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COLORADO BONE &
VOLUME I, ISSUE 1 JOINT QUARTERLY
A p ubli ca ti on of Col orad o Ce n t e r for A rt h ri t i s & Ost e op orosi s, PL L C
Cop yri gh t 2 01 0
Inside this issue:
Welcome to the inaugural lieve strongly that the best future topics. You may issue of the Colorado Bone medical care for this chal- contact us by e-mail at Immunosuppressed and Joint Quarterly, pub- lenging group of patients can [email protected] or cal
lished by Colorado Center only come through ongoing (720) 494-4700. More for Arthritis and Osteoporo- cooperation and col- information about our Reclast and Denosumab 3 sis. The fields of rheumatol- laboration between rheuma- practice can be found at ogy and metabolic bone tology specialists and pri- www.ccao.net. We are al-
disease have seen dramatic mary care providers. The ways happy to speak with advances in recent years. It is newsletter will focus on par- our col eagues and would be hard enough for those of us ticular areas that will affect happy to discuss a case over within the field to keep up your ability to evaluate the phone, to help you de- with developments, much patients with musculoskeletal termine whether a patient less those of you outside of complaints, decide when to would benefit from consul- the field! Thus, we have de- refer to a rheumatologist, tation with one of our signed this newsletter with and continue to provide ef- primary care providers and fective primary care to gists, or to coordinate the other non-rheumatologists in patients who are being care of a mutual patient. mind. treated for rheumatic dis- Please let us know what we can do to serve you and Our goal is to update you on your patients better. specific developments that We hope this information will affect your ability to care will be a valuable resource to Jeffrey D. Perkins, MD PhD for your patients with you. Please give us your Clinical Director diseases of bone, joint and feedback on this issue, as connective tissue. We be- wel as any suggestions for CARDIOVASCULAR RISK IN RHEUMATIC DISEASE by Joseph R. Lutt, MD Inflammatory arthritis as a
tion is comparable to that of type 2 dia- betes mel itus.3 matory arthritis CV risk factor
Compared with age-matched controls, Risk reduction: arthritis treat-
significantly over the risk of dying is twofold higher for the past decade. patients with rheumatoid arthritis (RA).1 With this in mind, the approach to pa- As we have moved to the earlier use of The data are less robust with regards to tients with inflammatory arthritis should oral and biological disease-modifying anti- psoriatic arthritis and ankylosing spondy- now focus not only on their joint com- rheumatic drugs (DMARDs), the preven- litis, but it appears that the mortality risk plaints but also on cardiovascular health. tion of joint destruction and disability has for those conditions is 1.5 to 1.9 times become a reality. It is also becoming ap- greater.2 The excess deaths are over- (Continued on page 2) parent that these medications may have whelmingly due to cardiovascular disease. benefits beyond the joints, especial y with Traditional risk factors probably occur ".the cardiovascular risk regards to heart disease and survival. The more frequently in these diseases but fol owing is a brief summary of what is seem to account for only part of the of the RA population is known about the cardiovascular disease increased risk. The inflammatory arthritis risk in patients with inflammatory arthri- itself appears to be an independent risk comparable to that of factor for cardiovascular disease. In fact, tis as wel as the effects of treatment. the cardiovascular risk of the RA popula- type 2 diabetes mellitus."

CARDIOVASCULAR RISK (Continued from page 1) Risk reduction: traditional
of cardiovascular risk modification during A recent meta-analysis of RA trials re- risk factors
our visit but will defer the management vealed that the rate of al -cause mortality of hypertension and dyslipidemia to pri- It is assumed that modification of tradi- was reduced by 50% and cardiovascular mary care providers. We hope that by tional risk factors and the addition of death by 70% in patients treated with working with you to target both the ar- low-dose aspirin would have benefits in methotrexate compared with those not thritis and cardiovascular disease, we wil arthritis patients similar to that seen with treated with methotrexate.4 The rates of improve the long-term outcome for the the general population, but no formal myocardial infarction and hospitalization studies specifical y with inflammatory vast majority of our patients. for heart failure were also reduced by arthritis have been conducted. We 1. Avina-Zubieta JA, et al. Arthritis Rheum approximately 20%. Another study con- would suggest using an approach similar 2008;59:1690-97. firmed the benefit of the older tumor to that of the diabetic population due to necrosis factor inhibitors (Enbrel, Remi- 2. Peters MJ, et al. Semin Arthritis Rheum the comparable cardiovascular risk. Stat- cade, and Humira) as wel , with a reduc- ins, ACE inhibitors, and ARBs may be tion in the incidence of myocardial infarc- especial y helpful due to their favorable 3. Peters MJ, et al. Arthritis Rheum tion.5 It is not clear whether these bene- effects on inflammation and endothelial 2009;61:1571-79. fits are due to an improvement in tradi- tional risk factors or reduction in the 4. Westlake SL, et al. Rheumatology effect of systemic inflammation on the In the end, we share a common goal with 2010;49:295-307. vasculature. While these DMARDs are our patients' primary care providers: to 5. Dixon WG, et al. Arthritis Rheum started with the arthritis in mind, the provide the best care for our patients. long-term cardiovascular and survival We wil typical y discuss the importance 2007;56:2905-12. benefits are certainly encouraging. IMMUNIZATION IN IMMUNOSUPPRESSED PATIENTS by Nguyet-Anh (Theresa) Tran, MD nasal flu vaccine is a live attenuated virus, tors include a history of multiple sexual tients with auto- this method of immunization should not partners in the past six months, house- be used in immunosuppressed patients or hold contacts with hepatitis B, IV drug in household contacts of these patients.1 abuse, and being a healthcare worker. suppressive medi-cations that may Pneumovax
make them susceptible to various infec- Al immunocompromised patients, re- Meningococcal disease is a devastating tions. Patients requiring chronic predni- gardless of age, should receive the pneu- infection that primarily affects children sone, disease modifying drugs (e.g., meth- mococcal polysaccharide vaccine (PCV7 and young adults. General recommenda- otrexate, Imuran, etc.), and biologic for children and PPSV23 for adults). It is tions are to immunize al children aged 2 agents (e.g., Enbrel, Humira, Rituxan, etc.), further recommended that immunocom- to 10 years and adolescents aged 11 to should al have current immunizations. promised patients receive a single revac- 18 years. Adults with increased risk The American Col ege of Rheumatology cination if it has been more than five (including military recruits, microbiolo- (ACR) and Centers for Disease Control years since the first dose. gists exposed to N. meningitides, individu- (CDC) have developed guidelines for als with asplenia, and travelers to en- routine immunization in these patients. Viral Hepatitis
demic areas) should also be considered Several disease modifying drugs for immunization. For patients with rheu- Influenza
(methotrexate, leflunomide, and some matic disease, it is recommended that Al immunosuppressed patients should be biologic agents) pose a significant risk of those with complement component defi- vaccinated against influenza every fal , hepatotoxicity. In those patients who ciencies (C3, properdin, Factor D, late regardless of age. In the 2009-2010 flu are at high risk, it is recommended that complement components) also be vacci- season, recommendations included both they receive the Hepatitis B vaccine prior seasonal and H1N1 immunization. Since to starting these medications. Risk fac- (Continued on page 3)

(Continued from page 2) prior to travel outside the U.S, with the are often more susceptible to infectious Live Virus Vaccines
exception that they should not receive diseases and are more likely to develop live attenuated vaccines. Specifical y, im- serious complications from infection, The general rule is to avoid live virus munosuppressed patients should not re- appropriate immunization is especial y vaccines in immunocompromised pa- ceive the yellow fever vaccine and the important in this population. Assuring tients. This includes the MMR vaccine typhoid vaccine. Hepatitis A and B vac- that these patients have updated vaccina- and the varicella and Herpes zoster vac- cines are inactivated, and are therefore tions is an important step in preventing cinations. More recent guidance from the serious infections and complications that Advisory Committee on Immunization safe for immunocompromised individuals. may lead to worsening morbidity and Practices more specifical y indicates that it is safe to give the zoster vaccination to mortality in these vulnerable individuals. ".avoid live virus vaccines patients being treated with meth- in immunocompromised otrexate, leflunomide, sulfasalazine and low-dose prednisone(<20 mg/d).2,3 The patients." shingles vaccine is stil not recommended for patients on biologic DMARDS (Enbrel, Humira, Remicade, Orencia, Do Immunizations Worsen
2. MMWR 57:RR-5, June 6, 2008 Rituxan, Kineret, Actemra) or on chronic doses of prednisone higher than 20 mg Autoimmune Disease?
To date, there is no evidence that vacci- nating patients with autoimmune rheu- Vaccines for Travel
matic disease worsens or exacerbates Unless otherwise noted, the recommenda- In general, immunosuppressed patients tions in this article can be found at the Cen- should receive recommended vaccines ters for Disease Control and Prevention Web Since patients with autoimmune diseases site: www.cdc.gov. RECLAST & DENOSUMAB: NEW OPTIONS FOR OSTEOPOROSIS by Heather L. Kramm, MD. Director of Bone Health include the treatment and prevention at increased risk for mandibular osteone- approach remains (given every 2 years if osteopenic) of crosis, patients limited by myalgia or prevention, there osteoporosis in postmenopausal women, (Continued on page 4) osteoporosis in men, treatment of gluco- corticoid –induced osteoporosis, preven- tion of new clinical fractures in patients Two alternatives to oral who have recently had a low-trauma hip fracture and Paget's disease. bisphosphonates The most common side effect of Reclast The advent of annual intravenous Re-
is a self-limited flu-like reaction. Jaw os- clast (zolendronic acid) has improved
teonecrosis and subtrochanteric frac- compliance with therapy and offers a IV bisphosphonate tures are extremely rare. Reports of an better alternative to oral bisphospho- Consider when oral association between bisphosphonate use nates when patients have limiting GERD, and atrial fibril ation have been conflicting bisphosphonate contraindicated other esophageal or GI comorbidity or and remain unsupported by meta- or not tolerated intolerance. The HORIZON study with almost 8,000 patients found that yearly Denosumab
5mg IV Reclast reduced the incidence of Denosumab
vertebral and nonvertebral fractures, and There stil remains great need for a treat- Given SQ q. 6 months the cumulative risk of hip fractures by ment class other than bisphosphonates. Presently under development 40% during a 3 year period .1 Forteo use is limited by cost and its re- Consider when bisphosphonates FDA approved indications for Reclast quired daily SQ administration. Patients fail or are contra-indicated

V O LUME 1, I SSUE 1
RECLAST AND DENOSUMAB (Continued from page 3) subcutaneous injection every 6 months For patients with intolerance, contraindi- bone pain, or patients who have declining for 36 months. Denosumab reduced the cation or failure of oral bisphosphonates, BMD or fracture while taking bisphos- risk of vertebral and nonvertebral frac- Reclast is an effective parenteral alterna- phonates need another option. The FDA tures, as wel as hip fractures with a rela- tive. In the near future, denosumab is currently reviewing denosumab
tive decrease of 40%.2 The indications for should offer another effective choice for (expected brand name Prolia), and ap- which Amgen is seeking FDA approval this chal enging subset of osteoporotic proval is expected in the near future. are treatment and prevention of post- Denosumab is a human antibody to menopausal osteoporosis in women and RANKL, which controls osteoclast differ- treatment and prevention of bone loss in 1. Black D, et al. New Engl J Med entiation, activation and survival. In the patients undergoing hormone ablation 2007;356:1809-1822. FREEDOM trial with almost 8000 pa- therapy for either prostate or breast 2. Cummings SR, et al. New Engl J Med tients, denosumab was administered as a 2009;361:756-765. ANTI-CCP: A NEW DIAGNOSTIC TOOL FOR RHEUMATOID ARTHRITIS by Jeffrey D. Perkins, MD PhD, Clinical Director has been widely available in commercial RA as a similar patient with a positive RF. few years, a new labs for about the last 5 years. Anti-CCP is occasional y present in other disease states (including lupus, psoriatic arthritis or tuberculosis infection). How- arthritis (RA) has "Anti-CCP antibodies are ever, highly positive anti-CCP levels are rare in other conditions. highly specific for RA. the anti-CCP [cyclic citrul inated peptide] Anti-CCP antibodies have been shown to Recent studies indicate a antibody (also known as anti-citrul ine be present several years before the clini- antibody). This laboratory test, readily specificity of about 95%. cal onset of rheumatoid arthritis. There available in al commercial labs, comple- is circumstantial evidence that anti- A patient with a positive ments the older rheumatoid factor (RF) citrul ine antibodies are pathogenic in RA test in the evaluation of patients with instead of being simply a marker of dis- anti-CCP is almost 3 times ease (in contrast to RF), and this is an inflammatory arthritis. as likely to actually have area of active research. Even though Background
positive anti-CCP antibodies may be able RA as a similar patient Citrul ine is a natural y-occurring amino to predict individuals at risk for develop- acid that is produced by post- ing RA, in absence of preventative treat- with a positive RF." translational modification of arginine by ments for RA there is no clinical utility in peptidyl arginine deaminase (PAD). identifying these patients in a pre-clinical Citrul ination of proteins can occur in Anti-CCP in RA
normal tissues, but is increased in pro- Anti-CCP antibodies are highly specific Anti-CCP antibodies are more likely than teins such as fibrinogen and col agen in for RA. Recent studies indicate a specific- RF to present in early symptomatic dis- rheumatoid joints. Antibodies directed ity of about 95% (compared to 85% for ease, prior to a patient meeting current against citrul inated peptides have been rheumatoid factor), with even higher classification criteria for RA. In these known to occur in patients with rheuma- specificities with highly positive tests. The undifferentiated arthritis patients, the toid arthritis several years before the sensitivity of anti-CCP for RA (67%) is presence of anti-CCP is a strong predic- onset of arthritis. The development of about the same as for rheumatoid factor tor of progression to RA.2 the anti-CCP assay has al owed these (69%). The increased specificity of the antibodies to be detected quickly and anti-CCP test results in a positive likeli- Anti-CCP antibodies have also been accurately by an automated enzyme- hood ratio of 12.46 (compared with 4.86 shown to be a strong predictor of persis- linked laboratory test, thus al owing the for rheumatoid factor).1 This means that tent, aggressive, joint damaging disease in commercial availability of anti-citrul ine a patient with a positive anti-CCP is al- RA patients. One study of patients with antibody detection. The anti-CCP assay most 3 times more likely to actual y have (Continued on page 5) ANTI-CCP ANTIBODIES (Continued from page 4) toid factor is negative. Another is a pa- body testing should never dissuade you early RA shows that, of al the risk tient with a positive RF, but without con- from referring a patient in whom your factors studied, a positive anti-CCP vincing clinical evidence of RA. Final y, clinical suspicion is high. With the highly was the strongest predictor of persis- the anti-CCP status of a patient with effective treatments available now for tent erosive disease.3 Thus, patients early RA can help to risk-stratify the pa- RA, prompt referral to a rheumatologist with a positive anti-CCP antibody tient, which can in turn guide the aggres- is more important than ever to minimize should be strongly considered for siveness of therapy. the chance of joint damage and resultant aggressive disease-modifying antirheu- matic drug (DMARD) treatment as It is important to keep in mind that nei- early after the onset of symptoms as ther the RF nor the anti-CCP are useful As always, don't hesitate to give us a cal in fol owing disease activity – they are if you have a question about interpreting only useful for initial diagnosis. Tests such a patient's test results or determining if When to Check
as sedimentation rate and C-reactive they are an appropriate patient for rheu- So, when should you check an anti- protein are more useful to fol ow disease matology consultation. CCP? I do not recommend this test as activity in diagnosed rheumatoid arthritis. 1. Nishimura K, et al. Ann Int Med 2007; a general screening test for patients There is a significant minority of patients with joint pain. However, it can pro- with rheumatoid arthritis who have nei- vide valuable information in at least ther a positive rheumatoid factor nor a 2. van Gaalen FA, et al., Arthritis Rheum three situations. One such situation is positive anti-CCP ("seronegative" rheu- 2004; 50:709-715. a patient in whom you are suspicious matoid arthritis). Thus, negative autoanti- 3. Visser H, et al., Arthritis Rheum 2002; of early RA but in whom the rheuma- Berger, PA-C, offer a ful range of CCAO Offices
rheumatology and bone health services. Longmont
Dr. Shiraz Moinuddin will be joining our Colorado Center for Arthritis and practice in October 2010. 1551 Professional Lane Osteoporosis has provided expert, Services offered by CCAO include compassionate care for patients with consultation and disease management Longmont, CO 80501 arthritis, autoimmune connective tissue services in the areas of rheumatology and disease and osteoporosis since 1998 to metabolic bone disease, and infusion the residents of Boulder County, with centers at al of our locations. In offices in Boulder and Longmont. In addition, we offer bone densitometry 3434 47th Street 2009, we undertook a significant (DXA) at our Longmont location. expansion in order to improve access to rheumatology and metabolic bone We strive to serve our patients and Boulder, CO 80301 services for residents of the northern referring physicians by providing prompt and western Denver metropolitan area. and convenient access to our services. Louisville
We are presently serving this region Patients can generally be seen for an initial from our temporary office in Louisvil e, consultation in 1 to 2 weeks and urgent 80 Health Park Drive while preparing to open our permanent cases can be accommodated in 1 to 2 Broomfield facility, near the intersection business days. Our physicians are readily Louisville, CO 80027 of U.S. 36 and U.S. 287, in the summer available by phone to give advice to our col eagues in the areas of rheumatology and metabolic bone disease. Phone: (720) 494-4700 Drs. Jeff Perkins, Heather Kramm, Joe Lutt and Theresa Tran are al Board Please visit us on line at www.ccao.net,
Fax: (720) 494-4706 Certified in internal medicine and or e-mail us at [email protected]. We'd
E-mail: [email protected] rheumatology. They, along with Sharin love to hear from you! Web: www.ccao.net

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