Ninety Percent or Greater Tumor Necrosis Is Associated With Survival and Social Determinants of Health in Patients With Osteosarcoma in the National Cancer Database.

BACKGROUND: The histologic response of osteosarcoma to chemotherapy is commonly cited as a prognostic factor and typically graded as the percent necrosis of the tumor at the time of surgical resection. Few studies, to our knowledge, have examined the relationship of tumor necrosis relative to other factors. Existing studies are limited by prolonged enrollment periods or analysis of patient subsets without the strongest predictor of mortality: metastasis at diagnosis. Additionally, the definitive threshold value for a good histologic response is commonly set at more than 90% tumor necrosis with little evidence; some authors advocate other values. QUESTION/PURPOSES: (1) Are there alternative cutoff values for a good response to chemotherapy in a large, national cohort of contemporarily treated patients with osteosarcoma? (2) How does the association of histologic response to survival in osteosarcoma compare with other clinicopathologic factors? (3) What patient and clinical factors are associated with the histologic response? METHODS: We identified 2006 patients with osteosarcoma diagnosed between 2010 and 2015 in the National Cancer Database (NCDB), a registry that includes 70% of all new cancers diagnosed in the United States with 90% follow-up. Patients were excluded for missing documentation of percent tumor necrosis (21% [425 of 2006]) or if definitive resection was not performed (< 1% [1 of 2006]). A total of 1580 patients were included in the analysis, with a mean follow-up duration of 37 ± 22 months. A Kaplan-Meier survival analysis, stratified by the percent tumor necrosis after chemotherapy, was performed for the 5-year period. Other covariates examined were sex, race, socioeconomic score composite, insurance type, Charlson/Deyo score, distance from the hospital, and location (metropolitan, urban, or rural). Clinical and sociodemographic data including patient-identified race from the patient's medical record is input into the NCDB by certified registrars. The NCDB only allows coding of one primary race for each patient; thus, most of our patients were grouped as White or Black race and the remaining were grouped as Other for our analysis. A multiple Cox regression analysis was performed to evaluate the effect of percent necrosis compared with other demographic, clinicopathologic, and treatment effects on survival. Finally, a multiple logistic regression analysis was performed to assess demographic and clinicopathologic characteristics associated with percent necrosis. RESULTS: Five-year overall survival for patients with histologic gradings of 90% to 94% necrosis (70% [95% confidence interval (CI) 60.6% to 79.7%) and 95% to 100% necrosis (74% [95% CI 68% to 80.3%) was not different between groups (p = 0.47). A comparison of histologic responses below 90% necrosis found no difference in survival between patients with decreasing histologic response (p > 0.05). Necrosis of less than 90% was associated with worse survival (HR 2.00 [95% CI 1.58 to 2.52]; p < 0.001 compared with more than 90% necrosis), and factors most associated with poor survival were metastasis (HR 2.85 [95% CI 2.27 to 3.59]; p < 0.001) and skip metastasis at the time of diagnosis (HR 2.52 [95% CI 1.64 to 3.88]; p < 0.001). On multivariate analysis, adjusting for demographic, clinicopathologic, and treatment factors, social determinants of health were negatively associated with percent necrosis of 90% or more, including uninsured status (OR 0.46 [95% CI 0.23 to 0.92]; p = 0.02 compared with private insurance) and lower socioeconomic status composite (OR for the lowest first and second quartiles were 0.63 [95% CI 0.44 to 0.90]; p = 0.01 and 0.70 [95% CI 0.50 to 0.96]; p = 0.03, respectively). Race other than White or Black (OR 0.61 [95% CI 0.40 to 0.94]; p = 0.02 compared with White race) was also negatively associated with percent necrosis of more than 90% after controlling for available covariates. CONCLUSION: This study suggests that a cutoff of 90% necrosis provides the best prognostic value for patients with osteosarcoma undergoing chemotherapy. Other threshold values did not show different survival benefits. Sociodemographic factors were associated with histologic response less than 90%. These associations must be carefully understood not as cause and effect but likely demonstrating the effects of health disparities and access to care. Although we controlled for multiple variables in our analysis, broad variables such as race may have been associated with histologic response due to unaccounted confounders. Medical providers should be aware of these associations to ensure equitable access and delivery of care because access to care may be responsible for these associations. Future studies should examine potential drivers of this observation, such as a delay in presentation or deviation from standard of care practices. LEVEL OF EVIDENCE: Level III, therapeutic study.

What Is the Prevalence of Clinically Important Findings Among Incidentally Found Osseous Lesions?

BACKGROUND: Patients with incidentally found musculoskeletal lesions are regularly referred to orthopaedic oncology. Most orthopaedic oncologists understand that many incidental findings are nonaggressive and can be managed nonoperatively. However, the prevalence of clinically important lesions (defined as those indicated for biopsy or treatment, and those found to be malignant) remains unknown. Missing clinically important lesions can result in harm to patients, but needless surveillance may exacerbate patient anxiety about their diagnosis and accrue low-value costs to the payor. QUESTIONS/PURPOSES: (1) What percentage of patients with incidentally discovered osseous lesions referred to orthopaedic oncology had lesions that were clinically important, defined as those receiving biopsy or treatment or those found to be malignant? (2) Using standardized Medicare reimbursements as a surrogate for payor expense, what is the value of reimbursements accruing to the hospital system for the imaging of incidentally found osseous lesions performed during the initial workup period and during the surveillance period, if indicated? METHODS: This was a retrospective study of patients referred to orthopaedic oncology for incidentally found osseous lesions at two large academic hospital systems. Medical records were queried for the word "incidental," and matches were confirmed by manual review. Patients evaluated at Indiana University Health between January 1, 2014, and December 31, 2020, and those evaluated at University Hospitals between January 1, 2017, and December 31, 2020, were included. All patients were evaluated and treated by the two senior authors of this study and no others were included. Our search identified 625 patients. Sixteen percent (97 of 625) of patients were excluded because their lesions were not incidentally found, and 12% (78 of 625) were excluded because the incidental findings were not bone lesions. Another 4% (24 of 625) were excluded because they had received workup or treatment by an outside orthopaedic oncologist, and 2% (10 of 625) were excluded for missing information. A total of 416 patients were available for preliminary analysis. Among these patients, 33% (136 of 416) were indicated for surveillance. The primary indication for surveillance included lesions with a benign appearance on imaging and low clinical suspicion of malignancy or fracture. A total of 33% (45 of 136) of these patients had less than 12 months of follow-up and were excluded from further analysis. No minimum follow-up criteria were applied to patients not indicated for surveillance because this would artificially inflate our estimated rate of clinically important findings. A total of 371 patients were included in the final study group. Notes from all clinical encounters with orthopaedic and nonorthopaedic providers were screened for our endpoints (biopsy, treatment, or malignancy). Indications for biopsy included lesions with aggressive features, lesions with nonspecific imaging characteristics and a clinical picture concerning for malignancy, and lesion changes seen on imaging during the surveillance period. Indications for treatment included lesions with increased risk of fracture or deformity, certain malignancies, and pathologic fracture. Diagnoses were determined using biopsy results if available or the documented opinion of the consulting orthopaedic oncologist. Imaging reimbursements were obtained from the Medicare Physician Fee Schedule for 2022. Because imaging charges vary across institutions and reimbursements vary across payors, this method was chosen to enhance the comparability of our findings across multiple health systems and studies. RESULTS: Seven percent (26 of 371) of incidental findings were determined to be clinically important, as previously defined. Five percent (20 of 371) of lesions underwent tissue biopsy, and 2% (eight of 371) received surgical intervention. Fewer than 2% (six of 371) of lesions were malignant. Serial imaging changed the treatment of 1% (two of 136) of the patients, corresponding to a rate of one in 47 person-years. Median reimbursements to work up the incidental findings analyzed was USD 219 (interquartile range USD 0 to 404), with a range of USD 0 to 890. Among patients indicated for surveillance, the median annual reimbursement was USD 78 (IQR USD 0 to 389), with a range of USD 0 to 2706. CONCLUSION: The prevalence of clinically important findings among patients referred to orthopaedic oncology for incidentally found osseous lesions is modest. The likelihood of surveillance resulting in a change of management was low, but the median reimbursements associated with following these lesions was also low. We conclude that after appropriate risk stratification by orthopaedic oncology, incidental lesions are rarely clinically important, and judicious follow-up with serial imaging can be performed without incurring high costs. LEVEL OF EVIDENCE: Level III, therapeutic study.

Topical Tranexamic Acid Increases Early Postoperative Pain After Total Hip Arthroplasty.

BACKGROUND: Tranexamic acid (TXA) has reduced blood transfusion following total hip arthroplasty (THA). However, non-human studies have linked TXA exposure with increased pain and decreased periarticular cell viability and cell death. This study evaluated early pain following THA performed with and without topical TXA. METHODS: A consecutive series of 213 THAs performed without TXA were compared to 169 THAs performed with topical TXA. A single surgeon using identical perioperative medical and pain control protocols performed procedures. Prospectively collected inpatient pain scores, time to first opioid, and opioid consumption in morphine milligram equivalents were evaluated in relation to TXA use and 10 additional covariates. Univariate relationships between independent and dependent variables with P ≤ .20 were entered into multivariate analysis using the General Linear Model. RESULTS: Patients who received topical TXA reported higher mean 24-hour pain scores compared to patients who did not receive TXA (P = .006). Patients with topical TXA requested opioids significantly sooner (means of 152 vs 246 minutes, P = .033). An average of 56.07 morphine milligram equivalents were consumed during the first 24 hours after post-acute care unit discharge by patients who received topical TXA compared to 31.26 by patients who did not receive TXA (P < .001). CONCLUSION: Topical TXA use was associated with greater early postoperative pain and opioid consumption in primary THA patients. Findings were supported by the magnitude of observed effects and the likelihood of clinical relevance. Replication and consideration of potential adverse consequences of TXA use in elective settings is encouraged.

Effectiveness of Constrained Liner Use During Harrington Hip Reconstruction in Oncology Patient.

BACKGROUND: Patients with destructive acetabular lesions are at high risk for morbidity. Harrington described reinforcing acetabular diseased bone with methylmethacrylate, supplemented by metal fixation, to allow total hip reconstruction. However, all published studies using this technique report dislocations. We believe that initial use of constrained liners would help alleviate dislocation risk, without increasing component loosening or polyethylene wear. METHODS: Sixty-eight patients who underwent Harrington hip arthroplasties for metastatic cancer from August 2005 to March 2015 were identified. All patients had a constrained acetabular liner implanted during their index procedure. Electronic medical records and radiographs were reviewed. A literature review of studies with similar technique was used as a historical control. RESULTS: Forty-seven patients (69.2%) died 22.7 ± 22.7 months after surgery, at age 62.4 ± 17.2 years. At an average clinical follow-up of 9.9 ± 14.2 months (range 2-50 months), we found no incidents of dislocation. No patients had component failure requiring revision or evidence of loosening on x-ray. Thirteen papers, comprising 185 patients, demonstrated 39 patients (21.1%) with dislocations and 13 patients (7.0%) requiring revision surgery for aseptic loosening. CONCLUSION: Modified Harrington technique has demonstrated relative durability when reconstructing metastatic acetabular disease, although dislocation occurs in approximately 20% of patients. This study demonstrates that initial use of a constrained liner can alleviate postoperative dislocations without increasing risk of perioperative complications. Even modest reduction in complications during the limited lifespan of oncologic patients can have dramatic positive effects on quality of life.

A dual-center review of compressive osseointegration for fixation of massive endoprosthetics: 2- to 9-year followup.

BACKGROUND: Aseptic failure of massive endoprostheses used in the reconstruction of major skeletal defects remains a major clinical problem. Fixation using compressive osseointegration was developed as an alternative to cemented and traditional press-fit fixation in an effort to decrease aseptic failure rates. QUESTIONS/PURPOSES: The purpose of this study was to answer the following questions: (1) What is the survivorship of this technique at minimum 2-year followup? (2) Were patient demographic variables (age, sex) or anatomic location associated with implant failure? (3) Were there any prosthesis-related variables (eg, spindle size) associated with failure? (4) Was there a discernible learning curve associated with the use of the new device as defined by a difference in failure rate early in the series versus later on? METHODS: The first 50 cases using compressive osseointegration fixation from two tertiary referral centers were retrospectively studied. Rates of component removal for any reason and for aseptic failure were calculated. Demographic, surgical, and oncologic factors were analyzed using regression analysis to assess for association with implant failure. Minimum followup was 2 years with a mean of 66 months. Median age at the time of surgery was 14.5 years. RESULTS: A total of 15 (30%) implants were removed for any reason. Of these revisions, seven (14%) were the result of aseptic failure. Five of the seven aseptic failures occurred at less than 1 year (average, 8.3 months), and none occurred beyond 17 months. With the limited numbers available, no demographic, surgical, or prosthesis-related factors correlated with failure. CONCLUSIONS: Most aseptic failures of compressive osseointegration occurred early. Longer followup is needed to determine if this technique is superior to other forms of fixation.

Increased Number of Medical Comorbidities Associated With Increased Risk of Presenting With Pathological Femur Fracture in Metastatic Bone Disease.

Background: Many cancers metastasize to bone and may lead to pathologic fracture or impending pathologic fracture. Prophylactically stabilizing bones before fracture has been shown to be more cost-effective with improved outcomes. Many studies have examined risk factors for pathological fracture, with radiographic and functional pain data serving as predominant indicators for surgery. Conditions associated with poor bone health and increased risk of fracture in the non-oncologic population, including diabetes mellitus, chronic obstructive pulmonary disease (COPD), cardiovascular disease, renal disease, smoking, corticosteroid use, and osteoporosis, have not been studied in the context of metastatic disease. Characterization of these factors could help providers identify candidates for prophylactic stabilization thereby reducing the number of completed pathological fractures. Methods: 298 patients over the age of 40 with metastatic bone disease of the femur treated between 2010-2021 were retrospectively identified. Patients without complete medical documentation or with non-metastatic diagnoses were excluded. 186 patients met inclusion and exclusion criteria, including 74 patients who presented with pathological femur fracture and 112 patients who presented for prophylactic stabilization. Patient demographics and comorbidities including diabetes mellitus, COPD, cardiovascular disease, renal disease, osteoporosis, active tobacco or corticosteroid use, and use of anti-resorptive therapy were collected. Descriptive statistics were compiled, with univariable analysis by Mann-Whitney or chisquared testing. Multiple logistic regression was then performed to identify the most significant patient variables for presenting with completed fracture. Results: On univariable analysis, patients with COPD were more likely to present with pathologic fracture (19/32 [59%] compared to 55/154 [36%], p = 0.02). A trend emerged for patients with an increasing number of comorbidities (28/55 [51%] for 2+ comorbidities compared to 18/61 [29%] with zero comorbidities, p = 0.06). On multivariable analysis, patients with two or more comorbidities (OR: 2.49; p=0.02) were more likely to present with a femur fracture. Conclusion: This analysis suggests that those with an increasing number of comorbidities may be at increased risk for pathologic fracture. This study raises the possibility that patient factors and/ or comorbidities alter bone strength and/or pain experiences and may guide orthopaedic oncologists weighing prophylactic stabilization of femur lesions. Level of Evidence: III.

Integrative Multi-OMICs Identifies Therapeutic Response Biomarkers and Confirms Fidelity of Clinically Annotated, Serially Passaged Patient-Derived Xenografts Established from Primary and Metastatic Pediatric and AYA Solid Tumors.

Establishment of clinically annotated, molecularly characterized, patient-derived xenografts (PDXs) from treatment-naïve and pretreated patients provides a platform to test precision genomics-guided therapies. An integrated multi-OMICS pipeline was developed to identify cancer-associated pathways and evaluate stability of molecular signatures in a panel of pediatric and AYA PDXs following serial passaging in mice. Original solid tumor samples and their corresponding PDXs were evaluated by whole-genome sequencing, RNA-seq, immunoblotting, pathway enrichment analyses, and the drug−gene interaction database to identify as well as cross-validate actionable targets in patients with sarcomas or Wilms tumors. While some divergence between original tumor and the respective PDX was evident, majority of alterations were not functionally impactful, and oncogenic pathway activation was maintained following serial passaging. CDK4/6 and BETs were prioritized as biomarkers of therapeutic response in osteosarcoma PDXs with pertinent molecular signatures. Inhibition of CDK4/6 or BETs decreased osteosarcoma PDX growth (two-way ANOVA, p < 0.05) confirming mechanistic involvement in growth. Linking patient treatment history with molecular and efficacy data in PDX will provide a strong rationale for targeted therapy and improve our understanding of which therapy is most beneficial in patients at diagnosis and in those already exposed to therapy.

Systems Biology Approach Identifies Prognostic Signatures of Poor Overall Survival and Guides the Prioritization of Novel BET-CHK1 Combination Therapy for Osteosarcoma.

Osteosarcoma (OS) patients exhibit poor overall survival, partly due to copy number variations (CNVs) resulting in dysregulated gene expression and therapeutic resistance. To identify actionable prognostic signatures of poor overall survival, we employed a systems biology approach using public databases to integrate CNVs, gene expression, and survival outcomes in pediatric, adolescent, and young adult OS patients. Chromosome 8 was a hotspot for poor prognostic signatures. The MYC-RAD21 copy number gain (8q24) correlated with increased gene expression and poor overall survival in 90% of the patients (n = 85). MYC and RAD21 play a role in replication-stress, which is a therapeutically actionable network. We prioritized replication-stress regulators, bromodomain and extra-terminal proteins (BETs), and CHK1, in order to test the hypothesis that the inhibition of BET + CHK1 in MYC-RAD21+ pediatric OS models would be efficacious and safe. We demonstrate that MYC-RAD21+ pediatric OS cell lines were sensitive to the inhibition of BET (BETi) and CHK1 (CHK1i) at clinically achievable concentrations. While the potentiation of CHK1i-mediated effects by BETi was BET-BRD4-dependent, MYC expression was BET-BRD4-independent. In MYC-RAD21+ pediatric OS xenografts, BETi + CHK1i significantly decreased tumor growth, increased survival, and was well tolerated. Therefore, targeting replication stress is a promising strategy to pursue as a therapeutic option for this devastating disease.

Orthopedic issues in pregnancy.

Pregnancy taxes the musculoskeletal system. The enlarging gravid uterus alters the maternal body's center of gravity, mechanically stressing the axial and pelvic systems, and compounds the stresses that hormone level fluctuations and fluid retention exert. While the pregnant woman is prone to many musculoskeletal injuries, most can be controlled conservatively, but some require emergent surgical intervention. This article describes pregnancy-related orthopedic problems and related conditions, and discusses their pathogenesis, signs, symptoms, physical examination findings, diagnostic work-up, and interventions. Topics specifically covered include the following: pregnancy-related posterior pelvic pain (PRPPP), lumbar disc herniation with cauda equine syndrome, low back pain, kyphoscoliosis and scoliosis issues for anesthesia during pregnancy and delivery, pubic symphysis rupture, transient osteoporosis versus osteonecrosis, management of pregnancy after hip replacement surgery, and carpal tunnel syndrome. Specific musculoskeletal systems discussed in this article include the spine, pelvis, hip joint, and wrist.

Does smoking affect implant survivorship in total hip arthroplasty? A preliminary retrospective case series.

This retrospective study aimed to explore the effects of smoking on hip implant survivorship. The study included 147 patients (165 hips) from 1985 to 1991 who underwent total hip arthroplasty (THA) with a particular uncemented cup, and either a cemented or uncemented femoral component of the same design. Thirty-one patients (34 hips, 21 percent of study group) smoked at the time of surgery. Of 13 components (seven cups, five cemented and one cementless stem) revised for aseptic loosening, eight (8/68, 11.8 percent) were revised in six smokers, and five (5/262, 1.9 percent) were revised in four nonsmokers (p = 0.0012). Multivariate covariate analysis revealed a 4.5 times greater risk of implant loosening in smokers (p = 0.0662). Based on this preliminary study, further larger studies should be performed to determine the extent that smoking may contribute to THA survivorship.

Elective primary total hip arthroplasty in octogenarians.

BACKGROUND: Total hip arthroplasty (THA) has resulted in decreased pain and increased function in people with end-stage hip arthritis for several decades. In elderly people, THA has been used most often following femoral neck fracture. However, with life spans increasing and people remaining healthy and active well into their eighties, arthroplasty surgeons are now performing primary THA as an elective procedure in octogenarians. The aim of this study was to demonstrate the efficacy of elective total hip arthroplasty in patients aged 80 years or older with end-stage hip arthritis. METHODS: Forty patients (46 THAs), aged 80 or older at the time of surgery, were identified for this study. Clinical assessment included amount of hip pain, limp, and use of assistive devices for ambulation at most recent follow-up. Radiographic assessment included implant stability, heterotopic bone formation, and osteolysis. Medical and hip-related complications, reoperations, and revisions were recorded from medical records. RESULTS: Eleven patients (27.5%) suffered a medical complication and six patients (15%) had a hip-related complication, all of which were treated and were not life threatening. Clinically, 80% were pain free and 70% walked without assistance at an average 4-year follow-up. Radiographically, all implants were stable without osteolysis. No components had been revised; however, four patients had undergone a reoperation, three for recurrent dislocation. CONCLUSIONS: Elective total hip arthroplasty is a safe and effective treatment for end-stage osteoarthritis of the hip in the elderly patient. However, the procedure is not without risk. Complications, often related to preexisting comorbidities, do occur, but mortality rates are low.

Abnormal rib number in childhood malignancy: implications for the scoliosis surgeon.

STUDY DESIGN: Retrospective review. OBJECTIVE: To determine if rib anomalies are present in pediatric malignancies in the United States. SUMMARY OF BACKGROUND DATA: Scoliosis surgeons view radiographs of the entire spine, counting the number of ribs. A European study noted that rib anomalies were more common in certain malignancies. We wished to determine if this is also true in the United States. If so, the potential for screening, early detection of malignancy, and a better understanding of tumor biology is possible. METHODS: A retrospective review of 218 children with malignancy and a control group of 200 children with polytrauma or suspected child abuse was performed. Chest radiographs were reviewed to determine the number of ribs, and the presence of rib anomalies. 24 ribs was considered normal, <24 or >24 was considered abnormal. P < 0.05 was considered significant. RESULTS: The average age was 6.8 +/- 5.5 years and number of ribs was 23.8 +/- 0.6. Rib number was normal in 86.8%. There were significant differences between the malignancy and control groups in age (control, 5.7 +/- 5.1 years; malignancy, 7.8 +/- 5.7 years, P = 0.00007), rib number (control, 23.9 +/- 0.5; malignancy, 23.7 +/- 0.7, P = 0.001), and normal/abnormal rib counts (control, 92% normal; malignancy, 82% normal, P = 0.003). In the malignant group, 50% had a lymphoproliferative malignancy, 33% a solid tumor, and 17.0% a neural tumor. Neural malignancies had a higher incidence of rib abnormalities compared with lymphoproliferative or solid malignancies (P = 0.01). Relative to the control group, those with a neural and lymphoproliferative malignancy were 6.23 (95% CI, 2.7-14.5) and 2.0 (95% CI, 1.0-4.1) times more likely to have an abnormal rib count. CONCLUSIONS: Homeobox genes, important in vertebral and rib sequencing, are abnormally expressed in many different malignancies. This association is a question of great interest. What is the potential for rib number being used as a predictor of childhood malignancy? Can these findings be expanded to adults? These questions require further research. The association noted in this study is interesting but should not yet be used to alarm parents regarding an increased risk of malignancy in their children.

Soft tissue sarcomas may present with deep vein thrombosis.

PURPOSE: To bring attention to our observation that soft tissue sarcomas may present initially as deep venous thromboses (DVTs). METHOD: A query of our health system database (1996 to 2004) for patients diagnosed with soft tissue sarcomas and DVTs was undertaken. Patient medical records were reviewed to select those patients whose DVT occurred before the diagnosis of their tumor. Patient demographics, tumor classification, presentation, and outcome were noted. RESULTS: Six of 19 patients were identified (four men, two women; aged 41 to 85 years). All tumors occurred in the lower extremities. All DVTs occurred in the same extremity as the tumor. Pathology specimens indicated four different types of sarcomas. In five cases, sarcoma diagnosis was delayed as treatment of the DVT occurred. In one, a mass was seen on the initial venous duplex screen. Four are deceased, one remains in treatment, and one was lost to follow-up. The average length of follow-up was 10 months. CONCLUSION: Soft tissue sarcomas can initially present as, or even be misdiagnosed as, DVT. Given a delay in diagnosis adversely affects prognosis, it is important that physicians be vigilante for associated tumors when evaluating for suspected DVT.

Natural history of multiple hereditary osteochondromatosis of the lower extremity and ankle.

In this study the authors evaluated the natural history of the ankle joint in patients with multiple hereditary osteochondromatosis. Thirty-eight subjects with an average age of 42 years completed a detailed subjective questionnaire and underwent clinical and radiographic evaluation of their ankles. Three subjects (8%) indicated their ankle involvement affected their vocation, and 12 (32%) were limited in recreational sports. Seven patients (18%) had pain in at least one ankle on a weekly basis, with an average ankle pain score of 2.2. Ankle range of motion averaged 50 degrees and subtalar motion was considered normal in two thirds of ankles. Radiographic evaluation documented an average tibiotalar tilt of 9 degrees of ankle valgus, with evidence of degenerative joint disease noted in 14 ankles (19%). Those with arthritic changes had significantly more tibiotalar tilt and diminished ankle range of motion compared with those without radiographic signs of osteoarthritis. These findings document measurable decreases in ankle function and suggest that correction or prevention of excessive tibiotalar tilt may be warranted to improve outcome.