What Is New in Osteoporosis?

In this episode, Michael R. McClung, MD, explains what is new in osteoporosis, including the evaluation and treatment of patients with osteoporosis, what the update of FRAX entails, and how it impacts clinical practice in rheumatology. Dr McClung presented on this topic at the Congress of Clinical Rheumatology in Destin, Florida on May 14, 2022. 

Michael R. McClung, MD, is an endocrinologist and the founding director of the Oregon Osteoporosis Center (Portland, OR).

For more information about CCR East and West 2022, visit https://www.ccrheumatology.com/

TRANSCRIPTION:

Jessica Bard: Hello everyone and welcome to another installment of Podcast360, your go-to resource for medical news and clinical updates. I'm your moderator, Jessica Bard with Consultant360 Specialty Network. It is estimated that 54 million people in the United States have osteoporosis and women are four times more likely to develop the disease compared with men, according to the Cleveland Clinic. Dr Michael McClung is here to speak with us today about his session, “What's New in Osteoporosis at Congress of Clinical Rheumatology 2022 East.” Dr McClung is an endocrinologist and the founding director of the Oregon Osteoporosis Center in Portland, Oregon. Thank you for joining us today, Dr McClung. How has the management of osteoporosis evolved in recent years?

Michael R. McClung, MD: Over the last 30 years, 2 things have happened. We can now identify patients who are at risk for fracture, which is a complication of osteoporosis. We can identify the patients who are most appropriate to be treated. Secondly, we've developed a whole menu of treatment options with multiple mechanisms of action, that have been shown in very well-done clinical trials to be effective in reducing patients' risk of fracture. What we've learned from all of that is that osteoporosis is a lifelong condition that requires very long-term management. We don't have short-term fixes for the problem of osteoporosis and we're now learning how to use the various treatment options that we have in the most appropriate and most effective sequences.

But despite all that we have learned in the last several years, our message to both patients and to primary care physicians about treating osteoporosis has not been as effective as we would wish it to be. There still is a huge treatment gap in that the majority of patients who are at high risk of fracture are still not being recognized and being treated. That's a focus that we'll need to work on more in the next several years.

Jessica Bard: What's new in the evaluation and treatment of patients with osteoporosis?

Michael R. McClung, MD: Two things: we've identified the important risk factors for osteoporosis, being advanced age, low bone density and a history of a previous fracture. Those are the big three and those risk factors are independent, meaning that if a person has more than one of them, they're at even higher risk. We have learned in just the last three or four years, that the recency of a fracture is by far the most powerful predictor of future fracture risk. In the first year or two after an osteoporotic fracture, after a spine fracture, a humerus fracture, or a wrist fracture, the risk of another fracture is very high. And that helps us identify patients who need treatments that rapidly increase bone density and rapidly reduce their risk of fracture.

Fortunately, the new bone-building drugs that we have are capable of doing that. Most of the drugs that we have for osteoporosis work by inhibiting bone metabolism, they inhibit bone resorption but they also inhibit bone formation. And while they can strengthen the skeleton, they cannot and do not restore the disordered architecture that is a part of osteoporosis. The bone-building drugs, by stimulating new bone formation, can rapidly increase bone density and improve this structure and architecture. And we've learned that those bone-building drugs in well-designed clinical trials are more effective than bisphosphonates, the standard treatment for osteoporosis in reducing fracture risk.

And we also know that when the bone building drug is given first, that the benefit is greater than if an anti-remodeling drug is given first followed by the bone-building drug. The sequence in which drugs are used turns out to matter importantly about that. We have incorporated or are incorporating those risk factors into a fracture risk assessment tool call FRAX, that was developed by a group at the University of Sheffield. And we will begin to incorporate the recent fracture and other things into FRAX, hopefully in the near future.

Jessica Bard: Would you tell us more about what the update of FRAX will entail?

Michael R. McClung, MD: FRAX was developed in 2008 and was based on meta analyses of nine or 10 different large databases from around the world. The FRAX team has worked to identify many new databases subsequently. We can now incorporate many new risk factors that either we knew about or some of which we didn't even know about back in 2008. That includes, as I've mentioned, the recency of a fracture, very importantly. The old FRAX only used the hip bone density but did not account for people with low spine bone density. That will be in included. We will also incorporate the role of falls as a risk factor for fracture, the role of type 2 diabetes as an important risk factor that we didn't appreciate back in 2008. And specifically for rheumatologists, that both the dose and the duration of glucocorticoid therapy can be factored into fracture to give us a more refined way to assess fracture risk.

Jessica Bard: How do these updates impact clinical practice in rheumatology specifically?

Michael R. McClung, MD: Well, the updates affect rheumatologists like they do the rest of us who care for patients with osteoporosis but there are some specific new things that affect rheumatologists uniquely, mostly having to do with the management of glucocorticoid induced or associated osteoporosis. Very recent studies that I'll report, demonstrate that denosumab, a monoclonal RANK ligand inhibitor, is clearly more effective than risedronate, a bisphosphate, in improving not only bone density but indices of bone strength in patients on glucocorticoid therapy. Romosozumab is one of the new bone-building drugs and we know that in glucocorticoid osteoporosis, the major deficit is a deficiency of bone formation, not high bone resorption. And so there's been a great interest in the role of bone-forming agents in patients on glucocorticoids and a study from Japan was just published, demonstrating that romosozumab should be very effective in treating patients with glucocorticoids. More refines and better strategies for managing those patients will be important for rheumatologists.

Then there was a very interesting paper that demonstrated that giving bisphosphonates to patients who undergo joint replacement was very beneficial for decreasing the likelihood of joint replacement failure. The data from that trial suggests that at least for an interval of six to 12 months after joint replacement, that one might consider bisphosphonates not for the treatment of osteoporosis but specifically to improve the outcome of the arthroplasty.

Jessica Bard: What would you say is next for the research on osteoporosis?

Michael R. McClung, MD: One, we need to learn more about optimizing the sequences with which we use therapy and to have better studies looking at important outcomes, both bone density and fracture risk with a variety of those sequences. What we've learned in recent years, that the level of bone density achieved on treatment is a very good predictor of the patient's current risk of fracture. And that helps guide and inform some of these decisions but we need more information about that.

 There are new strategies for treatment that are in early clinical development that are very exciting. There are some drugs that have the capability of indirectly activating bone formation, while inhibiting bone resorption that may be beneficial. But maybe more importantly strategies to approach the problem of cellular senescence, old cells stop functioning properly. They don't die but then they make a lot of inflammatory cytokines that turn out to be detrimental to many things, including bone health. And there are now strategies to help clear or remove senescent cells and to remove that problem and early studies in animals show that these senolytic therapies are beneficial for many aspects of aging, including osteoporosis. That I think is a very promising and exciting research path that we'll keep track of.

Jessica Bard: What are the overall take-home messages from our conversation today?

Michael R. McClung, MD: First of all, that osteoporosis is a problem that should not be ignored. Fractures are related to impaired bone strength and an older adult who experiences a fracture following a fall should be construed to have had a bone attack. They need to be evaluated and if found to have low bone density or at risk of fracture, we've got very effective treatments that can markedly improve their outcome and their quality of life over time. Osteoporosis is a problem that should not be ignored. And certainly seeing a patient with a fracture should turn on the risk assessment algorithm and alert people to at least think about what to do. And only by doing that, will we close the huge treatment gap that exists in our field.

Jessica Bard: Thank you very much for your time today. Is there anything else that you'd like to add that you think we missed?

Michael R. McClung, MD: No. I think we've covered all the things that I'm interested in and passionate about. Thank you for giving me that opportunity.

Jessica Bard: Absolutely. And thank you for all of your research and all of your work on this topic. It's very important