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Bone Health in PSC John J. Wysolmerski, M.D.

This article discusses the normal bone biology, osteoporosis, how primary sclerosing cholangitis (PSC) affects the skeleton, and provides tips on maintaining bone health in PSC.

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Bone Health in PSC John J. Wysolmerski, M.D.

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  1. Bone Health in PSC John J. Wysolmerski, M.D.

  2. Outline Normal Bone Biology Review of Osteoporosis How Does PSC Affect the Skeleton? How to Maintain Bone Health in PSC

  3. Trabecular bone Cortical bone

  4. Cortex Periosteum Trabecular Bone Endosteum

  5. Lamellar Bone Osteocyte lacuna

  6. Hydroxyapatatite crystals Collagen Type I Non-Collagenous Proteins

  7. Hydroxyapatite [Ca10 (PO4)6 (OH)2]

  8. Bone Structure Biomechanics • Collagen provides the cables – tensile strength and flexibility • Mineral (Ca & Phos as hydroxyapatite) fills in between the cables to provide rigidity and compressive strength required for posture and muscle action

  9. Bone Cells

  10. The Osteoclast and Bone resorption Ruffled border Sealing zone = Adhesion

  11. Enz H+ Cl- Seal Seal Bone Resorption Calcium, Phosphate, Collagen Fragments Bone

  12. Osteoblast Lineage Bone forming surface Osteoblasts Osteoid tissue Adipocytes Marrow space

  13. Osteoblasts Osteoid Osteoblast

  14. Bone Remodeling Andersen TL et al. AJP 2013

  15. Definition of Osteoporosis Loss of Bone Mass Deterioration of Bone Microarchitecture Fragility Fractures

  16. Vertebral Fractures

  17. Osteoporosis Epidemiology • Common - 50% of women and 20% of men over age 50 will have an osteoporotic fx of some type. • Dangerous - 10-20% excess mortality in 1st year following a hip fracture. • Costly - $20 billion US, $30 billion EU, $130 billion worldwide

  18. The pathogenesis of osteoporosis involves an imbalance in the bone remodeling cycle such that resorption outstrips formation.

  19. Imbalance in Bone Turnover Leads to bone Loss

  20. Measurement of BMD by DEXA has become The gold standard for estimating bone mass

  21. Diagnostic Categories by T-Score National Osteoporosis Foundation & World Health Organization* (T-score) Normal -1.0 and above Osteopenia < -1.0 to > -2.5 Osteoporosis -2.5 and below Severe Osteoporosis -2.5 and below w/fracture

  22. How Does PSC Affect the Skeleton?

  23. How Common is Bone Loss in PSC? • Mayo Clinic, 237 patients: 15% osteoporosis; 41% osteopenia • UPENN, 30 patients: 3% osteoporosis; 30% osteopenia • Mayo Clinic Study, 204 patients prior to liver transplant: 32% osteoporosis; 44% with osteopenia • German Study, 104 patients (PBC and PSC) prior to liver transplant: 24% osteoporosis

  24. Fractures • Polish Study – 18% of patients had fractures • Mayo Clinic Study - 16% of patients at time of liver transplant had fractures • German Study – 13% of patients at time of liver transplant had fractures

  25. Who Gets Osteoporosis? Other studies also suggest severity of liver disease and post-menopausal women at increased risk Angulo et al, Gastroenterology 140:180, 2011

  26. Progression of Bone Loss Lost bone at rate of 1% per year over 8 years Angulo et al, Gastroenterology 140:180, 2011

  27. Bone Loss and Recovery after Liver Transplantation

  28. Fractures After Liver Transplantation 20-45% Risk of Vertebral Fractures After Transplantation Risk predicted by pre-transplant osteoporosis and/or prior fx. Leidig-Bruckner et al, Lancet 357:342, 2001

  29. Mechanisms of Bone Loss in PSC X X Decreased Bone Formation Bilirubin Glucocorticoids Immobility Malnutrition/Low BMI Vitamin D deficiency Increased Bone Resorption Low Estrogen/Testosterone Inflammation – IBD Immobility ? Tacrolimus/cyclosporin Calcium Deficiency/Increased PTH

  30. Age and BMD interact to increase the risk for fracture 10 year risk of fracture in Swedish women

  31. How to Maintain Bone Health in PSC

  32. Therapy Goals (Prevent Fractures) • Diagnose patients at risk for fractures • Prevent Progressive Bone Loss • Prevent Increased Bone Loss/Fractures after Transplantation

  33. Diagnosis and Follow Up • DEXA bone density at Dx • Repeat DEXA every 1-2 years if baseline BMD < -1.5 to -2.0 • Repeat DEXA every 3-5 years if baseline BMD>-1.5 • DEXA pre-transplant and 3, 6 and 12 mos after transplant followed by yearly for 5 years

  34. General Therapy • Exercise and weight/resistance training for muscle preservation and balance • Calcium 1,000 – 1,500 mg per day • Vitamin D – 1,000 units per day • Nutrition - maintain body weight • Avoid Glucocorticoids if possible • Fall Prevention

  35. Drug Therapy • Estrogen or Testosterone Replacement if hypogonadal • Bisphosphonates • Alendronate (Fosamax), Residronate (Actonel), Zoladronic Acid (Reclast) • Zoledronic Acid at Transplant if prior fractures or T score < -2.0 • PTH (Forteo) - ? • Denosumab (Prolia) - ?

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