Bone health has long been a confusing and often neglected aspect of Duchenne care. There is very little knowledge of underlying bone health in Duchenne, which is further complicated by the possible effects of glucocorticoids on both bone development and bone density/strength.
This lack of research and information has resulted in many questions:
- What is the underlying effect of Duchenne on bone?
- Duchenne itself may cause changes in bone health and density/strength, which worsens with loss of ambulation. There have been a few studies that have demonstrated bone weakness/fractures in steroid naïve patients that worsen with age.
- What impact does glucocorticoid use have on bone development and density/strength?
- There have been a few studies looking at glucocorticoid use in Duchenne and increased fracture rates. Increased fracture rates are a sign of weakened bones. Unfortunately, long bone fractures often result in the loss of ambulation, so knowledge of the impact of glucocorticoids (types of glucocorticoids, doses, regimes, etc.) on bone is a big issue.
- We have no knowledge about how novel Duchenne therapies, including the proposed steroid replacement drugs, might affect bone health. This is an area of needed research.
- How should bone health/density/strength be monitored?
- DEXA scans have been the mainstay of bone health monitoring, but all endocrinologists/centers are not using this technology in the same way. Many providers do not use the DEXA numbers to treat (instead they use fractures and pain); some treat solely using DEXA numbers. No studies have shown that either way is best.
- Are DEXA scans enough, or should x-rays to watch for vertebral compression fractures (VCF) also be used?
- VCF is a strong indicator of bone health/density/strength. VCF are only seen with DEXA if the machine is capable of providing a lateral spine image.
- Most clinicians order spinal x-rays if patients complain of back pain. Because DEXA generally does not pick up VCF and because some VCF’s are asymptomatic (don't cause pain), routine X-rays of the spine looking for fractures have been proposed, even in the absence of back pain.
- How often should these scans be done?
- The Care Considerations recommended baseline DEXA at start of glucocorticoids then repeated every 1-2 years there after. There is no universal protocol for how often spine x-rays should be done in the absence of pain.
- When should bone health medications (bisphosphonates) be started?
- Some centers start bisphosphonates when they start steroids; some watch the DEXA numbers; some wait for fractures and/or pain. There is no agreed upon protocol and no studies to demonstrate that one plan is better than the other.
- Which preparation is better?
- Oral bisphosphonates: alendronate
- Fosomax: take weekly
- Actonel – take weekly
- Atlevia and Atelevia extended release (ER) – take weekly
- Ibandronate: Boniva – take monthly
- IV bisphosphonates:
- Pamidronate: infusion every 3-4 months
- zolendronic acid:
- Reclast - infusion once per year
- Zometa - infusion every 6 mos (pediatrics), annually (adults)
- Both oral and IV increase bone density. Data about VCF and low trauma long bone fracture is inconclusive. IV bisphosphonates may help more with vertebral body height and re-shaping. Very little is known in Duchenne.
- What doses are best?
- Most clinicians start with a high dose bisphosphonates for 2 years (until bone health has stabilized) then move to lower/half doses until adult height is reached, then discontinue. But the effectiveness of this dosing has not been studied.
- How long should bisphosphonates be used?
- Most clinicians agree that bisphosphonates should be discontinued when adult height has been reached. This is difficult to assess in Duchenne, due to growth and pubertal delays with glucocorticoids.
- Some adult clinicians recommend “drug holidays” off bisphosphonates for patients who are stable and have a lower risk of fracture. Adults who are on glucocorticoids continue to be at high risk of fracture. There are no studies around bisphosphonate drug holidays in Duchenne.
- How do we know if the bisphosphonates are working?
- Currently, clinicians are checking to see if pain gets better/goes away, there are no new VCF, energy/mobility/strength improve and DEXA scores improve. These are fairly subjective/inexact measurements.
- Other labs may need to be obtained (Ca, 25-OH Vitamin D); bone turnover markers are not well described in Duchenne and may need further study.
- Are there other agents, other than bisphosphonates, that might be better for bone health in Duchenne?
- Denosumab: targets RANKL, injection, preventing bone reabsorption and increases bone strength
- Forteo: Teriparatide (synthetic parathyroid hormone (PTH), injection, increases bone density and strength
- Anti-sclerostin antibodies: may improve bone mass and reduce long bone fractures
- Odanactib: suppresses CatK, oral, decreasing bone reabsorption and allows for continued new bone formation
- Anti-TGF-antibodies: decreases bone turnover in osteoporosis
These, and many other issues will be addressed in this week’s Bone Health and Osteoporosis meeting in Bethesda, MD.
More than 50 international experts in both pediatric and Duchenne bone health surveillance/monitoring/treatment will gather for 2 days to discuss these, and other important issues.
The goals of this meeting include:
- Reviewing clinical bone health issues and current management guidelines
- Providing recommendations and direction for future research
I am honored to be working with 2 highly esteemed experts in the bone health arena, Lynda Bonewald and Leanne Ward.
- Lynda Bonewald, PhD, is currently the Vice Chancellor for Translational and Clinical Research at the University of Missouri at Kansas City, MO. She has had a long and distinguished career studying the biology of bone, bone repair and bone-muscle interactions. She has served on numerous NIH committees and study sections and currently serves on the NIH NIAMS (National Institute of Arthritis and Musculoskeletal and Skin Diseases) Council. In addition, Lynda has served as a past president of the American Society for Bone and Mineral Research.
- Leanne Ward, MD, is Associate Professor of Pediatrics at the University of Ottawa, Canada, where she is Director of the Pediatric Bone Health Clinical and Research Programs. She has studied and published extensively on pediatric osteoporosis and the effects of chronic illness on the developing skeleton. Dr. Ward has worked with PPMD on past efforts to increase care and knowledge around the endocrine issues of Duchenne and is leading the effort to update the Bone Health section of the updated Care Considerations.
Both of these women are well-respected members of the bone community. We have worked diligently to develop a compelling and robust agenda and convene experts qualified to dive deeply into important topics around Duchenne bone health and osteoporosis.
We are looking forward to an interesting, compelling and productive discussion!
Thank You to Our Partners for Supporting PPMD's Bone Health and Osteoporosis Workshop:
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