Bone health in Duchenne muscular dystrophy. Hugo Sampaio
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1 Bone health in Duchenne muscular dystrophy Hugo Sampaio
2 Never mind the bones this is a MUSCULAR DYSTROPHY!! Fractures can be catastrophic Lead to significant pain May require surgery Happy bones Long life!
3 Scenario 1 9 year old boy DMD Steroid usage for 4 years Documented Vitamin D deficiency, taking supplementation daily
4 Scenario 1 Described immediate back pain after bring knocked onto his bottom by a wave in the surf Pain settled with some massage and pannadol but came and went thereafter Most noticeable when riding over bumpy surfaces in his wheelchair Led to significant discomfort
5
6 Questions Why this type of fracture? Why now? Why didn t Vitamin D prevent this? What is the treatment?
7 Scenario 2 6 year old boy DMD Not on steroid treatment Fell off his scooter onto an outstretched right hand
8
9 Further investigations Profoundly Vitamin D deficient Bone mineral density significantly below normal for age
10 Further investigations
11 Questions Is this a pathologic fracture? What is the treatment? What can be done to prevent this happening again?
12 Osteopenic bone
13 Risk factors Reduced weight-bearing activity and mobility Steroid therapy Delayed puberty Vitamin D deficiency Reduced sun exposure - Osteopenic bone Management Calcium and vitamin D Sunshine! Physical activity Bisphosphonate therapy +
14 Risk factors - Steroid therapy Incontrovertible evidence Change bone physiology Leading cause of secondary osteoporosis Problem compounded in DMD because of long duration of therapy - Osteopenic bone
15 Risk factors Vitamin D deficiency Aids absorption of calcium from the gut Source Oral (diet and supplements) Steroids may impair absorption Made in the skin from cholesterol Sun exposure required Good evidence to suggest increased fracture risk in both able bodied and disabled - Osteopenic bone
16 The SCH experience High rate of vitamin D deficiency Lots of fractures, most concerning was the number of vertebral compression fractures 2013 audit of how we re doing Reviewed the number of fractures and vitamin D status of 48 DMD patients in the clinic (current and recent past)
17 Fractures in DMD 43% 1 fracture; 43% of these multiple fractures Long bone fractures at significantly younger age Fracture in overweight or obese patients (86% vs 14%, P<0.05) 48% vertebral (age 13) 14% both 38% long bone (age 11)*
18 Probability of fracture over disease course Age at Age loss at of ambulation Age loss at of loss ambulation of ambulation ± 1SD ± 1SD ± 1SD Mean Mean age at loss of Mean age at age loss at loss of of ambulation ambulation (11.8 (11.8 years) ambulation (11.8 years) years)
19
20 Fracture probability according to type of fracture 100% of vertebral fractures in CS patients Latency to vertebral fracture 6.6 ± 1.2 years
21 Vitamin D deficiency 84% history of vitamin D deficiency 35% current deficiency Mean 25-OHD 54.3 nmol/l 38% deficient despite chronic vitamin D supplementation
22 In summary Bone health remains a substantial concern in DMD 43% of DMD patients fractured at least once 5 times higher than non DMD Loss of ambulation fracture Supplementation was effective in increasing and maintaining vitamin D levels, but not invariably
23 What to do hope on the horizon New synthetic corticosteroids Vitamin D replacement Induction of puberty Bisphosphonate treatments
24 Broken down Built up
25 Broken down Built up OSTEOPOROSIS
26 BISPHOSPHONATES Broken down Built up OSTEOPOROSIS
27 Adult recommendations Systematic review concluded that bisphosphonates were effective at reversing bone loss associated with long term steroid use Especially effective at improving vertebral bone density and consequently reducing pain associated with fractures in this region Cautions: Long tern effects unkown Mechanism of bone loss is different to primary osteoporosis Treatment not without side effects Transient flu like illness Osteonecrosis of the jaw, particularly in those with dental caries
28 Paediatrics No systematic review or consensus guidelines Not standard practice in the absence of a known fracture DMD represents a special group however because fractures in this group potentially catastrophic Current guideline recommends use in presence of known fracture Current multicentre study RCH, CHW, PMH, SCH comparing standard treatment vs early bisphosphonate treatment
29 Questions: Scenario 1, vertebral compression fracture Why this type of fracture? Well described complication of steroid treatment Why now? Expected timing in those on long term steroid treatment Why didn t Vitamin D prevent this? Ensuring vitamin D is adequate is only part of the treatment What is the treatment? Bisphosphonates effective at improving bone density and reducing pain associated with this type of fracture
30 Questions: Scenario 2, long bone fracture Is this a pathologic fracture? Yes Minor fall Bone density low What is the treatment? Standard treatment What can be done to prevent this happening again? Replace vitamin D (+sunlight!) Consider bisphosphonates in face of low bone density
31 Thank you
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