Adverse Effects of Smoking on Musculoskeletal Health

Abstract

Smoking remains a prevalent part of present day society, with over 42 million Americans who continue to use cigarettes. Smoking is strongly associated with a variety of conditions that result in increased morbidity and mortality. Research also indicates that smoking has an adverse effect on surgical outcomes. Its effect on the musculoskeletal system is evident and results in postoperative complications such as infection, nonunion, and malunion. These complications also come with a price, as there are severe economic implications of smoking. Patients who smoke may benefit from a period of perioperative cessation to help diminish some of these negative outcomes. It is the physician’s duty to educate patients preoperatively about these outcomes and the potential benefit of smoking cessation.

Introduction

This past year marked the 50^th anniversary of Surgeon General Luther L. Terry’s first report on smoking and health on January 11, 1964. His report aimed to bring to the forefront an issue that had been largely ignored by society: the ravaging effects of smoking on the body. The report was the first step of many that paved the way for crucial laws such as the Federal Cigarette Labeling and Advertising Act of 1965 that required health warnings on cigarette packages etc. More than 50 years later, a great deal of progress has been made towards limiting the toxicity of tobacco on the health of the American public. Despite the positive steps taken towards raising public awareness on the disastrous effects of smoking, there remains much work to be done as the epidemic continues. Over the past 50 years, the smoking rate in U.S. adults has been reduced by 50 percent; nonetheless 42 million people continue to smoke. It is estimated that more than 20 million Americans have died as a result of smoking, and 2.5 million of those deaths were due to diseases related to second hand smoke. Furthermore, almost half a million Americans die prematurely each year from smoking. It is estimated that the fiscal impact due to smoking is approximately $300 billion dollars annually with $130 billion of those dollars being attributed to health care costs.

Cigarette smoke has over 7,000 chemicals, 250 of which have been found to be toxic including ammonia, cyanide, as well as carbon monoxide. There have been at least 69 chemicals identified in cigarettes that are carcinogenic. These chemicals have been found to have a profound effect on surgical outcomes. According to the American Society of Anesthesiology, smoking increases mucus secretion meanwhile decreasing ability of the lungs to clear secretions. Furthermore, it narrows the bronchioles and makes them prone to collapse, resulting in increased pulmonary complications as well as increased susceptibility to infection.⁵ The American College of Surgeons recommends smoking cessation at least four weeks prior to surgery and cessation of smoking for an additional four to eight weeks postoperatively can decrease the incidence of wound complications by 50%.

Fifty years after the first Surgeon General’s report, there continues to be new evidence published each year linking tobacco to a variety of conditions. This alone is perhaps the most telling sign of the debilitating effects of tobacco use. This review will attempt to further highlight and discuss the detrimental effects of cigarette smoke particularly as it pertains to the musculoskeletal system, especially in the perioperative period.

Cellular Effects of Smoking

It is important to understand what happens at the microscopic level in order to better comprehend the ramifications of smoking on the body. On a cellular level smoking has been shown to decrease tissue oxygenation.¹ Nicotine, the primary addictive component of cigarettes, has several physiological effects that negatively impact wound healing. These effects are partially mediated through the peripheral vasoconstrictive effects of nicotine. Carbon monoxide binds to hemoglobin 200 times stronger than oxygen, displacing the oxygen dissociation curve to the left. This further interferes with the transport of oxygen molecules to tissues and contributes to tissue hypoxia.^1,2 In one study, smoking was found to decrease subcutaneous blood flow by approximately 50%.¹ Furthermore, smoking for merely ten minutes was found to decrease the oxygen tension for approximately one hour afterward. Hydrogen cyanide found in cigarette smoke primarily affects wound healing by impairing oxidative metabolism and oxygen transport.³

Smoking also has been found to induce platelet aggregation and subsequently produce microvascular occlusion, further compounding the detrimental effects on microperfusion.³

On a soft tissue level, smoking has repeatedly been shown to impede several steps in the wound healing process. The initial step of wound healing involves the formation of granulation tissue. This stage involves several key mediators including fibroblasts, growth factors, as well as appropriate blood flow via capillaries. Fibroblasts interact with growth factors secreted by macrophages to produce and lay down crucial components of the granulation tissue including fibronectin, collagen, and elastin. Nicotine in cigarette smoke has been found to decrease the proliferation as well as impair the migration of these cellular components.³.⁴

The immune and inflammatory response is the key cog behind the impediment of disease processes as well as resistance to infections. Cigarette smoke has long been documented to impair wound healing and to be the primary cause behind several diseases via its detrimental effects on the immune system. Reduction in blood flow hampers delivery of leukocytes to infected areas and decreases oxygen delivery to leukocytes; these effects combine to contribute to the overall decreased resistance to infections.⁵

Effects of Smoking on Bone Metabolism

The various aforementioned cellular effects on soft tissues also play a role in perpetuating the harmful effects of smoke on bone metabolism. Diminished vascular supply and the resultant thrombosis have been thought to play a role in osteonecrosis. Hirota and colleagues studied the association of smoking with femoral head necrosis and found that smokers had a four times increased risk of developing osteonecrosis.⁶

Another study concluded that the effects of nicotine on bone metabolism are dose-dependent. In low doses, nicotine was found to have a stimulatory effect on osteoblast cells. However in higher concentrations, similar to the exposure in a heavy smoker, nicotine was found to exhibit inhibitory effects on osteoblast proliferation and bone metabolism. ⁷

Iqbal and coinvestigators demonstrated that in addition to its inhibitory affects on osteoblasts, smoke toxins also play a role in osteoclast activation. These authors found that benzo(a)pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) found in cigarette smoke interacts with aryl hydrocarbon receptor to induce osteoclastic bone resorption. ⁸

Calcium and vitamin D, critical components of bone formation, are also affected by cigarette smoke. Vitamin D3 normally acts via the RANKL receptor to increase calcium and phosphate levels promoting bone formation. The Minos study in 2002 examined 719 patients and the effects of smoking on overall bone mineral density.¹⁵ Smokers were found to have decreased vitamin D and increased PTH. Compared to patients that had never smoked, former smokers were also found to have decreased bone mineral density, comparable to that of current smokers.⁹

Several studies demonstrate an association between postmenopausal smoking and the development of osteoporosis.¹⁰ Daniell studied the effects of smoking and lack of obesity on cortical bone loss. Postmenopausal smokers were found to have an average cortical bone loss of 1.02% per year versus 0.69% in nonsmokers. The rate in smokers increased to 1.19% per year in nonobese postmenopausal women indicating that body weight also plays a role in the development of osteoporosis. In a review of 3,617 hip fracture cases, smokers (n= 467) were younger, suggesting that smoking results in hip fractures at a younger age.¹¹

Impact of Smoking on Fracture Healing

Smoking has been demonstrated to compromise the quality of bone healing resulting in nonunion, malunion, and increased complication rates aftef nonsmokers. Overall, the study also showed that smokers had more outpatient visits and required more antibiotics compared to the patients that did not smoke, further indicating that smoking increases the overall rate of postoperative complications.¹²

Humerus fractures comprise 5–8% of fractures overall. Although uncommon, nonunions of the humerus are difficult to manage and thus risk factors must be minimized. Smokers have been found to have an increased rate of nonunions and complications in such fractures. In a study of patients with proximal humerus fractures, smoking was found to be a significant risk factor for complications and often resulted in revision surgery.

The Lower Extremity Assessment Project (LEAP) prospectively studied the time to union, development of infection, and osteomyelitis in 268 unilateral open tibial fractures treated operatively.¹³ Patients were divided into current smokers (n=105), previous smokers (n=82), and never smoked (n=81). The study enrolled patients over a 40-month period and they were followed for 3, 6, 12, and 24 months postoperatively. Smokers and previous smokers were 37% and 34% more likely to develop nonunion respectively. Smokers were also found to have an increased infection rate, were twice as likely to develop an infection, and 3.7 times as likely to develop osteomyelitis. Previous smokers were also more likely to develop osteomyelitis. Furthermore, current smokers were found to have slower fracture healing with 24.1% being unhealed at 24 months compared to 9.9% in nonsmokers.¹³

The effect of cigarette smoke on the outcomes of spinal surgery has also been well established.¹⁴ Pseudoarthrosis of spinal fusion surgery is a common complication in smokers. Brown in an early study retrospectively studied 100 patients who underwent a two level laminectomy and fusion. Forty percent of smokers (20 of 50 patients) developed pseudoarthrosis and overall were five times more likely to develop nonunion compared to nonsmokers.²³ In an animal study of the effects of nicotine on spinal fusion, rabbit models exposed to systemic nicotine were found to have a nonunion rate of 100%. In another a study examining 50 patients with spondylolisthesis treated surgically, all instances of pseudoarthrosis (n=6) were found to be in smokers.

Cobb and colleagues examined the relationship between smoking and nonunion in ankle arthrodesis.¹⁵ They found that smokers had a 3.75 times increased risk of nonunion. Assous and Bhamra examined 40 patients with intrarticular calcaneal fractures, fractures with poor functional outcome. They found that 70% of patients that smoked (9 of 13) went on to develop a deep tissue infection versus 15% of nonsmokers (4 of 27). They questioned whether smokers should be treated operatively as smoking significantly impairs wound and bone healing and placed patients at increased risk of surgical complications.

Operative treatment of nonunions has also been shown to have a higher failure rate in smokers. In a 2006 study of patients with established nonunion of the scaphoid bone, patients who smoked had a significantly lower surgical success rate (40% compared to 82.4%) than nonsmokers.¹⁶

Mallon and colleagues in a retrospective study showed that smoking has also been shown to negatively impact rotator cuff repairs.¹⁷ Patients were divided into two groups: smokers with at least a 40-pack year history and all others who were considered non-smokers. The results showed significant postoperative benefits in the non-smokers in terms of outcomes, which were measured by the UCLA assessment; this included function, pain status, strength, and range of motion. By this measure, non-smokers had significantly better outcomes than the smokers in this study and they did significantly better postoperatively. The investigators and other authors hypothesize that because the rotator cuff is primarily made of type 1 collagen, toxins from cigarettes likely had an effect on its deposition in some way, especially during wound healing. Smokers were found to have 1.8 times less mature collagen in surgical wounds post operatively. A second possible explanation could be attributed to the hypovascularity caused by the nicotine from cigarettes. Limited vascularity could have a direct negative impact on healing, possibly leading to the negative outcomes found.^17,18

Several studies have been performed examining the benefits of smoking cessation on postoperative complications. Mills and coworkers performed a large meta-analysis looking at 21 studies that attempted to determine the effects of smoking cessation on postoperative complications.¹⁹ Fifteen observational and six randomized trials were included in the criteria. In looking at the pooled data, cessation resulted in a 41% reduction in risk of postoperative complications (with a 95% confidence interval); cessation of at least four weeks preoperatively resulted in the most positive effects when compared to shorter cessation periods. Those postoperative complications included pulmonary complications, wound healing problems, duration of hospital stay, and mortality.¹⁹

Additional studies have better highlighted the postoperative complications of smoking.^20–21 Warner established criteria for post-operative complications, ranging from wound healing, cardiopulmonary, renal, and neurological complications to increased hospital stay. After defining criteria of complications, a control group and a test group of patients were organized to compare whether smoking cessation had any significant effects on the extent and severity of postoperative complications. Several studies have found that a 50% decrease in cigarette consumption showed a significant reduction in the post-operative complications studied.^20–21 Furthermore, it was found that at least 3–8 weeks of preoperative cessation of smoking had significant positive benefits postoperatively.²⁰ Length of hospital stay post-operatively is one the most significant criteria evaluated by these studies; the ramifications of these criteria are significant because of the effects on patient health, cost and mortality.

Another use explored by a few of the studies, is the ability to use the preoperative smoking cessation as a “teaching moment” to convince long-term smokers to stop permanently. Though tentative, the benefits were seen in some studies and listed as areas of future exploration.^20–21

From an orthopedic perspective, Nasell and coauthors looked at patients with upper or lower extremity fractures that required surgical intervention.²² The complications criteria were determined by one of the following effects/consequences: a need for additional medical or surgical treatment within 6–12 weeks of post operatively, a prolonged hospital stay, extra imaging, or unscheduled outpatient follow ups. This randomized, controlled trial was able to determine the significant effects of smoking cessation which they achieved by enrolling patients in an education program, designed to reduce or stop smoking completely, for at least six weeks after emergency fracture surgery. The investigators found that the odds of having a complication were 2.51 times lower than when smoking was continued.²²

While numerous studies have been conducted with regards to wound healing and perioperative smoking cessation, very few studies have considered the relationship between bone healing and smoking cessation. Truntzer and coworkers demonstrated that there was a significant benefit in bone healing at the four week point of preoperative smoking cessation. Cessation four weeks preoperatively was also stressed to have a significant benefit in minimizing complications post operatively.²³

Cost and Economics of Smoking

In addition to the perioperative effects, the impact of smoking has profound economic implications as well. In a cost analysis of surgical site infections, Urban found that the cost could vary from $400 per case to more than $30,000 depending on the severity of infection (superficial versus deep, etc.). There have been very few studies highlighting the economic benefits of preoperative smoking cessation on fracture surgery. However, Hak and coworkers found the average cost of nonunions to be significant, approximately $11,333 per case.²⁴ In a prospective study comparing patients with periprosthetic joint infections to noninfected cohorts at a tertiary center, Kapadia and colleagues found the infected group to have longer hospital stays, more readmissions, and increased clinic visits.²⁵ This amounted to a higher mean annual cost for the infected group at $116,383 compared to $28,249 for the noninfected group.

Discussion

Over the course of the past 50 years, cigarettes and smoking have been implicated in many adverse health effects. Numerous studies demonstrate that tobacco is a toxic product. Smoking has been shown to affect nearly every organ in the body and is a major cause of cardiovascular disease, a variety of malignancies, as well as many adverse musculoskeletal effects. Nevertheless, clinicians continue to see many patients who smoke. From a surgical standpoint, the detrimental effects of smoking can be reduced through intervention. Preoperative cessation has been shown to improve outcomes and help facilitate healing postoperatively. Education of patients and raising physician awareness of this issue is essential to diminish the overall incidence of tobacco-induced diseases.

Given the myriad adverse effects of smoking (nonunion, malunion, delayed fracture healing, etc.), some surgeons have advocated withholding elective surgeries to those patients who smoke. Physicians must uphold a moral obligation towards patients. Principles such as patient autonomy, physician autonomy, and nonmalificence are important considerations. According to the AMA’s Principles of Medical Ethics, a physician is free to choose the environment in which he/she provides medical care. This may encompass mitigating surgical risk factors, including smoking, in order to ensure that the best care possible is provided. Ultimately, the decision for surgery is a joint one made by the patient and surgeon after an informed consent discussion of the risks, potential benefits, and alternatives. Patients who smoke pose an additional surgical risk and their outcome may be compromised when compared to nonsmokers. The medical establishment has provided a strong push for risk factor modification over the past several decades to prevent and decrease the incidence of death by largely preventable diseases. It is time to view smoking as a modifiable risk factor in the surgical world. It is the physician’s duty to optimize the conditions for surgery and medical studies have repeatedly shown that quitting smoking saves lives and prevents surgical complications.

Biography

Belal Tarakji, BA, Akin Cil, MD, and Mark Bernhardt, MD, (above), are in the Department of Orthopaedic Surgery, University of Missouri—Kansas City School of Medicine, and Truman Medical Center. Richard E. Butin, MD, MSMA member since 1987, is in the Department of Internal Medicine, UMKC, and Truman Medical Center.

Contact: BernhardtM@umkc.edu