2009 Poster Abstracts
A Community-Based Program to Minimize Osteoporosis and Fractures Risks
S. J. Wimalawansa1, M. Bartello*2, K. Morgan*3, M. Wagner*4, K. Hodapp*5, S. Lachenmayr*6.
1Medicine, UMDNJ-RWJMS, New Brunswick, NJ, 2Memorial Hospital, Morristown, NJ, 3Rutgers University, New Brunswick, NJ, 4Rutgers University, Milltown, NJ, 5Morristown Memorial Hospital, Morristown, NJ, 6NJ Dept. of Health, Trenton, NJ, USA.
In New Jersey (NJ), ~1 million residents have low bone mass and ~8,000 individuals over 65 fractures a hip annually. The NJ Interagency Council on Osteoporosis (ICO) oversees osteoporosis (OP) education & prevention initiatives in the state. Since 1997, Project Healthy Bones, a 24-week, comprehensive, peer-led OP exercise & education program provides a public health approach to healthy behaviors improving BMD, dietary calcium intake, balance & strength, and minimize falls and associated fracture risk.
In 2004, reduced funding resulted in creating new training at local level for community class leaders, establish program sites for local program demand, provision of resources / technical assistance and provide program oversight. This model utilizes regional, trainers-training program with community-based partnerships. ICO provides 2-day training program in volunteer Peer Leader training, evaluation protocols and oversight accountability.
Our data demonstrated improved balance, increased strength and higher bone density through this program. The impact of Project Healthy Bones was evaluated through exercise tracking forms, pre-post- knowledge tests and food diaries. With the new program, 90% of participants increased weight lifting and exercise tolerance, and 68% increased their calcium intake (~500 mg per day).
From March 05 to December 06, a network of 82 agency staff and 318 volunteer peer leaders provided over two-hundred, 24-week programs to nearly 2,000 participants in every county in NJ. This project provides over 16,000 of volunteer hour contributions per year across the state of New Jersey. This is in addition to continuing of 80% regular classes beyond the initial 24-weeks. A statewide ICO list serve also provides a forum answers questions/challenges, disseminates current research and OP news, and coordinates local program offerings. Many physicians and one HMO are referring patients directly to the program based on improved DXA results (pre- and post-class) and decrease falls.
The Project Healthy Bones maintain existing community programs; create new programs based on local demand; and oversight to assure program integrity. The program is on CD-ROM, which is designed to use locally by peer leaders. Program demonstrated improve balance and nutrition; prevent falls, increased strength, morale and social well-being among participants. Despite lack of state funding, the modeled program has been strengthened and expanded with extensive community partnerships, fostered volunteerism, and has shown a positive impact in the health and quality of individuals’ lives.
Positive Changes of Marker of Bone Turnover Following Nitroglycerin Therapy in Postmenopausal Women
Carola Springer, Anoja Warusawithana, Sunil J. Wimalawansa.
Division of Endocrinology, Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
A variety of therapeutic options are studied for osteoporosis. Emerging therapies are effective, but prohibitively expensive; hence cost-effective therapies are necessary. At appropriate doses, nitroglycerin (NG), a nitric oxide (NO) donor has favorable effects on osteoblast and osteoclast. Since effects of estrogen on bone in part mediated via NO, NG is an alternative to estrogen for postmenopausal women.
We analyzed biomarkers, serum C-Telopeptide (CTx) and osteocalcin (OC) levels from IRB-approved, randomized, double-blind, controlled clinical trial (n=186) that used NG for preventing bone loss. Postmenopausal women were randomized to receive NG or placebo ointment over a 3-year period. Intent to treat analysis demonstrated no difference in the primary endpoint, lumbar spine BMD. Taking compliance (~75%), the dose of NG used was ~50% of that originally intended to use (sub-therapeutic). To understand the relationship of biomarkers with BMD, we analyzed changes of serum CTx and OC in those who responded vs. non-responders in both active and calcium + vitamin D treated groups.
Those subjects who had ↑BMD (responders) following NG-therapy had a significant ↓ of serum CTx (-0.43 ± 0.09 ng/ml, ↓ of 42%; p< 0.0002), and ↑ OC levels (1.32 ± 1.43, 7.7%; p=0.27). In NG-group, non-responders had change of CTx of -0.12 ± 0.05; ↓ of 15% p< 0.025), and OC -4.99 ± 1.2 ng/ml; ↓ by 22.5%; p<0.0008. In the NG-treated group, responders vs. non-responders for CTx was p<0.0005; and for OC, p<0.001. We cannot state whether this is due to adherence to therapy, or individuals needed different doses of NG to protect their skeleton.
In comparison, those who had ↑ BMD in the placebo-treated group had no major change in serum CTx (-0.16 ± 0.06 ng/ml; 18%, p<0.36), or OC levels (-4.11 ±1.23 ng/ml, 23%; p<0.054). Furthermore, in the NG-treated group, BMD changes observed were correlated with the baseline serum CTx (p<0.001) and change of OC (p<0.001) (levels from the baseline). But no such correlation was seen with the change of BMD with the baseline CTx or OC levels.
Those who had ↑ BMD in response to this novel therapy had a significant ↓ in serum CTx & stable OC levels. Correlations were restricted to NG-treated group only, suggesting that changes of these two biochemical markers are specific to NG-treated group. Hence, these markers could be used to identify responders to NG, adjusting its dose, and/or assess the adherence to therapy.
Nitric Oxide has a Unique and a Powerful Effect on Osteoclasts
Division of Endocrinology, Metabolism & Nutrition, Department of Medicine, UMDNJ-Robert Wood Johnson Medical School,
New Brunswick, NJ, 08903, USA.
Relative over-activation of osteoclast cells has been shown as one of the causes of age-associated as well as postmenopausal osteoporosis. Hence, in most cases, anti-osteoclastic agents have beneficial effects on improving bone mineral density (BMD), bone quality, as well as fracture reduction.
Others and we have demonstrated the effects of nitric oxide (NO) donor therapy as well as inhibition of NO synthase (NOS) enzymes with NOS inhibitors in vitro as well as in vivo animal studies. Here we demonstrate a dose-dependant effect of NO donor therapy as well as inhibition of NO/cGMP on the osteoclastic bone resorption activity in vitro cell culture system.
At very low doses or suppression of NOS activities with NOS inhibitors in culture over-activated osteoclast cells (i.e., increased bone resorption as indicated with the number of pits formed as well as the surface area/depth of pits. Whereas, adding NO donor therapies into the culture medium up to a certain level suppressed the osteoclast-induced bone resorption and higher doses enhanced pit resorption capacity of osteoclasts. Data confirmed the previous in vivo data in rats that the effects of NO-cGMP on osteoclasts are biphasic and the therapeutic margin is narrow.
Our previous studies also suggested that NO donor agents (at appropriate doses have biphasic effects of the osteoblasts including cell proliferation/apoptosis as well as their activities. Figure demonstrates the proposed overall in vivo biphasic effects of NO donors on bone. It is important to notice that the therapeutic margin is narrow and the correct dose is necessary to obtain beneficial effects from this therapy in animals as well as in humans.
Taken together in vitro and in vivo studies suggests that at correct dose-exposure, NO donor therapies have highly beneficial effects on bone cells and hence protective effect on the skeleton in general.
Wimalawansa S.J., Chapa MT., Yallampalli C., Zhang R., Simmons DJ. Prevention of corticosteroid-induced bone loss with nitric oxide donor nitroglycerin in male rats. Bone, 21: 275-280,1997.
Wimalawansa S.J. Nitroglycerin therapy is as effective as standard estrogen replacement therapy (premarin) in prevention of oophorectomy-induced bone loss: A human pilot clinical study. BMR, 15: 2240-2244, 2000.
Wimalawansa SJ: Rationale for using NO donor therapy for prevention and treatment of osteoporosis in human. NYAS, 1117: 283-297, 2007.
Wimalawansa SJ: Nitric Oxide: Novel Therapy of Osteoporosis. Expert Opinion in Pharmacotherapy, 9: 3025-44, 2008.
Wimalawansa, S.J., Grimes, JP, Wilson, A, Hoover, DR. Transdermal nitroglycerin Therapy may not prevent early postmenopausal bone Loss. Journal of Clinical Endocrinology & Metabolism, 94: 3356-3364, 2009.
The Anatomic Consequences of Arthroscopic Coracoplasty: An Anatomic Dissection Study
Aruna Seneviratne MD, Kenneth Montgomery MD, Babette Bevilacqua PAC, Bashir Zakria MD
Dept. of Orthopedic Surgery, Lenox Hill Hospital, New York, NY
Arthroscopic coracoplasty is a surgical technique that has recently been described to treat subcoracoid impingement. The goal of this investigation was to determine the anatomy of the soft tissue attachments onto the coracoid, and to assess how these structures may be compromised after an arthroscopic reduction of the coracoid tip.
Anatomic dissections were performed on fourteen cadaver shoulders to determine the soft tissue attachments onto the coracoid process. An arthroscopic coracoplasty was then performed from within the glenohumoral joint with the shaver placed in the rotator interval, removing 10-12 mm of bone from the distal coracoid tip. Follow-up dissections were then performed to evaluate the consequence of the coracoplasty on the soft tissues inserting on the coracoid.
The average coracoplasty removed 10.3 millimeters of bone from the coracoid tip. The structure most vulnerable to unintentional release during an arthroscopic coracoplasty was the coracobrachialis tendon. This tendon inserted directly over the coracoid tip in all fourteen specimens. The coracobrachialis insertion was elevated with a periosteal sleeve left intact over the remaining coracoid remnant in all cases. After the coracoplasty, seven of fourteen (50%) specimens demonstrated perforations in the coracobrachialis tendon that ranged from 2 to 10 millimeters in width. In all specimens, at least 50% of the coracobrachialis tendon remained firmly attached to the coracoid remnant, and this tendon could not be avulsed with firm manual traction on the tendon. The pectoralis minor was partially released in 1 of 14 (7%) specimens. The coracoacromial ligament and coracoclavicular ligaments were not affected by the coracoplasty. The musculocutaneous nerve entered an average of 33 mm (range 24-45) distal to the tip of the coracoid and was never at risk during the coracoplasty.
Arthroscopic coracoplasty is a procedure that can be safely and effectively performed through a rotator interval approach. Subperiosteal elevation of the coracobrachialis tendon occurs during the procedure. Care must taken to remove only coracoid bone, leaving the superficial periosteal sleeve of the coracobrachialis intact, in order to prevent complete detachment of the coracobrachialis tendon.
Clinical Evaluation of a Novel Technique of Impacting Osteochondral Grafts:
Center-Hole Technique vs. Standard Impaction
Ben B. Bedford, MD, Aruna M. Seneviratne, MD, Stephen J. Nicholas, MD
Dept. of Orthopedic Surgery, Lenox Hill Hospital, New York, NY
Osteochondral autograft and allograft transplantation is an accepted treatment strategy for chondral and osteochondral defects of the knee and shoulder. The purpose of this study was to retrospectively review the clinical outcome and graft morphology in patients with symptomatic osteochondral lesions treated with osteochondral transplantation. We hypothesize that using a novel center-hole technique for graft impaction will lead to similar clinical outcomes and will potentially protect articular cartilage by promoting chondrocyte viability.
Between 2006 and 2009 five patients with symptomatic chondral or osteochondral defects (four knees, one shoulder) were treated with either autologous osteochondral transplantation (two) or osteochondral allograft transplantation (three). The grafts were press-fit using either standard impaction or the center-hole technique. Frozen allograft plugs were used to backfill the autograft donor site in two knees. Mean age at the time of surgery was thirty-one years. The mean lesion size was 312 mm2. Clinical assessment was performed postoperatively using the International Knee Documentation Committee (IKDC) score, activity of daily living of the Knee Outcome Survey (ADL) score, and Short Form-36 (SF-36) at most recent follow-up. Magnetic resonance imaging was used to evaluate the morphologic and signal characteristics of the implanted grafts and the surrounding cartilage. Standard statistical methods using a paired Student’s t-test were used to analyze the data.
Five patients met the study criteria with a mean duration of follow-up of 15.6 months (range, four to thirty-one months). The mean preoperative IKDC score was 61.2 ± 17.5 and improved to 77.3 ± 22.3 (p= .016). The mean preoperative ADL score was 73 ± 9.3 and improved to 88.5 ± 10.3 (p=.008). The mean SF-36 score also improved from 83.4 ± 4.6 to 90.7 ± 5.9 (p=.013). At a mean follow-up of 15.8 months cartilage sensitive MRI demonstrated a flush plug appearance in all patients and osseous trabecular incorporation in 75% of patients. The graft cartilage had preserved thickness and was isointense to surrounding cartilage in all patients. With the exception of increased temporary bone edema in 50% of patients, the graft properties were similar in those press-fit with the center-hole technique to those treated with standard impaction.
Osteochondral transplantation is an effective treatment for osteochondral defects in the knee and shoulder. In our series there was a significant improvement in all three mean clinical outcome scores. MRI can be a valuable tool for postoperative evaluation of graft cartilage and osteointegration. On MRI the center-hole technique led to increased signal within the bone. This resolved on subsequent MRI and may not have any important clinical significance. From a technical standpoint, this technique allows greater control of the graft during insertion. Center-hole technique is a viable alternative to standard impaction resulting in similar clinical outcome scores, while potentially improving long term graft survival due to increased chondrocyte viability at the time of implantation.
Esophageal Adenocarcinoma Leading to Leptomeningeal Carcinomatosis
P. Viswanathan, M. Tharakan, R. Rajapakse
Stony Brook University Hospital, Centereach, NY
Esophageal adenocarcinoma (EA) commonly metastasizes to abdominal lymph nodes, liver, and lungs. EA very rarely metastasizes to the meninges; in the past 22 years there have been 8 reported cases. Leptomeningeal carcinomatosis (LC) is a rare complication of solid tumors. LC occurs in 5% of patients with cancer. It is associated with melanoma (17 to 25%), breast (12 to 34%), lung cancer (10 to 26%), gastrointestinal (4 to 14%), and cancers of unknown primary (1 to 7%).(1)
A 44 year old female with poorly differentiated t3n1 distal EA treated with partial esophagectomy and 3 cycles of chemotherapy (carboplatin, Taxol®, and Celebrex®) presented with severe headaches, nausea and vomiting. MRI revealed a 2.3 cm new left frontal lobe metastatic brain lesion. She had a craniotomy and tumor excision but postoperatively developed SIADH and altered mental status. Lumbar puncture cytology revealed metastatic adenocarcinoma. Repeat MRI showed a glomus lesion extending into the choroid fissure consistent with LC. In spite of treatment with intrathecal methotrexate and intravenous Depakote® for seizure prophylaxis, her mental status continued to deteriorate, and she died a week later.
LC is rare and predicts a poor prognosis in EA. It may coexist with cerebral metastases from the primary tumor. Patients may present with headaches, bilateral hearing loss, mental change, ataxia, nausea, vomiting, and seizures.(2) The diagnosis is established best by MRI using Gadolinium. Diagnostic features in the cerebrospinal fluid (CSF) include specific flow cytometry, selective tumor markers, elevated filling pressure, low glucose and elevated protein.(3) Current National Comprehensive Cancer Network guidelines for the treatment of LC with positive CSF cytology and high Karnofsky Performance Status recommend initial intrathecal or intraventricular chemotherapy with fractionated external beam radiation therapy to bulky disease and symptomatic areas. Treatment regimens include organ specific chemotherapy with good CNS penetration or intra-CSF chemotherapy such as liposomal cytarabine, methotrexate, cytarabine or thiotepa.
LC complicating EA is a rare occurrence with poor prognosis. With very few reported cases, a high level of suspicion is required for early diagnosis.
1. Kesari S, et al. Leptomeningeal metastases. Neurol Clin 2003;21(1):25-66.
2. Kaplan JG, et al. Leptomeningeal metastases: comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias. J Neurooncol 1990;9(3):225-9
3. Freilich RJ, et al. Neuroimaging and cerebrospinal fluid cytology in the diagnosis of leptomeningeal metastasis, Ann Neurol 1995;38(1):51-7.