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Pars injuries in athletes.

Low back pain is a common complaint among young athletes. In this population, pars injuries are one of the primary causes of back pain and include defects ranging from a stress reaction with interosseous edema to incomplete fracture to non-union. Spondylolysis is an anatomic defect in the pars interarticularis. A spondylotic or isthmic defect is the term used to describe a radiolucent gap within the pars interarticularis with sclerosis of the adjacent bone edges. Spondylolisthesis is characterized by the translation of one vertebra relative to the next caudal vertebral segment.

The incidence of pars injuries has been demonstrated to be 4.4% at age 6 with an increase of up to 6% by age 14. (1) Approximately, 85% of spondylotic defects occur at L5. Around 10% of the affected population develops injury at L4, and defects at this level are associated with increased pain. Bilateral pars injuries occur in 80% of individuals. There is a reported two-fold increased incidence in males; however, females are more prone to develop high-grade spondylolisthesis. (2)

The recent rise in amount and intensity of athletic participation by skeletally immature athletes is associated with a growing incidence of lower back injuries. Although the frequency of pars injuries in athletes was initially thought to be comparable to general population, approximately 47% of athletes between ages of 12 and 18 presenting with back pain were found to have isthmic spondylolisthesis. (3) There is a particularly high incidence in throwing athletes (27%), gymnasts (17%), rowers (17%), divers (43%), wrestlers (30%), and weightlifters (23%). (4, 5) The diagnosis and management of pars injuries in this population remain controversial and are further complicated by new developments in imaging modalities as well as both non-operative and operative treatments. In this article, we will review the diagnostic workup and management and will provide our preferred treatment algorithm based on the available literature.

Pathogenesis

The etiology of pars defects in young athletes is considered to be multi-factorial in origin with genetics, structural features, and repetitive loading all playing a role. Spondylolysis, especially, may have a greater genetic component than previously suspected. Studies report that 15% to 70% of first-degree relatives with spondylolysis are affected. (6, 7) Spondylolysis is also frequently associated with structural defects, such as spina bifida occulta. (8)

Repetitive loading of the lumbar spine in flexion, hyperextension, and rotation is the most prominent factor in the development of pars defects in athletes. The skeletally immature individual is particularly at risk for these injuries due to the unique anatomic features of the growth plate and apophyseal ring. Numerous biomechanical studies demonstrate that lesions in spondylolysis originate from the endplate or growth plate. (9-12) The pars interarticularis experiences the highest load stress in all six spinal motions. Repetitive extension exercises impart the highest load forced due to impingement of the pars interarticularis from the inferior facet of the cephalad vertebrae, resulting in microfracture and attempts at repair. (9) Rotational motions are most involved in the development of unilateral pars defects.

Although unilateral pars defects have not been found to be associated with spondylolisthesis or disability, (13) finite element analyses demonstrate that unilateral pars defects have a high risk for progression to bilateral defects. Unilateral stress reactions and eventual unilateral defects alter the biomechanics throughout the anterior and posterior spinal columns. Wang and coworkers demonstrated 15% to 104% higher stress in the contralateral pars. (12) Similarly, Sairyo found a 12.6 fold increase in stress in the contralateral pars and pedicle. (10, 11) Bilateral pars defects result in increased stresses in all structures, including the growth plate, apophyseal bony ring, endplate, ligaments, and disc. Therefore, patients with bilateral defects are at elevated risk for disc degeneration and spondylolisthesis.

Classification

The Wiltse-Newman classification is the most commonly used scheme for spondylolisthesis. (14) This classification system describes five types, with Type I and II applying to the pediatric population. Type I, dysplastic type, describes spondylolisthesis secondary to congenital abnormalities of the lumbosacral articulation. Type II, the isthmic type, is spondylolisthesis resulting from defects of the pars interarticularis and is further subdivided into three subtypes. Type IIA is the most frequent and is due to repetitive loading, causing a complete radiolucent defect. Type IIB is caused by elongation of the pars without disruption and is secondary to repeated healed microfractures. Type IIC is an acute fracture through the pars. Type III is degenerative and secondary to articular degeneration. Type IV is traumatic and is caused by fracture or dislocation of the lumbar spine, not involving the pars. Type V is pathologic and describes a spondylolisthesis caused by malignancy, infection, or other types of abnormal bone.

Marchetti and Bartolozzi proposed an alternative classification with two main categories: developmental and acquired. (15) The developmental category is comparable to the dysplastic and isthmic types of the Wiltse-Newman classification system. Within the acquired category are traumatic, post-surgery, pathologic, and degenerative types of slips.

Congeni and associates provide a clinical classification of spondylolysis. The first category includes hyperlordotic females with increased range of motion. The second category is muscular males with recent growth spurt, limited flexibility, and tight spinal muscles. The final category described is an athlete new to their sport with relatively weak abdominal muscles and poor trunk control. (16)

Clinical Presentation

Low back pain is the primary complaint for most patients presenting with pars injuries. The pain may occasionally radiate to the buttock or posterior thigh. Patients typically present with an insidious onset of pain; however, acute injury is not uncommon. It is important to obtain a thorough history of sports participation and training practices. Identifying high-risk sports and movements or activities that exacerbate the symptoms help point to the diagnosis of pars defects. A nutritional and menstruation history should be obtained for all female patients as the female athlete triad (amenorrhea, anorexia, and osteoporosis) places patients at greater risk for bony injury. Radicular symptoms and bowel or bladder disturbances are uncommon in spondylolysis in the absence of spondylolisthesis. Additionally, reports of night pain are not typically associated with these conditions and may indicate the presence of an occult neoplasm. (17)

The physical exam must include a thorough orthopaedic and neurologic evaluation with the patient fully undressed. On inspection, a loss of lordosis is commonly seen. Coronal spinal alignment is examined for scoliosis. During palpation, midline tenderness over the spinous process may indicate an acute fracture. In assessing range of motion, flexion and extension are often decreased. Hamstring tightness is present frequently and a popliteal angle should be recorded. Straight leg raise testing is typically normal for these patients. Analysis of gait reveals shortened stride with hip and knee flexion secondary to hamstring tightness in patients with advanced degrees of spondylolisthesis.

The clinical features of active spondylolysis do not strongly differentiate this condition from other causes of low back pain. The only reported pathognomonic finding of these pars injuries is reproduction of pain with the one-legged hyperextension test or Stork test. The test is performed by having subjects stand on one leg with the contralateral knee flexed 80[degrees] and the contralateral hip slightly raised. The test is considered positive if extension of the lumbar spine in this position reproduces the patient's pain. Masci and colleagues (18) performed a prospective cohort study of 71 subjects with low back pain aged 10 to 30 and with a clinical diagnosis of spondylolysis. The one-legged hyperextension test was found to be neither sensitive, nor specific (sensitivity 52.5%, specificity 56.4%) when correlated with magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and computed tomography (CT). (18) Therefore, the one-legged hyperextension test should not be relied upon to exclude the diagnosis of spondylolysis.

Although pars defects are among most common cause of low back pain in young athletes, the differential diagnosis for this frequent complaint remains broad. Alternative diagnoses to consider include disc disease (herniation, degeneration), muscle or ligament strain, hyperlordotic back pain, ring apophyseal injury, discitis, osteomyelitis, neoplasm, and non-spinal disorders.

Imaging

Imaging studies are essential for the diagnosis of pars injuries. Initial imaging studies include standing AP and lateral lumbar spine radiographs to assess alignment, spondylotic defects, and spondylolisthesis (Fig. 1). Signs of pars defects on the AP view include pedicle sclerosis and lateral deviation of the spinous process. Lateral views should be examined for the presence of spondylolisthesis. Oblique views have traditionally been part of a four view series to evaluate for pars defects. The anatomy of this view has been described to resemble a 'Scottie dog,' with the neck representing the pars. However, recent literature has called the utility of these views into question. Fractures are best identified when the fracture line is perpendicular to the beam. Saifuddin and coworkers (19) demonstrated that the mean angle of the pars defect as measured by CT is 23[degrees] with respect to the coronal plane. Additionally, they found only 32% of pars defects were within 15[degrees] of the 45[degrees] oblique plane. (19) This would suggest that standard oblique views are not ideal to visualize the pathology. Flexion-extension radiographs may also be useful to assess stability of involved segments.

Recent literature has focused on the utility and risk of subjecting the pediatric patient to multiple radiographic views during the workup of spondylolysis. In a review of 1,500 lumbar spine reports, Amato and associates found 56 cases of spondylolysis. (20) When evaluating all six views obtained for spondylolysis, they demonstrated that the single collimated lateral view showed the largest number of pars defects (84%).20 Although the oblique view can visualize the pars region, many have discouraged the use of this view due to the arguably unnecessary increase in gonadal radiation exposure. Beck and colleagues demonstrated that there was no significant difference in sensitivity (0.59 and 0.53) and specificity (0.96 and 0.94) between four-view and two-view studies. The radiation effective dose in this study was 1.26 mSv for four-views versus 0.72 mSv for two-views. (21)

Radiographs are unable to visualize early stress reactions and often fail to provide early diagnosis of pars defects. Despite negative radiographs, young athletes with persistent back pain should undergo advanced imaging with SPECT, CT, or MRI.

SPECT is frequently the next imaging modality of choice after radiographs fail to provide early evidence of pars defects in athletes with persistent low back pain. This study has the ability to detect stress reactions not visualized on x-ray and CT with increased radionuclide uptake occurring in areas of increased bone turnover. Yang and coworkers (22) compared results of SPECT versus thin slice CT for detecting stress injuries of the pars interarticularis. The investigators demonstrated that 19.6% (11 of 56) of the stress injuries were CT-negative and SPECT positive. (22) While SPECT is very sensitive for pars lesions, it is not specific and will also be positive in cases of malignancy and infection.

CT is another commonly used modality that is superior to plain radiographs in the ability to detect early stress fractures (Fig. 2). Thin cut CT has replaced the need for "reverse gantry method." CT studies provide the ability to classify the stage of the lesions and thus allow for prediction of osseous healing potential. Sairyo and associates (23) utilized a CT-based classification system to assess outcomes of conservative treatment of lumbar spondylolysis. The classification schema included early lesions (hairline fracture of pars interarticularis), progressive lesions (visible gap), and terminal lesions (pseudoarthrosis). (23) A major disadvantage of CT is the exposure to high levels of ionizing radiation.

MRI has been typically reserved for patients presenting with neurologic symptoms and low back pain. However, new studies demonstrate significant utility of MRI in the early detection of pars defects (Fig. 2). Areas of reactive edema are easily visualized on T2W and STIR images. T1 images also enhance the ability to see the anatomy of the defect. MRI helps to identify the stage of the lesion and assists in predicting the healing potential of the lesion with grading systems. (24) MRI also has the ability to reveal other spinal conditions that might be causing low back pain, such as intervertebral disc pathology, neural element compression, and neoplastic disease. (2) One disadvantage of MRI is the high cost of the study; however, MRI offers the major benefit of sparing the skeletally immature patient excessive doses of radiation.

Recent studies have sought to determine which advanced imaging modality is superior. (25-28) Gregory and colleagues retrospectively evaluated all patients studied with both SPECT and CT and concluded that SPECT was more sensitive than CT. (25) Campbell and coworkers (26) examined all three imaging modalities to determine whether MRI can be used as an exclusive imaging modality. Using SPECT/ CT as gold standard, MRI identified abnormalities in 39 of 40 pars defects and correctly graded 29 of 40 pars defects. Therefore, the investigators concluded that MRI can be used as an effective and reliable first line image modality for the diagnosis of juvenile spondylolysis. (26) Ganiyusufoglu and associates (27) provided further evidence in support of the use of MRI in a retrospective study comparing MRI and CT in evaluating stress injuries of the lumbar spine. MRI was found to have a similar diagnostic accuracy to CT in determining complete fractures with or without accompanying marrow edema and incomplete fractures with accompanying marrow edema (specificity 99.6%, sensitivity 86.7%, and accuracy 97.2%). (27) MRI has also been found to have the significant advantage of identifying signal changes that could be used as an indicator for early diagnosis of spondylolysis. Sairyo and colleagues (28) evaluated 37 pediatric patients with 68 defects identified and staged with CT scans. High signal changes of the pedicles on axial T2-weighted MRI were demonstrated in 100% of very early and late early stage defects. Of the defects demonstrating high signal changes, 79% showed bony healing with conservative treatment versus none of the lesions without high signal change demonstrated healing. Thus, these findings reveal the significance of MRI findings for guiding treatment options. (28)

With the many available imaging modalities, increasing attention has been directed towards the significance of the radiation exposure associated with these studies. The consideration of radiation exposure is particularly important for the diagnosis of pars injuries as these injuries have the highest incidence in young developing individuals. Table 1 lists the radiation doses associated with the commonly used imaging modalities. Although CT and SPECT are considered by many studies to be the gold standard radiological studies for diagnosing pars injuries, they incur a notably high radiation dose. Miglioretti and coworkers quantified use of CT in pediatrics and cancer risk. (29) The investigators noted a higher lifetime risk of cancer occurrence with CT exposure in younger patients and girls. One solid cancer was projected to result from every 270 to 800 spine CTs depending on age. Mathews and associates had similar findings through their cohort study and noted a 24% increased incidence of cancer if an individual had a CT scan between the ages of 0 and 19. (30) Given these findings of increased cancer risk with CT studies, MRI may be considered a preferred imaging modality due to lack of radiation and comparable efficacy in diagnosis and treatment monitoring, as demonstrated in recent literature.

Non-operative Treatment

Pars defects are most commonly managed non-operatively. The goals of non-operative treatment differ based upon the stage and severity of the pars lesions. Stress reactions or stress fractures of the pars interarticularis are treated with the primary intent of healing the injury and preventing the progression to a nonunion. On the other hand, spondylolysis with a symptomatic spondylotic defect is treated with the goal of pain alleviation and improvement of spinal mobility. A variety of non-operative treatment modalities are available and include avoidance of aggravating activity, physical therapy, NSAIDs, bracing, and bone stimulation. (31)

Stress reactions and stress fractures of the pars have the best possible outcomes with early diagnosis and subsequent early non-operative interventions. The mainstay of initial treatment includes removal from sport and full time immobilization in thoracolumbar orthotic for a period of 6 to 12 weeks. Sairyo and associates found that 86.7% of early-stage lesions demonstrated complete bony healing on CT after 3 months of conservative treatment with avoidance of sporting activity and soft TLSO bracing. (23) Progressive lesions with high signal intensity changes on MRI demonstrated a lower rate of healing with conservative treatment (60%), and terminal defects (pseudoarthrosis) failed to show any evidence of healing at all (0%). (28) Further studies have demonstrated that hard TLSO bracing for 3 months leads to greater than 90% complete bony union of early lesions. (32) A meta-analysis of observational studies by Klein and colleagues (33) aimed to identify and summarize the evidence for effectiveness of non-operative treatment modalities for spondylolysis. Acute lesions were found to have nearly 70% rate of healing with non-operative methods, while progressive and terminal lesions did not achieve bony union. Interestingly, the investigators found an 86% treatment success rate without bracing and an 89% rate of treatment success with bracing. Overall, the results of the study suggest that 83.9% of patients treated non-operatively will have successful clinical outcome after 1 year, and bracing did not seem to influence this outcome in the study. (33) However, this study had multiple limitations, and thus bracing remains the preferred initial treatment of early lesions.

Non-operative treatments for patients with spondylotic defects are directed more toward symptomatic management and functional improvement. Bracing is less frequently utilized for more advanced lesions as it has not been found to be as effective as in earlier lesions. (23, 33) Activity restriction and physical therapy, therefore, play a greater role in the clinical outcomes of these patients. Exercise treatment programs involving training of specific muscle groups have demonstrated efficacy in improving clinical outcomes of these patients. O'Sullivan and coworkers (34) compared a specific exercise treatment approach with commonly prescribed conservative treatment programs. The specific exercises aimed to strengthen the deep abdominal muscles with co-activation of the lumbar multifidus proximal to the pars defects. The investigators found a statistically significant reduction in pain intensity and functional disability levels in the group performing specific exercises, and this effect was maintained at 30-month follow-up. (34) Therefore, a well-prescribed therapy program is key for the non-operative management of these more advanced patients.

Return to play after non-operative treatment remains a controversial topic within the literature. Many studies have demonstrated excellent outcomes in terms of radiographic evidence of healing with cessation of all athletic activities in patients with pars stress reactions; however, the majority of these studies have failed to specify timing of return to sport. (23, 32, 33, 35) A prospective study by Congeni and associates (35) examined the natural course 40 athletically active patients with stress reactions treated conservatively. The patients were started on a protocol, including avoidance of hyperextension and non-rigid brace with rehab starting at 6 to 8 weeks. Patients were returned to sport at 8 weeks if they had no pain with extension and were pain-free at rest and during sport specific activity. Of the patients with acute stress reactions without chronic fracture, 100% classified themselves as "very active" and returned to pre-injury performance level. Patients found on follow-up CT to have chronic fractures were less active after return to play at same time period. (35) Another study evaluating elite athletes return to play after acute pars injuries by Sys and colleagues (36) showed similar outcomes in patients with acute injuries identified on SPECT but with negative radiographs. In this prospective study, highly competitive athletes with unilateral, bilateral, or "pseudo-bilateral" pars lesions underwent conservative treatment with cessation of sporting activities and bracing for a mean of 15.9 weeks. Approximately, 89.3% of athletes were able to return to their same level of competitive activity within an average of 5.5 months after the onset of treatment, and there was no difference in sports resumption between the three groups. (36) Iwamoto and coworkers had comparable findings in their study of athletes with severe low back pain and findings of pars defects on radiographs, with 87.5% of athletes returning to original sporting activities at an average of 5.4 months after onset of treatment. (37) Kurd and associates retrospectively showed a return to pre-activity level in all but 3 of 436 patients with symptomatic isthmic spondylolysis after conservative treatment with 3-month activity cessation and organized physical therapy program. (38) Therefore, these studies provide excellent evidence for successful return to pre-injury level after short course of non-operative treatment for early pars injuries.

Operative Treatment

Although non-operative treatment has been demonstrated to be highly effective in resulting in bony union and prompt return to sports, surgical treatment is indicated in a certain subgroup of patients with pars injuries. Surgical interventions are often necessary when there is failure of non-operative treatment for at least 6 months, symptomatic pars defects, preserved adjacent discs, less than a Meyerding grade II spondylolisthesis, and the patient's age is less than 20. Multiple techniques have been described for the direct repair of pars injuries and most commonly include Buck direct screw fixation, Scott wiring technique, and pedicle screw-sublaminar hook technique.

Buck's repair (Fig. 3) is a commonly used technique for the direct repair of pars defects due to its biomechanical stability and improved clinical results. In this form of direct fixation, the loose lamina and pars defects are exposed, and the pars defects are debrided and decorticated. A path is then drilled under direct visualization, and a noncannulated cortical screw is secured across the defect. The repaired area is then bone grafted. Sairyo and colleagues (39) conducted a finite element analysis examining the biomechanical effects of Buck's technique on disc stresses. The investigators found that before repair of a bilateral L5 spondylotic, lesion stresses at the annulus fibrosis and nucleus pulposus at L4/5 increased to 111% and 120%, respectively. After Buck's repair, the stresses recovered to 102% and 105%, correspondingly. At the L5/S1 level, stress at annulus and nucleus pulpous were increased to 168% and 155% and then reduced to 125% and 120%, respectively, after Buck's repair. (39) Thus, Buck's technique is effective for decreasing the disc stresses caused by spondylolysis, preventing disc degeneration and further back pain in these patients.

In addition to the favorable biomechanical effects, Buck's technique has also been found to produce good functional outcomes. Menga and coworkers (40) prospectively analyzed 31 competitive athletes with chronic lysis without disc degeneration treated with direct intralaminar screw fixation and bone grafting. At a mean of 60-month follow-up, 90% of the surgeries were deemed successful with improvement in activity, functional level, and low back pain. Additionally, 76% of patients returned to sports at a mean of 6 months after surgery. (40)

Pedicle screw and sublaminar hook fixation has also been found to produce favorable outcomes in patients with pars lesions meeting criteria for surgical intervention. This technique involves bridging the pars defect with a rod anchored by a cephalad pedicle screw and caudad laminar hook combined with bone grafting. The fixation provides a larger surface area and more stable construct than direct intralaminar screw fixation. (41) Kakiuchi reported 100% (16/16) osseous union at 1-year follow-up in patients treated with pedicle screws and sublaminar hooks. (42) A study by Roca and associates (43) found that the success of these constructs was largely age determinant. Of the patients under 20 years of age, 92% had fusion, and 84% had excellent or good clinical outcomes. On the contrary, none of the patients over 20 years of age had fusion, and 66% had excellent to good clinical outcomes. Therefore, the investigators concluded that this procedure is best indicated for a younger patient population. (43)

Although Scott wiring technique has been shown to be effective for achieving pars union, it has not been found to be as biomechanically and clinically successful as some of the other surgical treatment options. (39-44) Scott wiring technique involves decorticating the transverse process, the lateral aspect of superior facet, and lamina on each side. A figure of eight configuration is then made with braided wire passing through the transverse processes and the spinous process. Bone graft is then placed around the pars defect and the wires are tensioned to create a compressive force. Debnath and colleagues (44) compared the clinical outcomes and return to sport in professional athletes undergoing Buck's screw fixation and Scott wiring technique. In this study, none of the three patients who underwent Scott wiring returned to sport and two of the three required a posterior spinal fusion for nonunion. On the other hand, all but one of the patients who underwent Buck's screw fixation returned to sport. (44)

Treatment Algorithm

After a thorough review of the literature, we have devised a cohesive treatment algorithm as demonstrated in Figure 4. This algorithm focuses on identifying possible candidates for healing through the use of x-ray and MRI with bracing reserved for only those with HSC present. Surgery is reserved for those with symptomatic nonunions.

Conclusion

Pars injuries are common in the young athlete, and the clinician must have a high index of suspicion for these lesions for symptomatic low back pain within this patient population. There is no reliable pathognomonic sign on physical exam, thus making early radiologic studies essential. MRI has been demonstrated within the literature to be a reasonable alternative to SPECT or CT as the first line cross sectional imaging. Early diagnosis is critical to achieving bony union with non-operative interventions. While there is significant evidence to support bracing, there is no consensus as to the type and duration of such non-operative treatment. The prognosis for return to competition is very good with nonoperative treatment; however, return to play may take up to 6 months. If a patient develops symptomatic nonunion, refractory to non-operative measures for at least 6 months, surgical treatment is recommended with either motion sparing options or fusion.

Further research is needed for the evaluation and treatment of pars injuries in the young athletic population. More evidence is necessary to determine the type (hard versus soft) and duration of bracing for early and progressive lesions. Additional studies are also needed to evaluate the efficacy of bone stimulators and other new non-operative treatment modalities. Optimal repair techniques specific for different patient populations must also be further delineated to ensure the best possible outcomes.

Jonathan H. Oren, M.D., and Jason M. Gallina, M.D.

Jonathan H. Oren, M.D., and Jason M. Gallina, M.D., Hospital for Joint Diseases at NYU Langone Medical Center, Department of Orthopaedic Surgery, New York, New York.

Correspondence: Jonathan H. Oren, M.D., 301 East 17th Street, Suite 1401, New York, New York 10003; jonathan.oren@nyumc.org.

Disclosure Statement

None of the authors have a financial or proprietary interest in the subject matter or materials discussed, including, but not limited to, employment, consultancies, stock ownership, honoraria, and paid expert testimony.

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Caption: Figure 1 Spondylolysis without spondylolisthesis in adolescent female with back pain. AP (A) and lateral (B) radiographs demonstrating right-sided L5 spondylolysis with possible isthmic defect seen on lateral image. The arrow points to the L5 pars lesion.

Caption: Figure 2 CT (A and B) and MRI (C) of same patient demonstrating right sided chronic appearing L5 pars fracture (A and B) and left sided L5 pars stress reaction (B). The arrow denotes the right-sided lesion. The MRI (C) demonstrates high signal change on the right-sided lesion.

Caption: Figure 3 AP (A), right oblique (B) and lateral (C) postoperative radiographs of same patient 2 years after open iliac crest grafting with bilateral Buck's screw fixation. The oblique (B) demonstrates a now healed right-sided lesion with no evidence of disc degeneration or spondylolisthesis (C).

Caption: Figure 4 Algorithm for diagnosis and treatment of spondylolysis. HSC = High Signal Change, NSAID = non-steroidal anti-inflammatory drug, and PT = physical therapy.

Table 1 Radiation Doses Associated with the Commonly Used
Imaging Modalities *

Image                                              Radiation Level
                                                       (mSv)
AP and lateral chest x-ray                              0.1
AP, lateral, and spot lateral lumbar spine x-ray        1.5
Lumbar CT                                                 6
SPECT                                                   6.3
Background yearly exposure                                3

* > 5mSv exposure is linked with increase in solid organ and
hematologic malignancy.


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Author:Oren, Jonathan H.; Gallina, Jason M.
Publication:Bulletin of the NYU Hospital for Joint Diseases
Article Type:Report
Date:Jan 1, 2016
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