Advertisement

The Association of Lipids and Lipoproteins with Hip Fracture Risk the Cardiovascular Health Study

      CLINICAL SIGNIFICANCE

      • The associations of lipid levels and of lipoprotein levels and size with hip fracture risk are uncertain.
      • In this study, HDL-c and LDL-c levels had significant non-linear associations with fracture risk.
      • VLDL number and size, and HDL particle size, were positively associated with risk.
      • Elevated lipid and lipoprotein levels are associated with hip fracture risk, suggesting an unanticipated protective benefit of lipid lowering medications in people with elevated LDL-c levels.

      Abstract

      Background

      It is uncertain if lipids or lipoproteins are associated with osteoporotic fractures. In this study, incident hip fracture risk according to conventional lipid levels and lipoprotein levels and sizes was examined.

      Methods

      We followed 5832 participants aged ≥65 years from the Cardiovascular Health Study for hip fracture for a mean of 13.5 (SD 5.7) years. Standard enzymatic methods were used to determine lipid levels (HDL-c, LDL-c, triglycerides). Nuclear magnetic resonance spectroscopy was used to measure lipoprotein fractions (VLDL-P, LDL-P, HDL-P) in a subset of 1849 participants.

      Results

      We documented 755 incident hip fractures among women (1.19 fractures per 100 participant years [95% CI, 1.04, 1.35]) and 197 among men (0.67 fractures per 100 participant years [95% CI, 0.41, 1.10]) over an average follow-up. HDL-c and LDL-c levels had statistically significant non-linear U-shaped relationships with hip fracture risk (HDL-c, p=0.009; LDL-c, p=0.02). Triglyceride levels were not significantly associated with hip fracture risk.
      In fully adjusted conjoint models, higher VLDL-P concentration [HR per 1-standard (SD) increment 1.47 (1.13, 1.91)] and size [HR per 1-SD increment 1.24 [1.05, 1.46]) and higher HDL-P size (HR per 1-SD increment 1.81 [1.25, 2.62]) were all associated with higher hip fracture risk.

      Conclusions

      Lipids and lipoproteins are associated with hip fracture risk in older adults. The associations are complex. Mechanistic studies are needed to understand these findings.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Luegmayr E
        • Glantschnig H
        • Wesolowski GA
        • Gentile MA
        • Fisher JE
        • Rodan GA
        • Reszka AA.
        Osteoclast formation, survival and morphology are highly dependent on exogenous cholesterol/lipoproteins.
        Cell Death Differ. 2004; 11 (Suppl): S108-S118
        • Chung JY
        • Hong SH.
        Vitamin D status and its association with cardiometabolic risk factors in Korean adults based on a 2008–2010 Korean National Health and Nutrition Examination Survey.
        Nutr Res Pract. 2013; 7: 495-502
        • Kawai M
        • de Paula FJ
        • Rosen CJ.
        New insights into osteoporosis: the bone-fat connection.
        J Intern Med. 2012; 272: 317-329
        • Zhao Q
        • Shen H
        • Su KJ
        • Zhang JG
        • Tian Q
        • Zhao LJ
        • Qiu C
        • Zhang Q
        • Garrett TJ
        • Liu J
        • Deng HW.
        Metabolomic profiles associated with bone mineral density in US Caucasian women.
        Nutr Metab (Lond). 2018 Aug 10; 15: 57
        • El Maghraoui A
        • Rezqi A
        • El Mrahi S
        • Sadni S
        • Ghozlani I
        • Mounach A.
        Osteoporosis, vertebral fractures and metabolic syndrome in postmenopausal women.
        BMC Endocr Disord. 2014; 14: 93
        • Nielson CM
        • Srikanth P
        • Orwoll ES.
        Obesity and fracture in men and women: an epidemiologic perspective.
        J Bone Miner Res. 2012; 27: 1-10
        • Heath H
        • Melton LJ
        • Chu CP.
        Diabetes mellitus and risk of skeletal fracture.
        N Engl J Med. 1981; 304: 115-116
        • Sennerby U
        • Melhus H
        • Gedeborg R
        • et al.
        Cardiovascular diseases and risk of hip fracture.
        JAMA. 2009; 302: 1666-1673
        • Barzilay J
        • Buzkova P
        • Cauley JA
        • Robbins JA
        • Fink HA
        • Mukamal KJ.
        The associations of subclinical atherosclerotic cardiovascular disease with hip fracture risk and bone mineral density in elderly adults; the Cardiovascular Health Study.
        Osteoporos Int. 2018; 29: 2219-2230
        • Campos-Staffico AM
        • Freitas WM
        • Carvalho LSF
        • Coelho-Filho OR
        • Nadruz Jr, W
        • Oliveira RB
        • Sposito AC
        Brasilia Study on Healthy Aging and Brasilia Heart Study. Lower bone mass is associated with subclinical atherosclerosis, endothelial dysfunction and carotid thickness in the very elderly.
        Atherosclerosis. 2020; 292: 70-74
        • Wang Z
        • Li Y
        • Zhou F
        • Piao Z
        • Hao J.
        Effects of Statins on Bone Mineral Density and Fracture Risk: A PRISMA-compliant Systematic Review and Meta-Analysis.
        Medicine (Baltimore). 2016; 95 (May): e3042
        • Niemeier A
        • Niedzielska D
        • Secer R
        • Schilling A
        • Merkel M
        • Enrich C
        • Rensen PCN
        • Heeren J.
        Uptake of postprandial lipoproteins into bone in vivo: impact on osteoblast function.
        Bone. 2008; 43: 230-237
        • Alekos NS
        • Moorer MC
        • Riddle RC.
        Dual effects of lipid metabolism on osteoblast function.
        Front Endocrinol. 2020; 11578194
        • Tintut Y
        • Demer LL.
        Effects of bioactive lipids and lipoproteins on bone.
        Trends Endocrinol Metabol. 2014; 25: 53-58
        • Tian L
        • Yu X
        Lipid metabolism disorders and bone dysfunction–interrelated and mutually regulated (review).
        Mol Med Rep. 2015; 12: 783-794
        • Ghorabi S
        • Shab-Bidar S
        • Sadeghi O
        • Nasiri M
        • Khatibi SR
        • Djafarian K.
        Lipid Profile and Risk of Bone Fracture: A Systematic Review and Meta-Analysis of Observational Studies.
        Endocr Res. 2019; 44: 168-184
        • Fried LP
        • Borhani NO
        • Enright P
        • Furberg CD
        • Gardin JM
        • Kronmal RA
        • Kuller LH
        • Manolio TA
        • Mittelmark MB
        • Newman A
        • et al.
        The Cardiovascular Health Study: design and rationale.
        Ann Epidemiol. 1991; 1: 263-276
        • Kuller L
        • Arnold A
        • Tracy R
        • Otvos J
        • Burke G
        • Psaty B
        • Siscovick D
        • Freedman DS
        • Kronmal R.
        Nuclear magnetic resonance spectroscopy of lipoproteins and risk of coronary heart disease in the cardiovascular health study.
        Arterioscler Thromb Vasc Biol. 2002; 22: 1175-1180
        • Kuller L
        • Borhani NO
        • Furberg G
        • Gardin JM
        • Manolio T
        • O'Leary D
        • Psaty B
        • Robbins J
        Prevalence of subclinical atherosclerosis and cardiovascular disease and association with risk factors in the Cardiovascular Health Study.
        Am J Epidemiol. 1994; 139: 1164-1179
        • Cushman M
        • Cornell ES
        • Howard PR
        • Bovill EG
        • Tracy RP.
        Laboratory methods and quality assurance in the Cardiovascular Health Study.
        Clin Chem. 1995; 41: 264-270
        • Fried LP
        • Tangen CM
        • Walston J
        • Newman AB
        • Hirsch C
        • Gottdiener J
        • Seeman T
        • Tracy R
        • Kop WJ
        • Burke G
        • McBurnie MA
        Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype.
        Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156
        • Proschan MA
        • Dodd LE.
        Re-randomization tests in clinical trials.
        Stat Med. 2019; 38: 2292-2302
        • McFarlane SI
        • Muniyappa R
        • Shin JJ
        • Bahtiyar G
        • Sowers JR.
        Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link?.
        Endocrine. 2004; 23: 1-10
        • Madsen CM
        • Varbo A
        • Nordestgaard BG.
        Extreme high high-density lipoprotein cholesterol is paradoxically associated with high mortality in men and women: two prospective cohort studies.
        Eur Heart J. 2017; 38: 2478-2486
        • Hamer M
        • O'Donovan G
        • Stamatakis E.
        High-Density Lipoprotein Cholesterol and Mortality: Too Much of a Good Thing?.
        Arterioscler Thromb Vasc Biol. 2018; 38: 669-672
        • Zhao H
        • Li Y
        • Zhang M
        • Qi L
        • Tang Y.
        Blood lipid levels in patients with osteopenia and osteoporosis: a systematic review and meta-analysis.
        J Bone Miner Metab. 2021; 39: 510-520
        • Chen YY
        • Wang WW
        • Yang L
        • Cheng WW
        • Zhang HX.
        Association between lipid profiles and osteoporosis in postmopausal women: a meta-analysis.
        Eur Rev Med Pharmacol Sci. 2018; 22: 1-9
        • Papachristou NI
        • Blair HC
        • Kypreos KE
        • Papachristou DJ.
        High-density lipoprotein (HDL) metabolism and bone mass.
        J Endocrinol. 2017; 233: R95-R107
        • Ackert-Bicknell CL.
        HDL cholesterol and bone mineral density: is there a genetic link?.
        Bone. 2012; 50: 525-533
        • Zheng J
        • Brion MJ
        • Kemp JP
        • Warrington NM
        • Borges MC
        • Hemani G
        • Richardson TG
        • Rasheed H
        • Qiao Z
        • Haycock P
        • Ala-Korpela M
        • Davey Smith G
        • Tobias JH
        • Evans DM
        The Effect of Plasma Lipids and Lipid-Lowering Interventions on Bone Mineral Density: A Mendelian Randomization Study.
        J Bone Miner Res. 2020; 35: 1224-1235
        • Engelen SE
        • Robinson AJB
        • Zurke YX
        • Monaco C.
        Therapeutic strategies targeting inflammation and immunity in atherosclerosis: how to proceed?.
        Nat Rev Cardiol. 2022; 31 (Jan): 1-21
        • Gotto AM.
        Interrelationship of triglycerides with lipoproteins and high-density lipoproteins.
        Am J Cardiol. 1990; 66: 20A-23A
        • Ahmed LA
        • Schirmer H
        • Berntsen GK
        • Fonnebo V
        • Joakimsen RM.
        Features of the metabolic syndrome and the risk of non-vertebral fractures: the Tromso study.
        Osteoporos Int. 2006; 17: 426-432
        • Lee SH
        • Baek S
        • Ahn SH
        • et al.
        Association between metabolic syndrome and incident fractures in Korean men: a 3-year follow-up observational study using national health insurance claims data.
        J Clin Endocrinol Metab. 2014; 99: 1615-1622
        • Chang P-Y
        • Gold EB
        • Cauley JA
        • Johnson WO
        • Karvonen-Gutierrez C
        • Jackson EA
        • Ruppert KM
        • Lee JS.
        Triglyceride Levels and Fracture Risk in Midlife Women: Study of Women's Health Across the Nation (SWAN).
        J Clin Endocrinol Metabol. 2016; 101: 3297-3305
        • Johnell O
        • Kanis JA
        • Black DM
        • et al.
        Associations between baseline risk factors and vertebral fracture risk in the Multiple Outcomes of Raloxifene Evaluation (MORE) Study.
        J Bone Mineral Res. 2004; 19: 764-772