Nancy L. Kuntz, MD: Speaking of height, clearly bone health is something that is a new concept in neuromuscular medicine. Individuals who don’t bear weight, who particularly don’t bear weight with some degree of vibration or pressure or things of this sort that occur naturally as kids bounce and jump and run, don’t build the same mineral density. And that creates a whole new list of concerns with respect to comfort and well-being. How have you dealt with that with your team, Basil?
Basil Darras, MD: As you said, Nancy, the bone health has become very important during the last 10, 15 years in the entire field of muscular diseases, for the reasons you explained. And talking specifically about SMA [spinal muscular atrophy], we routinely discuss the issue about vitamin D intake and calcium intake. Of course most of this discussion is carried out by our nutritionist. But if the nutritionist is not available, then I will discuss it with the family to make sure the child has adequate calcium intake, and that the vitamin D levels somehow are monitored.
We do measure vitamin D levels in blood periodically, particularly during the winter and spring, when you don’t have a lot of sunshine, to see whether we have normal levels of vitamin D. And in most laboratories the cutoff value is 30 ng/mL: 3-0. And then we have a value, let’s say between 20 and 30 ng/mL, which reflects vitamin D insufficiency. Then we recommend vitamin D3 supplementation, which can be from 500 to as much as 2000 IU/day.
If the child has a value in the deficiency range below 20 ng/mL, we refer them to the Bone Health Program, which we happen to have at our institution [Boston Children’s Hospital]. Because many of these kids need DEXA [dual-energy x-ray absorptiometry] scans, they require a specific treatment of this vitamin deficiency with high doses and so on. That has become a routine part of our care in the SMA clinic. But as I said, it’s really the nutritionist and the gastroenterologist who deal with that most of the time.
Nancy L. Kuntz, MD: And I know that 1 of the issues that thin bones can make much more complicated is management and treatment of scoliosis. What have your colleagues in orthopedics added to this to help us out?
Elizabeth Kichula, MD, PhD: Sure. Well orthopedics is a part of the more disciplinary clinical care, so we routinely have an orthopedist in the SMA clinic who monitors and treats the orthopedic issues that arise in our patients. And as you said, scoliosis is a major 1 because many of our patients in the clinic, they have type 2 SMA, and of course some of them have type 3, and they’re prone to develop scoliosis. Now with type 1 babies living longer because of the interventions, many of them will also require long-term orthopedic care.
So it’s not unusual to have x-rays taken of that day to monitor the degree of scoliosis over time. And as you know, there is conservative management, which can be applied by using orthosis body jackets that are applied at different periods of time during the day. And at some point the scoliosis, which is a critical point, it may have to be corrected surgically.
And it is something that the orthopedists know how to deal with, but I have noticed that many of the children, they have growing rods implanted to stabilize the spine and prevent progression. And these rods, as you know, have to be lengthened periodically, and it used to be done surgically from time-to-time. But now we have these magic rods, which can be lengthened by using a magnet.
And then when the child gets older and requires fusion of the spine, that will be done by orthopedics to stabilize the spine long term.
Nancy L. Kuntz, MD: And as we’ll be talking about pretty quickly, some of the treatments for spinal muscular atrophy can involve intrathecal administration of medication. So the whole issue of presence or absence of scoliosis and what kind of treatment was used—whether it was a fixation, as was done in the past, or whether it’s a little bit more permissive growing rod—can affect treatment of spinal muscular atrophy over time.
Claudia A. Chiriboga, MD, MPH: Not only that, but the osteoporosis sometimes makes it difficult to use fluoroscopy, and you have to use CT [computed tomography] in order to access for treatment. But I just wanted to go back what Basil had said about SMN protein and its role outside the central nervous system. And when you spoke about the gastrointestinal dysmotility issues and the dysautonomia that the babies have, that’s oftentimes seen in type 1, that is likely related to the absence of systemic SMN protein.
And I recently read an article in which fractures and osteoporosis were equally present in type 1, type 2, and type 3, raising the possibility that it’s not just immobility that contributes to the osteoporosis and fractures, but that there may become systemic; at least some preclinical data showed some osteoclastic activity of SMN protein as well.