Smoking and fracture risk: a meta-analysis

Abstract

Smoking is widely considered a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex and bone mineral density (BMD). We studied 59,232 men and women (74% female) from ten prospective cohorts comprising EVOS/EPOS, DOES, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, Hiroshima and two cohorts from Gothenburg. Cohorts were followed for a total of 250,000 person-years. The effect of current or past smoking, on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex and BMD. The results of the different studies were merged using the weighted β-coefficients. Current smoking was associated with a significantly increased risk of any fracture compared to non-smokers (RR=1.25; 95% Confidence Interval (CI)=1.15–1.36). Risk ratio (RR) was adjusted marginally downward when account was taken of BMD, but it remained significantly increased (RR=1.13). For an osteoporotic fracture, the risk was marginally higher (RR=1.29; 95% CI=1.13–1.28). The highest risk was observed for hip fracture (RR=1.84; 95% CI=1.52–2.22), but this was also somewhat lower after adjustment for BMD (RR=1.60; 95% CI=1.27–2.02). Risk ratios were significantly higher in men than in women for all fractures and for osteoporotic fractures, but not for hip fracture. Low BMD accounted for only 23% of the smoking-related risk of hip fracture. Adjustment for body mass index had a small downward effect on risk for all fracture outcomes. For osteoporotic fracture, the risk ratio increased with age, but decreased with age for hip fracture. A smoking history was associated with a significantly increased risk of fracture compared with individuals with no smoking history, but the risk ratios were lower than for current smoking. We conclude that a history of smoking results in fracture risk that is substantially greater than that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Nelson HD, Morris CD, Kraemer DF, Mahon S, Carney N, Nygren P, Helfand M (2002) Osteoporosis in postmenopausal women: diagnosis and monitoring. In: Oregon Health and Science University Evidence-Based Practice Center (eds) Evidence report/technology assessment No. 28. Agency for Healthcare Research and Quality, Rockville, MD

  2. 2.

    Law MR, Hackshaw AK (1997) A meta-analysis of cigarette smoking, bone mineral density and risk of hip fracture; recognition of a major effect. Br Med J 315:841–846

    CAS  Google Scholar 

  3. 3.

    Huopio J, Kroger H, Honkanen R, Saarikoski S, Alhava E (2000) Risk factors for perimenopausal fractures: a prospective study. Osteoporos Int 11:219–227

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Bohannon AD, Hanlon JT, Landerman R, Gold DT (1999) Association of race and other potential risk factors with non-vertebral fractures in community-dwelling elderly women. Am J Epidemiol 149:1002–1009

    CAS  PubMed  Google Scholar 

  5. 5.

    Mallmin H, Ljunghall S, Persson I, Bergstrom R (1994) Risk factors for fractures of the distal forearm: a population-based case-control study. Osteoporos Int 4:298–304

    CAS  PubMed  Google Scholar 

  6. 6.

    Kelsey JL, Browner WS, Seeley DG, Nevitt MC, Cummings SR (1992) Risk factors for fracture of the distal forearm and proximal humerus. Am J Epidemiol 135:477–489

    CAS  PubMed  Google Scholar 

  7. 7.

    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. New Engl J Med 332:767–773

    Article  CAS  PubMed  Google Scholar 

  8. 8.

    National Osteoporosis Foundation (1998) Osteoporosis: review of the evidence for prevention, diagnosis and treatment and cost-effectiveness analysis. Osteoporos Int [Suppl 4] 8:1–88

    Google Scholar 

  9. 9.

    National Osteoporosis Foundation (1998) Physicians guide to prevention and treatment of osteoporosis. National Osteoporosis Foundation, Washington DC, pp 1–38

  10. 10.

    Brown J, Josse RG for the Scientific Advisory Council of the Osteoporosis Society of Canada (2002) Clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. Canad Med Assoc J [Suppl 10] 167:S1-S34

  11. 11.

    Kanis JA, Delmas P, Burckhardt P, Cooper C, Torgerson D on behalf of the EFFO (1997) Guidelines for the diagnosis and management of osteoporosis. Osteoporos Int 7:390–406

    CAS  PubMed  Google Scholar 

  12. 12.

    Royal College of Physicians (1999) Osteoporosis: clinical guidelines for prevention and treatment. Royal College of Physicians, London

  13. 13.

    Royal College of Physicians (2000) Osteoporosis: clinical guidelines for prevention and treatment. Update on pharmacological interventions and an algorithm for management. Royal College of Physicians, London

  14. 14.

    Kanis JA, Black D, Cooper C, Dargent P, Dawson-Hughes B, De Laet C, Delmas P, Eisman J, Johnell O, Melton J, Oden A, Papapoulos S, Pols H, Rizzoli R, Silman A, Tenenhouse A (2002) A new approach to the development of assessment guidelines for osteoporosis. Osteoporos Int 13:527–536

    Article  Google Scholar 

  15. 15.

    Kanis JA (2002) Diagnosis of osteoporosis and assessment of fracture risk. Lancet 359:1929–1936

    Article  PubMed  Google Scholar 

  16. 16.

    Kreiger N, Tenenhouse A, Joseph L et al (1999) The Canadian Multicenter Osteoporosis Study (CaMos): background, rationale, methods. Can J Aging 18:376–387

    Google Scholar 

  17. 17.

    Jones G, Nguyen TV, 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

    CAS  PubMed  Google Scholar 

  18. 18.

    Nguyen TV, Eisman JA, Kelly PJ, Sambrook PN (1996) Risk factors for osteoporotic fractures in elderly men. Am J Epidemiol 144:255–263

    CAS  PubMed  Google Scholar 

  19. 19.

    O’Neill TW, Felsenberg D, Varlow J, Cooper C, Kanis JA, Silman AJ (1996) The prevalence of vertebral deformity in European men and women: European vertebral osteoporosis study. J Bone Miner Res 11: 1010–1017

    PubMed  Google Scholar 

  20. 20.

    Felsenberg D, Silman AJ, Lunt M, Ambrecht G, Ismail AA, Finn JD, Cockerill WC, Banzer D, Benevolenskaya LI, Bhalla A, Bruges Armas J, Cannata JB, Cooper C, Dequeker J, Eastell R, Ershova O, Felsch B, Gowin W, Havelka S, Hoszowski K, Jajic I, Janot J, Johnell O, Kanis JA, Kragl G, Lopez Vaz A, Lorenc R, Lyritis G, Masaryk P, Matthis C, Miazgowski T, Parisi G, Pols HAP, Poor G, Raspe HH, Reid DM, Reisinger W, Scheidt-Nave C, Stepan J, Todd C, Weber K, Woolf AD, 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

    PubMed  Google Scholar 

  21. 21.

    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 HAP, 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

    Article  Google Scholar 

  22. 22.

    Svanborg A (1977) 70-year-old people in Gothenburg. A population study in an industrialised Swedish city II. Journal Presentation of Social and Medical Conditions. Acta Med Scand [Suppl] 611:5

  23. 23.

    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

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Stenstrom M, Olsson JO, Mellstrom D (2000) Thyroid hormone replacement is not related to increased risk of osteoporosis. Osteoporos Int [Suppl 2] 11:S144.

  25. 25.

    Fujiwara S, Kasagi F, Yamada M, Kodama K (1997) Risk factors for hip fracture in Japanese cohort. J Bone Miner Res 12:998–1004

    Google Scholar 

  26. 26.

    Fujiwara S, Fumiyoshi K, Masunari N, Naito K, Suzuki G, Fukunage M (2003) Fracture prediction from bone mineral density in Japanese men and women. J Bone Miner Res 18:1547–1553

    PubMed  Google Scholar 

  27. 27.

    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

    Article  CAS  PubMed  Google Scholar 

  28. 28.

    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

    PubMed  Google Scholar 

  29. 29.

    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

    PubMed  Google Scholar 

  30. 30.

    Hofman A, Grobbee DE, De Jong PT, van den Ouweland FA (1991) Determinants of disease and disability in the elderly: the Rotterdam study. Eur J Epidemiol 7:403–422

    CAS  PubMed  Google Scholar 

  31. 31.

    De Laet CE, Van Hout BA, Burger H, Hofman A, Weel AE, Pols HAP (1998) Hip fracture prediction in elderly men and women: validation of the Rotterdam study. J Bone Miner Res 13:1587–1593

    PubMed  Google Scholar 

  32. 32.

    Johansson H, Oden A, Johnell O, Jonsson B, De Laet C, Oglesby A, McCloskey EV, Kayan J, Jalava T, Kanis JA (2003) Optimisation of BMD measurements to identify high-risk groups for treatment—a test analysis. J Bone Miner Res (in press)

  33. 33.

    Kanis JA, Oden A, Johnell O, Jonsson B, De Laet C, Dawson A (2001) The burden of osteoporotic fractures: a method for setting intervention thresholds. Osteoporos Int 12:417–427

    Article  CAS  PubMed  Google Scholar 

  34. 34.

    Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. Br Med J 327:557–560

    Article  Google Scholar 

  35. 35.

    Marshall D, Johnell O, Wedel H (1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. Lancet 312:1254–1259

    CAS  Google Scholar 

  36. 36.

    Cornuz J, Feskanich D, Willett WC et al (1999) Smoking, smoking cessation and risk of hip fracture in women. Am J Med 106:311–314

    Article  CAS  PubMed  Google Scholar 

  37. 37.

    Sowers MR, Clark MK, Hollis B, Wallace RB, Jannausch M (1992) Radial bone mineral density in pre- and perimenopausal women: a prospective study of rates and risk factors for loss. J Bone Miner Res 7:647–657

    CAS  PubMed  Google Scholar 

  38. 38.

    Hannan MT, Felson DT, Dawson Hughes B, Tucker KL, Cupples LA, Wilson PWF, Keil DP (2000) Risk factors for longitudinal bone loss in elderly men and women. The Framingham Osteoporosis Study. J Bone Miner Res 15:710–720

    CAS  PubMed  Google Scholar 

  39. 39.

    Burger H, De Laet C, Van Daele P, Weel A, Witteman J, Hofman A, Pols H (1998) Risk factors of increased bone loss in an elderly population. The Rotterdam Study. Am J Epidemiol 147:871–879

    CAS  PubMed  Google Scholar 

  40. 40.

    Hermann AP, Brot C, Gram J, Kolthoff N, Mosekilde L (2000) Premenopausal smoking and bone density in 2,015 perimenopausal women. J Bone Miner Res 15:780–787

    Google Scholar 

  41. 41.

    McKinlay SM, Bifano NL, McKinley JB (1985) Smoking and age at menopause in women. Ann Intern Med 103:350–356

    CAS  PubMed  Google Scholar 

  42. 42.

    Seeman E (1996) The effects of tobacco and alcohol use on bone. In: Marcus R, Feldman D, Kelsey J (eds) Osteoporosis 1996. Academic, San Diego, pp 577–597

  43. 43.

    Kiel DP, Baron JA, Anderson JJ, Hannan MT, Felson DT (1992) Smoking eliminates the potential effects of oral estrogens on the risk for hip fractures among women. Ann Intern Med 116:716–721

    CAS  PubMed  Google Scholar 

  44. 44.

    Hoidrup S, Gronbaek M, Pedersen AT, Lauritzen JB, Gottschau A, Schroll M (1999) Hormone replacement therapy and hip fracture risk: effects of modifications by tobacco smoking, alcohol intake, physical activity and body mass index. Am J Epidemiol 150:1085–1093

    CAS  PubMed  Google Scholar 

  45. 45.

    Johnell O, Gullberg B, Kanis JA, Allander E, Elffors L, Dequeker J, Dilsen G, Gennari C, Lopez Vaz A, Lyritis G, Mazzuoli G, Miravet L, Passeri M, Perez Cano R, Rapado A, Ribot C (1995) Risk factors for hip fracture in European women: the MEDOS study. J Bone Miner Res 10:1802–1815

    CAS  PubMed  Google Scholar 

  46. 46.

    Gunnes M, Mellstrom D, Johnell O (1998) How well can a previous fracture indicate a new fracture? A questionnaire study of 29,802 postmenopausal women. Acta Orthop Scand 69:508–512

    CAS  PubMed  Google Scholar 

  47. 47.

    Ensrud KE, Nevitt MC, Yunis C, Cauley JA, Seeley DG, Fox KM et al (1994) Correlates of impaired function in older women. J Am Geriatr Soc 42:481–489

    CAS  PubMed  Google Scholar 

  48. 48.

    Nelson HD, Nevitt ME, Scott JC, Stone KL, Cummings SR (1994) Smoking, alcohol and neuromuscular and physical function of older women. JAMA 272:1825–1831

    CAS  PubMed  Google Scholar 

  49. 49.

    Svendsen OL, Hassager C, Skodt T, Christiansen C (1995) Impact of soft tissue on in vivo accuracy of bone mineral measurements in the spine, hip and forearm: a human cadaveric study. J Bone Miner Res 10:868–873

    CAS  PubMed  Google Scholar 

  50. 50.

    Kanis JA, Johnell O, Oden A, De Laet C, Jonsson B (2001) Intervention thresholds for osteoporosis. Bone 31:26–31

    Article  Google Scholar 

  51. 51.

    Van Staa TP, Leufkens HGM, Cooper C (2002) Does a fracture at one site predict later fractures at other sites? A British cohort study. Osteoporos Int 13:624–629

    Article  Google Scholar 

  52. 52.

    Klotzbeucher CM, Ross PD, Landsman PB, Abbot TA, Berger M (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 15:721–739.

    CAS  PubMed  Google Scholar 

  53. 53.

    Guidelines Writing Group (2002) Glucocorticoid-induced osteoporosis. Guidelines for prevention and treatment. Bone and Tooth Society of Great Britain, National Osteoporosis Society and Royal College of Physicians. Royal College of Physicians, London

  54. 54.

    Delmas PD, Eastell R, Garnero P, Seibel MJ, Stepan J (2000) The use of biochemical markers of bone turnover in osteoporosis. Osteoporos Int [Suppl 6] 11:S2-S17

Download references

Acknowledgements

We are grateful to the National Osteoporosis Foundation, the International Society for Clinical Densitometry and the European Union (FP3/5) for supporting this study. We also thank the Alliance for Better Bone Health, Hologic, IGEA, Lilly, GE Lunar, Novartis, Pfizer Roche and Wyeth for their unrestricted support. Personal potential conflicts of interest are acknowledged (J.A.K., O.J.), but in opposite directions.

Author information

Affiliations

Authors

Corresponding author

Correspondence to J. A. Kanis.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kanis, J.A., Johnell, O., Oden, A. et al. Smoking and fracture risk: a meta-analysis. Osteoporos Int 16, 155–162 (2005). https://doi.org/10.1007/s00198-004-1640-3

Download citation

Keywords

  • Body mass index
  • Hip fracture
  • Meta-analysis
  • Osteoporotic fracture
  • Smoking