Title: Calcium and Bone Metabolism: Implications for EB
1Calcium and Bone MetabolismImplications for EB
- Anna L. Bruckner, MD
- Stanford University School of Medicine
2Overview
- What leads to strong bones in normal individuals?
- What is known about bone health in EB?
- Why are bones at risk in EB?
- What can we do about it?
3Bones are like a bank
- Deposits into the savings account of bone
density are made in childhood, adolescence, and
early adulthood - Withdrawals are made after middle age
- Building an adequate reserve by early adulthood
is critical
4Changes in bone mass over time
Davies JH et al. Arch Dis Child 200590373-378.
5Goals of bone health
- An ounce of prevention is worth a pound of cure
- Optimize gains in bone mass
- Minimize losses
- Prevent fractures
6Bone health the players
- Heredity
- Many gene polymorphisms can affect bone mass
- Nutrition
- Physical activity
- Hormonal factors
- Modifiable factors
7Nutrition Adequate calories
- Nutritional inadequacy predisposes to osteopenia
- Adolescents with anorexia nervosa
- Overweight children also likely to have reduced
bone mineral density and increased fracture risk
8NutritionCalcium
- Contributes to accruing bone mass
- Anabolic effect on growing skeleton
- Helps prevent subsequent bone loss
9Recommended Calcium Intake
- Age (years)
- 1-3
- 4-8
- 9-18
- 19-50
- 51
- TOO Much
-
- Milligrams / day
- 500
- 800
- 1300
- 1000
- 1200
- gt2500
National Academy of Science, 1997
10Sources of calcium
- Milk / dairy products
- Calcium fortified orange juice
- Tofu / soy milk
- Beans
- Dark green leafy vegetables
- Calcium supplements
11Have a Coke and a fracture?
- Soft drink consumption associated with fractures
in girls - Due to displacement of milk from diet
12Nutrition Vitamin D
- Necessary for bone mineralization
- Primary source is skin
- Vitamin D precursors added to milk (in U.S.)
- Serum 25 OH-Vit D reflects stores
13Vitamin D Supplementation
- 200 I.U. recommended daily for
- Infants taking lt 500 ml/d vitamin D-fortified
milk or formula - Children adolescents who
- Do not get regular sun exposure
- Consume lt500 ml/d vitamin-D fortified milk
- Gartner LM and Greer FR. Pediatrics 2003111
908-910.
14Physical activity
- Weight-bearing activity is necessary to maintain
and increase bone mass - Immobility leads to bone loss
15Mechanostat theory
Bachrach LK. Trends Endocrinol Metab 20011222-8.
16Hormonal status
- Adequate thyroid hormone, growth hormone, IGFs,
sex steroids needed - GH acts on bones via IGF-1
- Anabolic effects of sex hormones
- Estrogen modulates bone remodeling
17Bones and EB
- Bones appear thin on plain films
- Wong WL and Pemberton J. Br J Radiol 1992
Jun65480-4. - One reported case of 25-yr-old with RDEB and
osteoporosis treated with calcium and vit D - Kawaguchi M et al. Br J Dermatol 1999141934.
18Bones and EB, cont.
- Study of 7 patients with RDEB, JEB-nH
- 3-8 years old
- Variables
- Nutritional intake
- Physical activity
- Height, BMI
- Bone mineral density
- Biochemical markers (e.g. 25 OH-Vit D)
Reyes ML et al. J Pediatr 2002140467-9.
19Results
- Caloric, calcium intake normal
- Moderate limitation on activity in 4 severe in 2
- Decreased bone mineral density (BMD) in 3
- Reyes ML et al. J Pediatr 2002140467-9.
Patients with lowest BMD had low 25-OH Vit D
levels and severe limitations on activity
20How EB impacts bones
- Nutritional adequacy
- Increased caloric needs
- Malnutrition / undernutrition
- Restricted intake
- Decreased absorption
- Undernutrition affects hormone levels reduced
IGF-1 expression, GH resistance, hypogonadism
21How EB impacts bones, cont.
- Calcium
- Adequate amount needed for EB patients unclear
22How EB impacts bones, cont.
- Vitamin D
- Less skin exposure to sunlight due to extensive
bandaging, limited outdoor exposure - Caloric supplements may not be Vit D fortified
23How EB impacts bones, cont.
- Inactivity
- Pain from blistering and joint contractures
limits weight-bearing activities
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25How EB impacts bones, cont.
- Does the chronic inflammation associated with
wound healing impact bone mineralization? - Certain medications (e.g. corticosteroids)
negatively affect bone density
26Changes in bone mass over time
27Optimizing bone health in EB
- Ensure adequate caloric intake
- Closely follow height and weight
- Ensure adequate intake of calcium
- Discourage soft drinks
- Vitamin D supplementation
28Optimizing bone health in EB
- Encourage weight-bearing activity
- Adequate padding of feet to minimize blistering
- Physical therapy to maintain joint mobility
- Are there other ways to optimize bone loading in
a way that is not traumatic to the skin?
29Measuring bone density
- Dual-energy x-ray absorptiometry (DXA) preferred
method
30DXA
- Few practice guidelines for pediatric patients
- Use clinical judgment based on disease severity
and other risks - Indications
- Bone pain
- Fracture after minimal trauma / recurrent
low-impact fractures - Osteopenia on plain films
31DXA, cont.
- Pediatric pitfalls in interpreting report
- Z scores (not T scores) are needed for patients
lt 20 years old - No standardized norms for pediatric BMD
- BMD based on pubertal stage or bone age may be
more appropriate
32DXA, cont.
- How will we use BMD information in practice?
- Low BMD ? osteoporosis
- Osteoporosis low BMD, bone deterioration,
increased fracture risk - Fracture threshold in pediatric (and EB) patients
unclear
33Bisphosphonates
- No published data on use in EB
- Pediatric bone experts recommend them for
- Osteogenesis imperfecta
- Children with fragility fractures
- Randomized controlled trials
- NOT low bone density alone
34In closing
- Need more studies about bone health in EB
patients - Need to determine optimal approach to preventing
and treating low BMD in EB
35Acknowledgment
- Laura Bachrach, MD, Professor of Pediatrics,
Division of Pediatric Endocrinology, Stanford
University School of Medicine
36References
- Bachrach LK. Trends Endocrinol Metab
20011222-8. - Bachrach LK. Endocrinol Metab Clin N Am
200534521-35. - Davies JH et al. Arch Dis Child 200590373-8.
- Gartner LM and Greer FR. Pediatrics 2003111
908-910. - Kawaguchi M et al. Br J Dermatol 1999141934.
- Lanou AJ et al. Pediatrics 2005115736-43.
- Reyes ML et al. J Pediatr 2002140467-9.
- Wong WL and Pemberton J. Br J Radiol
199265480-4. - Zacharin M. Curr Opin Pediatr 200416545-51.