COMMONWEALTH OF AUSTRALIA Copyright Regulations 1969 WARNING This material has been copied and communicated to you by or on behalf of the University of Sydney pursuant to Part VB of the Copyright Act (The Act). The material in this communication may be subject to copyright under the Act. Any further copying or communication of this material by you may be the subject of copyright protection under the Act. Do not remove this notice.

Dr Kylie Williams

Briefly discuss the aetiology, epidemiology and signs & symptoms of osteoporosis. Describe prevention strategies for osteoporosis. Discuss treatment options for osteoporosis.

A skeletal disorder characterised by compromised bone strength that increases risk of fracture. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis and Therapy, 2001

peak bone mass: by 30 years of age cortical and trabecular bone  menopausal trabecular bone loss  women have 30% less bone mass than men

age  prevalence  with age sex  women to men (4:1) people with osteoporosis  4 / 5 don’t know they have it  3 / 4 with a fracture not treated bone fractures  56% of women and 29% of men  significant morbidity and mortality  spine, hip, wrist fractures most common peak bone mineral density  max. 3 rd decade  genetic, environmental, lifestyle WHO criteria (bone densitometry)  normal: T-score > -1  low bone density:  osteoporosis: < -2.5

gender  ing age caucasian or asian family history small stature low weight early menopause or oophorectomy Non-modifiable

sedentary lifestyle/decreased mobility decreased sun exposure low calcium and/or Vitamin D intake excessive alcohol consumption cigarette smoking predisposing medical factors: hyperparathyroidism, Cushing’s syndrome medications: corticosteroids, thyroxine, anticonvulsants, SSRIs Modifiable Risk Factors

early: pain pain precipitated by usual activities restricted spinal movement loss of height curvature of the spine dowager’s hump

fracture history medical history risk factors indicators of bone turnover bone mineral density scan:  dual x-ray absorptiometry (DXA)

maximise bone mass  calcium / vitamin D  weight bearing exercise avoid or modify risk factors prevent postmenopausal bone loss  calcium / vitamin D  ? HRT bisphosphonates, raloxifene, strontium

prevention & treatment prevents postmenopausal bone loss benefit v risk 1   fractures   breast cancer and cardiovascular events oestrogen + progestogen if intact uterus no longer widely recommended for primary prevention of osteoporosis Hormone Replacement Therapy 1. Women’s Health Initiative Study, JAMA 2002;288:

calcium vitamin D HRT/tibolone bisphosphonates Selective oEstrogen Receptor Modulators densoumab teriparatide strontium ranelate +

mg/day before menopause, mg/day after menopause ideally from diet carbonate or citrate tablets vary in amount of elemental calcium S/Es: gastrointestinal, hypercalcaemia D/Is: calcitriol bisphosphonates iron, tetracyclines, quinolones Calcium

deficiency   Ca ++ absorption and  bone loss  falls cholecalciferol (vit D 3 ) [ergocalciferol (vit D 2 )]  prevention of vitamin D deficiency  may  bone density &  risk of fracture  dose: 200 (5mcg) IU (25mcg) daily Vitamin D

cholesterol (diet) provitamin D (skin) vitamin D 3 (cholecalciferol) 25-hydroxycholecalciferol 1,25-dihydroxycholecalciferol

calcitriol  metabolite of vitamin D 3   bone density & ?  risk of fracture  monitoring of calcium necessary  caution with calcium intake  hypercalcaemia: n & v, constipation, headache, polyuria, thirst, apathy Vitamin D

1 st line agents bind to active bone remodelling sites and inhibit bone resorption:  BMD,  fracture risk alendronate  10mg daily or 70mg weekly risedronate  5mg daily, 35mg weekly or 150mg monthly zoledronic acid  5mg IV yearly Bisphosphonates

poor oral absorption (&  by food, Ca, Fe) S/Es: GI; oesophagitis, oesophageal erosions/ulcers; osteonecrosis of the jaw (ONJ) D/Is: antacids, calcium, iron counselling:  take first thing in the morning  take with a full glass of water  take at least 30 mins before food, drink, other meds  do not lie down for 30 mins therapeutic effects last ~ 5yr after ceasing therapy

selective oestrogen receptor modulator (SERM) 2 nd line agent beneficial effects:   bone density (< oestrogen, bisphosphonates)  improves lipid profile (  LDL)   risk of breast cancer adverse effects:   risk of venous thromboembolism  may aggravate hot flushes 60mg daily Raloxifene

Teriparatide - parathyroid hormone  promotes bone formation  20mcg sc daily  max. 18 months treatment  ADRs:hypercalcaemia, nausea, leg cramps, dizziness New Therapies

Strontium ranelate   bone resorption &  bone formation  2g at bedtime  ADRs:nausea, diarrhoea, headache, dermatitis, eczema;  risk of VTE New Therapies

Denosumab   bone resorption &  bone formation  60mg sc every 6 months  ADRs: skin disorders, infections, pancreatitis, ONJ, hypocalcaemia; long term safety issues? New Therapies

use lowest effective dose of corticosteroid use topical or inhaled preparations when possible maintain adequate calcium intake (diet or supplements) bisphosphonates (prevention & treatment) calcitriol (prevention) modify risk factors eg alcohol, smoking, exercise, calcium

Osteoporosis Australia  Prevent the next fracture: Pharmacist Guide  Calcium, Vitamin D and Osteoporosis: A guide for Pharmacists