Archives of Osteoporosis

, 13:89 | Cite as

Moderate-to-heavy smoking in women is potentially associated with compromised cortical porosity and stiffness at the distal radius

  • Joshua E. JohnsonEmail author
  • Karen L. Troy
Original Article



Though smokers have poor clinical outcomes after treatment for fractures, the skeletal effects of smoking are still debated. Our results showed that female smokers had 33% higher cortical bone porosity. Smoking targets cortical compartment microstructure and mechanics, and micron-scale variables are essential to better understand the specific effects of smoking.


Smokers have poor outcomes in the clinic after treatment for fractures. However, skeletal effects of smoking are still debated. Inconsistencies in published data are likely due to macro-scale variables used to characterize bone differences due to smoking. Therefore, our goal was to characterize distal radius microstructure and macrostructure differences between smokers and non-smokers, and determine the degree to which smoking is associated with compartment-specific mechanical differences resulting from compromised cortical-trabecular microstructure.


Data were acquired from 46 female smokers (35 to 64 years old), and 45 age- and body mass-matched female non-smokers. Distal radius microstructure and mechanical variables were determined from high-resolution peripheral quantitative computed tomography (HR-pQCT) images and multiscale finite element analysis. Distal radius macro-scale variables (bone volume, bone mineral content, volumetric bone mineral density [vBMD]) were determined from low-resolution images.


Age- and body mass index-adjusted results showed that cortical porosity was 33% higher (p < 0.01), and that cortical vBMD and stiffness were 3% and 8% lower, respectively (p < 0.05), among smokers. We also observed unloading of the cortical compartment in smokers. There were no differences in the macro-scale variables. Average HR-pQCT-derived vBMD was 8% lower (p < 0.05) in smokers corresponding to 5 years of postmenopausal loss.


Skeletal effects of smoking become evident at the micron level through a structurally and mechanically compromised cortical compartment, which partially explains the inconsistent results observed at the macro-level, and the poor clinical outcomes. Smoking may also compound postmenopausal effects on bone potentially placing women having undergone menopause at a greater risk for fracture.


Nicotine FEM Osteoporosis High-resolution peripheral quantitative computed tomography 



The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We would also like to thank Michael DiStefano, Megan Pinette, and Tyler Marshall for assistance with image processing, and John Wixted, MD, for his mentorship.

Funding information

Research supported in this publication was supported by NIAMS of the National Institutes of Health under award number F32AR068839.

Compliance with ethical standards

The local IRB approved the study and all subjects provided written informed consent prior to participation.

Conflicts of interest



  1. 1.
    Castillo RC, Bosse MJ, MacKenzie EJ, Patterson BM (2005) Impact of smoking on fracture healing and risk of complications in limb-threatening open tibia fractures. J Orthop Trauma 19:151–157CrossRefGoogle Scholar
  2. 2.
    Nasell H, Ottosson C, Tornqvist H, Linde J, Ponzer S (2011) The impact of smoking on complications after operatively treated ankle fractures—a follow-up study of 906 patients. J Orthop Trauma 25:748–755. CrossRefPubMedGoogle Scholar
  3. 3.
    Einhorn TA, Trippel SB (1997) Growth factor treatment of fractures. Instr Course Lect 46:483–486PubMedGoogle Scholar
  4. 4.
    Antonova E, Le TK, Burge R, Mershon J (2013) Tibia shaft fractures: costly burden of nonunions. BMC Musculoskelet Disord 14:42. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    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. CrossRefPubMedGoogle Scholar
  6. 6.
    Kanis JA, Oden A, Johansson H, Borgstrom F, Strom O, McCloskey E (2009) FRAX and its applications to clinical practice. Bone 44:734–743. CrossRefPubMedGoogle Scholar
  7. 7.
    Tanaka H, Tanabe N, Suzuki N, Shoji M, Torigoe H, Sugaya A, Motohashi M, Maeno M (2005) Nicotine affects mineralized nodule formation by the human osteosarcoma cell line Saos-2. Life Sci 77:2273–2284. CrossRefPubMedGoogle Scholar
  8. 8.
    Rothem DE, Rothem L, Soudry M, Dahan A, Eliakim R (2009) Nicotine modulates bone metabolism-associated gene expression in osteoblast cells. J Bone Miner Metab 27:555–561. CrossRefPubMedGoogle Scholar
  9. 9.
    Ho YC, Yang SF, Huang FM, Chang YC (2009) Up-regulation of osteolytic mediators in human osteosarcoma cells stimulated with nicotine. J Periodontal Res 44:760–766. CrossRefPubMedGoogle Scholar
  10. 10.
    Broulik PD, Rosenkrancova J, Ruzicka P, Sedlacek R, Kurcova I (2007) The effect of chronic nicotine administration on bone mineral content and bone strength in normal and castrated male rats. Horm Metab Res 39:20–24. CrossRefPubMedGoogle Scholar
  11. 11.
    Ma L, Zheng LW, Sham MH, Cheung LK (2010) Uncoupled angiogenesis and osteogenesis in nicotine-compromised bone healing. J Bone Miner Res 25:1305–1313. CrossRefPubMedGoogle Scholar
  12. 12.
    Taes Y, Lapauw B, Vanbillemont G, Bogaert V, De Bacquer D, Goemaere S, Zmierczak H, Kaufman JM (2010) Early smoking is associated with peak bone mass and prevalent fractures in young, healthy men. J Bone Miner Res 25:379–387. CrossRefPubMedGoogle Scholar
  13. 13.
    Law MR, Cheng R, Hackshaw AK, Allaway S, Hale AK (1997) Cigarette smoking, sex hormones and bone density in women. Eur J Epidemiol 13:553–558CrossRefGoogle Scholar
  14. 14.
    Hu JF, Zhao XH, Chen JS, Fitzpatrick J, Parpia B, Campbell TC (1994) Bone density and lifestyle characteristics in premenopausal and postmenopausal Chinese women. Osteoporos Int 4:288–297CrossRefGoogle Scholar
  15. 15.
    Orwoll ES, Bauer DC, Vogt TM, Fox KM (1996) Axial bone mass in older women. Study of Osteoporotic Fractures Research Group. Ann Intern Med 124:187–196CrossRefGoogle Scholar
  16. 16.
    Macneil JA, Boyd SK (2008) Bone strength at the distal radius can be estimated from high-resolution peripheral quantitative computed tomography and the finite element method. Bone 42:1203–1213. CrossRefPubMedGoogle Scholar
  17. 17.
    Tsai JN, Uihlein AV, Burnett-Bowie SA, Neer RM, Zhu Y, Derrico N, Lee H, Bouxsein ML, Leder BZ (2015) Comparative effects of teriparatide, denosumab, and combination therapy on peripheral compartmental bone density, microarchitecture, and estimated strength: the DATA-HRpQCT Study. J Bone Miner Res 30:39–45. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Ding M, Odgaard A, Linde F, Hvid I (2002) Age-related variations in the microstructure of human tibial cancellous bone. J Orthop Res 20:615–621. CrossRefPubMedGoogle Scholar
  19. 19.
    Johnson JE, Troy KL (in Press 2017) Simplified boundary conditions alter cortical-trabecular load sharing at the distal radius; a multiscale finite element analysis. J BiomechGoogle Scholar
  20. 20.
    Bono CM, Einhorn TA (2003) Overview of osteoporosis: pathophysiology and determinants of bone strength. Eur Spine J 12(Suppl 2):S90–S96. CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    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. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    (2015) Massachusetts Department of Public Health. Who smokes. Massachusetts fact sheet. Massachusetts Behavioral Risk Factor Surveillance System. Massachusetts Department of Public Health, Tobacco Cessation and Prevention ProgramGoogle Scholar
  23. 23.
    (2014) U.S. Department of Health and Human Services. The health consequences of smoking—50 years of progress: a report of the Surgeon General. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and HealthGoogle Scholar
  24. 24.
    Sebring NG, Denkinger BI, Menzie CM, Yanoff LB, Parikh SJ, Yanovski JA (2007) Validation of three food frequency questionnaires to assess dietary calcium intake in adults. J Am Diet Assoc 107:752–759. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Dolan SH, Williams DP, Ainsworth BE, Shaw JM (2006) Development and reproducibility of the bone loading history questionnaire. Med Sci Sports Exerc 38:1121–1131. CrossRefPubMedGoogle Scholar
  26. 26.
    Laib A, Hauselmann HJ, Ruegsegger P (1998) In vivo high resolution 3D-QCT of the human forearm. Technol Health Care 6:329–337PubMedGoogle Scholar
  27. 27.
    Hildebrand T, Rüegsegger P (1997) A new method for the model-independent assessment of thickness in three-dimensional images. J Microsc 185:67–75. CrossRefGoogle Scholar
  28. 28.
    Parfitt AM, Mathews CH, Villanueva AR, Kleerekoper M, Frame B, Rao DS (1983) Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis. Implications for the microanatomic and cellular mechanisms of bone loss. J Clin Invest 72:1396–1409. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Burghardt AJ, Buie HR, Laib A, Majumdar S, Boyd SK (2010) Reproducibility of direct quantitative measures of cortical bone microarchitecture of the distal radius and tibia by HR-pQCT. Bone 47:519–528. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Nishiyama KK, Macdonald HM, Buie HR, Hanley DA, Boyd SK (2010) Postmenopausal women with osteopenia have higher cortical porosity and thinner cortices at the distal radius and tibia than women with normal aBMD: an in vivo HR-pQCT study. J Bone Miner Res 25:882–890. CrossRefPubMedGoogle Scholar
  31. 31.
    Troy KL, Edwards WB, Bhatia VA, Bareither ML (2013) In vivo loading model to examine bone adaptation in humans: a pilot study. J Orthop Res 31:1406–1413. CrossRefPubMedGoogle Scholar
  32. 32.
    Edwards WB, Schnitzer TJ, Troy KL (2013) Torsional stiffness and strength of the proximal tibia are better predicted by finite element models than DXA or QCT. J Biomech 46:1655–1662. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Johnson JE, Troy KL (2017) Validation of a new multiscale finite element analysis approach at the distal radius. Med Eng Phys 44:16–24. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Genant HK, Engelke K, Hanley DA, Brown JP, Omizo M, Bone HG, Kivitz AJ, Fuerst T, Wang H, Austin M, Libanati C (2010) Denosumab improves density and strength parameters as measured by QCT of the radius in postmenopausal women with low bone mineral density. Bone 47:131–139. CrossRefPubMedGoogle Scholar
  35. 35.
    Kaji H, Kosaka R, Yamauchi M, Kuno K, Chihara K, Sugimoto T (2005) Effects of age, grip strength and smoking on forearm volumetric bone mineral density and bone geometry by peripheral quantitative computed tomography: comparisons between female and male. Endocr J 52:659–666CrossRefGoogle Scholar
  36. 36.
    Synek A, Chevalier Y, Baumbach SF, Pahr DH (2015) The influence of bone density and anisotropy in finite element models of distal radius fracture osteosynthesis: evaluations and comparison to experiments. J Biomech 48:4116–4123. CrossRefPubMedGoogle Scholar
  37. 37.
    Bhatia VA, Edwards WB, Troy KL (2014) Predicting surface strains at the human distal radius during an in vivo loading task—finite element model validation and application. J Biomech 47:2759–2765. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Khosla S, Riggs BL, Atkinson EJ, Oberg AL, McDaniel LJ, Holets M, Peterson JM, Melton LJ 3rd (2006) Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment. J Bone Miner Res 21:124–131. CrossRefPubMedGoogle Scholar
  39. 39.
    Lakens D (2013) Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs. Front Psychol 4.
  40. 40.
    Kasperk C, Wergedal J, Strong D, Farley J, Wangerin K, Gropp H, Ziegler R, Baylink DJ (1995) Human bone cell phenotypes differ depending on their skeletal site of origin. J Clin Endocrinol Metab 80:2511–2517. CrossRefPubMedGoogle Scholar
  41. 41.
    Marsell R, Einhorn TA (2011) The biology of fracture healing. Injury 42:551–555. CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Zheng LW, Ma L, Cheung LK (2008) Changes in blood perfusion and bone healing induced by nicotine during distraction osteogenesis. Bone 43:355–361. CrossRefPubMedGoogle Scholar
  43. 43.
    Rudang R, Darelid A, Nilsson M, Nilsson S, Mellstrom D, Ohlsson C, Lorentzon M (2012) Smoking is associated with impaired bone mass development in young adult men: a 5-year longitudinal study. J Bone Miner Res 27:2189–2197. CrossRefPubMedGoogle Scholar
  44. 44.
    Lee JJ, Patel R, Biermann JS, Dougherty PJ (2013) The musculoskeletal effects of cigarette smoking. J Bone Joint Surg Am 95:850–859. CrossRefPubMedGoogle Scholar
  45. 45.
    Ward KD, Klesges RC (2001) A meta-analysis of the effects of cigarette smoking on bone mineral density. Calcif Tissue Int 68:259–270CrossRefGoogle Scholar
  46. 46.
    Nieves JW, Golden AL, Siris E, Kelsey JL, Lindsay R (1995) Teenage and current calcium intake are related to bone mineral density of the hip and forearm in women aged 30-39 years. Am J Epidemiol 141:342–351CrossRefGoogle Scholar
  47. 47.
    Bass S, Pearce G, Bradney M, Hendrich E, Delmas PD, Harding A, Seeman E (1998) Exercise before puberty may confer residual benefits in bone density in adulthood: studies in active prepubertal and retired female gymnasts. J Bone Miner Res 13:500–507. CrossRefPubMedGoogle Scholar
  48. 48.
    Riggs BL, Melton LJ 3rd (1992) The prevention and treatment of osteoporosis. N Engl J Med 327:620–627. CrossRefPubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  1. 1.Department of Biomedical EngineeringWorcester Polytechnic InstituteWorcesterUSA

Personalised recommendations