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CME

Managing Osteoporosis: New Insights Into an Old Problem (Slides with Transcript)

  • Authors: M Susan Burke, MD, FACP
  • THIS ACTIVITY HAS EXPIRED
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Target Audience and Goal Statement

This educational activity will provide radiologists, endocrinologists, rheumatologists, technologists, and other healthcare and managed-care professionals attending the ISCD the opportunity to learn more about function of the human skeletal structure.

By examining the impact of several issues involved in the maintenance and/or evaluation of bone health, attendees will be better able to treat their patients suffering from debilitating conditions such as osteoporosis. Discussion of recent pharmacologic data relating to bone mineral density and biochemical markers of turnover will enhance the attendees' store of knowledge for the optimum treatment of bone patients. In addition, assessment of vitamin D in terms of fall reduction and antifracture efficacy is a promising field of investigations as is the Hip Structure Analysis (HSA) methods in the measurement of bone strength, in both its current form and its development toward even greater accuracy. Moreover, examining mechanical and structural properties of bone in terms of cortical and trabecular architecture can aid clinicians in delineating bone health and the impact of its debilitation.

Upon completion of this activity, participants should be able to:

  1. Identify recent pharmacological data in the context of selecting optimum treatment strategies.
  2. Explain the role vitamin D has in antifracture efficacy.
  3. Describe the mechanical and structural properties of cortical and trabecular bone in order to better distinguish the determiners of bone strength.
  4. Define current bone quality measurement methodologies, including the utility and current limitations of HSA.


Disclosures

Postgraduate Institute for Medicine (PIM) assesses conflict of interest with its instructors, planners, managers, and other individuals who are in a position to control the content of CME activities. All relevant conflicts of interest that are identified are thoroughly vetted by PIM for fair balance, scientific objectivity of studies utilized in this activity, and patient care recommendations. PIM is committed to providing its learners with high quality CME activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of a commercial interest.

The faculty reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CME activity:


Author(s)

  • M. Susan Burke, MD, FACP

    Director, Internal Medicine Clinical Care Center, Lankenau Hospital, Wynnewood, Pennsylvania

    Disclosures

    Disclosure: Fees for Non-CME Services: Merck & Co., Inc.

  • Sydney L. Bonnick, MD, FACP

    Medical Director, Clinical Research Center of North Texas; Adjunct Professor, Departments of Biology and Kinesiology, University of North Texas, Denton, Texas

    Disclosures

    Disclosure: Contracted Research: Amgen, Roche/GlaxoSmithKline, Wyeth Pharmaceuticals; Consultant: Amgen, Merck & Co., Inc., Roche/GlaxoSmithKline, Wyeth Pharmaceuticals; Fees for Non-CME Services: Merck & Co., Inc., Roche/GlaxoSmithKline; Ownership Interest: Procter & Gamble

  • Robert P. Heaney, MD, FACP, FASNS

    John A. Creighton University Professor, Professor of Medicine, Creighton University, Omaha, Nebraska

    Disclosures

    Disclosure: No financial interest/relationships with financial interests relating to the topic of this activity.

  • Anthony I. Sebba, MD, FACR

    Assistant Clinical Professor, Department of Rheumatology, University of South Florida, Tampa, Florida

    Disclosures

    Disclosure: Contracted Research: Amgen Pharmaceuticals, Eli Lilly and Company, Merck & Co., Inc., Roche Pharmaceuticals; Consultant: Amgen Pharmaceuticals, Eli Lilly and Company, Merck & Co., Inc., Roche Pharmaceuticals; Fees for Non-CME Services: Amgen Pharmaceuticals, Eli Lilly and Company, Merck & Co., Inc., Roche Pharmaceuticals

  • Trace Hutchison, PharmD

    Postgraduate Institute for Medicine, Englewood, CO

    Disclosures

    Disclosure: No financial interest/relationships with financial interests relating to the topic of this activity.


Accreditation Statements

    For Physicians

  • This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME). The Postgraduate Institute for Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

    Postgraduate Institute for Medicine designates this educational activity for a maximum of 2.0 AMA PRA Category 1 Credits. Physicians should only claim credit commensurate with the extent of their participation in the activity.

    Contact This Provider

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]


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This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.

Follow these steps to earn CME/CE credit*:

  1. Read the target audience, learning objectives, and author disclosures.
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You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.

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CME

Managing Osteoporosis: New Insights Into an Old Problem (Slides with Transcript)

Authors: M Susan Burke, MD, FACPFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

processing....

Welcome and Introduction

I want to welcome all of you and it's my pleasure to introduce our first speaker this evening, Dr. Susan Burke, who is a Clinical Assistant Professor at Thomas Jefferson University and an internist and geriatrician and director of the Internal Medicine Clinical Care Center, Lankenau Hospital, Wynnewood, Pennsylvania.

Managing Osteoporosis: New Insights Into an Old Problem

Introduction

  • I'm going to offer you a clinician's perspective on some new insights into managing osteoporosis. I'd like to focus on, first, patient identification and then look at new insights into available treatment options.

  • Managing Osteoporosis: New Insights Into an Old Problem

    Slide 1.

    Managing Osteoporosis: New Insights Into an Old Problem

    (Enlarge Slide)

Case Study in Identifying High-risk Patients

  • First to look at how to identify high-risk patients.

  • New Insights Into Identifying High-risk Patients

    Slide 2.

    New Insights Into Identifying High-risk Patients

    (Enlarge Slide)
  • I'll begin with a case of Mrs. Brown, a 70-year-old who presents for a physical. Like the song, she has a lovely daughter, because she's moved in with her daughter and has relocated to your area and is coming to you for a physical. She has a past history of hypertension, asthma, depression, and breast cancer, and her medications right now are amlodipine, montelukast, albuterol, and sertraline. She's appearing pretty healthy. She's petite, 5'3", and 118 pounds. Her pressure is normal, and she appears to be in no acute distress. Routine labs and studies are ordered, including a dual energy x-ray absorptiometry (DXA), appropriate for a 70-year-old.

  • Case

    Slide 3.

    Case

    (Enlarge Slide)
  • Her DXA shows a T-score of -1.3 at the lumbar spine and -1.4 at the femoral neck. So the question is, what if anything, would you do for this patient? And what is her risk for fracture? Well, at first blush, you'd say, wow a T-score of -3, -4, not really all that bad and doesn't quite meet standard criteria for treatment.

  • Case (cont'd)

    Slide 4.

    Case (cont'd)

    (Enlarge Slide)

Assessing Fracture Risk

  • If you look at her 10-year probability (and this was a study by John Canus looking at Swedish women, so we may need to extrapolate this a little bit to US women), looking at age and femoral neck T-score, her 10-year probability for fracture is actually around 14%, and that really is even higher than say a 50-year-old with a T-score of -2.5 or -3, someone who we would identify much more clearly as being at risk for fracture. The World Health Organization is working on a new algorithm to help us identify patients at higher risk.

  • 10-year Probability of Fracture in Women by Age and FN T-Score

    Slide 5.

    10-year Probability of Fracture in Women by Age and FN T-Score

    (Enlarge Slide)
  • Age and bone mineral density (BMD) are independent risks for hip fracture, and right now the T-score, as we know, that defines osteoporosis is a T-score of -2.5. Traditionally, these are the patients, highlighted in blue, who we would target, anybody below a T-score of -2.5 really regardless of age, but if we factor in age and look at a different number, an absolute fracture risk, and look at a 10-year fracture probability, we can really change this paradigm to identifying those with a certain fracture risk and those highlighted here in yellow would really be the ones we would want to target. Our 70-year-old with a hip T-score of -1.4 and other factors, including asthma and perhaps being on steroids periodically and a history of breast cancer in the past, may put this patient really over the top to where we'd want to treat her. Exactly what that absolute fracture risk is going to be is a wavering line right now. Is it going to be 5% 10 year, 10%, 8%? It is going to vary perhapsfrom country to country depending on a country's resources, but this just helps us in changing our look at a high-risk patient and maybe targeting someone whom we might not otherwise have targeted 5 or 6 years ago.

  • Age and BMD Are Independent Risk Factors for Hip Fracture

    Slide 6.

    Age and BMD Are Independent Risk Factors for Hip Fracture

    (Enlarge Slide)
  • The WHO has proposed an approach to fracture risk assessment and is including other risks, advanced age obviously being at the top of that list, a history of fracture over age 50, family history of hip fracture, use of corticosteroids, alcohol greater than 2 drinks a day, so fortunately it's not just at two, it's greater than two, so most of us should be okay there -- (laughter) -- smoking, and a history of rheumatoid arthritis. Those are under proposal, and hopefully we'll hear more about this shortly.

  • WHO: Proposed Approach to Fracture Risk Assessment

    Slide 7.

    WHO: Proposed Approach to Fracture Risk Assessment

    (Enlarge Slide)

New Insights Into Treatment Options

  • I am just going to highlight some recent developments with regard to medications. I think you are all pretty familiar with the medications listed here, but I have highlighted in yellow proton pump inhibitors and selective serotonin reuptake inhibitors, which have been recently demonstrated to increase risk for fracture.

  • Medications Contributing to Bone Loss

    Slide 8.

    Medications Contributing to Bone Loss

    (Enlarge Slide)
  • With regard to new insights into treatment options, let's again turn to our case.

  • New Insights Into Treatment Options

    Slide 9.

    New Insights Into Treatment Options

    (Enlarge Slide)
  • Mrs. Brown is admitted 2 years later with a hip fracture after tripping over her grandson's toy. Her hip was pinned. She was sent to rehab. She now returns to your office using a walker. Her orthopedist tells her to be sure and check with you concerning whether treatment is needed. Her meds are the same with the addition of calcium and vitamin D that was started a couple of years earlier.

  • Case

    Slide 10.

    Case

    (Enlarge Slide)
  • Well, why did Mrs. Brown break her hip? In addition to bad genes, genetic predisposition perhaps, she has weakness, perhaps, or a fall risk due to physical inactivity, due to low vitamin D, which we'll hear more about by Dr. Heaney later. She might have poor vision, she didn't see the toy, low BMD due to lifestyle, or she didn't drink milk growing up. Her medications might be contributing. She might have increased bone turnover, leading to both trabecular and cortical issues, which we will hear more about from Dr. Sebba. So, no matter why she broke her hip, what are we going to do about it?

  • Why Did This Patient Break Her Hip?

    Slide 11.

    Why Did This Patient Break Her Hip?

    (Enlarge Slide)
  • She's encouraged to do gait and balance exercises and resume calcium with an appropriate dose of vitamin D. Based on recent studies, what could have been done for this patient to have prevented her hip fracture?

  • Case

    Slide 12.

    Case

    (Enlarge Slide)

Fracture Reduction Efficacy

  • Well, if we look at hierarchy of evidence, we do have the ORAG data from 2002 -- Osteoporosis Research Advisory Group -- looking at a meta-analysis of fracture reduction efficacy. And with regard to vertebral fracture reduction, we see that alendronate, risedronate, raloxifene and calcitonin were all shown to reduce spine fractures. With regard to nonvertebral fracture risk reduction, we see that only alendronate and risedronate met the criteria that were significantly reducing those fractures.

  • ORAG: Meta-analyses of Fracture Reduction Efficacy

    Slide 13.

    ORAG: Meta-analyses of Fracture Reduction Efficacy

    (Enlarge Slide)
  • They did find in the ORAG analysis that hip fractures were reduced with alendronate, but at the time there was insufficient evidence that other agents reduce hip fractures. More recently, Lieberman evaluated data on nonspine and hip fracture reductions with the available antiresorptive agents.

  • Background

    Slide 14.

    Background

    (Enlarge Slide)
  • So he looked at this again, this meta-analysis of randomized, controlled trials and found that, with regard to treatment effects on nonspine fracture risk, with alendronate, whether you break it down to 10 mg or more a day, there was a .51 relative risk of nonspine fracture; with alendronate greater than 5 mg a day, a .66 relative risk for nonspine fracture; with hormone therapy, a .75 relative risk, contributed to in large part by data from the Women's Health Initiative; and with risedronate at 2.5 mg or 5 mg or even at 5 mg a day only, not much difference there, with a .73 or .68 relative risk of nonspine fracture. What about hip fracture risks?

  • Antiresorptive Agents: Treatment Effects on Nonspine Fracture Risk

    Slide 15.

    Antiresorptive Agents: Treatment Effects on Nonspine Fracture Risk

    (Enlarge Slide)
  • Again, with alendronate at 5 mg or 10 mg a day, looking at hip fracture risk, we have a .5 relative risk. If you look at 5 mg or 10 mg a day and slightly less osteoporotic group, either osteoporotic or a T-score of -2, we have a .55 risk; and with hormone therapy, a .64 risk; and risedronate offers a .74 risk of hip fracture.

  • Antiresorptive Agents: Treatment Effects on Hip Fracture Risk

    Slide 16.

    Antiresorptive Agents: Treatment Effects on Hip Fracture Risk

    (Enlarge Slide)
  • This analysis, even though it was more recent, looked at ibandronate data, calcitonin, etidronate, and raloxifene data, and there was insufficient evidence of fracture treatment effects with regard to hip fracture with these agents. A post publication note from this study did describe the RUTH (Rationale and Overview of the Raloxifene Use for the Heart) trial, which had 10,000 women in it looking at raloxifene use and the heart, but also captured fractures, and there was no evidence of nonvertebral fracture benefit with raloxifene. So the conclusion of this paper was that alendronate reduces hip fractures by 45% to 55%, hormone therapy by 25% to 35%, and risedronate by 26% to 27%. These could have been agents that might have helped Mrs. Brown not break her hip.

  • Antiresorptive Agents: Treatment Effects on Fracture Risk With Other Agents

    Slide 17.

    Antiresorptive Agents: Treatment Effects on Fracture Risk With Other Agents

    (Enlarge Slide)
  • Well let's do a little case flashback, because you would have started Mrs. Brown on a bisphosphonate at the appropriate time. She never ended up having the hip fracture. So now she is coming in after 5 years of bisphosphonate treatment. Her T-scores are improved.

  • Case Flashback

    Slide 18.

    Case Flashback

    (Enlarge Slide)

Treatment With Bisphosphonates

  • Now the question is, what evidence do we have with regard to long-term bisphosphonate treatment? Can they be used safely? There are a lot of questions in the press, a lot of questions in our minds, and there is evidence of long-term safety and efficacy? So what is the data?

  • What Evidence Do We Have With Regard to Long-term Bisphosphonate Treatment?

    Slide 19.

    What Evidence Do We Have With Regard to Long-term Bisphosphonate Treatment?

    (Enlarge Slide)
  • Well, I can't discuss safety in bisphosphonates without bringing up osteonecrosis of the jaw (ONJ), otherwise referred to by our dental compatriots as bisphosphonate-related osteonecrosis of the jaw or BRON, or B-R-O-N, but I will refer to it fondly as ONJ, which is a poorly-healing oral lesion, usually seen with tooth extraction without head or neck malignancy or radiation resulting in a poorly healing lesion that can be quite annoying for any patient who has it. The known risk factors for ONJ include a diagnosis of cancer. Concomitant therapy such as chemotherapeutic agents, radiation, corticosteroid therapy, and poor oral hygiene, which is really found to be a significant contributor. A recent Australian study showed that this was definitely a factor in their ONJ cases that were reported. Comorbid disorders including significant dental problems, anemia, diabetes, which can affect healing, smoking, and alcohol use.

  • ONJ/BRON

    Slide 20.

    ONJ/BRON

    (Enlarge Slide)
  • Well, most cases of ONJ are associated with the IV formulation. Oral bisphosphonates account for approximately 5% of total patients reported worldwide and in the Merck database, the reported incidents with alendronate is .7 per 100,000 person years of exposure. So in all of the clinical trials of alendronate, there have been no reported cases of ONJ, including trials looking at use of alendronate in periodontal disease. Rare cases of ONJ have been seen without risk factors or even without bisphosphonate treatment. In the Horizon study with IV zoledronic acid, there were 3 cases of ONJ noted in that trial, it was the IV trial, but 2 cases were in the placebo group. We clearly need to study this further, but we really don't yet have full definitive answers with regard to ONJ and bisphosphonate. One thing that may be emerging, and is being seen, is that risk may be associated with an increased duration of treatment.

  • ONJ/BRON (cont'd)

    Slide 21.

    ONJ/BRON (cont'd)

    (Enlarge Slide)
  • The American Association of Oral and Maxillofacial Surgeons (AAOMS) has issued a position paper on bisphosphonate-related osteonecrosis of the jaw. And this is one of the few times I am referring to hypothesis, rather than evidence-based data, but this is really all we have with regard to ONJ. We don't have any randomized, placebo-controlled, prospective trials evaluating this, except to look at the trials that have already been conducted. It is clearly a very rare event. But their recommendation is, if systemic conditions permit, to delay the start of bisphosphonate until dental health is optimized. So, if you have a patient you've diagnosed with osteoporosis and it looks like their teeth are in great need of repair, you may want to hold off on bisphosphonate therapy, let them get their teeth addressed, then begin treatment 2 to 3 months after healing or after those dental procedures have been carried out. For asymptomatic patients with no clinical risk factors, who are receivingoral bisphosphonates, if they've taken them for less than 3 years, no delay in planned surgery should be done. But if they've been on it for greater than 3 years, these dental surgeons are recommending to suspend bisphosphonate therapy for 3 months, if conditions permit and then restart these agents after healing has occurred. Again, this is based on hypothesis. So keep that in mind that they have issued this, this is why patients are coming into our offices saying, hey doc, my dentist isn't going to do anything to me until you say that it is okay for him to do something. I urge you to go to their Web site, and you can download their paper. You can actually just Google AAOMS and this will pop right up, and you can go right to their site and see this position paper. Well, what about other safety data besides ONJ? Do we have other evidence of long-term safety with bisphosphonates?

  • American Association of Oral and Maxillofacial Surgeons Position Paper

    Slide 22.

    American Association of Oral and Maxillofacial Surgeons Position Paper on Bisphosphonate-related Osteonecrosis of the Jaws

    (Enlarge Slide)
  • And we have with risedronate triple iliac crest biopsies collected at baseline and at 3 to 5 years showing normal mineralization in those biopsies, follow-up with VERT (vertebral efficacy with risedronate) multinational study shows a low incidence of radiographic vertebral fracture after up to 7 years.

  • Long-term Data: Risedronate

    Slide 23.

    Long-term Data: Risedronate

    (Enlarge Slide)

Incidence of Vertebral Fracture

  • What you can see here is the annualized incidents from the VERT multinational carried out through 7 years. You can see with risedronate after 3 years, after 5 years, and after 7 years, that the number of fractures is not increasing, so we have a low incidence of fractures with risedronate carried out through 7 years.

  • Annualized Incidence of Subjects Experiencing Any New Vertebral Fracture Over Years 0-3, 4-5, or 6-7

    Slide 24.

    Annualized Incidence of Subjects Experiencing Any New Vertebral Fracture Over Years 0-3, 4-5, or 6-7

    (Enlarge Slide)

FLEX Study Data

  • We also have data now 10 years with alendronate from the fracture intervention trial long-term extension or FLEX, the purpose of which was to examine the effects of continuation of alendronate for 10 years, vs 5 years and then placebo for 5 years. Primary endpoint was change in BMD at the total hip, various secondary endpoints, including safety and intolerability and also looking at bone histomorphometry.

  • Fracture Intervention Trial Long-term Extension (FLEX)

    Slide 25.

    Fracture Intervention Trial Long-term Extension (FLEX)

    (Enlarge Slide)
  • Very briefly, the FLEX study design is the (Fracture Intervention Trial) FIT trial and then 2 year, 1 to 2 years of open-label alendronate and then patients who were on alendronate for those first 5 years were randomized to receive placebo, alendronate 5 mg or alendronate 10 mg.

  • FLEX Study Design

    Slide 27.

    FLEX Study Design

    (Enlarge Slide)
  • Looking at the primary endpoint total hip BMD, you can see that for 10 years of alendronate treatment, that you're having only a 1% decrease from FLEX baseline carried out through 10 years with the use of alendronate. If you use alendronate for 5 years and then use placebo for 5 years though, of note total hip BMD returns to the FIT baseline and the difference between the 2 groups is 2.4% and the difference from FLEX baseline is 3.4%. You really get a loss of hip BMD with cessation of alendronate therapy after 5 years of therapy.

  • Total Hip BMD Change From FIT to FLEX

    Slide 28.

    Total Hip BMD Change From FIT to FLEX

    (Enlarge Slide)
  • With regard to time for first nonvertebral fracture, identical lines here with regard to the curves alendronate for 5 years or alendronate for 10 years.

  • FLEX: Survival Curve for Time-to-First Nonvertebral Fracture

    Slide 29.

    FLEX: Survival Curve for Time-to-First Nonvertebral Fracture

    (Enlarge Slide)
  • Of interest again, with regard to time for first clinical vertebral fracture, there was a significant difference between the use of alendronate for 10 years, which offered a 55% reduction in clinical vertebral fracture compared with alendronate for 5 years and placebo for 5 years.

  • FLEX: Survival Curve for Time-to-First Clinical Vertebral Fracture

    Slide 30.

    FLEX: Survival Curve for Time-to-First Clinical Vertebral Fracture

    (Enlarge Slide)
  • Adverse events were really comparable in the 2 groups and comparable to other data on alendronate.

  • Adverse Experiences During FLEX

    Slide 31.

    Adverse Experiences During FLEX

    (Enlarge Slide)
  • Reassuringly, bone biopsies of the 5-year alendronate, 5-year placebo and 10-year alendronate showed bone of normal mineralization and no quantitative or qualitative differences.

  • FLEX: On Edge View of Trabecular Bone

    Slide 32.

    FLEX: On Edge View of Trabecular Bone

    (Enlarge Slide)

Summary

  • To sum up, the use of the 10-year absolute fracture risk may enhance our ability to identify patients at higher risk for fracture. Recent meta-analyses have demonstrated that alendronate hormone therapy and risedronate reduce hip fractures.

  • Summary

    Slide 33.

    Summary

    (Enlarge Slide)
  • ONJ is fortunately a rare event with oral bisphosphonates, and we can be reassured that bisphosphonate use for up to 10 years maintains the increases in BMD and reduces the relative risks for clinical vertebral fractures, and, most important, there is no evidence of an increase in adverse events or abnormal bone on biopsy. Thank you.

    Dr. Bonnick: Thank you, Dr. Burke. I neglected to suggest to all of you that you take a moment to look at the biographies of the speakers in the program book. My introductions from the podium are necessarily short and don't remotely do their careers justice. It is my pleasure to introduce next, Dr. Robert Heaney. Dr. Heaney is the holder of the John A. Creighton University Chair and a Professor of Medicine at Creighton University in Omaha, Nebraska.

  • Summary

    Slide 34.

    Summary

    (Enlarge Slide)