The new 2018 standards of care for Duchenne muscular dystrophy (DMD) recently published in Lancet Neurology in January include major revisions in areas of bone health monitoring and endocrine care. It is very important families and adults with DMD are aware of these new standards of care and discuss them with their treating doctors.
On 21 June 2018, Muscular Dystrophy UK held a live Facebook chat where Dr. Jarod Wong (Consultant Paediatric Endocrinologist, with an interest in bone) from the University of Glasgow answered questions on these new standards of care. Below are summaries of the questions and answers relating to the standards of care, bone and endocrine issues.
Q: Would you be able to summarise the endocrine aspects of new standards of care for DMD please?
A: This area of monitoring relates to:
- Growth and short stature
- Adrenal insufficiency and steroid management during severe illness/emergency.
Growth and short stature
Boys with DMD do not grow well and a proportion will end up being very short. Short stature may be part of DMD itself, but no doubt is worsened with steroid treatment. Height monitoring is important. However, there is very little to recommend treating short stature in DMD. One small study using growth hormone in DMD boys show very mild improvement in height for these boys and can be associated with side effects. Growth hormone is not recommended routinely by the standards of care, but may be discussed on a case by case situation in conjunction with a paediatric endocrinologist.
Summary: Height should be closely monitored but there is no clear cut evidence for the use of growth hormone to improve height in DMD.
We now recognise that if adolescent boys with DMD stay on steroid therapy for long periods of time, DMD boys will not go through puberty. The new standards of care recommend that puberty is examined regularly from the age of 9 years old. Examining puberty should ideally be done by doctors experienced doing it. Healthy boys would on average have signs of puberty from age 11 years. To be pragmatic, I would suggest that boys with DMD should have their puberty examined no later than 13 years. As DMD adolescents and young men are growing up and going on to do different things in life, being like their peers is extremely important. It is not correct to assume that having puberty is not important to these adolescents with many other health issues. Very importantly, bone mass improves significantly during puberty as sex hormone levels rise. We know that in women who go through the menopause as hormones levels decline, bone loss increases leading to osteoporosis. Bone health will be discussed later but there are already many reasons why bone health is affected in DMD. Therefore, in boys with DMD with no signs of puberty by 14 years (remember that average age of healthy boys entering puberty is about 11 years), treatment with testosterone is recommended. Testosterone can be given in a few ways, and should be prescribed by a paediatric endocrinologist. It is likely that most adult men with DMD who stay on steroid treatment will also require on-going treatment with testosterone as their levels will likely be low, but we need more research in this area. If you are an adult with DMD and remain on steroid treatment, it will be useful to have your testosterone levels checked. Please discuss this with your treating nurse or doctor.
Summary: Puberty should be monitored from age 9 years (or by 13 years at least) and testosterone therapy should be discussed if there are no signs of puberty by 14 years.
Adrenal insufficiency and emergency steroid plan
A very important part of the new endocrine standards of care is the acknowledgement that adrenal insufficiency (sleepy adrenal glands) as a result of long term use of steroid (usually after 6-12 months of treatment with steroids) occurs in steroid treated DMD boys. The adrenal glands make natural steroid hormone (cortisol) which helps all of us cope with stress, infection and illness. Normally, the adrenal glands make more cortisol hormones during times of severe stress or illness to help cope with the situations. Boys with DMD on steroids are on very high doses of steroids and that makes the adrenal glands go into a deep sleep. In situations like severe sickness especially with vomiting, DMD boys will not have enough steroids on board and will need steroids given in a different way. This may include an injection of steroid into the muscle (similar to an injection given to people with nut allergy for example), or given into the veins if in the hospital with a vomiting or severe illness where the person with DMD is unable to take steroids by mouth (eg sickness or for an operation). It is very important you have an emergency steroid plan in place and the hospital knows what to do when you or your son is sick. Please discuss this issue and emergency plan with your nurse or doctor.
Summary: Long term steroid treatment in DMD leads to adrenal insufficiency. An emergency steroid plan needs to be in place for severe or vomiting illness or during procedures when the DMD boy is unable to take steroids by mouth (eg operations/surgery).
For information on puberty and adrenal insufficiency which we have developed for use in Glasgow, please visit this link. However, please discuss specifics of monitoring and management with your own nurse or doctor.
Q: What are the new standards of care for monitoring bone health in DMD?
A: There is considerable change in the bone monitoring standards of care for DMD in the 2018 updated standards of care. The following are tests that should be done:
Lateral spine x-ray monitoring
The main change is that the care consensus now focuses on the identification of vertebral fracture (compression fracture of the back bone) by performing routine screening lateral spine imaging (usually with x-rays but can be done on some modern DXA machines-see section below) as diagnosis of osteoporosis and therefore the threshold for starting bone protective medicines (bisphosphonates) in DMD. This should apply for ambulant and non-ambulant boys.
Vertebral compression fractures can cause severe back pain but often they can be present without any pain. However, when they are present, this suggests that the bones are very fragile. The new standards of care recommends that all boys with DMD should have routine lateral (taken from the side) spine x-ray to identify vertebral fractures. These should be done at diagnosis (or as close as possible to the time of diagnosis) as a baseline scan, and to be repeated at least every 2 years if the boy is on steroid, regardless of whether the boy has back pain or not. The new standards of care recommend that lateral spine x-ray should be done at least every 3 years for those non on steroids.
X-rays taken for monitoring scoliosis (curvatures of the spine) are usually not taken from the side. Performing routine X-ray of the back (lateral spine X-rays) to detect vertebral fractures allows bone protective medicines to be started at the earliest possibility, without waiting for severe pain and avoid further progression of these fractures. Vertebral fractures can also occur in those not treated with steroid but this is probably less common, although we do not have very good information on this yet. Of course, if there is bad back pain which is new pain without any reason, an x-ray should be done to rule out vertebral fracture.
Getting those X-rays done may become more challenging as the adolescent/young man will need to be hoisted onto the X-ray bed. If there is curvature of the spine (scoliosis), or if there is already a metal rod in the spine to correct scoliosis, then interpretation of those x-rays for vertebral fractures are much more difficult.
Summary: All DMD boys and men on steroid should have lateral spine imaging to detect vertebral fracture at least every 2 years. For DMD individuals not on steroid, lateral spine imaging should be considered every 3 years.
DXA bone density scan
Annual monitoring with bone density or DXA scans are recommended in DMD. In DMD, DXA bone density results are often low. However, DXA bone density results have not been shown to predict who will develop fractures. Doctors should not routinely start bone protective medicines (bisphosphonates) based on DXA bone density results itself. Spine x-rays can be done in every hospital but not all hospitals have access to a DXA bone density scan. Therefore, it is more important for a lateral spine x-ray to be done than a DXA bone density if there are difficulties accessing DXA. Measuring DXA bone density is, however, very important if bone protective medicines (bisphosphonates) are prescribed. Some hospitals have access to modern DXA scans that can give such excellent quality images that can replace a spine x-ray to detect vertebral fractures.
Summary: Annual DXA bone density scan is recommended. However, if there are difficulties in accessing a DXA bone density scan, a lateral spine x-ray should be prioritised.
Vitamin D monitoring
All DMD boys on steroid should also have vitamin D supplements and should have regular blood test for vitamin D levels once a year. Vitamin D treatment is generally needed for all boys and men with DMD on steroid and generally a higher dose of vitamin D is needed to get blood levels in normal ranges. There are many types of vitamin D preparation- some need to be taken daily, some every 3-6 monthly.
Summary: Vitamin D levels should be checked once a year.
Q: When should a boy with DMD receive bisphosphonate therapy? Some boys are on it and some not. Can you clarify?
A: Bisphosphonates (eg Pamidronate, Zoledronate) are bone strengthening medicines which work by reducing the amount of bone being broken down. It is very effective in elderly women with osteoporosis as a result of the menopause as the underlying bone problem is increased bone breakdown. There have also been a lot of studies of bisphosphonate for osteoporosis in elderly post-menopausal women. There are simply no good quality studies of the effects of preventative treatment with bisphosphonate in DMD. The standards of care do not recommend preventative treatment with bisphosphonates. However, the new standards of care recommends that bisphosphonates should be administered when there are fractures, especially vertebral fractures. This is regardless of whether the person with DMD has back pain or not. As discussed above, vertebral fractures when present suggest that the bones are very weak. So, the identification of vertebral fractures should prompt the discussion of bisphosphonate use, regardless of how low the DXA bone density scan is. Long bone fractures especially if sustained without clear cut injury eg from standing position, or from a chair, should also prompt the consideration of bisphosphonate therapy. Bisphosphonate therapy should be given through a drip usually every 6 monthly, and is very effective in improving bone pain due to fractures, and probably reduces fractures although does not completely stop fractures. Bisphosphonates can be given by tablets but are not very effective especially in growing children. We need good quality trials to help us prevent the first fracture in DMD and trials to study better treatment after the first fracture is identified or sustained.
Summary: Bisphosphonate therapy should be considered in DMD after a fracture, especially vertebral fractures, regardless of presence or absence of back pain and the DXA bone density result.
A: In Glasgow, we have been conducting a series of clinical studies on fractures and osteoporosis in DMD with funding from Muscular Dystrophy UK, Action Duchenne and the Chief Scientist Office in Scotland. Our studies confirm for the first time that vertebral fracture is common and can be present if you do not do a routine lateral spine X-ray. This therefore supports the recommendation of the 2018 DMD standards of care.
We have also been able to utilise high resolution MRI scans to study bone quality and shape in DMD. This can give detailed information on bone health which the DXA bone density scan cannot give. In addition, as MRI of muscle is increasingly used as an outcome measure in DMD clinical trials, we believe that in the future MRI scan may be a comprehensive outcome measure for bone and muscle in DMD.
We are still continuing our research in bone health in DMD. We recognize that there are very little long term outcome studies, especially in adults. We are keen to look into such studies in adults with DMD.
For more information on clinical bone research in DMD conducted by the Glasgow team please visit:
Q: With all these discussions of bone problems and osteoporosis especially in DMD, what research or trials are being done?
A: Fractures are very common in DMD and can be as common as 75%. Fractures can lead to poor outcome including pain and poor quality of life. We need good quality clinical trials to study how we can prevent the first ever fracture in DMD.
I was involved in organizing a European Neuromuscular Centre (ENMC) workshop which gathered experts in the bone field, neuromuscular, patient organization and two adults with DMD to discuss the issue of bone health and how we can develop osteoporosis trials in DMD.
We plan to develop a European /international working group to develop research and trials in the area of bone health and endocrine issues in DMD and other neuromuscular conditions as we recognised that it is understudied and requires a close working relationship with different specialties.
We believe that in DMD, there is a need for a well-designed trial of a bone protective therapy before any fracture is present to study if that medicine can prevent the first ever fracture. There is also a need to study how we improve bone health in adults with DMD. In addition, we feel that there is also a need to compare bisphosphonate therapy with new bone protective medicines in boys with DMD who already have fractures.
For more information on the ENMC workshop on bone protective therapies please visit:
A: There are multiple reasons why bone health is affected in DMD. Whilst there is no doubt that steroids play a large role, the underlying muscle weakness/immobility and muscle inflammation also play a strong role. It is also possible that weak bones are part of DMD independent of muscle weakness. We know that healthy adults who sustain spinal cord injury or astronauts who go into space and therefore do not weight bear, develop osteoporosis. Osteoporosis can already be present in some boys with Duchenne before steroids and in animal models of DMD before significant muscle wasting. Fractures including vertebral fractures can be present in boys with DMD before starting steroids. We do not know enough about the osteoporosis in DMD and hence our approach is to perform clinical studies (funded by Muscular Dystrophy UK, Action Duchenne and Chief Scientist Office Scotland) and also laboratory studies (funded by Muscular Dystrophy UK and the Medical Research Council). There is no doubt that vertebral fractures are commoner in steroid treated DMD people. However, vertebral fractures can still present in people treated with intermittent steroid and those not on steroids. Hence, the new standards of care recommend that lateral spine imaging is also performed in those not on steroids. There are many possible benefits of steroids, and benefits of continuing steroids. There are also many steroid related side effects. It is difficult to give clear cut rules. The decision to stay on steroids for long periods of time needs to be considered on a case by case basis, balancing benefits and side effects. This needs to be carefully discussed with your own doctor.
For further information on pre-clinical studies of bone health in DMD please visit:
Q: Do people with spinal muscular atrophy (SMA) have problems with osteoporosis and vertebral fractures?
A: Whilst not as well known, osteoporosis is also a problem in SMA. New studies suggest that those with more severe forms of SMA have higher frequency of osteoporosis and fractures, including vertebral fractures. The SMA standards of care have not recommended lateral spine imaging to detect vertebral fracture. However, in my opinion this should be performed at least intermittently
Q: I have Charcot Marie Tooth Disease. Back in February I have a tibial plateau fracture from a fall I had. Does Charcot-Marie-Tooth disease affect the strength of our bones? I was told in hospital this was a very bad break to get just from falling from standing height.
A: There have been very few studies on bone health in CMT subjects. Fractures are probably much commoner but more likely as a result of increased risk of falls. However, as far as I am aware, there have been no studies looking carefully at bone health in CMT. Most people with healthy bones tend not to fracture from standing position, however does depend on how you fall. It may be worthwhile asking to have your bone health reviewed.
A: It is important to ensure sufficient calcium in your diet. Vitamin D is also very important- all DMD boys especially those on steroid should take vitamin D supplements. For other conditions, there is a case to take them as well (but please discuss with your doctor) or at least have vitamin D levels monitored. Maintaining as much weight bearing exercise as possible to the limits of your condition is very important as exercise and muscle helps bone development. It is very important for adolescents with DMD to have puberty assessed in adolescence and for testosterone to be discussed if there are no signs of puberty by 14 years. Often adolescents with poor nutrition, chronic ill health may also not go through puberty. It is worth asking your doctor to ensure your adolescent son or daughter’s puberty is checked if you have concerns.
Q: I have Ullrich congenital muscular dystrophy and am 40 and went to my local hospital to discuss my bone health. I want to be as prepared for the impact of the menopause as I can be given that I don’t weight bear more than ten minutes a day. Is there anything I can do now? I am not able to lie flat for a DXA scan so they cannot predict if I’m likely to be a risk for osteoporosis.
A: I think you need to tackle things from a few angles. Take adequate amounts of calcium and would not harm taking a vitamin D supplement. The National Osteoporosis Society has useful information on diet and exercise for people with osteoporosis and you may wish to have a look at their information. Maintaining as much weight bearing as possible is of course useful. There are other ways at looking at bone density other than DXA scans but unfortunately majority only in research setting. Some centres may be able to do DXA scans on the hand but normal values are lacking.
For further information on diet and exercise for bone health:
Q: What can us with muscular dystrophy do to help us maintain maximum bone health? Whilst my joints are now becoming loose in my knees I really do want to keep either side as healthy as they can be. My local physios refuse any form of treatment so it would be extremely valuable to know how we can help ourselves.
A: A good balanced diet, vitamin D supplements and as much weight bearing exercise as possible (depending on your underlying diagnosis and which stage of the condition you are at). Some movement is better than nothing so physio may help to some degree and definitely useful for muscles. Please consult your physio as there may be issues relating to your underlying diagnosis.
Q: Is there a water exercise program that has a positive effect on bones for DMD patients and is hydrotherapy beneficial?
A: Hydrotherapy for bone health in DMD has not been studied. In fact, very little on exercise and physical therapy has been studied in DMD. Hydrotherapy may have benefits for DMD over all. However, exercises to improve bone health needs to be weight bearing in nature. Whilst exercise and maintaining movement in an ambulant boy is useful for bones, it is unlikely that on its own they will be able to prevent the bone loss as a result of the multiple factors that affect bone health in DMD. The benefits and negative effects of hydrotherapy needs to be discussed on a case by case basis, as there are some contraindications to hydrotherapy, like severely reduced heart function (reduced cardiac output) in which case hydrotherapy would not be safe. So it is best to discuss with the therapy team or cardiologist. In DMD boys and all neuromuscular conditions, advice on exercise need to be considered in a case by case basis and discussed with your physio or treating team. Balancing risk benefit is of course very important.
Q: What are the benefits of passive assisted stretches to protect bones and joints for males or females in the 30+ group. Any documented advice to show NHS Physio who refuse to treat muscular dystrophy?
A: Muscle movement and exercise is very important for bone development. Of course, weight bearing exercise is most important in stimulating bone development. It is unclear how much passive stretches will assist in bone development for people with neuromuscular conditions who are not weight bearing. It is however very important to prevent contractures of course. It is possible that some stimulation on the muscle may be sufficient to at least stimulate bone development.
You can pass information about MDUK’s physiotherapy module to any unspecialised physiotherapists.
Information videos on how to perform stretches are available on the Scottish Muscle Network website but please discuss this with your treating team first.
Q: What are the benefits of supplements those with muscular dystrophy e.g. Calcium, folic acid?
A: A healthy diet is very important for bone health. Taking sufficient calcium in the diet is very important for bone health especially in growing children. For most people in the UK, if the person takes dairy products, calcium supplements are usually not needed. However, for DMD boys who take steroids, vitamin D supplementation is recommended. There is a case for people with other neuromuscular conditions who probably do not spend as much time out in the sun to take vitamin D supplementation as well. Sufficient vitamin D helps calcium absorption. Vitamin D is synthesised by being exposed to the sun. In some areas of the UK, like where I live in Glasgow, we do not get much sun any way! Other than vitamin D supplements and calcium supplements (if the person is not able to take dairy products), other food supplements have not been shown to be effective in preventing bone loss in DMD.
Q: We are aware having healthy muscles is also beneficial to good bone health – would taking protein supplement have any positive impact like you have mentioned with calcium?
A: Having a balance diet is very important and the right amount of protein as well. However, it is unclear if having extra protein more than is recommended for daily consumption is beneficial. Protein is important for growth, muscle and bone development. It would be useful to discuss with a dietician if you are concerned about your or your child’s protein intake.
Q: Would taking a supplement like Calcium Ascorbate with vitamins for example be beneficial for bone health for a 27 year old man towards the late stage of DMD or is it only beneficial to someone in the earlier stages?
A: Calcium supplements should not be necessary if you take a dairy based diet like most of us with a westernised diet. Vitamin D would be recommended. High dose of calcium supplements and used over a long period of time can in rare occasions lead to calcium build up in the kidneys which can lead to stones. You will want to make sure you have sufficient fluid in the day. It may be useful to have blood and urine test if you are taking calcium supplements on an on-going basis.
Q: Is there a dose of vitamin d that you would recommend as there are so many strengths around?
A: There are indeed multiple types of vitamin D. This can confuse some people but I guess it is also good to have choice. Boys with DMD on steroids tend to need relatively high doses of vitamin D to maintain a normal blood level of vitamin D, usually at least 1000-2000 international units in a day. You can take medicines daily, or there are now very large dose of vitamin D which you may only need to take about three or six monthly. It is recommended that vitamin D levels in the blood should be greater than 50 nmol/L.
Q: I have recently read a lot on vitamin K2 and how beneficial it is to bone health and osteoporosis, particularly when taking vitamin D and calcium supplements. Good to know your thoughts on this.
A: Vitamin K is very abundant in day to day food. It also has a weak effect on bone development. The impact of vitamin K on bone health is underwhelming, and in the face of the underlying muscle issues in most muscle conditions and steroid treatment in DMD which has a very strong negative effect on bone, vitamin K is unlikely to help. Having a healthy balanced diet would be important.
- Bone and endocrine standards of care in DMD
- ENMC summary of workshop on bone health in DMD
- Exercise advice for adults
- Physiotherapy module
- National Osteoperosis Society: healthy eating for strong bones
- Research: Bone health development in DMD
- Research: Using MRI to monitor changes in bone health in DMD
- Research: Fracture risk in DMD