Bisphosphonates & Pain in OI

Interview with Mercedes Rodriguez Celin, pediatrician at Shriners Hospital for Children, Chicago

Who are you & what experience do you have with Pain & OI?Mercedes

I am Mercedes Rodriguez Celin; I am a pediatrician from Argentina with a specialty in Growth and Development. I worked for ten years at the Skeletal Dysplasia Clinic at Garrahan Pediatric Hospital, Buenos Aires. Since I moved to the US 5 years ago, I have been doing clinical research in OI at Shriners Hospital for Children, Chicago and most recently completing a Postdoctoral Fellowship in Advanced Rehabilitation Research Training through NIDILRR. I had the opportunity of treating many patients with OI over the years, and I have been involved in many research studies that directly or indirectly analyzed pain in OI.

Tell us about the project “Do Bisphosphonates alleviate pain in children? A systematic review”

We were invited by Current Osteoporosis Reports to review this topic, as our OI research group at Shriners Hospital for Children Chicago has previously been working on related topics such as mobility, rodding, and the effectiveness of bisphosphonates (BPs) to improve mobility in OI. Also, at that point, we were starting to develop our proposal to conduct the “Multicenter Study of Pain Characteristics in OI“, so this question was aligned with our research topics and interests.

We decided to conduct a systematic review, so that we could use rigorous and transparent methods to summarize all the available evidence in the literature. We included all the publications from the last ten years (2010-2019) where the pain was measured in children and adolescents under BPs treatment. We included studies done on OI and on a wide range of skeletal diseases to understand better the role of BPs in alleviating bone pain.

How was it financed?

My work has been financed through Shriners Hospital for Children, the Orthopaedic and Rehabilitation Engineering Center (OREC) at Marquette University in Milwaukee, WI and a grant from the U.S. Department of Health and Human Services.

How do you define pain?

Pain has been defined by the International Association for the Study of Pain (IASP) as “An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage.” Interestingly in the last few years, the definition was expanded to include relevant concepts such as: always considering pain as a personal experience that might be influenced by multiple factors. The IASP also reinforces the importance of respecting an individual’s pain report. Additionally, the IASP recognized that pain might have adverse effects on function and social and psychological well-being.

So, if I have to define pain, I would say that pain is a personal and complex experience with components of the individual’s physical, emotional and psychosocial aspects. Therefore, we are speaking about a multidimensional experience that needs to be addressed and understood.

Are there different types of pain that people with OI struggle with?

Pain has been broadly categorized as acute or chronic, depending on the duration, but some patients may have an overlap between these types of pain. The IASP has adopted three major divisions to classify pain as nociceptive, neuropathic, or nociplastic, depending on actual or threatened tissue damage, or the lesion of the somatosensory system causing the pain, or pain that arises from altered nociception (nervous system processing), respectively. Also, pain could be classified regarding the source of pain as bone pain, joint pain, muscle pain, etc. Some individuals with OI may have pain from different sources and in various sites at the same time. Therefore, pain in OI could be complex and multifactorial.

Group foto

What were your most interesting findings from the review?

We found that more than 80% of the studies included in the systematic review reported a positive effect of BPs for alleviating pain in different pathologies, but 58% of the studies were categorized as having a high risk of bias. So, we concluded that intravenous BPs might help alleviate bone pain in children and adolescents. However, we advised that our results should be interpreted with caution due to the heterogeneity of doses used, the duration of treatments, and the types of conditions included. Our review shows the lack of high-quality evidence in the available literature. Future research should prospectively study the effectiveness of BPs using a control group or placebo when possible. I was surprised by the wide variety of pediatric conditions, other than OI, that uses BPs for pain relief. For example, we found that BPs were used for pain relief for conditions such as osteonecrosis related to chemotherapy, chronic non-bacterial osteitis, and unresectable benign bone tumor.

What is the most important take-home message for clinical work?

It is essential to keep in mind that BPs are widely used in adults to treat osteoporosis, and they have been used for their analgesic effect in several bone-related conditions. However, in children, BPs are used off-label for many conditions to improve bone density and decrease fracture risk. So, if the decision to use BPs for pain relief is made, providers and families should consider that the scientific evidence for this recommendation in children is weak. Therefore, we encourage to monitor clinically the real benefits of using this medication to treat bone pain.

In one of your talks, you called pain in OI “The elephant in the room”. What did you mean by this?

We decided to refer to pain as “the elephant in the room” because, in many opportunities, we might want to avoid addressing and managing “the pain issue”.  As we explained before, the pain might be complex, multifactorial, and challenging to treat in OI, so providers, patients, and families could have difficulties approaching this topic. Therefore a multidisciplinary approach to pain would be essential to dealing with pain in OI.

What is the most important topic the OIFE pain & OI resource group should focus on?

It has been described that pain is not only an unpleasant but also disabling experience in OI. Therefore, this group has many challenges ahead regarding improving the assessment and treatment of pain in OI. But, in my opinion, we should start by trying to improve the evaluation of pain. So, in that aspect, we should work as a team, exploring which are the available validated, multidimensional tools to assess pain that could be more useful in individuals with OI. A better understanding of pain may help delineate the possible causes and identify the more optimal treatments for each patient.

Mercedes Rodriguez Celin is a member of the Pain & OI Project organized by OIFE and the OIF.

This interview has previously been published in OIFE Magazine 3-2022.

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