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Osteoporosis

Osteoporosis. Catherine Molloy Cons Rheumatologist MD MSc FRCP CCD Sept 2015. A systemic skeletal disease characterised by low bone mass m icroarchitectural deterioration of bone. Osteoporosis (OP). Compromised bone strength. F racture. Whom to suspect? How to diagnose

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Osteoporosis

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  1. Osteoporosis Catherine Molloy Cons Rheumatologist MD MSc FRCP CCD Sept 2015

  2. A systemic skeletal disease characterised by low bone mass microarchitectural deterioration of bone Osteoporosis (OP) Compromised bone strength Fracture

  3. Whom to suspect? • How to diagnose • Lifestyle, Exercise • Medication • Side-effects • When to review

  4. Whom to suspect of OP…?

  5. Mrs M O’S, 55yo Postmenopausal, no fracture history Family history hip # Routine DEXA

  6. Risk factors/history • Postmenopausal • Family history OP • Coeliac, Infl bowel disease, malabsorption • Thyroid, parathyroid disease • Steroid use • Antiepileptic meds

  7. How to diagnose osteoporosis • Presence of a fragility fracture • DEXA • T-score ≤-2.5 only hip and L1-4 (IOS, ISCD, NOS) • Bone biopsy

  8. DEXA Radiation= ambient daily dose Only C/I pregnancy, widespread metalwork WHO 1994 criteria use the T-score for classification into three main groups: 1. Normal BMD: T-score ≥ -1.0 2. Osteopenia: T-score -1.0 to -2.49 3. Osteoporosis: T-score ≤ -2.5 , e.g. -3.5 With prevalent fragility fractures and T-scores <-2.5 ‘severe OP’

  9. FRAX calculator www.shef.ac.uk/FRAX

  10. Screening for secondary causes • FBC, CRP • UE LFT, ferritin • TFT, Ca, PO4, Alk phos, PTH • TTG • SPEP • Testosterone, SHBG • Oestradiol, prog

  11. Management

  12. Osteoporosis therapies • Ca, Vit D • HRT/ Raloxifene • Bisphosphonates • Denosumab (Prolia) • PTH (Forsteo) • Strontium • Compliance • Nature of condition (silent) • Nature of medication, mode of admin

  13. Daily Ca+2 requirements • Adults 1000mg/d • Teens, pregnant 1200mg/d • Breastfeeding 1500mg/d Each of following 250- 300mg: • 1 glass fortified milk • 1 matchbox size of cheese • 1 carton yoghurt

  14. Vitamin D deficiency • Ireland: 74% adults, 88% primary school children have <50% recommended daily intake •  Risk in • elderly • obese • darker skinned • malabsorption incl. coeliac • Hepatic or renal disease

  15. All adults over 50IOF Recommendations, 2013 Universal guidance • Counsel on the risk of osteoporosis and related fractures • Advise on a diet rich in fruits and vegetables, includes adequate amounts of total calcium intake (1,000 mg/d for men 50-70; 1,200 mg/d for women ≥ 51 and men ≥ 71) • Advise on vitamin D intake (800-1,000 IU per day), including supplements if necessary for individuals ≥ 50 • Recommend regular weight-bearing and muscle-strengthening exercise to improve agility, strength, posture and balance and reduce the risk of falls and fractures. • Assess risk factors for falls and offer appropriate modifications (e.g. home safety assessment, balance training exercises, correction of vitamin D insufficiency, avoidance of certain medications and bifocals use when appropriate). • Advise on cessation of tobacco smoking and avoidance of excessive alcohol intake. • Measure height annually, preferably with a wall mounted stadiometer

  16. Exercise • 30 minutes weight-bearing exercise > 3 times a week • Up and down a flight of stairs 10 times is 1/3 daily requirement • Dancing best of all- constant changes of direction and intensity

  17. Pharmacologic Treatment recommendations (IOF) • hip or vertebral # (clinical/asymptomatic) • T-scores < -2.5 at the femoral neck (FN), total hip (TH) or lumbar spine (LS) by DXA, after appropriate evaluation • postmenopausal women and men ≥ 50 with osteopaenia (DXA, FN/TH/LS) and a 10-year hip fracture probability > 3% or a 10-year major osteoporosis-related fracture probability > 20% based on the (Irish-)adapted WHO absolute fracture risk model (FRAX) • Not indefinite After 3-5 year treatment period, reassess

  18. OP drug overview

  19. Inhibitory effect on osteoclasts Decrease bone resorption and risk of # vert and hips Alendronate (Fosamax, Fosavance with 5600IU VitD) Risedronate (Actonel, Actonel plus calcium and D) and SIOP Zoledronic acid (Aclasta)- annual IVI; Pagets and SIOP Ibandronate (Bonviva)- 3mg IV per 3/12 Contraindications: GORD, hiatus hernia, gastritis, impaired renal function, hypocalcaemia, pregnancy Bisphosphonates

  20. Osteonecrosis of jaw (ONJ) • Exposed bone and slow healing • Infection+ trauma + poor healing (+/- immunocompromise) • Chemotherapy > OP doses • Oral hygiene critical • ? Pre therapy dental review • Cave dental implants/ extractions

  21. Atypical femoral fractures (AFFs) • located in the subtrochanteric region and diaphysis of the femur • reported in patients taking BPs and denosumab, also occur with no meds

  22. Risk of AFF • 1000 females treated with BP for 5 years • Prevents 35-50 nonvert, 50-115 vert #= 85-165 typical # • Versus ‘causing’ 5 AFF • Relative risk of patients with AFFs taking BPs is high, but the absolute risk is low, from 3.2 -50 per 100,000 pt-yrs • Duration of treatment: • long‐term use may be associated with higher risk (100 per 100,000 pt‐yrs) • when BPs are stopped, risk of an AFF may decline JBMRes 2014 ASBMR

  23. ONJ and AFF • Increased risk with • Malignancy (disease and higher doses) • Poor oral hygiene • Steroid use • Prolonged BP use (>5-7 years)

  24. Human monoclonal antibody against RANKL which is a member of the TNF superfamily of ligands and receptors inhibits maturation of osteoclasts, reduces bone breakdown 60mg sc every 6 months x 4 Compliance # risk reduction = IV bisphos Denosumab (Prolia)

  25. Denosumab ctd • Increases spine BMD by 9% and hip BMD by 6% • RR for vertebral fracture 0.32 and for hip fracture 0.6 • Potential infectious complications but no significant difference in serious adverse events compared to placebo • Recent reports AFF and ONJ Cummings S, et al "A Phase III Study of the Effects of Denosumab on Vertebral, Nonvertebral, and Hip Fracture in Women With Osteoporosis: Results from the FREEDOM Trial" JBMR 2008; 23: Abstract 1286

  26. Bone-FORMING High-tech prescription 100mcg od sc x 24 months Serum Ca at 1, 3 and 6 months Repeat DEXA at 18-24 months C/I severe renal disease, Ca BF, pregnant, met bone other than OP Parathyroid hormone (teriparatide)

  27. Summary of Drug Therapies • * Data for Alendronate, ** Data for Teriparatide, $ Hip fracture data • $$ Strontium content can account for up to 50% change in BMD

  28. Monitoring patients (IOS) Perform BMD testing 1 to 2 years after initiating therapy to reduce fracture risk and every two years thereafter. More frequent testing may be warranted in certain clinical situations. The interval between repeat BMD screening may be longer for patients without major risk factors and who have an initial T-score in the normal or upper low bone mass range.

  29. Intolerant of meds Questionable compliance After 5years of bisphosphonates Declining T-scores ?? new # When to stop or change therapy..

  30. Conclusion • Prevalent silent disease, suspect everyone! • # = fall + quality + density • Information, Calcium and Vit D, exercise • DEXA • Drug compliance esp BP • ONJ, AFF • Screen for secondary causes • Follow-up essential

  31. Steroid-induced OP (SIOP) treatment guidelines • Lifestyle, etc • Postmenopausal F and M> 50 • treat ALL patients on pred≥ 7.5/d • treat those on pred< 7.5/d, if FRAX 10Y risk major #>10% • Premenopausal F and M <50 • Only if # history • Males, non-childbearing F if ≥ 5mg/d • Childbearing F ≥ 7.5/d • ZART (Zol, alend, rised, teriparatide) ACR criteria Grossmann, 2010

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