G, (2004) Randomized controlled trial of hip protectors among women living in the community. Osteoporos Int 15:701–706
Mann R, Birks Y, Hall J, Torgerson D, Watt I (2006) Exploring the relationship between fear of falling and neuroticism: a cross-sectional study in community-dwelling women over 70. Age Ageing 35:143–147
Lu Y, Fuerst T, Hui S, Genant HK (2001) Standardization of bone mineral density at femoral neck, trochanter and Ward’s triangle. Osteoporos Int 12:438–444
Looker AC, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP, Johnston CC Jr, Lindsay R (1998) Updated data on proximal femur bone mineral levels of US adults. Osteoporos Int 8:468–489
Binkley N, Kiebzak GM, Lewiecki EM, Krueger D, Gangnon RE, Miller PD, Shepherd JA, Drezner MK (2005) Recalculation of the NHANES database SD improves T-score agreement and reduces osteoporosis prevalence. J Bone Miner Res 20:195–201
Kanis JA, Johanson H, Harvey NC, Gudnason V, Sigurdsson G, Siggeirsdottir K, Lorentzon M, Liu E, Vandenput L, McCloskey E (2021) The effect on subsequent fracture risk of age, sex and prior fracture site by recency of prior fracture. Osteoporos Int 32:1547–1555
Kanis JA, McCloskey E, Johansson H, Oden A, Leslie WD (2012) FRAX((R)) with and without bone mineral density. Calcif Tissue Int 90:1–13
Strom O, Lauppe R, Ljunggren O, Spangeus A, Ortsater G, O’Kelly J, Akesson K (2020) Real-world effectiveness of osteoporosis treatment in the oldest old. Osteoporos Int 31:1525–1533
Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes–a meta-analysis. Osteoporos Int 18:427–444
Vilaca T, Schini M, Harnan S, Sutton A, Poku E, Allen IE, Cummings SR, Eastell R (2020) The risk of hip and non-vertebral fractures in type 1 and type 2 diabetes: a systematic review and meta-analysis update. Bone 137:115457
Bai J, Gao Q, Wang C, Dai J (2020) Diabetes mellitus and risk of low-energy fracture: a meta-analysis. Aging Clin Exp Res 32:2173–2186
Kanis JA, Hans D, Cooper C, Baim S, Bilezikian JP, Binkley N, Cauley JA, Compston JE, Dawson-Hughes B, El-Hajj Fuleihan G, Johansson H, Leslie WD, Lewiecki EM, Luckey M, Oden A, Papapoulos SE, Poiana C, Rizzoli R, Wahl DA, McCloskey EV, Task Force of the FI (2011) Interpretation and use of FRAX in clinical practice. Osteoporos Int 22:2395–2411
Schwartz AV, Vittinghoff E, Bauer DC, Hillier TA, Strotmeyer ES, Ensrud KE, Donaldson MG, Cauley JA, Harris TB, Koster A, Womack CR, Palermo L, Black DM, Study of Osteoporotic Fractures Research Group, Osteoporotic Fractures in Men Research Group, Health And Body Composition Research Group (2011) Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA 305:2184–2192
Giangregorio LM, Leslie WD, Lix LM, Johansson H, Oden A, McCloskey E, Kanis JA (2012) FRAX underestimates fracture risk in patients with diabetes. J Bone Miner Res 27:301–308
Leslie WD, Rubin MR, Schwartz AV, Kanis JA (2012) Type 2 diabetes and bone. J Bone Miner Res 27:2231–2237
Wallander M, Axelsson KF, Nilsson AG, Lundh D, Lorentzon M (2017) Type 2 diabetes and risk of hip fractures and non-skeletal fall injuries in the elderly: a study from the fractures and fall injuries in the elderly cohort (FRAILCO). J Bone Miner Res 32:449–460
Schacter GI, Leslie WD (2021) Diabetes and osteoporosis: part II, clinical management. Endocrinol Metab Clin North Am 50:287–297
Vestergaard P, Rejnmark L, Mosekilde L (2011) Are antiresorptive drugs effective against fractures in patients with diabetes? Calcif Tissue Int 88:209–214
Masud T, Morris RO (2001) Epidemiology of falls. Age Ageing 30(Suppl 4):3–7
Gardsell P, Johnell O, Nilsson BE, Nilsson JA (1989) The predictive value of fracture, disease, and falling tendency for fragility fractures in women. Calcif Tissue Int 45:327–330
Albrand G, Munoz F, Sornay-Rendu E, DuBoeuf F, Delmas PD (2003) Independent predictors of all osteoporosis-related fractures in healthy postmenopausal women: the OFELY study. Bone 32:78–85
Gillespie LD, Gillespie WJ, Robertson MC, Lamb SE, Cumming RG, Rowe BH (2003) Interventions for preventing falls in elderly people. Cochrane Database Syst Rev CD000340
Geusens P, Milisen K, Dejaeger E, Boonen S (2003) Falls and fractures in postmenopausal women: a review. J Br Menopause Soc 9:101–106
Kaptoge S, Benevolenskaya LI, Bhalla AK, Cannata JB, Boonen S, Falch JA, Felsenberg D, Finn JD, Nuti R, Hoszowski K, Lorenc R, Miazgowski T, Jajic I, Lyritis G, Masaryk P, Naves-Diaz M, Poor G, Reid DM, Scheidt-Nave C, Stepan JJ, Todd CJ, Weber K, Woolf AD, Roy DK, Lunt M, Pye SR, O’Neill TW, Silman AJ, Reeve J (2005) Low BMD is less predictive than reported falls for future limb fractures in women across Europe: results from the European Prospective Osteoporosis Study. Bone 36:387–398
Wainwright SA, Marshall LM, Ensrud KE, Cauley JA, Black DM, Hillier TA, Hochberg MC, Vogt MT, Orwoll ES, Study of Osteoporotic Fractures Research Group (2005) Hip fracture in women without osteoporosis. J Clin Endocrinol Metab 90:2787–2793
Sambrook PN, Cameron ID, Chen JS, Cumming RG, Lord SR, March LM, Schwarz J, Seibel MJ, Simpson JM (2007) Influence of fall related factors and bone strength on fracture risk in the frail elderly. Osteoporos Int 18:603–610
Frost M, Abrahamsen B, Masud T, Brixen K (2012) Risk factors for fracture in elderly men: a population-based prospective study. Osteoporos Int 23:521–531
Henry MJ, Pasco JA, Sanders KM, Nicholson GC, Kotowicz MA (2006) Fracture Risk (FRISK) Score: Geelong Osteoporosis Study. Radiology 241:190–196
Cameron ID, Gillespie LD, Robertson MC, Murray GR, Hill KD, Cumming RG, Kerse N (2012) Interventions for preventing falls in older people in care facilities and hospitals. Cochrane Database Syst Rev 12:CD005465
Gillespie LD, Robertson MC, Gillespie WJ, Sherrington C, Gates S, Clemson LM, Lamb SE (2012) Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev CD007146
Gill TM, Pahor M, Guralnik JM, McDermott MM, King AC, Buford TW, Strotmeyer ES, Nelson ME, Sink KM, Demons JL, Kashaf SS, Walkup MP, Miller ME, Investigators LS (2016) Effect of structured physical activity on prevention of serious fall injuries in adults aged 70–89: randomized clinical trial (LIFE Study). BMJ 352:i245
Bhasin S, Gill TM, Reuben DB, Latham NK, Ganz DA, Greene EJ, Dziura J, Basaria S, Gurwitz JH, Dykes PC, McMahon S, Storer TW, Gazarian P, Miller ME, Travison TG, Esserman D, Carnie MB, Goehring L, Fagan M, Greenspan SL, Alexander N, Wiggins J, Ko F, Siu AL, Volpi E, Wu AW, Rich J, Waring SC, Wallace RB, Casteel C, Resnick NM, Magaziner J, Charpentier P, Lu C, Araujo K, Rajeevan H, Meng C, Allore H, Brawley BF, Eder R, McGloin JM, Skokos EA, Duncan PW, Baker D, Boult C, Correa-de-Araujo R, Peduzzi P, Investigators ST (2020) A randomized trial of a multifactorial strategy to prevent serious fall injuries. N Engl J Med 383:129–140
Lamb SE, Bruce J, Hossain A, Ji C, Longo R, Lall R, Bojke C, Hulme C, Withers E, Finnegan S, Sheridan R, Willett K, Underwood M, Prevention of Fall Injury Trial Study Group (2020) Screening and intervention to prevent falls and fractures in older people. N Engl J Med 383:1848–1859
Masud T, Binkley N, Boonen S, Hannan MT, Members FPDC (2011) Official Positions for FRAX(R) clinical regarding falls and frailty: can falls and frailty be used in FRAX(R)? From Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX(R). J Clin Densitom 14:194–204
McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, Adami S, Fogelman I, Diamond T, Eastell R, Meunier PJ, Reginster JY, Hip Intervention Program Study G (2001) Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med 344:333–340
Harvey NC, Oden A, Orwoll E, Lapidus J, Kwok T, Karlsson MK, Rosengren BE, Ljunggren O, Cooper C, McCloskey E, Kanis JA, Ohlsson C, Mellstrom D, Johansson H (2018) Falls predict fractures independently of FRAX probability: a meta-analysis of the Osteoporotic Fractures in Men (MrOS) Study. J Bone Miner Res 33:510–516
Leslie WD, Morin SN, Lix LM, Martineau P, Bryanton M, McCloskey EV, Johansson H, Harvey NC, Kanis JA (2019) Fracture prediction from self-reported falls in routine clinical practice: a registry-based cohort study. Osteoporos Int 30:2195–2203
Lorentzon M, Johansson H, Harvey N, Liu E, Vandenput L, Crandall C, McCloskey E, Kanis J (2020) Hormone therapy reduces the risk of fracture regardless of baseline FRAX probability or prior falls – results from the Women’s Health Initiative hormone therapy trials. J Bone Miner Res 33 (Suppl 1) (Available at https://www.asbmr.org/education/AbstractDetail?aid=14f38954-f17b-4c7f-a336-d2cd794f4a0a) Accessed December 23, 2020
Kayan K, Johansson H, Oden A, Vasireddy S, Pande K, Orgee J, Kanis JA, McCloskey EV (2009) Can fall risk be incorporated into fracture risk assessment algorithms: a pilot study of responsiveness to clodronate. Osteoporos Int 20:2055–2061
Reid IR, Horne AM, Mihov B, Stewart A, Garratt E, Wiessing KR, Bolland MJ, Bastin S, Gamble GD (2019) Anti-fracture efficacy of zoledronate in subgroups of osteopenic postmenopausal women: secondary analysis of a randomized controlled trial. J Intern Med 286:221–229
Johansson H, Kanis JA, Oden A, McCloskey E, Chapurlat RD, Christiansen C, Cummings SR, Diez-Perez A, Eisman JA, Fujiwara S, Gluer CC, Goltzman D, Hans D, Khaw KT, Krieg MA, Kroger H, LaCroix AZ, Lau E, Leslie WD, Mellstrom D, Melton LJ 3rd, O’Neill TW, Pasco JA, Prior JC, Reid DM, Rivadeneira F, van Staa T, Yoshimura N, Zillikens MC (2014) A meta-analysis of the association of fracture risk and body mass index in women. J Bone Miner Res 29:223–233
Kanis JA, Johansson H, Oden A, Johnell O, de Laet C, Melton IL, Tenenhouse A, Reeve J, Silman AJ, Pols HA, Eisman JA, McCloskey EV, Mellstrom D (2004) A meta-analysis of prior corticosteroid use and fracture risk. J Bone Miner Res 19:893–899
Kanis JA, Johnell O, Oden A, Johansson H, De Laet C, Eisman JA, Fujiwara S, Kroger H, McCloskey EV, Mellstrom D, Melton LJ, Pols H, Reeve J, Silman A, Tenenhouse A (2005) Smoking and fracture risk: a meta-analysis. Osteoporos Int 16:155–162
Hippisley-Cox J, Coupland C (2009) Predicting risk of osteoporotic fracture in men and women in England and Wales: prospective derivation and validation of QFractureScores. BMJ 339:b4229
Nguyen ND, Frost SA, Center JR, Eisman JA, Nguyen TV (2007) Development of a nomogram for individualizing hip fracture risk in men and women. Osteoporos Int 18:1109–1117
Nguyen ND, Frost SA, Center JR, Eisman JA, Nguyen TV (2008) Development of prognostic nomograms for individualizing 5-year and 10-year fracture risks. Osteoporos Int 19:1431–1444
Kanis JA, Oden A, Johansson H, McCloskey E (2012) Pitfalls in the external validation of FRAX. Osteoporos Int 23:423–431
Breslow NE, Day NE (1987) Statistical methods in cancer research. Volume II--The design and analysis of cohort studies. IARC Sci Publ 1–406
Albertsson-Wikland K, Martensson A, Savendahl L, Niklasson A, Bang P, Dahlgren J, Gustafsson J, Kristrom B, Norgren S, Pehrsson NG, Oden A (2016) Mortality is not increased in recombinant human growth hormone-treated patients when adjusting for birth characteristics. J Clin Endocrinol Metab 101:2149–2159
Kanis JA, Johnell O, De Laet C, Johansson H, Oden A, Delmas P, Eisman J, Fujiwara S, Garnero P, Kroger H, McCloskey EV, Mellstrom D, Melton LJ, Pols H, Reeve J, Silman A, Tenenhouse A (2004) A meta-analysis of previous fracture and subsequent fracture risk. Bone 35:375–382
Kanis JA, Johansson H, Oden A, Johnell O, De Laet C, Eisman JA, McCloskey EV, Mellstrom D, Melton LJ 3rd, Pols HA, Reeve J, Silman AJ, Tenenhouse A (2004) A family history of fracture and fracture risk: a meta-analysis. Bone 35:1029–1037
Kanis JA, Johansson H, Johnell O, Oden A, De Laet C, Eisman JA, Pols H, Tenenhouse A (2005) Alcohol intake as a risk factor for fracture. Osteoporos Int 16:737–742
Kanis JA, Johansson H, Oden A, De Laet C, Johnell O, Eisman JA, Mc Closkey E, Mellstrom D, Pols H, Reeve J, Silman A, Tenenhouse A (2005) A meta-analysis of milk intake and fracture risk: low utility for case finding. Osteoporos Int 16:799–804
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 3rd, O’Neill T, Pols H, Reeve J, Silman A, Tenenhouse A (2005) Predictive value of BMD for hip and other fractures. J Bone Miner Res 20:1185–1194
De Laet CE, Kanis JA, Oden A, Johanson H, Johnell O, Delmas P, Eisman JA, Kroger H, Fujiwara S, Garnero P, McCloskey EV, Mellstrom D, Melton LJ 3rd, Meunier PJ, Pols HA, Reeve J, Silman A, Tenenhouse A (2005) Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int 16:1330–1338
Johansson H, Kanis JA, Oden A, Leslie WD, Fujiwara S, Gluer CC, Kroger H, LaCroix AZ, Lau E, Melton LJ 3rd, Eisman JA, O’Neill TW, Goltzman D, Reid DM, McCloskey E (2014) Impact of femoral neck and lumbar spine BMD discordances on FRAX probabilities in women: a meta-analysis of international cohorts. Calcif Tissue Int 95:428–435
McCloskey EV, Oden A, Harvey NC, Leslie WD, Hans D, Johansson H, Barkmann R, Boutroy S, Brown J, Chapurlat R, Elders PJM, Fujita Y, Gluer CC, Goltzman D, Iki M, Karlsson M, Kindmark A, Kotowicz M, Kurumatani N, Kwok T, Lamy O, Leung J, Lippuner K, Ljunggren O, Lorentzon M, Mellstrom D, Merlijn T, Oei L, Ohlsson C, Pasco JA, Rivadeneira F, Rosengren B, Sornay-Rendu E, Szulc P, Tamaki J, Kanis JA (2016) A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX. J Bone Miner Res 31:940–948
Steyerberg EW, Moons KG, van der Windt DA, Hayden JA, Perel P, Schroter S, Riley RD, Hemingway H, Altman DG, for the PROGRESS Group (2013) Prognosis Research Strategy (PROGRESS) 3: prognostic model research. PLoS Med 10:e1001381
Leslie WD, Lix LM, Johansson H, Oden A, McCloskey E, Kanis JA, Program MBD (2010) Independent clinical validation of a Canadian FRAX tool: fracture prediction and model calibration. J Bone Miner Res 25:2350–2358
Fraser LA, Langsetmo L, Berger C, Ioannidis G, Goltzman D, Adachi JD, Papaioannou A, Josse R, Kovacs CS, Olszynski WP, Towheed T, Hanley DA, Kaiser SM, Prior J, Jamal S, Kreiger N, Brown JP, Johansson H, Oden A, McCloskey E, Kanis JA, Leslie WD, CaMos Research G (2011) Fracture prediction and calibration of a Canadian FRAX(R) tool: a population-based report from CaMos. Osteoporos Int 22:829–837
Hoff M, Meyer HE, Skurtveit S, Langhammer A, Sogaard AJ, Syversen U, Dhainaut A, Skovlund E, Abrahamsen B, Schei B (2017) Validation of FRAX and the impact of self-reported falls among elderly in a general population: the HUNT study, Norway. Osteoporos Int 28:2935–2944
Acknowledgements
We thank the Gothenburg University Library for assistance with the systematic review. We are grateful to Dr Östen Ljunggren for contributing the MrOS Sweden cohort.
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Human and animal rights
This review does not contain any original studies with human participants or animals performed by any of the authors.
Ethics
All individual cohorts with candidate risk factors available have been approved by their local ethics committees and informed consent has been obtained from all study participants. General ethics approval for the use of these cohorts is also given by the University of Sheffield. Participant data will be stored in coded, de-identified form. Only summary statistics and aggregate data will be published, not allowing for identification of individual study participants.
Conflicts of interest
JA Kanis led the team that developed FRAX as director of the WHO Collaborating Centre for Metabolic Bone Diseases; he has no financial interest in FRAX. EV McCloskey, WD Leslie, M Lorentzon, NC Harvey, E Liu, L Vandenput and H Johansson are members of the FRAX team. JA Kanis, NC Harvey and EV McCloskey are members of the advisory body to the National Osteoporosis Guideline Group. JA Kanis reports no additional competing interests. KE Åkesson has no financial interest related to FRAX; chaired the National SALAR Group for Person-Centered Care Pathway Osteoporosis. FA Anderson led the team that developed GLOW, while director of the Center for Outcomes Research at the University of Massachusetts Medical School; he has no financial interest in FRAX. R Azagra has received funding for research from Instituto Carlos III of Spanish Ministry of Health, IDIAP Jordi Gol of Catalan Government and from Scientific Societies SEMFYC and SEIOMM. CL Bager is employed at Nordic Bioscience and owns stock in Nordic Bioscience. She declares no competing interests in relation to this work. HA Bischoff-Ferrari has no financial interest in FRAX. For the DO-HEALTH trial cohort, Prof. Bischoff-Ferrari reports independent and investigator-initiated grants from European Commission Framework 7 Research Program, from the University of Zurich, from NESTEC, from Pfizer Consumer Healthcare, from Streuli Pharma, plus non-financial support from DNP. For the study cohort extension, she reports independent and investigator-initiated grants from Pfizer and from Vifor. Furthermore, Prof. Bischoff-Ferrari reports non-financial support from Roche Diagnostics and personal fees from Wild, Sandoz, Pfizer, Vifor, Mylan, Roche, Meda Pharma, outside the submitted work with regard to speaker fees and travel fees. JR Center has received honoraria for speaking at educational meetings and for advisory boards from Amgen and honoraria for an advisory board from Bayer. R Chapurlat has no financial interest in FRAX. He has received grant funding from Amgen, UCB, Chugai, MSD, Mylan and Medac. He has received honoraria from Amgen, UCB, Chugai, Galapagos, Biocon, Abbvie, Haoma Medica, Pfizer, Amolyt, MSD, Lilly, BMS, Novartis, Arrow, PKMed, Kyowa-Kirin and Sanofi. C Christiansen owns stock in Nordic Bioscience. He declares no competing interests in relation to this work. C Cooper reports personal fees from Alliance for Better Bone Health, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda and UCB. A Diez-Perez reports personal fees from Amgen, Lilly, Theramex and grants from Instituto Carlos III and owns shares of Active Life Scientific, all outside the submitted work. JA Eisman declares consulting and research support from Actavis, Amgen, Aspen, Lilly, Merck Sharp and Dohme, Novartis, Sanofi-Aventis, Servier and Theramex. PJM Elders has no financial interest in FRAX. PJM Elders reports support for the SOS study by Stichting Achmea Gezondheidszorg, Achmea and VGZ zorgverzekeraar. Additional support was given by the stichting Artsenlaboratorium en Trombosedienst. Outside the submitted work, she did receive independent investigator driven grants by Zonmw, the Netherlands, de Hartstichting, the Netherlands, the European foundation for the study of Diabetes, Amgen the Netherlands, TEVA, the Netherlands and Takeda, the Netherlands. NC Harvey has received consultancy/lecture fees/honoraria/grant funding from Alliance for Better Bone Health, Amgen, MSD, Eli Lilly, Radius Health, Servier, Shire, UCB, Consilient Healthcare and Internis Pharma. DP Kiel has no financial interest in FRAX but has received support for his work in the Framingham Study over the past 30 years by the National Institutes of Health, Astra Zeneca, Merck, Amgen and Radius Health. MA Kotowicz has received funding from the National Health and Medical Research Council (NHMRC) Australia, and the Medical Research Future Fund (MRFF) Australia. He has served on advisory boards for Amgen Australia, Novartic and Eli Lilly — all unrelated to this work and is the Director of the Geelong Bone Densitometry Service. M Lorentzon has received lecture fees from Amgen, Lilly, Meda, Renapharma and UCB Pharma and consulting fees from Amgen, Radius Health, UCB Pharma, Renapharma and Consilient Health, all outside the presented work. EV McCloskey has received consultancy/lecture fees/grant funding/honoraria from AgNovos, Amgen, AstraZeneca, Consilient Healthcare, Fresenius Kabi, Gilead, GSK, Hologic, Internis, Lilly, Merck, Novartis, Pfizer, Radius Health, Redx Oncology, Roche, Sanofi Aventis, UCB, ViiV, Warner Chilcott and I3 Innovus. C Ohlsson is listed as a coinventor on two patent applications regarding probiotics in osteoporosis treatment. ES Orwoll reports consulting fees from Amgen, Biocon, Radius and Bayer, and research support from Mereo. JA Pasco has received funding from the National Health and Medical Research Council (NHMRC) Australia, and the Medical Research Future Fund (MRFF) Australia, all unrelated to this work. MC Zillikens has received honoraria in the past for lectures or advice from Alexion, Amgen, Eli Lilly, Kyowa Kirin, Shire and UCB, unrelated to the current work. M Zwart has received research funding from national societies (SEMFYC and SEIOMM). C Beaudart, E Biver, O Bruyère, JA Cauley, CJ Crandall, SR Cummings, JAP da Silva, B Dawson-Huges, AB Dufour, S Ferrari, Y Fujita, S Fujiwara, C–C Glüer, I Goldshtein, D Goltzman, V Gudnason, J Hall, D Hans, M Hoff, RJ Hollick, M Huisman, M Iki, S Ish-Shalom, H Johansson, G Jones, MK Karlsson, S Khosla, W–P Koh, F Koromani, H Kröger, T Kwok, O Lamy, A Langhammer, B Larijani, WD Leslie, K Lippuner, E Liu, D Mellström, T Merlijn, A Nordström, P Nordström, TW O´Neill, B Obermayer-Pietsch, F Rivadeneira, B Schei, A-M Schott, EJ Shiroma, K Sigeirsdottir, EM Simonsick, E Sornay-Rendu, R Sund, KMA Swart, P Szulc, J Tamaki, DJ Torgerson, L Vandenput, NM van Schoor, TP van Staa, J Vila, NJ Wareham, NC Wright and N Yoshimura declare no competing interests in relation to this work.
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Vandenput, L., Johansson, H., McCloskey, E.V. et al. Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan. Osteoporos Int 33, 2103–2136 (2022). https://doi.org/10.1007/s00198-022-06435-6
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DOI: https://doi.org/10.1007/s00198-022-06435-6