bone health in celiac disease · • recognize the mechanisms by which celiac disease can affect...
TRANSCRIPT
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Bone Health in Celiac Disease
Partha S. Sinha MD, PhDOctober 29th, 2017
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No Disclosures
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Objectives• Recognize the mechanisms by which celiac
disease can affect bone health
• Review what diagnostic tests are useful
• Understand the role of nutrition and proper supplementation
• Gain awareness when pharmacologic or other intervention may be needed
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Celiac Disease• Intestinal disorder characterized by auotimmune
reaction to gliadin fraction of gluten
• Associated with human leucoctye antigen (HLA) genes
• Multiple non intestinal manifestations– Type 1 Diabetes– Thyroiditis/Hypothyroidism– Metabolic bone disease
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Prevalance of bone disease in celiac
• Low bone density is more prevalent
Kemppainen, Bone 1999
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Celiac Disease and Fracture Risk
• Fracture risk appears modestly higher
West, Gastroenterology 2003
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Why does celiac disease affect bone?
Image from: Dickey, Scand J Gastroenterol 2011
Vitamin DCalcium
? Inflammation
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Calcium and Bone
• Avg human with ~ 1 kg of calcium
• 99% in bone• Essential for
bone strength
Emkey, Endocrinol Metab Clin N Am 2012
Image from: Poole, PLoS One 2011
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Osteomalacia
• Calcium deficiency can lead to bone demineralization
• A distinct mechanism from osteoporosis
Emkey, Endocrinol Metab Clin N Am 2012
Image from: Jones, J Musculoskel Med 2009
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Calcium Absorption
• Primarily in intestine– duodenum
• Vitamin D has essential role
Khanal, Ann Rev Nutr 2008
Image from:The American Heritage® Medical Dictionary. 2007
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Calcium Homeostasis
Potts, Harrison’s Principles of Internal Medicine 2014
Images from:The American Heritage® Medical Dictionary. 2007
Ca2+
PTHPTH
Vit D
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Calcium Malabsorption in Celiac Disease
• Villous atrophy– less surface area for absorption
• Intestinal Inflammation– Loss of calcium transport proteins
• Impaired Vitamin D absorption– Particularly if fat malabsorbed
Krupa-Kozak, Nutrition 2014
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Celiac Disease Villous Atrophy
Normal
Celiac
Kambol, Clin Trans Gastroenterol, 2014
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Calcium Malabsorption in Celiac Disease
Potts, Harrison’s Principles of Internal Medicine 2014Krupa-Kozak, Nutrition 2014
Ca2+ Vit D
PTH
Ca2+
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Secondary Hyperparathyroidism in Celiac Disease
• Parathyroid gland key regulator of calcium balance
• In response to decreased calcium and vitamin D absorption, parathyroid glands react by removing calcium from bone
Khanal, Ann Rev Nutr 2008Potts, Harrison’s Principles of Internal Medicine 2014
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Calcium Malabsorption in Celiac Disease
Potts, Harrison’s Principles of Internal Medicine 2014Krupa-Kozak, Nutrition 2014
Ca2+ Vit D
PTH
Ca2+
Direct Inflammatory Effects?
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How to assess risk to bone health
• Blood tests• Bone densitometry
• Low impact fractures-this warrants more urgent attention
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Blood Tests• Creatinine (kidney
function)• Calcium• Vitamin D 25 OH• Parathyroid hormone
(PTH)
Imagefrom:mayomedicallaboratories.com
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Serum Calcium Level• Low serum calcium
suggests deficiency• High serum calcium
needs further testing• Normal serum
calcium can be deceptive
Ca2+
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24 Hour Urine Calcium• More accurate
reflection of calcium asborption
• Creatinine should be tested on same sample
Imagefrom:“TheOffice”2010
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Bone Densitometry (BMD)• Surrogate for bone
strength• T score -1 to -2.5
osteopenia• T score < -2.5
osteoporosis• Spine and hip usually
analyzed
Melton, J Bone Miner Res 1992
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When to get a BMD• Consider doing after allowing for some time
to treat the celiac disease and getting adequate calcium and vitamin D
• May do earlier in situations where osteoporosis medication may be needed– Post menopausal– -on glucocorticoids (steroids)– High risk of fracture (type I diabetes, family
history of hip fracture)
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Treating Celiac Bone Disease
• Gluten Free Diet
• Calcium through diet and/or supplement
• Vitamin D
• Osteoporosis medications
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Gluten Free Diet
• Improves BMD in children
• Recommended but may not be enough for the bone loss in adults
Bianchi, Calcif Tissue Int 2002
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Optimizing Calcium Intake
• 1200 mg calcium is RDA
• May be higher requirement in celiac disease
• Feasible to get via diet
Yogurt: 300-450 mg Milk: 250-350 mg
Broccoli 70-100 mg Tofu 300-450 mg
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Calcium Supplements
• Fat Malabsorption (aka steatorrhea)
• Lactose Intolerance
• Diet too difficult
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Calcium Supplements• Calcium carbonate
– TUMS– Caltrate– -more common– Not absorbed when
on heartburn medication
• Calcium Citrate– Citracal
500 mg Calcium Carbonate PIll
400 mg Calcium Citrate PIll
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Assessing Calcium Intake
• Serum calcium (can be deceptive if normal)
• Parathyroid hormone level
• 24 hour urine calcium
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Vitamin D and Bone Health• Integral to calcium
absorption and homeostasis
• May have direct role in bone formation and regneration
Lips, Best Pract Res Clin Endocr Metab 2011
Goltzman, Ann NY Acad Sci 2011
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Vitamin D
• More difficult to get via diet• 400 to 2000 units vitamin D (presuming
limited sun exposure)• May need more if steatorhea/severe GI
symptoms
National Osteoporosis Foundation, 2013 Image from: webmd.com
50000unitsvitaminD
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Assessing Vitamin D Intake
• Replacement guided by serum levels
• Goal level > 30, though 20-30 may be acceptable
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When Osteoporosis Medications are Needed
• If BMD T scores persistently below 2.5
• Fragility fracture
• Post menopausal women
• Glucocorticoid Use– Prednisone, solumedrol
• Other risk factors – Family History– Type I Diabetes
Lee, Yonsei J Med 2011
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Oral Bisphosphonates• Alendronate (Fosamax)
– 70 mg weekly
• Risedronate (Actonel)– 35 mg weekly or 150 mg
monthly
• Ibandronate (Boniva)– 150 mg monthly
Rosen, UptoDate, 2014
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If oral medication not tolerated or severe osteoporosis
• Zoledronate (Reclast)– 5 mg yearly
• Denosumab (Prolia)– 60 mg every 6 months– No adjustment for renal
insufficency
• Teriparatide (Forteo)– 20 mcg SC daily– Only anabolic agent
Rosen, UptoDate, 2014
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Osteoporosis Medications
• Ideally, calcium and vitamin intake should be optimized before starting these medications
– Possible risk of hypocalcemia with more potent medications
Rosen, UptoDate, 2014
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Conclusions
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Celiac Disease Has Significant Impact on Bone Health
Ca2+ Vit D
PTH
Ca2+ INFLAMMATION
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Medical Testing Can Guide Maintenance of Bone Health
• Creatinine (kidney function)• Calcium• Vitamin D 25 OH• Parathyroid hormone (PTH)• 24 hour urine calcium• Bone densitometry
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Diet and supplements can make an impact
• May be higher requirement in celiac disease
• Feasible to get via diet, but pills can be effective if needed
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Osteoporosis Medications May Sometimes Be Warranted
• Ultimate goal is to avoid fractures
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Acknowledgments
Harold Rosen, MDAlan Malabanan, MDHenry Kronenberg, MDMelinda Dennis, MS, RD, LDNNational Celiac Association