The National Osteoporosis Foundation defines osteoporosis

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1 106 Vertebroplasty and Kyphoplasty Treatment Techniques for Managing Osteoporotic Vertebral Compression Fractures Michael S. Shen, M.D., and Yong H. Kim, M.D. The National Osteoporosis Foundation defines osteoporosis as a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures. Osteoporosis as defined by the World Health Organization compares an individual s bone mineral density to that of the mean of a young reference population. Individuals can be categorized as having low bone mass, osteoporosis, or severe osteoporosis. Osteoporosis can be further classified as primary or secondary, depending on the underlying etiology (Table 1). Approximately 10 million people in the United States carry the diagnosis of osteoporosis, while an additional 34 million are classified as having low bone mass. Osteoporosis affects females four times more than males and is more frequently found in Caucasians and individuals of Asian descent. The lifetime incidence of fragility fractures secondary to osteoporosis in females over the age of fifty years of age is approximately 1 in 2, and in males over the age of fifty, it is 1 in 4. Fragility fractures due to osteoporosis place a severe financial strain upon the health care industry. Estimates show there were approximately 1.5 million osteoporotic-related fractures in the United States in 2001, the care of which cost about 17 billion dollars, or approximately 47 million dollars a day. However, as the population over the age of fifty continues to grow, costs are predicted to rise to an estimated 60 billion dollars a year by the year 2030, costing a record Michael Shen, M.D., was a Chief Resident in the NYU Hospital for Joint Diseases Department of Orthopaedic Surgery, New York, New York. Yong H. Kim, M.D., is Clinical Assistant Professor, NYU School of Medicine and an Attending in the Spine Service, NYU Hospital for Joint Diseases Department of Orthopaedic Surgery, New York, New York. Correspondence: Yong Kim, M.D., 301 E. 17th Street, NYU Hospital for Joint Diseases, New York, New York million dollars a day. 1 Diagnostic Imaging Modalities Many different imaging modalities (plain film radiographs, ultrasound, computed tomography (CT) can used to evaluate bone mineral density and diagnose osteoporosis. Bone mineral density can be evaluated either centrally (i.e., hip, spine, femur), peripherally (i.e., foot, hand), or both. Despite the multiple imaging techniques available, the DEXA (dual energy X-ray absorptiometry) scan remains the most widely used bone density measurement technology. Its advantages are that it is easily reproducible and has the highest sensitivity and specificity of all imaging techniques available. Because of this, DEXA remains the gold standard for measuring bone mineral density. Osteoporosis: Risk Factors There are many factors that can put an individual at risk for the development of osteoporosis (Table 2). Osteoporosis due to estrogen deficiency or menopause is found more in Caucasian females and females of Asian descent. Increased age puts individuals at risk for developing type 2, or senile osteoporosis. Increased risk for developing osteoporosis is seen in individuals with a family history of low bone mass or having a primary relative with a fragility fracture. Early menopause that occurs naturally or secondary to surgery or amenorrhea, the latter due to conditions such as excessive physical exercise or eating disorders, increases the risk of developing osteoporosis. Chronic diseases and the medications used to treat them can damage bone and interfere with bone formation. Lifestyle choices including smoking, excessive alcohol intake, a poor diet, and a lack of weightbearing exercise can increase one s risk for developing osteoporosis. Individuals at high risk for developing osteoporosis may be able to delay or prevent the onset of osteoporosis by

2 107 Table 1 Classification of Osteoporosis Normal: BMD within 1 S.D. of the mean of a young adult reference population Osteopenia : 1.0 to 2.5 S.D. Below Osteoporosis: < 2.5 S.D. Below Severe osteoporosis: Osteoporosis with one or more 1 fragility fractures Classification of osteoporosis: Primary Type 1 (Postmenopausal/Estrogen deficient) Type 2 (Age-related/Senile) Secondary minimizing these modifiable risk factors early on, as an attempt to obtain and maintain a higher peak bone mass. Vertebral Compression Fractures Epidemiology Vertebral compression fractures (VCFs) are the most common fragility fracture in the United States, accounting for approximately 700,000 injuries per year. The incidence of VCF in females over the age of 50 is about 17.8 per 1000 person-years. Upon adjusting for age, the incidence increases with aging. In females 50 to 54 years of age, the incidence is approximately 5.8 per 1000 person years, rising to 26.1 per 1000 person years in females 75 to 79 years. 2 Lindsay and colleagues found a relative incidence of VCF after one year to be 6.6%, increasing to 19% the year following if an individual sustained a VCF. 3 Studies focusing on bone mineral density have shown the relative risk for developing a VCF to be increased four to six times when bone mineral density drops by two standard deviations. 4,5 Ross and associates Table 2 Risk Factors for Osteoporosis Female Caucasian or Asian History of fracture in a first degree relative (parent, sibling, child) Thin or small frame Advanced age Family history Estrogen deficiency Amenorrhea Anorexia and bulimia Excessive physical exercise Low lifetime calcium and vitamin D intake or deficiency Inactive lifestyle Smoking Excessive alcohol intake Medications Corticosteroids Excessive thyroid hormones Anticonvulsants Aluminum containing antacids Methotrexate Gonadotropin releasing hormones (GnRH) Cyclosporine A Low testosterone levels (males) found the risk for subsequent fracture to increase five-fold after the first VCF and twelve-fold after sustaining two or more VCFs. 6 However, despite having a history of having suffered VCF or having low bone mineral density, neither variable has been shown to be predictive in diagnosing which individuals will go on to actually sustain a new VCF. Presentation It is estimated that approximately 20% to 25% of individuals have symptoms severe enough to seek medical attention after having sustained a VCF. 3 Patient presentation can vary, but the most common complaint is that of pain (Table 3). The onset of pain usually occurs after only minor trauma and tends to be postural, made worse by standing erect. The pain can be debilitating to the point of confining an individual to a wheelchair or bed. On physical examination, the pain may be reproducible with deep pressure over the spinous process of the involved level. Deformity due to VCF can cause both visable changes (kyphosis, protuberant abdomen) and psychological changes (depression). Increased kyphosis secondary to VCF has been found to be associated with decreased truncal strength and pulmonary function. 7,8 Individuals with VCF are two to three times more likely to die secondary to pulmonary causes like pneumonia or chronic Table 3 Patient Presentation with VCF Severe back pain following minor injury Pain worse by standing erect Pain usually limits ambulation Wheelchair Stooped forward Deep pressure over spinous process at involved level reproduces pain Kyphotic deformity and postural changes Changes in balance Knees bend, hips flex, and pelvis tilts to offset center of gravity moving forward Increased muscle fatigue Protuberant Abdomen Urinary retention GI symptoms (Ileus) Decreased gait velocity Psychosocial issues due to appearance Neurologic deficits are rare

3 108 obstructive pulmonary disease (COPD) and, overall, have an increased risk for hospitalization and mortality. 9,10 Urinary retention and GI symptoms are also common in individuals with VCF. Neurologic deficits can also occur; however, symptoms often resolve with less than 5% of patients requiring surgical decompression. 11 Classification and Evaluation of VCFs Vertebral compression fractures are most commonly classified according to their morphologic appearance. Three basic types of VCFs exist: wedge, biconcave, and crush (Fig. 1). Wedge type fractures as well as crush injuries are found more frequently in the midthoracic and thoracolumbar regions, while biconcave VCFs are predominantly seen in the lumbar region. Ismail and coworkers found in their large study that wedge fractures far surpassed all the other types of injuries in number, accounting for more than 50% of all VCFs. Followed by this were biconcave injuries at 17% and crush injuries at 13%. 12 Radiographs remain the mainstay of diagnosing VCF, many of which are simply detected incidentally on chest radiographs. If indicated, additional imaging can be done to further evaluate the injury. Bone scans are very sensitive, but because they can stay positive for up to two years, they are a poor test when attempting to establish chronicity. CT scans are good for delineating bony anatomy. Although not as good as CT scan in evaluating bony anatomy, magnetic resonance imaging (MRI) is excellent in evaluating surrounding soft tissue structures, establishing chronicity, and aiding in determining the underlying etiology of the lesion (osteoporosis versus pathologic abnormality) as well. Nonoperative Treatment Modalities The chief complaint of many individuals after sustaining a VCF is pain. In patients not requiring bed rest, activity modification, bracing, or using assistive devices in conjunction with the use of narcotic analgesics can be effective in controlling symptoms. Once mobilized, a physical therapy regiment can be instituted to further aid in rehabilitation. Radiotherapy for individuals with pathologic lesions, particularly those with radiosensitive tumors (prostate, myeloma, breast), has been found to provide pain relief in up to 50% of patients. 13 Medical treatment for osteoporosis has been shown to decrease the incidence of VCF by 40% to 60% after just one year of treatment. Several medications like teriparatide and calcitonin have not only been found to be efficacious in relieving pain but treat the underlying osteoporosis as well. 14,15 However, despite the efficacy of medical treatment for osteoporosis, only 50% of females with VCF, diagnosed incidentally on chest plain radiograph films, are started on any pharmacologic treatment for their underlying disorder. 16 Outpatient management is unsuccessful in approximately 15% to 20% of patients seeking medical attention after VCF. These individuals often require hospitalization for bed rest and installation of intravenous analgesics. However, bed rest in the elderly is associated with progressive deconditioning. Patients are at increased risk for developing decubitus ulcers, pulmonary complications, urinary tract infections (UTI), Figure 1 Classification of vertebral compression fractures: wedge (top), crush (middle), biconcave (bottom). Figure 2 Vertebroplasty.

4 109 and deep vein thrombosis (DVT). Bone mineral density has also been found to decrease 0.25% to 1% per week of bed rest. 17,18 In an individual that is often already osteoporotic, long-term bed rest can rapidly increase the risk of suffering not only additional VCFs but also other fragility fractures. Vertebroplasty and Kyphoplasty Indications Vertebroplasty (VP) was first used by Galibert, in 1987, for the treatment of painful vertebral hemangiomas (Fig.2). Kyphoplasty (KP) was later developed and first introduced by Reileyin, in 1998, to treat painful osteoporotic VCF. Both procedures are minimally invasive and involve percutaneous injection of cement into the collapsed vertebral body. Current indications for VP and KP are for individuals with intractable pain who suffer VCF secondary to osteoporosis, multiple myeloma, or other osteolytic metastatic lesions. Contraindications include use in young patients, pregnant females, high energy injuries, cases of local spine infection, and in patients with bleeding disorders; differences between the two techniques include both practical and clinical considerations. Fracture Reduction One area in which the VP and KP differ involves how the vertebral body is prepared prior to cementing. Fracture reduction during VP is accomplished through a combination of patient positioning and the outward pressure exerted by the cement during injection. In static fractures (fractures without an observable and mobile radiolucent intravertebral cleft), the average increase in anterior height after VP is 2.5 mm. 19 In mobile fractures, fracture reduction through patient positioning can help to restore up to 40% to 70% of normal anterior height. 20 Unlike VP, the cement injected during KP is placed into a cavity created by a balloon tamp. The tamp also assists in fracture reduction, improving both vertebral body height and kyphosis. Height restoration can be improved postoperatively by 50% to 70% and segmental kyphosis improved 6 to ,22,23,24 Results in terms of fracture height restoration, kyphosis reduction, and pain relief are improved more after treating acute fractures (less than ten weeks) than with chronic ones (more than four months). 25 Clinical Results Short term results show anywhere from 75% to 100% and 85% to 100% of individuals with osteoporotic VCF have good to moderate pain relief postoperatively after VP (Table 4) and KP (Table 5), respectively. 21,24-39 Many patients reported substantial pain relief almost immediately postoperatively and were able to be mobilized within 24 hours. Factors such as age, sex, baseline bone mineral density, history of tobacco or steroid use, and presence or absence of dynamic mobility within the fracture all have been found to have no influence on the degree of postoperative pain relief. 35 Alvarez and colleagues identified individuals possessing an ASA (American Society of Anesthesiologists) score of 1, symptomatic VCF levels confirmed by MRI, and a vertebral body height loss of less than 70% to have improved and more predictable postoperative pain relief. 40 Not only is considerable pain relief obtained short term, long-term studies show pain relief to be maintained even four to five years after undergoing VP. 31,36 Long-term results on patient satisfaction and pain relief for KP are still pending. Complications Although infrequent, VP and KP are not without complications (Table 6). Cement extravasation is one complication that can be encountered during VP and KP. Cement leakage can be due to cement overflow, outflow through cortical breeches and improper placement. 41 The incidence of extravasation ranges from 30% to 70% after VP and is less than 10% following KP. 42 The frequency of cement extravasation is much higher after VP than KP for several reasons. First, the inflatable balloon utilized during KP acts to tamp open a space within the vertebral body, forming a cavity that is surrounded by impacted cancellous bone. This compacted shell of bone serves as a barrier to help prevent cement extravasation. Second, the volume of the cavity and, thus, Table 4 Vertebroplasty Results Number of Percent Percent Number of Levels Good to Moderate Poor Follow-up Subsequent Study Patients Injected Pain Relief Pain Relief (Months) Fractures Barr Cyteval Cortet Perez Grados Heini Zoarski Kobayashi Fourney McKiernan

5 110 Table 5 Kyphoplasty Results Number Number of of Levels Good to Moderate Poor Follow-up Subsequent Study Patients Injected Pain Relief Pain Relief (Months) Fractures Berlemann % 4% 12 1 Wilhelm % 0% 12 Phillips % 14% 12 5 Crandall % (A) / 87% (C) 10% (A) / 13% (C) 18 Gaitanis % 3% 12 2 Fribourg Lane % 17% 3 Fourney % 9% 4.5 Rhyne VAS 9.16 to > 2.91 (0 to 10) 9 7 (patients) VAS: Visual Analog Scale, A: Acute, C: Chronic the amount of cement to be used is easily determined by measuring the amount of fluid used to insufflate the balloon tamp. This prevents the overuse of cement and, thus, cement overflow. Third, unlike VP, which is considered to be a high pressure system, the cavity formed during KP provides a low-pressure environment, allowing cement with increased viscosity to be utilized with lower injection pressure, both of which decreases the incidence of cement leakage through cortical breeches. The vertebral venous system is another site of cement leakage and embolization. Case reports of cement embolization throughout the body have been reported in the literature. Histologic evaluation of VP or KP treated vertebrae has revealed cement infiltration of vascular spaces throughout the vertebral body and venous system. 43 Groen and associates looked at the vertebral venous system attempting to identify possible sites of cement leakage. They postulated that the pressure differential between the injected cement and venous system could be lessened and may even be reversed by increasing vertebral venous pressure intraoperatively, thus, lessening the likelihood of cement extravasation. Increasing vertebral venous pressure can be done through patient Table 6 Vertebroplasty and Kyphoplasty Complications Transient Radiculopathy Local pain Fever Fat emboli Pedicle fracture Balloon rupture Infection Rib fractures Reaction to cement Adjacent level fracture Pulmonary embolization Cement extravasation or embolization Cement pulmonary emboli Nerve root compression or injury Spinal cord compression or injury Cerebral emboli positioning and by anesthesiology in patients under general anesthesia. 44 The incidence of adjacent level fracture following VP and KP varies between 12% to 50% and 20% to 30%, respectively. 30,31,45-47 A majority of adjacent level fractures occur within the first sixty to ninety days postoperatively. 30,47 The etiology of postoperative adjacent level fractures has yet to be found but is most likely multifactorial. Biomechanical studies have demonstrated that overly stiff vertebrae and attempts to obtain maximum height correction are possible risk factors in causing adjacent level fractures. 48 Complete fills are not encouraged and attempts are now made to restore vertebral stiffness to better resemble preoperative levels. 49,50,51 Different brands of cement have been found to require different fill volumes to restore vertebral stiffness. 52 Adjacent level fractures are seen more often when the initial VCF is located in the thoracolumbar region and less so in either thoracic or lumbar levels. 48 Intradiscal cement leakage can increase the risk of adjacent level fractures as well. 53 However, despite the biomechanical research that has been accomplished, a major contributing factor to the occurrence of adjacent level fractures may be a reflection of the natural progression of osteoporosis within the spine. Future Directions More recent research on VP and KP has centered about the use and development of alternative materials to polymethyl methacrylate (PMMA). These materials include calcium phosphate cement (CPC), hydroxyapatite, and coral granules. Unlike PMMA, less heat is produced during polymerization, decreasing the chance of heat induced thermal necrosis and damage to surrounding structures. Although theoretical and yet to be observed in elderly osteoporotic individuals in vivo, alternative materials also allow for bone ingrowth and subsequent replacement. Disadvantages of these newer materials include difficulty of use due to their high viscosity and increased cost. Experience with these alternative materials is growing and preliminary results are encouraging. Biomechanically, no statistically significant difference has been found between

6 111 PMMA and CPC in restoring both vertebral strength and stiffness. 54 Short-term pain relief and functional improvement has been similar when comparing PMMA and CPC treated individuals. 55,56 Long-term follow-up studies are still pending. Prophylactic reinforcement of osteoporotic vertebral bodies, prior to injury, is a concept that has recently been addressed in the literature. A computer-generated biomechanical model, introduced recently by Sun and Liebschner, looked at the effect of virtually implanted cement on compression strength in vertebrae with varying bone mineral density prior to injury. Samples designated as high fracture risk (100% fracture risk in vertebral bodies able to sustain less than 1.6 MPa of stress) required a 20% fill to improve mechanical integrity to low fracture risk (able to endure stress over 2.7 MPa and 0% fracture risk). 57 Although vertebral body reinforcement prior to injury is an interesting concept, identifying which at-risk individuals will go on to suffer VCF and, thus, benefit from prophylactic intervention still remains a problem. Discussion Osteoporosis is a major medical concern not only in the United States but throughout the world. If projections about future costs are correct, treatment of individuals with fragility fractures secondary to osteoporosis alone could ostensibly bankrupt the health care industry. The best treatment for osteoporosis remains early intervention and, if diagnosed, medical management. By instilling good lifestyle choices early on and aggressively medically treating those already with osteoporosis, countless numbers of individuals will be saved from enduring the debilitation brought with sustaining a fragility injury later in life. When compared to individuals who undergo nonoperative treatment, patients who undergo VP or KP have improved pain relief, decreased time to functional recovery, use less analgesic medication, and have an overall decreased hospital stay. 58 Opponents to these two techniques argue that results between nonoperative and operative intervention often parallel one another in the long term. Although true, the ability to drastically improve time to functional recovery, pain, and mobilize patients almost immediately after performing either procedure is critical in preventing the almost certain complications and deterioration seen in those that would otherwise become bed bound. Long-term results for KP and for cases in which CPC is used are still pending, but preliminary results appear very promising. KP and VP also have the advantage of reducing segmental kyphosis, thus, improving or even preventing some of the physical and emotional problems seen in individuals having suffered VCF. Both procedures are relatively safe and the incidence of symptomatic complications postoperatively remains low. With continued biomechanical study, further refinement of alternative materials will occur. With continued advancement in clinical experience, applied properly and under the correct surgical indications, KP and VP will provide an excellent method for improving patient morbidity and long-term outcome. References 1. Ray NF, Chan JK, Thamer M, Melton LJ 3rd. Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: Report from the National Osteoporosis Foundation. J Bone Miner Res Jan;12(1): Melton LJ 3rd, Lane AW, Cooper C, et al. 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8 113 15;26(2): Liebschner MA, Rosenberg WS, Keaveny TM. Effects of bone cement volume and distribution on vertebral stiffness after vertebroplasty. Spine Jul 15;26(14): Molloy S, Mathis JM, Belkoff SM. The effect of vertebral body percentage fill on mechanical behavior during percutaneous vertebroplasty. Spine Jul 15;28(14): Belkoff SM, Mathis JM, Jasper LE, Deramond H. The biomechanics of vertebroplasty. The effect of cement volume on mechanical behavior. Spine Jul 15;26(14): Lin EP, Ekholm S, Hiwatashi A, Westesson PL. Vertebroplasty: Cement leakage into the disc increases the risk of new fracture of adjacent vertebral body. Am J Neuroradiol Feb;25(2): Tomita S, Kin A, Yazu M, Abe M. Biomechanical evaluation of kyphoplasty and vertebroplasty with calcium phosphate cement in a simulated osteoporotic compression fracture. J Orthop Sci. 2003;8(2): Hillmeier J, Meeder PJ, Noldge G, et al. [Balloon kyphoplasty of vertebral compression fractures with a new calcium phosphate cement] Orthopade Jan;33(1): Matsuyama Y, Goto M, Yoshihara H, et al. Vertebral reconstruction with biodegradable calcium phosphate cement in the treatment of osteoporotic vertebral compression fracture using instrumentation. J Spinal Disord Tech Aug;17(4): Sun K, Liebschner M. Biomechanics of Prophylactic Vertebral Reinforcement. Spine. 2004;29(13): Diamond TH, Champion B, Clark WA. Management of acute osteoporotic vertebral fractures: A nonrandomized trial comparing percutaneous vertebroplasty with conservative therapy. Am J Med Mar;114(4): Cortet B, Cotton A, Boutry N, et al. Percutaneous vertebroplasty in the treatment of osteoporotic vertebral compression fractures: An open prospective study. J Rheumatol.1999;26: