Skip to main content
Top
Published in: Archives of Osteoporosis 1/2018

01-12-2018 | Original Article

Prediction of changes in bone mineral density in the elderly: contribution of “osteogenomic profile”

Authors: Thao P. Ho-Le, Hanh M. Pham, Jacqueline R. Center, John A. Eisman, Hung T. Nguyen, Tuan V. Nguyen

Published in: Archives of Osteoporosis | Issue 1/2018

Login to get access

Abstract

Summary

The contribution of genetic variants to longitudinal bone loss has not been well documented. We constructed an “osteogenomic profile” based on 62 BMD-associated genetic variants and showed that the profile was significantly associated with bone loss, independently from baseline BMD and age. The osteogenomic profile can help predict bone loss in an individual.

Introduction

The rate of longitudinal bone loss (ΔBMD) is a risk factor for fracture. The variation in ΔBMD is partly determined by genetic factors. This study sought to define the association between an osteogenomic profile and ΔBMD.

Methods

The osteogenomic profile was created from 62 BMD-associated SNPs from genome-wide association studies (GWAS) that were genotyped in 1384 elderly men and women aged 60+ years. Weighted genetic risk scores (GRS) were constructed for each individual by summing the products of the number of risk alleles and the sex-specific regression coefficients [associated with BMD from GWAS]. ΔBMD, expressed as annual percent change-in-BMD, was determined by linear regression analysis for each individual who had had at least two femoral neck BMD measurements.

Results

The mean ΔBMD was − 0.65% (SD 1.64%) for women and − 0.57% (SD 1.40%) for men, and this difference was not statistically significant (P = 0.32). In women, each unit increase in GRS was associated with 0.21% (SE 0.10) higher ΔBMD at the femoral neck (P = 0.036), and this association was independent of baseline BMD and age. In logistic regression analysis, each unit increase of GRS was associated with 41% odds (95%CI: 1.07–1.87) of rapid bone loss (ΔBMD ≤ − 1.2%/year; mean of rapid loss group = − 2.2%/year). There was no statistically significant association between ΔBMD and GRS in men.

Conclusions

We conclude that the osteogenomic profile constructed from BMD-associated genetic variants is modestly associated with long-term changes in femoral neck BMD in women, but not in men.
Appendix
Available only for authorised users
Literature
1.
go back to reference Nguyen TV, Sambrook PN, Eisman JA (1998) Bone loss, physical activity, and weight change in elderly women: the Dubbo osteoporosis epidemiology study. J Bone Miner Res 13(9):1458–1467CrossRef Nguyen TV, Sambrook PN, Eisman JA (1998) Bone loss, physical activity, and weight change in elderly women: the Dubbo osteoporosis epidemiology study. J Bone Miner Res 13(9):1458–1467CrossRef
4.
go back to reference Ensrud KE, Palermo L, Black DM, Cauley J, Jergas M, Orwoll ES, Nevitt MC, Fox KM, Cummings SR (1995) Hip and calcaneal bone loss increase with advancing age: longitudinal results from the study of osteoporotic fractures. J Bone Miner Res Off J Am Soc Bone Miner Res 10(11):1778–1787. https://doi.org/10.1002/jbmr.5650101122 CrossRef Ensrud KE, Palermo L, Black DM, Cauley J, Jergas M, Orwoll ES, Nevitt MC, Fox KM, Cummings SR (1995) Hip and calcaneal bone loss increase with advancing age: longitudinal results from the study of osteoporotic fractures. J Bone Miner Res Off J Am Soc Bone Miner Res 10(11):1778–1787. https://​doi.​org/​10.​1002/​jbmr.​5650101122 CrossRef
5.
go back to reference Jones G, Nguyen T, Sambrook P, Kelly PJ, Eisman JA (1994) Progressive loss of bone in the femoral neck in elderly people: longitudinal findings from the Dubbo osteoporosis epidemiology study. Br Med J 309(6956):691–695CrossRef Jones G, Nguyen T, Sambrook P, Kelly PJ, Eisman JA (1994) Progressive loss of bone in the femoral neck in elderly people: longitudinal findings from the Dubbo osteoporosis epidemiology study. Br Med J 309(6956):691–695CrossRef
7.
go back to reference Styrkarsdottir U, Halldorsson BV, Gretarsdottir S, Gudbjartsson DF, Walters GB, Ingvarsson T, Jonsdottir T, Saemundsdottir J, Center JR, Nguyen TV, Bagger Y, Gulcher JR, Eisman JA, Christiansen C, Sigurdsson G, Kong A, Thorsteinsdottir U, Stefansson K (2008) Multiple genetic loci for bone mineral density and fractures. N Engl J Med 358(22):2355–2365. https://doi.org/10.1056/NEJMoa0801197 CrossRefPubMed Styrkarsdottir U, Halldorsson BV, Gretarsdottir S, Gudbjartsson DF, Walters GB, Ingvarsson T, Jonsdottir T, Saemundsdottir J, Center JR, Nguyen TV, Bagger Y, Gulcher JR, Eisman JA, Christiansen C, Sigurdsson G, Kong A, Thorsteinsdottir U, Stefansson K (2008) Multiple genetic loci for bone mineral density and fractures. N Engl J Med 358(22):2355–2365. https://​doi.​org/​10.​1056/​NEJMoa0801197 CrossRefPubMed
8.
go back to reference Estrada K, Styrkarsdottir U, Evangelou E, Hsu YH, Duncan EL, Ntzani EE, Oei L, Albagha OME, Amin N, Kemp JP, Koller DL, Li G, Liu CT, Minster RL, Moayyeri A, Vandenput L, Willner D, Xiao SM, Yerges-Armstrong LM, Zheng HF, Alonso N, Eriksson J, Kammerer CM, Kaptoge SK, Leo PJ, Thorleifsson G, Wilson SG, Wilson JF, Aalto V, Alen M, Aragaki AK, Aspelund T, Center JR, Dailiana Z, Duggan DJ, Garcia M, Garcia-Giralt N, Giroux S, Hallmans G, Hocking LJ, Husted LB, Jameson KA, Khusainova R, Kim GS, Kooperberg C, Koromila T, Kruk M, Laaksonen M, Lacroix AZ, Lee SH, Leung PC, Lewis JR, Masi L, Mencej-Bedrac S, Nguyen TV, Nogues X, Patel MS, Prezelj J, Rose LM, Scollen S, Siggeirsdottir K, Smith AV, Svensson O, Trompet S, Trummer O, van Schoor NM, Woo J, Zhu K, Balcells S, Brandi ML, Buckley BM, Cheng S, Christiansen C, Cooper C, Dedoussis G, Ford I, Frost M, Goltzman D, González-Macías J, Kähönen M, Karlsson M, Khusnutdinova E, Koh JM, Kollia P, Langdahl BL, Leslie WD, Lips P, Ljunggren Ö, Lorenc RS, Marc J, Mellström D, Obermayer-Pietsch B, Olmos JM, Pettersson-Kymmer U, Reid DM, Riancho JA, Ridker PM, Rousseau F, lagboom PES, Tang NLS, Urreizti R, van Hul W, Viikari J, Zarrabeitia MT, Aulchenko YS, Castano-Betancourt M, Grundberg E, Herrera L, Ingvarsson T, Johannsdottir H, Kwan T, Li R, Luben R, Medina-Gómez C, Th Palsson S, Reppe S, Rotter JI, Sigurdsson G, van Meurs JBJ, Verlaan D, Williams FMK, Wood AR, Zhou Y, Gautvik KM, Pastinen T, Raychaudhuri S, Cauley JA, Chasman DI, Clark GR, Cummings SR, Danoy P, Dennison EM, Eastell R, Eisman JA, Gudnason V, Hofman A, Jackson RD, Jones G, Jukema JW, Khaw KT, Lehtimäki T, Liu Y, Lorentzon M, McCloskey E, Mitchell BD, Nandakumar K, Nicholson GC, Oostra BA, Peacock M, Pols HAP, Prince RL, Raitakari O, Reid IR, Robbins J, Sambrook PN, Sham PC, Shuldiner AR, Tylavsky FA, van Duijn CM, Wareham NJ, Cupples LA, Econs MJ, Evans DM, Harris TB, Kung AWC, Psaty BM, Reeve J, Spector TD, Streeten EA, Zillikens MC, Thorsteinsdottir U, Ohlsson C, Karasik D, Richards JB, Brown MA, Stefansson K, Uitterlinden AG, Ralston SH, Ioannidis JPA, Kiel DP, Rivadeneira F (2012) Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet 44(5):491–501. https://doi.org/10.1038/ng.2249 CrossRefPubMedPubMedCentral Estrada K, Styrkarsdottir U, Evangelou E, Hsu YH, Duncan EL, Ntzani EE, Oei L, Albagha OME, Amin N, Kemp JP, Koller DL, Li G, Liu CT, Minster RL, Moayyeri A, Vandenput L, Willner D, Xiao SM, Yerges-Armstrong LM, Zheng HF, Alonso N, Eriksson J, Kammerer CM, Kaptoge SK, Leo PJ, Thorleifsson G, Wilson SG, Wilson JF, Aalto V, Alen M, Aragaki AK, Aspelund T, Center JR, Dailiana Z, Duggan DJ, Garcia M, Garcia-Giralt N, Giroux S, Hallmans G, Hocking LJ, Husted LB, Jameson KA, Khusainova R, Kim GS, Kooperberg C, Koromila T, Kruk M, Laaksonen M, Lacroix AZ, Lee SH, Leung PC, Lewis JR, Masi L, Mencej-Bedrac S, Nguyen TV, Nogues X, Patel MS, Prezelj J, Rose LM, Scollen S, Siggeirsdottir K, Smith AV, Svensson O, Trompet S, Trummer O, van Schoor NM, Woo J, Zhu K, Balcells S, Brandi ML, Buckley BM, Cheng S, Christiansen C, Cooper C, Dedoussis G, Ford I, Frost M, Goltzman D, González-Macías J, Kähönen M, Karlsson M, Khusnutdinova E, Koh JM, Kollia P, Langdahl BL, Leslie WD, Lips P, Ljunggren Ö, Lorenc RS, Marc J, Mellström D, Obermayer-Pietsch B, Olmos JM, Pettersson-Kymmer U, Reid DM, Riancho JA, Ridker PM, Rousseau F, lagboom PES, Tang NLS, Urreizti R, van Hul W, Viikari J, Zarrabeitia MT, Aulchenko YS, Castano-Betancourt M, Grundberg E, Herrera L, Ingvarsson T, Johannsdottir H, Kwan T, Li R, Luben R, Medina-Gómez C, Th Palsson S, Reppe S, Rotter JI, Sigurdsson G, van Meurs JBJ, Verlaan D, Williams FMK, Wood AR, Zhou Y, Gautvik KM, Pastinen T, Raychaudhuri S, Cauley JA, Chasman DI, Clark GR, Cummings SR, Danoy P, Dennison EM, Eastell R, Eisman JA, Gudnason V, Hofman A, Jackson RD, Jones G, Jukema JW, Khaw KT, Lehtimäki T, Liu Y, Lorentzon M, McCloskey E, Mitchell BD, Nandakumar K, Nicholson GC, Oostra BA, Peacock M, Pols HAP, Prince RL, Raitakari O, Reid IR, Robbins J, Sambrook PN, Sham PC, Shuldiner AR, Tylavsky FA, van Duijn CM, Wareham NJ, Cupples LA, Econs MJ, Evans DM, Harris TB, Kung AWC, Psaty BM, Reeve J, Spector TD, Streeten EA, Zillikens MC, Thorsteinsdottir U, Ohlsson C, Karasik D, Richards JB, Brown MA, Stefansson K, Uitterlinden AG, Ralston SH, Ioannidis JPA, Kiel DP, Rivadeneira F (2012) Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet 44(5):491–501. https://​doi.​org/​10.​1038/​ng.​2249 CrossRefPubMedPubMedCentral
9.
go back to reference Mitchell JA, Chesi A, Elci O, McCormack SE, Roy SM, Kalkwarf HJ, Lappe JM, Gilsanz V, Oberfield SE, Shepherd JA, Kelly A, Grant SFA, Zemel BS (2016) Genetic risk scores implicated in adult bone fragility associate with pediatric bone density. J Bone Miner Res Off J Am Soc Bone Miner Res 31(4):789–795. https://doi.org/10.1002/jbmr.2744 CrossRef Mitchell JA, Chesi A, Elci O, McCormack SE, Roy SM, Kalkwarf HJ, Lappe JM, Gilsanz V, Oberfield SE, Shepherd JA, Kelly A, Grant SFA, Zemel BS (2016) Genetic risk scores implicated in adult bone fragility associate with pediatric bone density. J Bone Miner Res Off J Am Soc Bone Miner Res 31(4):789–795. https://​doi.​org/​10.​1002/​jbmr.​2744 CrossRef
12.
go back to reference Nguyen T, Sambrook P, Kelly P, Jones G, Lord S, Freund J, Eisman J (1993) Prediction of osteoporotic fractures by postural instability and bone density. Br Med J 307(6912):1111–1115CrossRef Nguyen T, Sambrook P, Kelly P, Jones G, Lord S, Freund J, Eisman J (1993) Prediction of osteoporotic fractures by postural instability and bone density. Br Med J 307(6912):1111–1115CrossRef
14.
go back to reference Simons LA, McCallum J, Simons J, Powell I, Ruys J, Heller R, Lerba C (1990) The Dubbo study: an Australian prospective community study of the health of elderly. Aust NZ J Med 20(6):783–789CrossRef Simons LA, McCallum J, Simons J, Powell I, Ruys J, Heller R, Lerba C (1990) The Dubbo study: an Australian prospective community study of the health of elderly. Aust NZ J Med 20(6):783–789CrossRef
19.
go back to reference Burger H, de Laet CE, van Daele PL et al (1998) Risk factors for increased bone loss in an elderly population: the Rotterdam study. Am J Epidemiol 147(9):871–879CrossRef Burger H, de Laet CE, van Daele PL et al (1998) Risk factors for increased bone loss in an elderly population: the Rotterdam study. Am J Epidemiol 147(9):871–879CrossRef
22.
go back to reference Genuer R, Poggi J-M, Tuleau-Malot C (2015) VSURF: an R package for variable selection using random forests. The R J 7(2):19–33CrossRef Genuer R, Poggi J-M, Tuleau-Malot C (2015) VSURF: an R package for variable selection using random forests. The R J 7(2):19–33CrossRef
23.
go back to reference Liaw A, Wiener M (2002) Classification and Regression by randomForest. R News 2(3):18–22 Liaw A, Wiener M (2002) Classification and Regression by randomForest. R News 2(3):18–22
24.
go back to reference Eriksson J, Evans DS, Nielson CM, Shen J, Srikanth P, Hochberg M, McWeeney S, Cawthon PM, Wilmot B, Zmuda J, Tranah G, Mirel DB, Challa S, Mooney M, Crenshaw A, Karlsson M, Mellström D, Vandenput L, Orwoll E, Ohlsson C (2015) Limited clinical utility of a genetic risk score for the prediction of fracture risk in elderly subjects. J Bone Miner Res Off J Am Soc Bone Miner Res 30(1):184–194. https://doi.org/10.1002/jbmr.2314 CrossRef Eriksson J, Evans DS, Nielson CM, Shen J, Srikanth P, Hochberg M, McWeeney S, Cawthon PM, Wilmot B, Zmuda J, Tranah G, Mirel DB, Challa S, Mooney M, Crenshaw A, Karlsson M, Mellström D, Vandenput L, Orwoll E, Ohlsson C (2015) Limited clinical utility of a genetic risk score for the prediction of fracture risk in elderly subjects. J Bone Miner Res Off J Am Soc Bone Miner Res 30(1):184–194. https://​doi.​org/​10.​1002/​jbmr.​2314 CrossRef
28.
go back to reference Jones G, Nguyen T, Sambrook P, Kelly PJ, Eisman JA (1994) Progressive loss of bone in the femoral neck in elderly people: longitudinal findings from the Dubbo osteoporosis epidemiology study. BMJ (Clinical research ed) 309(6956):691–695CrossRef Jones G, Nguyen T, Sambrook P, Kelly PJ, Eisman JA (1994) Progressive loss of bone in the femoral neck in elderly people: longitudinal findings from the Dubbo osteoporosis epidemiology study. BMJ (Clinical research ed) 309(6956):691–695CrossRef
29.
go back to reference Kemp JP, Morris JA, Medina-Gomez C, Forgetta V, Warrington NM, Youlten SE, Zheng J, Gregson CL, Grundberg E, Trajanoska K, Logan JG, Pollard AS, Sparkes PC, Ghirardello EJ, Allen R, Leitch VD, Butterfield NC, Komla-Ebri D, Adoum AT, Curry KF, White JK, Kussy F, Greenlaw KM, Xu C, Harvey NC, Cooper C, Adams DJ, Greenwood CMT, Maurano MT, Kaptoge S, Rivadeneira F, Tobias JH, Croucher PI, Ackert-Bicknell CL, Bassett JHD, Williams GR, Richards JB, Evans DM (2017) Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis. Nat Genet 49(10):1468–1475. https://doi.org/10.1038/ng.3949 CrossRefPubMedPubMedCentral Kemp JP, Morris JA, Medina-Gomez C, Forgetta V, Warrington NM, Youlten SE, Zheng J, Gregson CL, Grundberg E, Trajanoska K, Logan JG, Pollard AS, Sparkes PC, Ghirardello EJ, Allen R, Leitch VD, Butterfield NC, Komla-Ebri D, Adoum AT, Curry KF, White JK, Kussy F, Greenlaw KM, Xu C, Harvey NC, Cooper C, Adams DJ, Greenwood CMT, Maurano MT, Kaptoge S, Rivadeneira F, Tobias JH, Croucher PI, Ackert-Bicknell CL, Bassett JHD, Williams GR, Richards JB, Evans DM (2017) Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis. Nat Genet 49(10):1468–1475. https://​doi.​org/​10.​1038/​ng.​3949 CrossRefPubMedPubMedCentral
30.
go back to reference Coalition TPM (2014) The Case for Personalized Medicine, 4th edn. Personalized Medicine Coalition, Washington, DC Coalition TPM (2014) The Case for Personalized Medicine, 4th edn. Personalized Medicine Coalition, Washington, DC
Metadata
Title
Prediction of changes in bone mineral density in the elderly: contribution of “osteogenomic profile”
Authors
Thao P. Ho-Le
Hanh M. Pham
Jacqueline R. Center
John A. Eisman
Hung T. Nguyen
Tuan V. Nguyen
Publication date
01-12-2018
Publisher
Springer London
Published in
Archives of Osteoporosis / Issue 1/2018
Print ISSN: 1862-3522
Electronic ISSN: 1862-3514
DOI
https://doi.org/10.1007/s11657-018-0480-2

Other articles of this Issue 1/2018

Archives of Osteoporosis 1/2018 Go to the issue