Vol 9, No 1, January/February 2001 9 Cigarette smoking has come under increasing attack by a number of different groups both within the United States and worldwide. This has been fueled, in part, by recog- nition of the increasing number of diseases with which smoking has been directly or indirectly associated. Currently, there are more than 50 million smokers in this country, and approximately 800 billion ciga- rettes are smoked each year. 1 The adverse effects of smoking on the cardiovascular system are common knowledge. 2,3 Smoking is implicated in the etiology of a multitude of cancers as well. 2,4 Smoking is now the leading avoidable cause of mor- bidity and mortality in the United States. According to one report, more than 500,000 deaths per year in the United States alone can be at- tributed to smoking. 2 Cigarette smoke has two phases: a volatile phase and a particulate phase. The volatile phase is the longer phase and accounts for 95% of the cigarette smoke. Nearly 500 different gases are released during the volatile phase, including nitro- gen, carbon monoxide, carbon di- oxide, ammonia, hydrogen cyanide, and benzene. The roughly 3,500 different chemicals released in the particulate phase include nicotine, nornicotine, anatabine, and anaba- sine. 5 Stripped of water, the partic- ulate matter that remains, or “tar,” contains the majority of the car- cinogens of cigarette smoke. 6 Nico- tine, which is considered the addic- tive component of cigarette smoke, has been implicated in the patho- genesis of a variety of diseases. 6 Nicotine has been shown to in- crease platelet aggregation, de- crease microvascular prostacyclin levels, and inhibit the function of fibroblasts, red blood cells, and macrophages. 6,7 Carbon monoxide has a stronger affinity for hemoglo- bin than oxygen, resulting in the displacement of oxygen from the hemoglobin and a lower oxygen tension in tissues. 8 For years, orthopaedic sur- geons have known about the rela- tionships that putatively exist between smoking and an array of orthopaedic conditions and com- plications. In the past, there have been many reports that deal with these relationships as separate entities but very few published comprehensive reviews. This arti- cle will summarize the currently available literature regarding the relationships between smoking and musculoskeletal diseases, as well as the effect on the treatment of those diseases, to provide infor- mation that can be used clinically by both the practitioner and the patient. Dr. Porter is Harry Winkler, Jr, Orthopaedic Surgery Research Fellow, Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, NC. Dr. Hanley is Chair- man, Department of Orthopaedic Surgery, Carolinas Medical Center. Reprint requests: Dr. Porter, Department of Orthopaedic Surgery, Carolinas Medical Center, PO Box 32861, Charlotte, NC 28232. Copyright 2001 by the American Academy of Orthopaedic Surgeons. Abstract Currently, there are more than 50 million smokers in this country, and approxi- mately 800 billion cigarettes are smoked each year. Smoking is now the leading avoidable cause of morbidity and mortality in the United States. According to one report, over 500,000 deaths per year in the United States alone can be attrib- uted to smoking. For years, orthopaedic surgeons have known about the rela- tionships that putatively exist between smoking and an array of orthopaedic con- ditions and complications. It has been shown to adversely affect bone mineral density, lumbar disk disease, the rate of hip fractures, and the dynamics of bone and wound healing. Although scientific and clinical information on smoking and its consequences suggests differing degrees of correlation between smoking and orthopaedic conditions, most available data do suggest a real and repro- ducible relationship. In the past, there have been many individual reports that deal with these relationships separately but very few published comprehensive reviews. This summary of the current literature regarding the relationship between smoking and musculoskeletal diseases and their treatment provides information that can be used clinically by both the practitioner and the patient. J Am Acad Orthop Surg 2001;9:9-17 The Musculoskeletal Effects of Smoking Scott E. Porter, MD, and Edward N. Hanley, Jr, MD Osteoporosis Osteoporosis is a common finding in postmenopausal women and elderly men. It is a complex disor- der that occurs earlier in life and more often in women than in men. Osteoporosis is characterized by a decrease in bone mass with a resul- tant increased risk of fractures of the radii, femoral necks, and vertebral bodies. 9,10 Honkanen et al 11 have warned against generic compar- isons of studies that deal with osteo- porotic fractures. They emphasize that the relationships between the risk factors associated with pre- menopausal, perimenopausal, and postmenopausal fractures differ by fracture type, which precludes their general comparability. In an early study by Daniell, 12 fractures of the weight-bearing spine occurred more frequently in os- teoporotic postmenopausal women who smoked than in women of similar age who did not smoke. He determined that smokers had an ap- parent cortical bone loss of roughly 1.02% per postmenopausal year, compared with only 0.69% for non- smokers (P<0.001). This rate in- creased to 1.19% for nonobese osteo- porotic women who smoked. 12 A later study by Stevenson et al 13 sup- ported the findings of Daniell by also documenting that the vertebrae of women who smoke have appre- ciably less bone mass. Many authors believe that this increase in the rate of osteoporosis observed in women who smoke is mediated by the complex and often inhibitory interaction between smoking and estrogen. 14-18 The effects of this interaction include unfavorable lipid profiles, a reduc- tion in the rate of endometrial can- cer, earlier menopause, and reduced rates of estrogen receptor–positive breast cancers. 16,17,19-21 Williams et al 14 showed that smoking adversely affected women who were not users of exogenous estrogen. In their study, they dem- onstrated an increase in the rates of hip and forearm fractures in postmenopausal women smokers. However, this increase was statisti- cally significant only for the subset of thin women who smoked and were not estrogen users. In a recent prospective study of more than 115,000 nurses, Cornuz et al 17 demonstrated a small in- crease (1.3%) in the risk of sustain- ing a hip fracture in smokers and a greater increase (1.6%) in this risk for women who smoked more than 25 cigarettes per day. This risk decreased to a level below that of control subjects after smoking ces- sation, but only after a mean of 10 years. The authors concluded that their observed results might be attributable to the inhibitory effects smoking has on circulating estro- gen. This inhibition would decrease the protective effects of estrogen on bone mass. La Vecchia et al 19 showed simi- lar results in their study of over 200 women. They demonstrated that women smokers had a 1.6% in- crease in the relative risk of sus- taining a hip fracture compared with age-matched controls. This risk increased to 2.8% for the women who smoked more than 25 ciga- rettes per day. A smaller subset of women who were actively taking hormone replacement therapy (HRT) had a nonsignificant de- crease in their relative risk to 0.4; however, the authors conjectured that the small numbers in this sub- set may have prevented the dem- onstration of statistical significance. Melhus et al 15 postulate that it is the increase in reactive oxygen intermediates, or free radicals, found in the circulation of smokers that is directly antagonizing to estrogen. They were able to dem- onstrate a nearly fivefold increase in the relative risk of hip fractures in smokers with a low intake of the antioxidant vitamins C and E when compared with a control group, after adjustment for other major osteoporosis risk factors. Jensen and Christiansen 18 stud- ied oral and percutaneous HRT and the effects of smoking on these modalities. Oral HRT resulted in a decrease in the rate of bone loss for nonsmokers, but this beneficial re- sponse to oral HRT was significantly lessened for smokers (P<0.01). In- cidentally, they also reported that smoking is antagonistic to the effect of the favorable lipid profile shared by women as a result of HRT. Osteoporosis afflicts men as well. Recent estimates based on bone den- sitometry studies suggest that be- tween 250,000 and 2,000,000 white men have osteoporosis of the femoral neck. 22 The prevalence is roughly 1% in white men over the age of 80. 10 Grisso et al 10 and Kanis et al 23 have shown that many of the risk factors for hip fractures in women also apply to men. Specifically, lean body mass, the absence of physical activity, and smoking were all associated with an increased risk of hip fracture. The authors of the National Health and Nutrition Examination Survey study exam- ined the possible risk factors for hip fracture in more than 2,500 white men. 22 Although the differences failed to reach statistical signifi- cance, the results did demonstrate an increase in the number of hip fractures sustained by men who smoke. Forsén et al 24 also demon- strated increases in the relative risk of hip fractures for smokers in their study of 35,000 men and women (5.0 and 1.9, respectively). Further- more, they reported that this in- creased risk persisted in their subjects even if they had stopped smoking within 5 years of the in- ception of the study. De Vernejoul et al 25 suggest that at the root of a decrease in bone mineral content is a defect in os- teoblast function that is caused by smoking. They demonstrated a Musculoskeletal Effects of Smoking Journal of the American Academy of Orthopaedic Surgeons 10 statistically significant decrease in trabecular volume and thickness (P<0.05) and mean wall thickness (P<0.001) of iliac-crest biopsy sam- ples from smokers compared with samples from nonsmokers. The bone resorptive properties of these individuals were normal. The ability to form bone, however, was mark- edly decreased, and this uncoupled resorption could result in osteo- porosis. Galvin et al 26 demonstrated this same relationship experimentally in a study of the effects of smokeless tobacco. Tibias from chick embryos were cultured in nicotine and smoke- less tobacco extracts, and the effects on bone glucose metabolism and col- lagen synthesis were measured. The authors concluded that tobacco extracts, in concentrations found in saliva, resulted in a nearly 25% de- crease in oxygen consumption and an 88% reduction in collagen synthe- sis. This relationship between smok- ing and osteoblast function could explain the relationships between smoking, osteoporosis, and altered bone healing that many investigators have shown. 9,12,18,25,27-29 In contrast to these findings, many other studies have not demon- strated a relationship between smok- ing and the risk of osteoporotic frac- tures. 9,16,24,30-33 In a recent study, Christensen et al 34 were unable to support the conclusions drawn by de Vernejoul et al 25 implicating osteo- blasts that have been rendered defec- tive by nicotine as a cause of osteo- porosis. Admittedly, the cohorts and purposes of the two studies differed. Nevertheless, Christensen et al found no differences in the function of osteoblasts harvested during postero- lateral fusion procedures in smokers and nonsmokers. In the Framingham Study, 33 the authors were unable to demonstrate a relationship between smoking and hip fractures in either men or women. They reexamined this rela- tionship in a follow-up study be- cause of the large amount of data that suggested some type of an association. 9,10,12,13,16,17 They specifi- cally focused their efforts on women and were once again unable to prove a statistically significant dif- ference between smokers and non- smokers who were not receiving oral HRT. This was true regardless of the number of cigarettes smoked. There was a trend toward increased fracture rate in the heavy (>20 ciga- rettes per day) smokers, but this did not reach statistical significance. When they stratified the smokers and nonsmokers by their HRT histo- ry, however, the women who had used HRT and were currently smok- ing had a substantially greater risk of sustaining a hip fracture com- pared with women who had never smoked (adjusted odds ratio, 3.44). 16 This, too, could be explained by the adverse effects of nicotine on estrogen. Hemenway et al 32 examined the data on 96,000 women in a prospec- tive study and found no difference in the rates of hip and forearm fractures in smokers and nonsmokers. The authors postulated that the relatively young age of the subjects, which ranged from 35 to 59 years, might have influenced the results. In sepa- rate studies, Hemenway et al 30,31 also looked at the rates of hip and wrist fractures in men. The researchers were unable to find a correlation between smoking and an increase in the rates of these fractures. Again, the authors noted that the subjects in this study were young, with ages ranging between 44 and 75 years. Most of the 50,000 men who partici- pated were less than 70 years of age. Furthermore, very few (<3%) of the subjects in one study were heavy smokers. 30 Low Back Pain Causal Link Low back pain is a very com- mon complaint that can be costly in time, money, and resources for the patient, the physician, and society as a whole. Studies indicate that in the Western world, 60% to 80% of the population will have an epi- sode of incapacitating low back pain at some point during their lives. Fortunately, 80% to 90% of these persons will return to being functional within a period of 4 to 8 weeks and will not experience long-term disability. However, in some individuals, the condition will progress to become chronic low back pain. 35-38 A study con- ducted in The Netherlands demon- strated that as much as 1.5% of the Gross National Product was spent on patients with low back pain. Surprisingly, only 3% of that cost was actually medically related; the remainder of the costs were for such work-related events as leaves of absence, early retirements, and job changes. 39 In the recent era of antismoking campaigns waged by health advo- cates and lobbying groups, smok- ing has come under fire from the orthopaedic community as being a possible cause of low back pain. There has been scientific evidence to both support and refute this notion. The findings from several epi- demiologic studies have suggested an association between smoking and low back pain. 35,36,40-52 Using questionnaires, Frymoyer et al 49,52 determined that low-back-pain sufferers were likely to be cigarette smokers (P<0.001), particularly when smoking was accompanied by a chronic cough (P<0.001). The authors postulated that the chronic cough of smokers might adversely affect intradiskal pressure, causing the symptom of low back pain. Al- ternatively, smoking or one of the ingredients within cigarette smoke may directly and unfavorably af- fect the spine. Later studies by Symmons et al 51 and Kelsey et al, 53 however, were unable to support a Scott E. Porter, MD, and Edward N. Hanley, Jr, MD Vol 9, No 1, January/February 2001 11 link between chronic cough and low back pain. Svensson et al 54 determined that there was a weak relationship be- tween smoking and low back pain, but found other variables with a stronger relationship to low back pain, such as calf pain on exertion, the degree of physical activity at work, and worry or tension. With the exception of the latter, all of these findings are common to other smoking-related diseases, such as heart disease and peripheral vascu- lar disease. 2,3 Smoking may simply be an indi- cation of poor health and lifestyle more than a direct cause of low back pain. Biering-Sørensen and Thomsen 55 felt that although there is an apparent causal relationship between cigarette smoking and low back pain, it is not as strong as ini- tially suggested. In nearly 1,000 subjects, they found that the contri- bution of smoking to the develop- ment of low back pain was statisti- cally significant (P<0.05), but that it had no significance as a risk factor for recurrent or persistent low back pain. Moreover, they postulated that it might not necessarily be smoking that contributes to low back pain, but rather poor general health. In a study by Cox and Trier, 41 it was found that smokers were much more likely to have low back pain and were more likely to exclude exercise from their daily routine. This finding was echoed by Deyo and Bass, 42 who suggested that smoking might be indicative of a complex interaction of personal and social traits that together are associ- ated with the increased risk of low back pain purported to occur in smokers. The complex etiology of low back pain is supported by the work of Heliövaara et al. 50 In their study of over 5,500 subjects, they demon- strated a weak relationship between smoking and low back pain and proposed that the risk of low back pain seems to be better determined by the overall quality of one’s work, lifestyle, and health behavior. Notably, they showed differences in the association between smoking and low back pain in groups gener- ated by sex, age, and quantity of cigarettes smoked. The relationship was strong in men aged 50 to 64 who smoked 20 cigarettes a day or more (odds ratio, 1.9). Interestingly, in women aged 30 to 49, there was no association with any quantity of cigarettes smoked (odds ratio, 1.0). Moreover, this apparent dichotomy was reversed for women aged 50 to 64 years. In this age group, the women who smoked more than 20 cigarettes a day had an odds ratio for the development of low back pain of 2.7. 50 This suggests that there may be some type of protection conferred on younger women. This protection can also be appreciated in relation to cardiovascular disease. 2 Boshuizen et al 44 suggest that the link between smoking and low back pain may never be fully elucidated. Leboeuf-Yde and co-workers con- ducted several studies to evaluate the relationship between smoking and low back pain. 46-48,56 Their most recent study surveyed a popu- lation of 29,424 twins and found an association between smoking and low back pain (odds ratio, 2). 47 The odds ratio increased to 3 for the group of subjects with long-standing (>30 days) complaints of low back pain. Furthermore, the cessation of smoking did not reverse these find- ings. More important were the find- ings in a large group of monozygotic twins who were discordant in their smoking histories (264 pairs of iden- tical twins composed of a smoking and a nonsmoking sibling). There was no difference in the prevalence of low back pain in the chronic- smoker group compared with their siblings in the nonsmoker group. This supports earlier work by Battié et al 57 on a much smaller sample of identical twins. The large popula- tion size in the study by Leboeuf- Yde et al 47 also allowed a critical look at the possibility of a dose response between total cigarette consumption and degree of low back pain. It was obvious from their data that this rela- tionship did not exist. This contra- dicts the earlier work by Frymoyer et al, 49 Heliövaara et al, 50 and Kelsey et al. 53 Although these findings may appear to refute any biologic or causal link between smoking and low back pain, there is still a wealth of epidemiologic, circumstantial, and anecdotal evidence supporting the earlier claims that smoking has adverse effects on the lumbar spine. Furthermore, some cases of low back pain have recognizable etio- logic factors that may be linked to smoking. 50,57-59 Disk Disease Lumbar disk disease and hernia- tion has become a popular diagno- sis in cases of low back pain, in part because a potential cure can be sought with surgical intervention. 58 Some authors believe that smoking adversely affects the intervertebral disks, predisposing patients to disk disease and low back pain. 45,53,60 Ernst 45 believes that the interverte- bral disks are “malnourished” due to many of the vascular and hema- tologic changes that result from long-term smoking. He postulates that tissues such as the vertebrae and vertebral disks have a tenuous blood supply and are not able to compensate for the decrease in blood flow that occurs in the micro- vasculature of chronic smokers. Over time, the diffusion capacity for the delivery of oxygen and nutrients becomes insufficient, leaving the in- tervertebral disks more vulnerable to insults. 45 Kelsey et al 53 determined in their epidemiologic study that ciga- rette smoking in the year prior to a patient’s presentation to a physi- Musculoskeletal Effects of Smoking Journal of the American Academy of Orthopaedic Surgeons 12 cian increased the risk of having a prolapsed disk (odds ratio, 1.7). Furthermore, they discerned a weak dose response for smoking and the subsequent risk of disk pro- lapse; for every 10 cigarettes that were smoked per day, the risk of having a prolapsed disk increased by 20%. Hanley and Shapiro 61 deter- mined that a smoking history longer than 15 years was an impor- tant factor in determining the post- operative success of lumbar diskec- tomies performed to treat severe radiculopathies. They postulate that the persistent back pain after the procedure may be a manifesta- tion of the vascular effects of nico- tine. Furthermore, the metabolic changes within the disk may render it more susceptible to mechanical problems. 61 Battié et al 57 examined differ- ences in magnetic resonance (MR) imaging studies of the lumbar spines of identical twins who were highly discordant in their smoking histories. They found no differences in the reported rate of occurrence of low back pain between the smok- ing and nonsmoking groups but did demonstrate a difference in the disk degeneration scores (based on MR imaging criteria) used to evalu- ate the intervertebral regions of the two groups. Stronger evidence comes from An et al. 60 In their study, the rates of smoking in a population of pa- tients with surgically confirmed cer- vical or lumbar disk disease were examined. The relative risk values for lumbar and cervical disk disease for smokers were 2.2 (P = 0.00029) and 2.9 (P = 0.0025), respectively. When the authors excluded those patients who had recently quit smoking from the “smokers” group, the relative risks increased to 3.0 and 3.9, respectively. They demon- strated that the association between cigarette smoking and documented disk disease, not just the subjective complaint of low back pain, is quite significant. Continued smoking in light of these problems could actually worsen the diskogenic or radicular symptoms that accompany disk disease. So how does smoking exert these changes in the intervertebral disks that render them more susceptible to disease? As stated earlier, Ernst 45 believes that the macrovascular and microvascular changes that occur in smoking may affect the blood sup- ply around intervertebral disks. The decreased blood flow renders the disks susceptible to pathologic changes. The study by Battié et al 57 sup- ports this notion. In that study, the authors used MR imaging to evalu- ate disk integrity in pairs of identi- cal twins discordant in their smok- ing histories. Although there was no difference in complaints of low back pain, the mean score for lum- bar spine disk degeneration was 18% higher for the smokers (P = 0.015). Furthermore, because their results demonstrated involvement of the entire lumbar spine, the au- thors postulated that the mecha- nism of action must be systemic. In a recent article, Newby et al 3 showed that smoking has dramatic adverse effects on the endogenous fibrinolytic capacity of the vascular endothelium of smokers, leading to a systemic increase in the risk of atherothrombotic disease or micro- vascular occlusive disease. Jayson and co-workers 62-64 have performed several studies demonstrating that a decrease in fibrinolytic activity is common in many chronic back pain syndromes. It is feasible that this mechanism is active in a large num- ber of patients who smoke and have low back pain. It is also feasi- ble that this is a mechanism that results in the local hypoperfusion of the lumbar spine, as well as the alterations in disk metabolism that some authors believe occur in smokers. 3,45,60-64 Wound Healing The effects of cigarette smoking on soft-tissue wound healing, skin physiology, and the complex vari- ables that control these entities have been studied by several groups of researchers. In a review by Leow and Maibach, 8 most of the studies analyzed showed a de- crease in cutaneous blood flow in subjects exposed to nicotine or cig- arette smoke. Jensen et al 65 noted an acute decrease in the subcuta- neous tissue oxygen tension in the forearms of subjects after smoking cigarettes. The authors attributed these effects to the pharmacologic actions of nicotine. In 1977, Mosely and Finseth 66 were among the first to demonstrate that smoking impairs wound heal- ing in the soft tissues of the hand. They postulated that the vasocon- striction and moderate blood levels of carbon monoxide secondary to smoking could retard proper wound healing, especially in the extremi- ties. It was noted that severe digital vasoconstriction can occur after smoking a single cigarette. The fol- lowing year, they demonstrated that systemic nicotine given to rabbits re- sulted in decreased wound healing in an established rabbit-ear injury model. 67 Several authors have noted changes in the blood flow and oxy- gen tension of the cutaneous and subcutaneous tissues that can be related to smoking. 8,65-67 Forrest et al 68 specifically examined the skin hemodynamics of random-pattern skin flaps from rats that had been given either low-dose or high-dose subcutaneous nicotine for the 24 weeks prior to a surgical procedure. The capillary blood flow and distal perfusion were lessened in these animals, resulting in flaps with a much smaller area of viability. When the nicotine was withheld during the 2 weeks before surgery, the hemodynamics of the skin flaps Scott E. Porter, MD, and Edward N. Hanley, Jr, MD Vol 9, No 1, January/February 2001 13 returned to near-control levels. Nolan et al 69 and Lawrence et al, 70 in separate studies, also showed that the survival of skin flaps in rats exposed to a cigarette smoke–filled environment was appreciably less than the survival of skin flaps in control rats. Abidi et al 71 demonstrated a dif- ference in wound healing after open reduction and internal fixation of calcaneal fractures in smokers who either were or were not allowed to smoke perioperatively. A major complication associated with this surgery is poor healing of the lateral surgical wound; although the differ- ence was not statistically significant, the authors noted that those who continued to smoke perioperatively had prolonged wound healing times. Nicotine has been shown to me- diate many other actions within the body. In their review, Sherwin and Gastwirth 1 note that the prolifera- tion of cells within the extracellular matrix and the process of epithelial regeneration are decreased by the damaging effects of nicotine and carbon monoxide. In a prospective human trial, Jorgensen et al 7 showed that collagen synthesis was hin- dered in the wounds of those sub- jects who smoked more than a pack per day compared with the matched nonsmoking group. Mature colla- gen is the main determinant of the tensile strength in a healing wound, and its assembly is dependent on sufficient perfusion and oxygena- tion. The authors concluded that wound healing is definitely impeded by smoking. It is believed by many that this interference with the natural process of wound healing may lead to higher rates of postoperative wound infec- tions in smokers. Calderone et al 72 determined that the additional costs involved in treating deep postopera- tive spinal infections could increase the total cost of caring for a patient by more than four times. Capen et al 73 included smoking as a preoperative risk factor for postoperative wound infections after lumbar fusion. Thalgott et al 74 retrospectively reviewed the cases of 32 patients in order to develop a classification scheme for identifying populations at risk for postoperative spinal wound infections and for guiding therapy. In their classification scheme, cigarette smokers, patients with systemic diseases, and immu- nocompromised patients are con- sidered to be at high risk for post- operative wound infections. In the group of patients who sustained an infection after elective spinal fusion and instrumentation, 90% were cig- arette smokers. Furthermore, the only patients to have a superficial or deep infection worsen to an in- fection that included myonecrosis were heavy smokers. The findings of these authors led them to con- clude that patient smoking is a con- trollable variable that should be stopped in the perioperative period. Fracture Healing In addition to its effects on the soft tissues and vasculature of the body, it is believed that cigarette smoking also retards the healing of bone. Silcox et al 75 reported that union did not occur in the lumbar spines of rab- bits after a single-level lumbar fusion with use of autologous iliac-crest bone graft if the rabbits were subse- quently exposed to systemic nicotine. Cobb et al 76 evaluated the rela- tive risk of nonunion in smokers versus nonsmokers in a case-control study. Although they had a rela- tively small study group, and their results only approached statistical significance, they demonstrated that the relative risk of progression to a nonunion after ankle arthrodesis was 16 times greater for smokers than for nonsmokers. Brown et al 77 reported that the pseudarthrosis rate for lumbar ar- throdesis in 50 of their patients approached 40%. The rate for the 50 nonsmokers in that study was only 8%. Carpenter et al 78 furthered the work presented by Brown et al and reported that the outcomes of repeat procedures for pseudarthrosis that developed after an attempted local arthrodesis of the lumbar spine were significantly more favorable for nonsmokers (P = 0.02). Patients who stopped smoking also had a better mean outcome score and were more likely to return to work than those who continued to smoke. These findings have led several inves- tigators to recommend periopera- tive cessation of smoking as a gener- al measure to improve the outcome of surgical procedures. 1,7,71,79,80 De Vernejoul et al 25 have identi- fied a possible explanation for these findings. They demonstrated that smoking impairs osteoblast func- tion in osteoporotic individuals. The quantity of bone resorbed re- mained normal, but the rate of bone formation was decreased. This could result in the defective healing response demonstrated clinically in the previously mentioned studies. Campanile et al 80 suggest that the effects of smoking are mediated by the vasoconstrictive and platelet- activating properties of nicotine, the hypoxia-promoting effects of car- bon monoxide, and the inhibition of oxidative metabolism at the cellular level by hydrogen cyanide. There are no conclusive studies that have generated definite guide- lines about perioperative cessation of smoking. Campanile et al 80 note that suggestions range from 1 day to 3 weeks preoperatively and from 5 days to 4 weeks postoperatively. Sherwin recommends that smoking be stopped at least 12 hours before surgery because it takes the body roughly this amount of time to clear the carbon monoxide. 1 Abidi et al 71 noted that cessation of smoking 5 days before surgical procedures had a favorable outcome on subsequent wound healing. Lind et al 81 recom- Musculoskeletal Effects of Smoking Journal of the American Academy of Orthopaedic Surgeons 14 mend 1 week of cessation, on the basis of the pharmacokinetics of free radicals and thrombotic compo- nents. Mosely et al 67 demonstrated that healing was impaired for a period of 4 to 10 days after wound creation in rabbits. After 12 days, the wounds of rabbits either exposed or not exposed to nicotine contracted at nearly the same rate. Whitesides based his recommen- dations concerning perioperative smoking on studies showing that a nonsmoker can make 1 cm of bone in 2 months, but that it takes a smok- er an average of 3 months to make the same amount of bone. 82 He, therefore, feels that it is not prudent to perform elective spinal surgery on smokers unless they demonstrate abstinence from smoking for a period of 60 days. In contrast, Hanley of- fers the argument that many of the effects of chronic smoking are irre- versible and that medical care should not be withheld from patients with- out firm evidence. 82 Summary Tobacco smoking has come under relentless attack as more and more medical and social ills have been proved to be the direct result of smoking, which is now the most preventable cause of morbidity and mortality in the United States. The scientific and clinical information on smoking and its consequences sug- gest varying degrees of correlation between smoking and musculo- skeletal conditions. Smoking has been shown to adversely affect bone mineral density, lumbar disk health, the relative risk of sustaining hip and wrist fractures, and the dynam- ics of bone and wound healing. In response to these findings, many surgeons have recommended that some type of smoking cessa- tion program be instituted in con- junction with musculoskeletal treatment for patients with a signif- icant smoking history. The physi- cian should not necessarily delay or withhold elective treatment from such patients. At the very least, however, a detailed smoking history should be obtained from all patients who present with muscu- loskeletal conditions. Furthermore, the risks and complications that appear to be associated with smok- ing should be discussed in detail, and assistance in smoking cessa- tion should be offered. The patient and the physician should both thoroughly understand the impli- cations and effects of smoking on a disease process or planned medical intervention. Scott E. 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