CURRENT CHALLENGES IN THE MANAGEMENT OF OSTEOPOROSIS Natalie Horwood PhD MRCP Consultant Rheumatologist CROYDON UNIVERSITY HOSPITAL March 2014
Contents Definitions and Background Clinical need and NICE recommendations Treatments benefits and pitfalls Calcium supplements (risks vs vitamin D alone) Bisphophonates (ONJ / atypical # / Cancer risk) Strontium and risk of CV disorders Donesumab Vertebroplasy Teriparatide Clinical cases
Definitions BMD bone mineral density DEXA dual energy absorptiometry Fragility fracture fall from standing height T score number of SDs below peak bone mass Osteoporosis T score -2.5 SD or less (low bone mass) Osteomalacia poor mineralisation leading to soft bone and low T score (BMD)
Background In England and Wales, it is estimated that: over 2 million women have osteoporosis 180,000 osteoporosis-related fractures occur annually 1 in 3 women over 50 years of age will sustain a vertebral fracture 2 million bed days annually are a result of fractures annual social and hospital care costs 1.8 billion
Clinical need Fragility fractures are the clinically apparent outcome of osteoporosis. In the absence of fracture, osteoporosis is asymptomatic. Hip fractures are associated with increased mortality. 50 70% of vertebral fractures do not come to clinical attention.
NICE clinical guideline 146 (Aug 2012) Osteoporosis: assessing the risk of fragility fracture Targeting risk assessment F >65, M >75 Previous fragility fracture Steroids (>7.5mg 3 months or frequent usage) Falls Family history hip fracture (X 5) Low BMI (<18-20 kg/m²) ETOH (> 4 U / day) Smoking Other causes secondary osteoporosis Rheumatoid Crohns Prolonged Immoblitiy Untreated premature menopause
Technologies Bisphosphonates: Alendronate, risedronate, ibandronate, zolendronate inhibitors of bone resorption and increase BMD by altering osteoclast activation and function. Risks adressed later. Raloxifene (selective oestrogen receptor modulator) SERMs have selective activity as weak oestrogen-receptor agonist or antagonist.protect bone density but risk DVT and hot flushes. Strontium ranelate an element with properties similar to calcium with a dual effect on bone metabolism, increasing formation and decreasing resorption.new cardiovascular restrictions addressed later. Teriparatide (parathyroid hormone) a recombinant fragment of human parathyroid hormone which stimulates new formation of bone. Denosumab. Human monoclonal antibody to RANKL (key mediator of bone resorption).
Calcium supplements (+/- vitamin D) Marginal anti-fracture efficacy (not hip) 1000-1500mg / day Increased kidney stones and GI intolerance (abdominal pain and constipation). Increased risk myocardial infarction and stroke in 5 large RCTs US Preventive Services Task Force recommended against calcium supplements for the primary prevention of fractures in non-institutionalized postmenopausal women [Moyer, 2013) Independent of dietary calcium intake
Primary and secondary prevention: Bisphosphonates Initial treatment offered: alendronate or risedronate Postmenopausal women with confirmed osteoporosis Fracture risk reduction over 3-5 years A DEXA scan may not be required in women aged 75 or over after a fragility fracture Sit upright, take with tap water 30-60 mins before food If severe GI intolerance or compliance problems, intravenous treatment with Zolendronate annually Flu-like symptoms probably a class effect
Atypical femoral fractures (AFFs)on long term bisphosphonate (& denosumab) therapy? Drug holidays; Who, when and how long? Data collected form on-going observation from original pharmecutical studies Accumulate in bone with persistent anti-fracture activity? drug holiday Binding affinity zolendronate>alendronate>ibandronate>risedronate But patients who continued treatment also benefitted up to 10 years use in high risk cases (steroids or multiple #s) Higher risk AFF in osteopenia than osteoporosis not recommended Length of treatment dependent on risk and stability BMD. Duration of holiday until reduction in BMD or fracture Consider raloxifine during holiday (or teriparatide)
Mrs B H 76 years old thigh pain after twisting to get off the toilet 22/11/11 11.30 22/11/11 14.45
History On alendronate since 2008? osteoporosis GP didn t receive DEXA report never had steroids DEXA 2008 T score -1.4 spine and 1.5 hip 2012 T score 0.3 spine and 1.3 hip
Osteonecrosis of the jaw Greater in patients receiving IV bisphosphonates for cancer than oral for osteoporosis or Pagets Dental check up and remedial work completed ideally prior to treatment Good oral hygiene, reduce smoking regular dental check ups
? Avoid if severe GORD or Barrats OSTEOPOROSIS DRUG DOUBLES CANCER RISK 1,150 Hip # related deaths per month in UK MHRH & Green et al, 2010 Oxford risk of oral bisphosphonates and cancer oesophagus, stomach, colon. Small increase in oesophageal Ca if taken > 5years Incidence rate 60-79yrs increases to 0.5 to 1 per 1000 women, 1.5 to 3 per 1000 men Findings not replicated in other studies. UK Commission on Human Medicines evidence not strong enough for definate causal relationship.
Strontium ranelate - Protelos New restricted usage for postmenopausal women adult men Prescribed by physician with experience in osteoporosis management Established, current or past history IHD, PVD, CVD, uncontrolled hypertension should not be treated Assess risk of CVD before starting treatment Monitor risk every 6-12 months
Denosumab for primary & secondary prevention of osteoporosis NICE TA204 October 2010 Postmenopausal women with osteoporosis Subcutaneous injection (Prolia) 60mg every 6 months Human monoclonal antibody to RANKL, a cytokine involved in mediating osteoclast activity For secondary prevention if oral bisphosphonates CI, not tolerated or unable to comply. Severe OP ( T scores below 3.5 plus risk factors) Relatively safe in renal impairment Risk ONJ / atypical # / hypocalcaemia / hypersensitivity
Percutaneous Vertebroplasty & balloon kyphoplasty for osteoporotic vertebral compression fractures (NICE TA 279 April 2013) Severe ongoing pain despite analgesia Recent, unhealed fracture confirmed at level of pain clinically and radiologically Vertebroplasty injecting bone cement to relieve pain / prevent further # Balloon kyphoplasty- baloon inflated to restore height, cement injected +/- metal stent
What next?? CASE 1 Mrs MA 75 years Rheumatoid Arthritis (1984), MGUS Intermittent ETA, MTX 20mg, Prednisolone 2.5-10mg DXA 2002 femoral neck BMD = 0.677 (t= -2.52) Actonel 35mg, ADCAL D3 2008 # NOF left DHS,??? Pathological # (not borne out on bone biopsy) Vertebral crush fracture detected on skeletal survey Failed bisphosphonate therapy
Teriparatide - Forsteo Daily subcutaneous injection 18/12-2years Recombinant fragment of human parathyroid hormone Stimulates bone formation Intolerance or contraindication to bisphophonates / strontium or unsatisfactory response (deterioration in BMD and #) 55-64 yrs T score -4 plus > 2 #s 65 yrs T score -3.5 plus > 2 #s > 65 yrs T score -4 Generally well tolerated, restart bisphosphonate after tratment course
2002 RCP guidelines on gluco-corticoid induced osteoporosis 1% UK population on steroids at any one time Increased fracture risk even <7.5mg, rapid increase after onset treatment Fracture risk above the effect of low BMD (T score -1.5) High risk patients (>65yrs or prev #) should start bone protection along with steroids Reduce ETOH & smoking Encourage impact exercise, dietary calcium and vitamin D
Case 2 Mrs PQ 46 years, very early menopause Tibial fracture skiing, falling onto snow skiing from standing height Non-smoker, little ETOH, no steroids Normal vitamin D Height 145cm Weight 53kg (BMI = 25) DEXA T score -1.5 hip, -2.5 spine Would You Treat???
Case 3 Mrs CH 56 yrs female Psoriatic arthritis, osteoporosis No steroids On alendronate since 2007 DEXA -2.7 spine, -2.5 femur (stable) What would you do?