Osteoporosis International

, Volume 23, Issue 8, pp 2081–2092

The effects of smoking on bone metabolism

Authors

  • V. Yoon
    • The Charles and Jane Pak Center for Mineral Metabolism and Clinical Research and Department of Internal MedicineUniversity of Texas Southwestern Medical Center
  • N. M. Maalouf
    • The Charles and Jane Pak Center for Mineral Metabolism and Clinical Research and Department of Internal MedicineUniversity of Texas Southwestern Medical Center
    • The Charles and Jane Pak Center for Mineral Metabolism and Clinical Research and Department of Internal MedicineUniversity of Texas Southwestern Medical Center
Review

DOI: 10.1007/s00198-012-1940-y

Cite this article as:
Yoon, V., Maalouf, N.M. & Sakhaee, K. Osteoporos Int (2012) 23: 2081. doi:10.1007/s00198-012-1940-y

Abstract

Osteoporosis is a common, morbid and costly disorder characterized by deterioration in bone strength. Cigarette smoking is associated with reduced bone mineral density (BMD) and increased fracture risk. There are basic, clinical, and observational studies that define several of the underlying pathophysiologic mechanisms that predispose smokers to bone loss. Such mechanisms include alterations in calciotropic hormone metabolism and intestinal calcium absorption, dysregulation in sex hormone production and metabolism, alterations in adrenal cortical hormone metabolism and in the receptor activator of nuclear factor kappa-B (RANK), receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) system (RANK–RANKL–OPG system), and direct cellular effects of cigarette use on bone cells. In addition, there is evidence of reversibility in the aforementioned mechanisms with smoking cessation. In summary, cigarette smoking is a reversible risk factor for osteoporosis and osteoporotic fractures through diverse pathophysiologic mechanisms.

Keywords

OsteoporosisSmokingSmoking cessation

Introduction

Osteoporosis is a complex heterogeneous disorder characterized by an imbalance in bone remodeling which culminates in reduced BMD, deterioration of microarchitectural integrity of the bone, and increased risk of fracture. It has a major economic [1] and health [2, 3] impact. Osteoporotic fractures are associated with increased morbidity [4] and mortality [5].

There is ample evidence that smoking is an independent risk factor for low BMD [68]. Recent evidence has also shown adverse effects of passive smoking on BMD [9]. Based on the Centers for Disease Control and Prevention (CDC), the prevalence of cigarette smoking in the USA has decreased over the past 5 decades (Fig. 1), and it remains stable at around 20% over the past few years despite public education and escalating restrictions on places where people can smoke [10]. In comparison, the worldwide prevalence of smokers for 2040–2050 is projected to increase from 1.3 billion to 1.5 billion [11]. Therefore, smoking is expected to continue to be a global and major risk factor for osteoporosis and osteoporotic fractures for a significant number of individuals worldwide.
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Fig. 1

Smoking prevalence in the USA from 1965 to 2010 based on CDC data

Clinical: effect of smoking on bone mass and fracture risk

Bone mineral density

The unhealthy lifestyle habits seen in smokers, including alcohol use, lack of physical activity, lack of sun exposure, and low calcium intake, impact overall health as well as bone health [12, 13]. However, smoking has a central role in the development of bone loss. Although genetic factors contribute significantly to bone mass, a cross-sectional study has shown a significant association between smoking and BMD in same-sex twin pairs independent of age, sex, and genetic disposition [7]. The deleterious impact of smoking on BMD involves all skeletal sites [14, 15]. The effect of smoking on bone is specifically influenced by dose and duration of smoking and body weight [1618]. Greater exposure to cigarettes (expressed as number of years as a smoker, cigarettes per day or pack-years) has been associated with greater decline in BMD at multiple skeletal sites in a large meta-analysis [8]. Similarly, greater exposure to smoking was associated with lower bone mass in twin studies, confirming a dose effect independent of age, gender, and genetic composition [7, 19, 20].

With respect to body weight, a cross-sectional study showed that premenopausal female smokers with lower body mass index (BMI) < 25 kg/m2 had a significant decline in BMD compared to those with a BMI > 25 kg/m2 who had no significant change in BMD compared to controls [14].

Smoking is associated with changes in BMD independent of age and gender. Within the population of individuals aged 60 years and older, there is as significant difference in BMD in smokers compared with nonsmokers independent of other confounding variables such as age, BMI, exercise activity, etc [15, 18]. This effect has also been seen in a younger cohort with studies showing premenopausal women and young men with decreased BMD at all sites compared to age-matched nonsmokers [14, 21]. In conclusion, epidemiologic studies have demonstrated an independent effect of smoking on BMD [6, 15, 16, 21]. Nevertheless, this independent effect of smoking on BMD could not be confirmed in a few studies [2224].

Fracture risk

A larger number of studies have demonstrated that smoking increases the risk of bone fracture at all skeletal sites [2553] (Table 1). The independent effect of smoking on fracture risk was shown in a meta-analysis of ten large cohorts after adjustment for age, BMD, and BMI [6]. It is on this basis that smoking is included in the widely used FRAX calculation of absolute risk of fracture developed by the World Health Organization (WHO) that calculates a 10-year probability of hip and other major osteoporotic fractures [54].
Table 1

Smoking exposure and risk for fracture

Reference

Study design

Study population

Age of subjects (years)

Smoker classification

Dose of smoking and/or duration

Results

Baron et al. (2001) [25]

Case–control

4640 women from Sweden

Post-menopause

Current smoker

Current smoker—smoked continuously or smoked ≥100 cigarettes in a lifetime

Odds ratio for hip fracture in current smokers at 1.66a

   

Former smoker

Quartiles with years of smoking (years): 1–14, 15–30, 31–45, > 45

 
   

Never smoker

  

Hoidrup et al. (2000) [26]

Cohort

30,000 men and women from Copenhagen

20–93

Current noninhaling/inhaling smoker

Current tobacco consumption (gram tobacco/day): 1–14, ≥15

Relative risk for hip fracture in male current smokers at 1.74a and female current smokers at 1.39a

    

Ex-smoker: quit smoking <5 years and ≥5 years

 
    

Smoking duration (pack-years of smokingb): 1–14, 15–29, ≥30

 

Jutberger et al (2010) [27]

Cohort

3003 men from Sweden

69–80

Current smoker

Not specifically stated

Hazard ratio for hip fracture in current smokers at 2.34

   

Ex-smoker

  
   

Never smoker

  
   

Nonsmoker (ex-smoker + never smoker)

  

Taes et al. (2010) [28]

Cross-sectional

677 males from Belgium

25–45

Current smoker

Early smoker <16 y/o

Odds ratio for all fractures in current smokers at 2.13

   

Former smoker

Late smoker ≥16 y/o

 
   

Never smoker

  

Hippisley-Cox et al. (2009) [29]

Cohort

> 2 million men and women from England

30–85

Current smoker

Heavy smoker ≥20 cig/day

Relative risk for osteoporotic fracture in male heavy smokers at 1.70a and for hip fracture at 1.36.a Relative risk for osteoporotic fracture in female heavy smokers at 1.21a and for hip fracture at 1.55a

   

Former smoker

Moderate smoker 10–19 cig/day

 
   

Nonsmoker

Light smoker <10 cig/day

 

Stolee et al. (2009) [30]

Cohort

40,279 home care clients from Canada

65 and older

Smoked or chewed tobacco daily

Not specifically stated

Relative risk for hip fracturea in current smokers at 1.41

Jenkins et al. (2008) [31]

Case–control

488 women from Texas

Post-menopause

Current smoker

Not specifically stated

Odds ratio for hip fracture in current smokers at 3.72

   

Former smoker

  
   

Never smoker

  

Robbins et al. (2007) [32]

Cohort

93,676 women in the observational component of the Women’s Health Initiative

Post-menopause

Current smoker

Not specifically stated

Odds ratio for hip fracture in current smokers at 2.33a

   

Past smoker

  
   

Never smoker

  

Ojo et al. (2007) [33]

Cohort

2,621 Mexican American men and women from the USA

72 and older

Current smoker

Not specifically stated

Hazard ratio for hip fracture in current smokers at 1.11 and for non-hip fracture at 1.51

   

Former smoker

  
   

Never smoker

  

Van Geel et al. (2006) [34]

Cohort

759 women from Europe

Post-menopause

Present smoking

Present smoker: average cig/day 3.9 ± 7.7

Hazard ratio for 5 years probability of fracture in current smokers at 1.7

   

Past smoking

Average years of smoking 9.2 ± 16.3

 
    

Past smoker: average cig/day 3.4 ± 8.5

 
    

Past average

 
    

Years of smoking 4.8 ± 11.3

 

Van Staa et al. (2006) [35]

Cohort

366,104 women from the UK

50 and older

Generally stated as smoker %

Not specifically stated

Relative risk for hip fracture in smokers at 1.44, for vertebral fracture at 1.45, and for other osteoporotic fracture at 1.13

Kelsey et al. (2005) [36]

Case–control

192 pelvic fracture cases and 2,402 controls in men and women from California

45 and older

Current smoker

Not specifically stated

Odds ratio for pelvic fracture in current smokers at 2.17

   

Nonsmoker

  

Bensen et al. (2005) [37]

Cohort

3426 women in CANDOO

Post-menopause

Smoking

Not specifically stated

Odds ratio for vertebral fracture in smokers at 1.95 and for hip fracture at 1.48

   

No smoking

  

Kato et al. (2000) [38]

Cohort

5817 women from New York

34–65

Current smoker

Current smoking dose (cig/day): 0, 1–10, 11–20, 21+

Relative risk for all fractures in women who smoke 21+ cigarettes/day at 1.31

   

Past smoker

  
   

Never smoker

  

Forsén et al. (1998) [39]

Cohort

35,767 men and women from Norway

50 and older

Current smoker

Not specifically stated

Relative risk for hip fracture in women 50–64 y/o at 1.5, for 65–74 y/o women at 2.2, and for 75+ y/o women at 1.7. Relative risk for hip fracture in men 50–64 y/o at 4.0, for 65–74 y/o men at 5.3, and for 75+ y/o men at 1.6

   

Ex-smoker

  
   

Never daily smoker

  

Forsén et al. (1994) [40]

Cohort

34,856 men and women from Norway

50 and older

Current smoker

Not specifically stated

Relative risk for hip fracture with current smoking males and females at 1.8a

   

Nonsmoker

  

Grisso et al. (1997) [41]

Case–control

356 1st hip fracture cases and 402 controls of men from Pennsylvania and California

45 and older

Current smoker

Smoking within the past year

Odds ratio for hip fracture in smokers ≥1 pack/day at 3.3

   

Former smoker

Smoking ≤1 cig/day for ≥6 months or smoking a pipe once a day for ≥6 months or 1 cigar/day for ≥6 months

 
   

Nonsmoker

Current smoker <1 pack/day

 
    

Current smoker ≥1 pack/day

 

Grisso et al. (1994) [42]

Case–control

144 hip fracture cases compared to 218 controls of African American women from New York and Philadelphia

45 and older

Current smoker

Smoker defined as smoking ≤1 cig/day for ≥6 months

Odds ratio for hip fracture with current smokers ≥1 pack/day at 2.0a

   

Former smoker

Current smoker <1 pack/day

 
   

Nonsmoker

Current smoker ≥1 pack/day

 

Cooper et al. (1988) [43]

Case–control

300 hip fracture cases and 600 controls of men and women from Britain

50 and older

Not specifically stated

Not specifically stated

Relative risk for hip fracture in current smokers at 1.7

Meyer et al. (1993) [44]

Cohort

52,313 men and women from Norway

35–49

Current smoking

Smoking defined as: <15 cig/day, ≥15 cig/day, or pipes, cigars

Relative risk for hip fractures with smoking ≥15 cigarettes/day in women at 1.46a and for men at 1.81a

   

Ex-smoking

Unknown number of cigarettes

 
   

Never smoking

  

Kiel et al. (1992) [45]

Cohort

2873 women from the Framingham study

55 and older

Current smoker

Light smoker 1–20 cig/day

Relative risk for hip fracture with smoking >1 pack/day at 1.84a

   

Former smoker

Heavy smoker ≥21 cig/day

 
   

Never smoker

Former smoker have not smoked within 2 years

 

Cummings et al. (1995) [46]

Cohort

9516 white women from the USA

65 and older

Current smoker

Not specifically stated

Relative risk for hip fracture with current smoking at 1.4a

   

Never smoker

  

Paganini-Hill et al. (1991) [47]

Cohort

8600 women and 5049 from California

Post-menopause and median age 73

Current smoker

Not specifically stated

Relative risk for hip fracture with current smoking males at 1.94a and females at 1.63a

   

Past smoker

  
   

Never smoker

  

Paganini-Hill et al. (1981) [48]

Case–control

91 hip fracture cases compared to 242 controls of women from California

< 80

Based on number of cigarettes smoked/day

Smoking definition: 0 cig/day, 1–10 cig/day, >10 cig/day

Risk ratio for hip fractures for current smoking (11+ cigarettes/day) after menopause at 1.96a

La Vecchia et al. (1991) [49]

Case–control

209 hip/femoral fracture cases compared to 1449 controls of women from Italy

29–74

Current smoker

Dose defined (cig/day): <15, 15–24, ≥25

Relative risk for hip fracture with current smoking at 1.5a

   

Ex-smoker

Duration defined (smoking years): <20, ≥20

 
   

Never smoker

  

Williams et al. (1982) [50]

Case–control

353 hip/forearm fracture cases compared to 576 controls of women from Washington

50–74

Ever smoked

Not specifically stated

Relative risk for hip fracture with ever smoking females at 13.5 compared to never smoking females at 4.4

   

Never smoked

  

Michaëlsson et al. (1995) [51]

Case–control

247 hip fracture cases and 893 controls of women from Sweden

Any

Current smoker

Smoking duration (pack-years of smokingb): <20, ≥20

Odds ratio for hip fracture with current smokers >20 pack-years at 1.63a

   

Former smoker

  

Kreiger et al. (1992) [52]

Case–control

102 hip fracture cases, 154 wrist fracture cases, and 277 controls of women from Canada

Post-menopause

Current smoker

Not specifically stated

Odds ratio for hip fracture with current smokers at 1.73a

   

Former smoker

  
   

Never smoker

  

Cumming et al. (1994) [53]

Case–control

209 hip fracture cases compared to 207 controls of men and women from Australia

65 and older

Current smoker

Smoking defined as (cig/day): 0, 1–19, ≥20

Odds ratio for hip fracture with current smoking at 2.2a

   

Ever smoked

Duration based on age 20, 50, and current age

 
   

Ex-smoker

  
   

Never smoker

  

aAdjustment for potential confounding variables (example: age, BMI, alcohol use, and physical activity)

bPack-years of smoking defined as years of smoking multiplied by packs currently consumed. One pack-year of smoking equals smoking a pack daily for 1 year

While smoking has a negative impact on BMD and increases the risk of fracture, its impact may differ between men and women. Compared to men, women may exhibit an earlier evidence of decline in BMD at the hip even after adjusting for BMI, estrogen use, exercise, and alcohol use [15]. In a large meta-analysis, smoking was associated with a greater relative risk of fracture in men than in women for all osteoporotic fractures except for hip fracture [6]. Few studies have looked at gender differences in smokers and BMD, and it remains unclear if these differences are significant. Further studies are needed to observe if such differences exist between male and female smokers.

Pathophysiology: mechanism of smoking and osteoporosis

The pathophysiologic mechanisms underlying osteoporosis in cigarette smokers have not been fully explored. The alteration of bone metabolism induced by cigarette smoking may occur indirectly by altered calciotropic hormone metabolism [55, 56], by derangements in the production, metabolism, and binding of estradiol [5759], alterations in adrenal cortical hormone metabolism [60, 61], and/or direct effects on osteogenesis including alteration in the RANK–RANKL–OPG system [62, 63], collagen metabolism [64], and bone angiogenesis [65] (Fig. 2).
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Fig. 2

Pathophysiologic mechanisms due to cigarette smoking that leads to decreased bone mineral density and increased fracture risk. Tobacco use increases risk through bone mineral density-dependent factors, as well as through direct effects that are independent of BMD

Smoking and calciotropic hormones

The parathyroid hormone (PTH)–vitamin D axis plays an integral part in calcium homeostasis and bone mineralization, as PTH regulates serum ionized calcium through alteration of bone resorption and renal calcium reabsorption [66] while 1,25 dihydroxyvitamin D (1,25-OH2-D) regulates intestinal calcium absorption [67, 68]. Two cross-sectional and cohort studies have demonstrated lower serum 25-hydroxyvitamin D (25-OH-D) and 1,25-OH2-D levels in current smokers compared to nonsmokers [6972]. Although this has not been investigated, smoking may alter hepatic metabolism of vitamin D by influencing 25 hydroxylase (CYP2R1) in the liver and lowering serum 25-OH-D, similar to the effect of smoking on enhanced hepatic degradation of estrogen [57, 73]. The pathophysiologic mechanism for low 1,25-OH2-D levels in smokers has not been fully explored. However, it has been hypothesized that low calcitriol levels may be due to low availability of 25-OH-D, a metabolic precursor to 1,25-OH2-D, or potentially due to suppression of PTH release [71]. Whether smoking or nicotine directly influences renal 1α hydroxylase activity has not been studied.

Reports on the effect of smoking on serum PTH have been conflicting. Few studies have shown a vitamin D-dependent rise in PTH [56, 70]. On the contrary, other studies demonstrated suppressed PTH levels despite low vitamin D levels [69, 71, 74]. The underlying mechanisms for this difference in serum PTH have not been fully investigated. However, confounding effects of weight, alcohol consumption, estrogen use, physical activity, sun exposure, and variability in calcium and vitamin D intake may account for the inconsistent PTH levels in published studies [69, 75].

There is evidence that smoking alters gastrointestinal calcium absorption through changes in calciotropic hormone metabolism, consequently affecting bone status [56, 69]. Intestinal calcium absorption assessed either directly using stable calcium isotope or indirectly following an oral calcium load was lower in smokers compared to nonsmokers [55, 56, 76, 77]. These results suggest that adequate calcium and vitamin D intake is essential to attain sufficient intestinal calcium absorption in this population. However, it is evident that smokers have an unhealthier lifestyle such as low calcium/vitamin D intake and lack of exercise that affects calciotropic hormones and overall bone health [13, 78].

Smoking and sex hormones

Estrogen plays a protective role in bone metabolism, primarily through suppression of bone resorption [7981]. The effects of estrogen deficiency in the pathogenesis of osteoporosis have been known for years in postmenopausal women but also in men with low estradiol levels [82, 83]. Several studies show that smokers have lower luteal phase urinary excretion of estradiol and estriol [73], experience an earlier onset of menopause [84, 85], and have an attenuated response in serum estradiol levels to incremental doses of oral estrogen [86] which effectively create an estrogen deficient state and adversely affect their bone health. There are three possible ways smoking alters estrogen production and metabolism (Fig. 3): 1) Nicotine and its metabolite cotinine reduce estrogen production by inhibiting the enzyme aromatase in a reversible fashion [58]. 2) In both genders, smoking enhances the hepatic metabolism of estradiol [59] through 2α-hydroxylation, leading to the irreversible conversion of estrone to 2-methoxyestrone, an inactive metabolite [57, 73]. 3) Smokers have higher serum sex-hormone binding globulin (SHBG) levels compared to nonsmokers, potentially reducing free estradiol concentration [22, 59]. However, other studies have shown no association between smoking and estradiol [87] or a paradoxical rise in estradiol levels in post-menopausal smokers compared to nonsmokers [88]. The variability in the results from these studies can be explained by differences in study population, study design, and timing of lab draws.
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Fig. 3

Alteration in production, metabolism, and binding of estradiol with cigarette smoking. Estrogen synthesis and metabolism: effects of smoking are highlighted in red. Smoking: 1 reduces estradiol production (by inhibiting aromatase), 2 increases 2-hydroxylation and irreversible production of 2-methoxyestrone, an inactive estrogen metabolite, and 3 increases SHBG levels which decreases amount of active free estradiol

Testosterone has an indirect role in bone health [8991] through aromatization to estrogen [83]. However, testosterone may also have a direct effect on bone health given the presence of androgen receptors expressed in bone [92, 93]. A number of studies have shown that low serum testosterone levels are associated with risk of osteoporotic fractures in elderly men [94, 95]. Male hypogonadism is associated with significant deterioration of trabecular bone [96] and with worse frailty status that may indirectly have an impact on fracture risk [97]. The effect of smoking on testosterone metabolism is not clearly understood. Few studies have looked at this association and showed no difference [98, 99] or a paradoxical rise [72, 100, 101] in testosterone levels in male smokers compared to nonsmokers. The paradoxical rise in testosterone levels in male smokers could be related to a diminished negative feedback to the hypothalamus–pituitary axis due to low estradiol levels leading to a rise in gonadotropins and therefore a rise in testosterone levels seen in smokers [101]. In addition, smoking may inhibit aromatase and prevent the conversion of testosterone to estradiol [58]. Finally, it is possible that nicotine may stimulate adrenocorticotropic hormone (ACTH), resulting in stimulation of cortisol as well as androgens [60, 102, 103] which will be explained in the next section.

Smoking and adrenal hormones

Glucocorticoid excess can affect bone metabolism directly by alterations in osteoblastic and osteoclastic cell activity, or indirectly through changes mediated by altered gonadal hormone metabolism, impaired gastrointestinal absorption of calcium, and/or defective renal tubular calcium reabsorption [104109]. An in vitro study using a cat adrenocortical cell model showed that nicotine can independently increase cortisol release and have a synergistic role to ACTH in stimulating cortisol release [60]. A few studies have demonstrated that smokers have higher levels of cortisol, dehydroepiandrosterone (DHEAS), and androstenedione levels compared to nonsmokers [61, 102, 103]. However, these results were not confirmed by other studies showing similar cortisol levels in smokers and nonsmokers [110, 111]. In conclusion, the potential underlying metabolic pathways have not been fully elucidated in human subjects.

Direct effects on bone cells

Bone is a dynamic organ with osteoblasts regulating bone formation while osteoclasts promote bone resorption. These two cell types are regulated by several factors including the RANK–RANKL–OPG system, estradiol, various cytokines, and calciotropic hormones [81]. The effect of nicotine on osteoblastic bone formation and osteoclastic bone resorption is complex. Nicotine alters proliferation of osteoblast cells and markers of bone formation [112]. However, in a dose-dependent manner, nicotine at lower concentrations stimulates bone formation and at higher concentrations inhibits bone formation [112, 113]. This pattern may be receptor mediated through nicotinic acetylcholine receptors found in osteoblast cells [114, 115].

The effect of nicotine on osteoblastic release of IL-6, a regulator of bone resorption, appears to be species-specific [116], with a lack of response in IL-6 levels to nicotine in human osteoblast cells [117]. On the other hand, two in vitro studies have shown a decrease or no change in osteoclast-like cells formation after nicotine exposure based on tartrate-resistant acid phosphatase (TRAP), a biomarker of osteoclastic cell activity [118, 119].

Additionally, non-nicotine constituents of tobacco have a direct effect on bone cells [120122]. In vitro studies have shown cigarette smoke extract inhibits osteoblast-like cell proliferation and differentiation [121] as well as bone repair and remodeling [120].

Effects on other bone-related factors

The RANK–RANKL–OPG system plays an important role in osteoclast formation and activity [123125]. The interaction between RANKL and RANK promotes osteoclast formation while OPG competes with RANKL for RANK and inhibits osteoclastogenesis [123126]. Few studies have investigated the relationship between smoking and the RANK–RANKL–OPG system. Rats exposed to cigarette smoke inhalation had an upregulation in RANKL/OPG ratio compared to the rats without exposure [127]. In addition, two studies comparing smokers to nonsmokers who were susceptible for periodontitis showed that smokers had lower OPG levels without a statistical difference in RANKL levels [62, 63].

Nicotine has an inhibitory effect on osteogenesis but may also have the same effect on angiogenesis, which can play a detrimental role in bone dynamics. An in vitro study, using nicotine pellets in rabbits, showed that nicotine not only had a dose-dependent inhibitory effect on rabbit osteoblast cell proliferation but also on transforming growth factor-β1 (TGF-β1), bone morphogenetic protein-2 (BMP-2,) platelet-derived growth factor-AA (PDGF-AA), and vascular endothelial growth factor (VEGF). The latter factors play a role in either osteogenesis or angiogenesis [65]. In addition, impaired bone formation in smokers may be directly attributed to defective collagen synthesis [64]. Finally, smokers may be more likely to fall than nonsmokers, in part because of a decline in physical function that leads to weakness and poor balance [128].

Effects of smoking cessation

Few studies have observed the reversible effect of smoking cessation on bone health. Two cross-sectional studies have shown that the bone density of ex-smokers improves as early as <10 years and approaches that of never smokers with >30 years of smoking cessation [129] and that the fracture risk of ex-smokers is intermediate between that of current smokers and never smokers with 10 or more years of smoking cessation [130]. Studies specifically addressing the effects of smoking cessation or reduction in postmenopausal women have shown an improvement in markers of bone formation and bone resorption and gonadal hormone abnormalities as early as 6 weeks of smoking reduction/cessation and 1 year with improvement in bone density [110, 131]. The long-term effect of nicotine replacement [132] or other pharmacological treatments for smoking cessation on bone dynamics has not been fully investigated, and an improved understanding of the role of nicotine vs. non-nicotine components of cigarettes on bone health will allow for better smoking cessation strategies in smokers with bone disease who wish to quit smoking.

Conclusions

Cigarette smoking and osteoporosis are highly prevalent among adults worldwide. Cigarette smoking is associated with lower BMD in a dose-related and duration-related fashion. Tobacco use is also a risk factor for osteoporotic fractures independent of body mass and of BMD. The deleterious effects of tobacco use on bone health may be reversible. Multiple mechanisms link tobacco use to greater fracture risk, and the understanding of these underlying mechanism(s) require careful clinical and basic investigation to help improve the management of bone disease in individuals who smoke.

Acknowledgment

The study was supported by The Endocrine Society Amgen Scholars Fellowship Award to VY.

Conflicts of interest

None.

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2012