2011 Poster Abstracts

Atypical Subtrochanteric Femoral Fractures Following Anti-Resorptive Therapy

Sunil Wimalawansa1, Carlos Sagebien2, Robert Masella2, David Redziniak2, Jason Nitche3; 1UMDNJ-RWJMS, 2Ortopedic Surgery, 3RWJMS

Introduction:

For more than 2 decades bisphosphonates were used to treat bone diseases. The therapy maintains bone mineral density (BMD), reduces bone remodeling and fractures. However, there are no credible evidence indicates that bisphosphonate therapy beyond 5 to 6 years has added benefits for fracture reduction. Recent articles suggested an association of prolonged use of bisphosphonate and stress fractures or atypical subtrochanteric fractures. Characteristics of such fractures include classic thickened cortices, suppressed bone turnover, and cortical beaking. Prolonged use of bisphosphonate increase the incidence of atypical subtrochanteric fractures in vulnerable patients.

Method:

Eight patients with antecedent thigh pain had subtrochanteric femoral fractures, including two with bilateral femoral fractures. All had been treated for osteoporosis with alendronate for at least 6 years prior to sustaining a low-energy subtrochanteric femur fracture through a clear region of chronic stress reaction in the bones and had choke stick-like horizontal fractures (Fig 1). There was no radiographic evidence of thin, osteoporotic cortices at any of the fracture sites or the contralateral femur; instead, all had bilateral thickened cortices around the fracture sites.

Conclusions:

The reported numbers of atypical subtrochanteric femoral fractures are insufficient to make conclusions about their etiology. Suggested reasons include genetic susceptibilities, preexisting conditions, inappropriate treatment with bisphosphonates, and long-term bisphosphonate use. The authors speculate that the incidence of such fractures and the correlation of long-term use of bisphosphonates may have been overlooked. This is important in that bisphosphonates such as alendronate have been on the market for about 16 years, and long-term complications are beginning to surface. Since suppression of bone turnover is one of the key etiological factors, fractures are likely to appear the prolonged use of all potent anti-resorptive agents inlcuding denosumab.

The authors suggest physicians to have an index of suspicion for all patient taking bisphosphonate longer than 5 years who presents with thigh pain or dysfunction. Imaging with a 99Tc-bone scan or MRI are helpful in identifying patients vulnerable for such fractures, while plain x-rays are not helpful. Proactive identification and discontinuing of bisphosphonate therapy, and treating such patients with teriparatide would be helpful in preventing and heeling these fractures.

Review of Increased Risk for Bone Loss and Fractures in Persons with Disability

Patricia Graham, MD 1 and Sunil Wimalawansa, MD, PhD, MBA 2
University Medical Center Princeton, Rehab Medicine, Princeton, NJ 08540,1
Department of Medicine,2 UMDNJ-RWJMS, New Brunswick, NJ, 08903, USA

Introduction:

In 2006, 15.7% of Americans reported disability. We hypothesize that Persons with Disability (PWD) are under-represented and under-treated for osteoporosis screening, research, and out-of-home activity. These place adults and children with disabilities at a higher risk for falls, and fractures in comparison to non-disabled peers.

Method:

Literature review for PWD, pediatric and adult, and Bone Mineral Density (BMD), Falls, Fractures and Utilization of Electronic Medical Records.

Results:

Adult PWDs are under-represented in BMD research, and not evaluated properly or frequently for low BMD. They have lower vitamin D levels, and earlier onset of low BMD and fractures than non-disabled peers. Onset of disability and immobility are independent predictors of BMD in both hip and spine. Adults with childhood-onset disabilities can result in low BMD, and marked increase in osteoporosis and fractures relative to non-disabled adults. Most PWD have higher risk of low BMD, especially those with Spina Bifida, SCI, CP, MS, CVA, amputations, COPD and RA. Patients with childhood onset brain disorders and adults with developmental disabilities have lower BMD and vitamin D (prevalence of 70 to 80%) and high fracture rates (2.7%) (local and NJ-DHSS/NJCHS data) (1).

Over 90% of hip fractures in the elderly are due to osteoporosis. Falls and injuries are common, and a significant cause of fracture and hospitalization in PWD, and they occur at a younger age. Even though risk factors for falls are higher in PWD, they are rarely addressed in preventive care models (Table 1). Unlike the FRAX, Garvan nomogram includes fall risk with 10-year hip fracture risk assessment and medication guidance. e.g., early medication use in acute SCI reduces BMD loss. EHR optimize capture patients with low BMD and high risk for falls. This should allow health professionals to screen & treat PDWs promptly (Figure 1); decrease fractures & health care costs

Conclusions:

More research is needed to define the demographics/aetiology of low BMD, falls and fracture risks in PWD. Such should establish uniform best practice parameters, including safe exercise regimens, timing of medication, and usefulness of FRAX and Garvan tools (Figure 1). This should incorporate rehabilitation medication strategies with traditional care. Focus should be to minimize injuries, and eliminate disparity in health care delivery, optimize early screening for falls and BMD, manage pain and disability, and provide safe exercise strategies, home safety and psychosocial support for PWD. The use of EHR system is essential to targeting PWD for preventative care.

Ref: P. May, H. Chahal, A. Warusawithana, SJ Wimalawansa. Prevalence of low BMD and higher fracture rates in patients with developmental disabilities. Abst. 122, ISCD, 2011

Drug-induced Osteomyelitis (ONJ-OMJ) of Jaw: Guidelines for Practicing Clinicians

Sunil J. Wimalawansa, MD, PhD, MBA, DSc
Professor of Medicine, UMDNJ-RWJMS, New Jersey, USA

Background:

Bisphosphonates have been widely used for the past three decades for treatment of bone diseases in particular osteoporosis, Paget’s disease, and complications associated with bone malignancy. A number of bisphosphonate-related osteonecrosis of the jaw (ONJ) had been reported since 2003. However, in clinical trials, recently FDA-approved potent anti-osteoporosis agent, denosumab (Prolia) has also implicated in ONJ. Nevertheless, infections of the exposed jaw bones seem to be the fundamental cause of ONJ. Therefore, instead of using bisphosphonate or denosumab-associated ONJ, it is advisable to use the term drug-associated osteomyelitis of the jaw (DI-OMJ).

Incidences of OMJ:

The estimated incidence of BAOMJ for patients treated for osteoporosis and Paget’s are about one in 70,000; but for incidences for cancer patients treated with high dose, higher frequency of bisphosphonates or denosumab, it is between 1% to 4%. There is no evidence suggesting that amino-containing bisphosphonates have a greater likelihood of triggering BAOMJ that other bisphosphonates. Regardless of the route of administration, cancer patients receive 10 to 12 times higher doses of bisphosphonates at a greater frequency per year, compared to patients with osteoporosis or Paget’s disease.

Mechanisms:

OMJ is not a simple avascular event; evidence support immune and infectious etiology, and perhaps precipitated by over-suppression of the bone turnover in this metabolically highly active site. The exact mechanism of developing OMJ is unclear, but several predisposing factors have been identified. The key factor is exposure of jaw bones following oral surgery and dental extractions, leading to infection. Both bisphosphonate and denosumab are very potent anti-resorptive agents. High frequency and high doses administered of these potent anti-resorptive agents are likely to be a key factor in triggering OMJ in cancer patients. Following guidelines can decrease the risks of DI-OMJ in vulnerable patients (1,2).

Conclusions:

The risk benefit ratio and the necessity of administration of high doses and frequency of bisphosphonates and denosumab need to be addressed. Both denosumab and bisphosphonates are very useful therapies not only for osteoporosis, but also patients with cancer, controlling hypercalcemia of malignancy, and bone metastasis. In patients with cancer, bone diseases, osteoporosis, and Paget’s disease of bone these therapeutic agents could reduce complications by 60%. The incidences and the risks of OMJ are low when weighed against the major benefits of denosumab and bisphosphonate therapies. While there is a temporal association with these agents with OMJ, no direct causal relation has been established. Current evidence supports local infections and, immune impairment (aggravated by bisphosphonates) as key causes of precipitating BAOMJ (Table 1).

1. Wimalawansa Sunil J. Expert Opinion on Drug Safety, 7: 491-512, 2008
2. Wimalawansa Sunil J. Endocrine Practice, 14: 1150-1168, 2008

Persons with Developmental Disabilities have a High Prevalence of Vitamin D Deficiency and Low Bone Density

Philip May1, Harpreet Chahal1, Anoja Warusawithana2, Robin May1, Sunil Wimalawansa2; 1Hunterdon Developmental Center, 2UMDNJ-RWJMS, NJ

Introduction:

Patients with developmental disabilities (DD) who reside in the seven NJ State DD centers seem to have high incidence of fractures; several fold higher than the New Jersey Department of Health statistics indicate especially for those who older than 50 years.

Method:

We collected data over a four year period from one of these Centers (Hunterdon Development Center, Clinton, NJ), and compared it with data from ambulatory healthy people in the community. DD center residents had an approximately 30-fold increased incidence of hip fractures. The age-adjusted prevalence of osteoporosis in New Jersey residents age 50 years and older is about 13% [confidence interval (CI)―http://nj.gov/health/senior/osteo/ (2005, BRFSS), in comparison with residents older than 85 years, which is 23% (CI, 19–26). For patients with DD in HDC, the age-adjusted prevalence is approximately 66%. Thus, persons with DD have a much higher incidence of osteoporosis and fragility fractures.

Results:

Initial evaluation of overall “Bone Health” and risk for fracture at the HDC, revealed only 110 of the 580 (19%) residents were receiving vitamin D supplements. The doses they were receiving were only between 400 and 600 IU per day, and very few had undergone measurement of serum 25(OH)D levels, despite the fact that low bone mineral density (BMD) and fractures were common in these residents. Our evaluation revealed 80% of the 400 residents who had undergone dual-energy X-ray absorptiometry (DXA) BMD evaluation had low BMD, with fragility fracture rates varying from 4.6% to 6.9% per annum. To address these issues, we conducted a series of face-to-face and online continuing medical education (CME) programs in collaboration with UMDNJ-CCOE. Initially, a series of three online programs were offered to the staff physicians. Before the lecture series, 9 of 22 (41%) of the patients on one unit were receiving vitamin D supplements, and none (0%) had ever had serum 25(OH)D levels measured. After the CME series, serum 25(OH)D was determined in 100% (22/22). These educational activities at HDC then led to additional BMD and vitamin D testing, initiation of vitamin D therapy, or increased dosages of vitamin D in most of the patient population.

Conclusions:

Data suggest that low BMD and vitamin D deficiency is very common in patients who are residing in DD centers. The incidence of low bone mass is approximately 80%, and fracture rates are about 6% in this population. Direct teaching programs for physicians and nurses who care for this highly vulnerable population can be successful in changing their practice behavior and improve clinical outcomes for their patients.

Comparison of Mini-Open vs. Arthroscopic Harvesting of Osteochondral Autografts in the Knee

David Epstein MD, Edward Choung MD, ImranAshraf MD, Stephen Nicholas MD, Aruna Seneviratne MD
Department of Orthopedic Surgery and NISMAT, Lenox Hill Hospital, New York

Introduction:

Despite the limitations of osteochondralautograft harvest in the knee, such as donor site morbidity and the limited number of donor graft sites available, the use of osteochondralautograft transfer is a successful procedure for treating osteochondral lesions. In harvesting osteochondralautograft plugs, emphasis is placed on ensuring perpendicularity of the graft to allow for adequate filling of the recipient site. Prior studies have shown no statistical difference in graft perpendicularity when comparing open versus arthroscopic harvest techniques, however they have used imprecise methods of graft angle measurements and failed to take into account the variable thickness of the harvest site cartilage cap. We believe that assessment of graft perpendicularity with Magnetic Resonance Imaging will allow for a precise multiplanar measurement of Osteochondral graft perpendicularity and allow for improved comparison of arthroscopic versus mini-open harvest techniques.

Materials &Methods:

Ten fresh cadaveric knees (average age 39.4 years old)underwent harvest of 6mm osteochondral plugs using the OATS (Arthrex Inc; Naples, FL) system. A total of 8 plugs were harvested per knee from three donor sites including the lateral supracondylar ridge, medial supracondylar ridge and the lateral intercondylar notch. Two surgeons performed the graft harvest, alternating between mini-open (5 specimens) and arthroscopic techniques (5 specimens) to minimize bias. The osteochondral plugs were then labeled and underwent MRI imaging to measure graft perpendicularity in both the sagittal and coronal plane as well as cartilage thickness. The data was then analyzed to look for a significant difference in perpendicularity between the two techniques, as well as overall graft acceptability and graft acceptability per harvest site.

Results:

When comparing open versus arthroscopic harvest technique, the mean angle of perpendicularityat the lateral intercondylarnotch harvest site was 84.08 and 84.20degrees respectively (p = 0.958). At the medial supracondylar ridge harvest site, the mean angle of perpendicularity for the open and arthroscopic technique was 89.38 and 81.00 respectively, with an average difference of 7.62 degrees (p = 0.0006). At the lateral supracondylar ridge harvest site, the mean angle of perpendicularity for the open and arthroscopic technique was 85.67 and 87.07 respectively (p = 0.237). When comparing the angle of perpendicularity in reference to the cartilage surface versus that of the subchondral bone, the mean angle was 85.19 and 83.92 respectively (p =0.116).Additionally, we found that 88% of plugs harvested from all harvest sites, using either the open or arthroscopic technique were greater than angle of 71.6 degrees, and thus felt suitable for transfer.

Discussion:

Significant difference in osteochondralautograftperpendicularity was noted at the medial supracondylar ridge when comparing the open and arthroscopic harvesting techniques. No significant difference in graft perpendicularity was notedbetween the two harvest techniques at the lateralintercondylar notch and lateral supracondylar ridge. When comparing the difference in graft perpendicularity with MRI using a cartilage versus and subchondral bone referencing technique, no significant difference was noted, however, the study had inadequate power to assess for this difference.

Interference Screw Divergence with the use of a Flexible Reamer during
Anatomic Anterior Cruciate Ligament Reconstruction through the Anteromedial Portal

David Epstein MD, Edward Choung MD, ImranAshraf MD, Malachy McHugh PhD, Aruna Seneviratne MD, Stephen Nicholas MD
Lenox Hill Hospital, Department of Orthopedic Surgery and NISMAT, New York

Introduction:

When performing anatomic anterior cruciate ligament (ACL) reconstruction, accurate insertion of the femoral interference screw with minimal divergence is a difficult problem in graft fixation. Divergence of the femoral interference screw commonly occurs when the portal used for femoral screw insertion differs from that used to ream the tunnel and can lead to graft laceration, guide wire breakage, posterior wall blowout and decrease strength of fixation. Trans-tibial drilling of the femoral tunnel makes anatomic graft placement challenging and the recent popularization of the use of an accessory anteromedial (AM) portal allows for easier access to the femoral insertion of the ACL for tunnel placement during surgery. Additionally, the use of commercially available flexible reamers and 42-degree femoral guides results in longer femoral interosseous tunnel length than can be achieved with a straight guide pin. Concern of increased femoral tunnel and interference screw divergence angle using this technique has limited the use of this technique in our institution. We hypothesize that the use of a flexible reamer for femoral tunnel drilling will result in a clinically unacceptable divergence angle when performing anatomic single-bundle ACL reconstruction through the AM portal.

Materials & Methods:

Ten fresh cadaveric kneesunderwent anatomic single bundle ACL reconstruction through the AM portal with the use of a commercially designed flexible reamer system for femoral tunnel drilling and guide-pin placement. Femoral fixation of the patella tendon graft was achieved with a bioabsorbable interference screw placed with a standard screwdriver. Femoral tunnel and screw divergencewas measured radiographically, using a 2.0mm Steinmann pin placed through the interference screw and drilled out the lateral femoral cortex, marking the interference screw trajectory, and a 2.4mm guide pin placed antegrade through the exit point of the femoral tunnel guide pin, marking the graft trajectory. All specimens then underwent fluoroscopic examination in the anteroposterior (AP), lateral and oblique plane, to observe the maximum angle of divergence between the femoral tunnel and the interference screw, which wasmeasured and recorded using a digital protractor (ImageJ v.1.45h, Bethesda, MD) by three independent examiners.

Results:

The average radiographic divergence between the femoral tunnel on the AP and Lateral radiograph was found to be 8.03 and 8.19 degrees respectively. The average maximum divergence angle, in either the AP, Lateral or Oblique plane, was found to be 13.73 degrees. The average sum of divergence on the AP and Lateral radiographs was 16.23 degrees. A20-degree divergence in the lateral plane was observed in one specimen. There was strong inter-examiner agreement for AP and Lateral radiograph divergence (r=.99-.95), with the 95% limits of agreement less than 5 degrees.

Discussion:

The use of a flexible reamer during femoral tunnel drilling for anatomic ACL reconstruction through the AM portal results in an acceptable amount of femoral screw divergence. The results of this study minimize the concern of screw divergence when performing ACL reconstruction with a flexible reamer through the AM portal.

Interference Screw Divergence with the use of a Flexible Reamer during
Anatomic Anterior Cruciate Ligament Reconstruction through the Anteromedial Portal

David Epstein MD, Edward Choung MD, ImranAshraf MD, Malachy McHugh PhD, Aruna Seneviratne MD, Stephen Nicholas MD
Lenox Hill Hospital, Department of Orthopedic Surgery and NISMAT, New York

Introduction:

Materials & Methods:

Results:

Discussion:

Activity of STS-1 in Patients with Inflammatory Bowel Disease

Guo Jun Huang MD, Ramona Rajapakse, MD, Nicholas Carpino, PhD
Departments of Medicine and Molecular Biology, Stony Brook University Medical Center, Stony Brook NY 11794

Purpose:

Suppressor of TCR Signaling-1 & -2 (STS-1 & STS-2) are phosphatases that have been shown tonegatively regulate T cell signaling pathways. Cells isolated from STS-1/2-/-mice display a striking hypersensitivity to in vitro TCR cell stimulation. Mutant mice also have increased susceptibility to auto-immunity, in a mouse model of multiple sclerosis. To determine if the STS proteins were involved in the etiology of IBD (Crohn’s colitis and ulcerative colitis), STS protein and enzyme activity levels were examined in diseased patients.

Method:

STS-1 was obtained from peripheral lymphocytes by cell lysis, followed by immunoprecipitation.STS-1 phosphatase activity toward the artificial substrate pNPP was measured, and protein levels wereassessed by Western analysis.

Results:

Ninety-one patients were enrolled and 63 patients [32 controls, 9 males; 31 IBD patients, 13 males]completed the study. The ratio of phosphotase activity over STS-1 activity/concentration (STS-1 activity ratio)was compared between 1) controls and IBD group, 2) controls compared to IBD with & without inflammationon colonoscopy, and 3) IBD patients on anti-TNF agents, steroids plus mesalamine, mesalamine, and6-mercaptopurine (6MP). Using the Mann-Whitney test, the STS-1 activity ratio between the control group(median = 0.190) & the IBD group (median = 0.124) was not significant (p = 0.280). Using the Krukal-Wallistest, the STS-1 activity ratio between the control group (median = 0.190), IBD with inflammation group (median = 0.199), and IBD without inflammation group (0.0688) were not significant (p = 0.195). Using theKrukal-Wallis test, the STS-1 activity ratio between groups using the anti-TNF (median = 0.151), steroids plusmesalamine (median = 0.470), mesalamine (median = 0.101), and 6MP (median = 0.0636) were notsignificant (p = 0.621).

Conclusions:

While the above data is preliminary, it suggests that levels of STS-1 protein and phosphataseactivity do not correlate with the occurrence of IBD. We are currently examining the possible correlation ofSTS-2 activity and expression level with the development of IBD.

2011 Poster Abstracts

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