Intravenous bisphosphonate therapy of young children with osteogenesis imperfecta

Read Full Text: Intravenous Bisphosphonate Therapy of Young Children with Osteogenesis Imperfecta: Skeletal Findings During Follow Up Throughout the Growing Years (Free to access!)
Journal: Journal of Bone and Mineral Research (2018 Impact Factor is 5.7)
Year Published: 2015
Ranked 24th on our 2014-2019 list of the 50 most influential articles

Article overview for OTs

This study looks at bisphosphonate therapy as a mainstay treatment of osteogenesis imperfecta (OI). However, as we see with almost all complex diagnoses, multidisciplinary care is indicated—which is why we find mention of occupational therapy and our role in treatment.

The article provides a good big-picture overview of OI and treatment, and it also helps paint a picture of why occupational therapy is so beneficial at this point for these children. After all, pharmacological treatments for OI have definitely progressed, but there is still much room for improvement.

In this article, children with OI who received bisphosphonate therapy demonstrated overall improvements in bone density and vertebral reshaping. However, the rate of long-bone fractures remained high (the prevention of which is one of the primary goals of treatment)— and the majority of patients still developed scoliosis.

Important review of our current understanding of osteogenesis imperfecta (OI)

OI is a heritable disorder which is typically caused by a genetic mutation that impacts type-1 collagen production. This type of collagen is the most abundant protein in bone, skin, and other connective tissues that provide structure and strength to the body.

So, while OI is also known as “brittle bone disease,” it is important to remember that multiple systems, notably connective tissues, are often affected.

The severity of OI varies widely. Here are the types listed by the article, though I believe there are up to eight forms.

  • OI Type 1: Represents the least-severe end of the spectrum
  • OI Type 2: Represents the most-severe end of the spectrum, and children do not survive infancy
  • OI Type 3: Represents the most severe type of OI in survivors
  • OI Type 4: Represents intermediate severity between Type 3 and 1

Bisphosphonates work by slowing the activity of the cells that break down bone (osteoclasts). This allows the cells that build bone (osteoblasts) more time to work and reduce the imbalance.

More details about the study

The study population was composed of young patients who visited The Shriners Hospital in Canada.

37 children were identified who met the following criteria:

  • Intravenous bisphosphonate treatment was started before age five
  • Age was 14 years or older at time of last follow-up
  • Bisphosphonates had been given for at least six years
  • Absence of treatment with oral bisphosphonates

Measures from a chart review were compared with 37 children who matched for age, gender, and OI type—but who had not received bisphosphonate prior to the assessment.

The children who received bisphosphonate therapy did show significantly better bone density scores, on average. They were also, on average, 10 cm taller than those who had not received treatment.

However, these children still sustained an average of six femur fractures and five tibia fractures during the time they were tracked by the study. (This rate of fractures is still considered high.)

Other fractures were not tracked, and this is because such fractures aren’t usually documented with the same precision as long bones of the lower extremity (LE). It’s also important to note that these numbers were not compared to pre-treatment fracture rates. Nor, from what I can tell, were they compared with the control cohort.

Children who had bisphosphonate treatment sustained fewer vertebral compression fractures than those who did not receive the treatment. In fact, at baseline for the treatment group, 35% of vertebra were affected by compression fractures—and this dropped to 6% at the final evaluation.

Unfortunately, even though the vertebral bones had more integrity, the rate of scoliosis was still high, indicating that the scoliosis associated with OI might be influenced by soft-tissue abnormalities.

How OT was involved

A multidisciplinary approach was utilized for the patients. So, in addition to the infusions, many of them also received surgical interventions (such as spinal fusions and rodding surgery).

All patients followed underwent physiotherapy and occupational therapy evaluation and intervention. The article states that this treatment included:

  • Exercises
  • Provision of special devices for ambulation, mobility, positioning, and ADLs.

The article states that the level of ambulation was determined by a physiotherapist or occupational therapist utilizing the Bleck Scale. (I had difficulty finding info on this assessment!)

Takeaways for OT

(These are my personal takeaways, and were not mentioned in the article.)

These patients should be on our caseload.

In the absence of a cure or treatment that prevents fractures, patients with OI should be on your caseload—especially if they have never seen an OT before.

The fact that all of the children at Shriners received occupational therapy is important, as Shriners is one of the premier hospital systems for children.

As UpToDate says, occupational therapists can address the impairments in activities of daily living (ADLs) secondary to upper or lower limb deformity. We can also help brainstorm and plan for safe participation in meaningful activities. Safe exercise is especially important for these patients.

Multidisciplinary care works best.

We’ve said this plenty of times in the Club, but it bears repeating: a team approach is necessary for complex cases.

OTs should continually be honing their skills as team players, which is part of the goal of this Club. We want to always be looking at cases from different perspectives.

Change is hard, but it is needed.

Bisphosphonates are the mainstay of treatment for OI and, from what I can tell, the evidence for their ability to prevent a certain percentage of fractures might have already improved, even since this study was published in 2015.

That being said, there continues to be room for much-needed improvements in OI treatments.

In my opinion, as we consider changes that are coming to our healthcare systems, we can get wrapped up in worrying about things like reimbursements and changes to our daily routine.

However, we also need to look toward the future with optimism, and think of the positive changes that the future might hold for patients like these. And we can remain hopeful that, among the many medical advancements we will see in the next few decades, there will likely be improved treatments for OI.

And in the meantime, let’s continue to work to provide the best care possible.

Listen to a summary in podcast form:

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What questions/thoughts does this article raise for you?

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Sarah, This article is interesting. I found it helpful to understand the treatment of osteogenesis imperfecta (OI) and was somewhat disheartened that the use of bisphosphonate therapy was not more helpful. Children were taller and had better bone density but still sustained fractures of long bones and developed scoliosis. I appreciate learning that other fractures may have occurred but that these were not documented as precisely as long bone LE fractures. Additionally, vertebral compression fractures decreased from 35% to 6% which would decrease the pain these children often experience with vertebral compression fractures. As an occupational therapist, I see assisting individuals to manage their pain in non-traditional and non-pharmaceutical methods as important to support the quality of life.
The conclusion of the article which states that “bisphosphonate therapy is not a cure for OT but rather an adjunct treatment for rehabilitation and orthopedic therapies” stands out to me. The role of OT than appears to follow prevention and rehabilitative models. Solomon and O’Brien (2016) indicate osteoporosis may be a secondary condition experienced by an individual with osteogenesis Imperfecta. Further, Solomon and O’Brien (2016) indicate therapy should include weight-bearing activities to facilitate bone development, family and caregiver education on precautions related to handling and brittle bones and methods of improving ADl’s, IADL’s, Play and socialization with friends as well as bracing to prevent contractures. In the world of preventative health care, I see the need for occupational therapy to document their value in assisting to prevent fractures through education of caregivers, parents, and educators as well as adapting environments to facilitate play and socialization. The article did not elaborate or help support OT practice as much as I would have liked but appreciate your thoughts on how OT would be involved with these individuals. I appreciate the article this week and the attention to osteogenesis imperfecta.
I am researching the Bleck scale and have requested the article cited in the article from a source that I have access to, so more to come.
Solomon, J., & O’Brien, J. (2016). Pediatric skills for occupational therapy assistants (4th ed.). St.Louis, Missouri: Elsevier.

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Hey @sherry! I’m really glad you highlighted that concluding sentence:

bisphosphonate therapy is not a cure for OI but rather an adjunct treatment for rehabilitation and orthopedic therapies

That highlights why OT and rehabilitation are so important, because according to this conclusion, they are a primary intervention for OI.

I also wanted to let you know that a member sent me this article (which you can download for free) that walks through the Bleck Scale!

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The thoughts that arose while reading this article and considering Sarah’s takeaways definitely ignited an interest to explore OT’s role on these children’s healthcare teams. Especially since the medical management of OI seems to be inconsistently and potentially minimally beneficial, though thankfully improving. I presented a poster in 2017 on the role of OT on the healthcare teams of children and adolescents with CF, so considering OT’s contributions on the teams of children with potentially complex conditions is already an interest of mine.

I found a 2017 article in the Journal of Multidisciplinary Healthcare (side note: what a perfect journal to find an article including OT, right?) that elaborates on the therapeutic contributions and perspectives both OT and PT offer children in three different age groups (toddler, child, adolescent) in addition to the roles of other team members. One of my favorite quotes from this article was “The therapy team supports children with OI to overcome the many obstacles to independent living, encouraging and respecting their individual problem-solving approaches” (Marr et al, 149). Here also is a link to an article that includes the OI Pediatric Specific Quality of Life Questionnaire, which the authors sited along side the Brief Assessment of Motor Function (BAMF) as the most valid/reliable outcome measures to use with children with OI.

If you also found yourself craving more information about OT’s unique role on the healthcare teams of children with OI then give these articles a look! They are definitely validating for what Sarah (and I’m sure all of us) advocate for: that these patients should be on our caseload and that multidisciplinary care works best!

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Wow! The article that you found is an incredible resource for how specific it is in describing the therapeutic approaches for kids with OI.

Their review of care filled in a lot of blanks for me about what OT care would look like logistically. Thank you so much for your research ninja skills! I hope that anyone who has a child with OI on their caseload is able to look at both articles!

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@SarahLyon That is definitely one of the best compliments I’ve received lately! I’ve always been an OT research nerd, but being a member of the OT Potential Journal Club has apparently unleashed my inner OT research ninja! Thankfully both these articles are free access, so hopefully more OTs and PTs who work with children with OI will be able to access them and apply the wisdom they contain into their practice.

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Very interesting and informative article. In addition to the positive effects on bone density and vertebral fractures cited by this article (which is huge in itself), the treatment with IV bisphosphonate for OI may also help with reducing pain (this was stated in the article 1 posted by Maggie).
“There are anecdotal reports that bisphosphonates reduce bone pain, and certainly a consistent report from patients under our care is that they “slow down”
and “ache more” when their next course of treatment is due.” (Marr, Seasman & Bishop, 2017, Journal of Multidisciplinary Healthcare).
This article gives intervention options to use in various stages of OI such as infants, toddlers, child and adolescent) which is very helpful for practitioners working with this population. Thank you Maggie for posting this article.
Since I work in the NICU, I am interested to know how I can help this fragile population. I don’t recall seeing a baby with OI recently in the NICU. (On another note, I saw a preemie with Noonan syndrome last Saturday).

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I didn’t know there was a Journal of Multidisciplinary Healthcare! I’ll be looking it up. Thank you for your comment!

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One of the most enjoyable aspects of the OT Potential Club is being introduced to new settings, diagnoses, and populations that I have not yet experienced clinically. These articles inspire me to continue learning and not get stuck into the day-to-day in whichever setting I’m currently working. In addition, reading comments on each of the articles has helped me to add to my OT Toolbox with treatments/interventions and/or assessment tools. I’ve only worked with one patient with OI and it was not as severe as some of the other cases I’ve read about as a result of this article. Thank you, @SarahLyon for posting another interesting and inspiring article and thank you, @maggie for posting additional resources! It’s such a pleasure to be a member of this group!

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