May 2012

 Df: A progressive systemic skeletal disorder characterised by a low bone mass and micro- architectural deterioration of bone.  T score of < -2.5 when measuring bone mineral density on DEXA scan (Dual –energy x-ray absorptiometry)  Osteopenia: T score -1 to -2.5.

 Z score- bone strength compared to other people in your own age  T score- compares bone density to that of a 25 year old.  Measures bone mineral density using central hip and/or spine DEXA scanning and is expressed in the number of standard deviations below peak bone mineral density.

 70,000 hip and 120,000 spine and 50,000 wrist # a yr due to osteoporosis. 1  > 1/3 rd of women sustain a # relating to osteoporosis. 2  Costing NHS > 940 M a yr. 2

 Bone remodelling predominates yrs (once longitudinal growth ceases)  Consists of: i. bone dissolution/resorption by osteoclasts + ii. bone formation by osteoblasts  Adults, remodelling cycle is balanced so resorption = bone formation ( days)

 However remodelling can become imbalanced so result in significant bone loss  Age-related bone loss starts in 40’s/50’s as a result of: i) ↑ed bone breakdown by osteoclasts ii) ↓ed bone formation by osteblasts

1. Hormonal.  Late menarche, early menopause, long hx of oligomenorrhoea.  During menopause oestrogen deprivation ↑ed bone resorption, so→ bone loss. 2. Smoking 3. Excessive alcohol intake

4. Lack of weight bearing exercise 5. Vitamin D deficiency 6. Glucocorticoid exposure.  ↓ Ca absorption, ↑ bone resorption, ↓ bone formation, thus → bone loss.

1. < 75 yrs DEXA scan 3 2. Bloods:  FBC, ESR, TSH, U+E’s, bone and LFTs.  Consider checking serum paraproteins /urinary Bence Jones proteins to exclude other causes for # such as:

 Other possible causes of #: 1. Malignancy, 2. Osteomalacia, 3. Hyperparathyroidism 4

 If ≥ 75 yrs + DEXA clinically inappropriate clincial assessment is sufficient for diagnosis. 3

Management Non-pharmacologicalPharmacological

1. Diet.  1000 mg Calcium daily intake for postmenopausal women →24 % reduction in hip #. 5  1000 mg equivalent to 1 pint milk/50 g cheese/50 g sardines/1 pot of yogurt.  Avoid caffeinated products. Evidence inconclusive. 2. Regular exercise. Weight bearing exercise > 30 mins/day ↓# rate. 4

3. Stop smoking. Pre-menopause leads to 25 % ↓# rate postmenopausal 4 4. ↓alcohol consumption to < 21 units/wk male, <14 units/wk women 4

1. osteoporosis, no # 2. osteoporosis, already sustained #

1 st line Alendronate 2 nd line Risedronate and Etidronate 3 rd line Strontium Ranelate 4 th line Denosumab

1 st line alendronate 2 nd line risedronate/etidronate 3 rd line strontium ranelate/raloxifene 4th line teriparatide

 If there are contraindications, intolerances or side effects then the next line of treatment should be tried.  As an adjunct to treatment calcium and vitamin D supplementation should be considered in patients with a diagnosis of osteoporosis.

 Alendronic acid/risedronate/etidronate  MOA: adsorbed onto hydroxyapatite crystals in bone, slowing both their rate of growth + dissolution so ↓ the rate of bone turn over. 6  Poorly absorbed.1-5 % of oral dose actually absorbed. 5

 Special instructions:  To be swallowed whole, with water while sitting or standing on an empty stomach 30 mins before breakfast.  Pt should then stand or sit upraight for at least 30 mins after taking the tablet.  Side effects:  oesophageal reactions- oesophagitis/ulcers/stricture/erosions.

 Alendronic Acid Dose: 6  Men 10 mg daily  Women i. 70 mg OW if postmenopausal, ii. 10 mg daily if corticosteroid induced osteoporosis not on HRT.

 MOA: stimulates bone formation + reduces bone resorption. 6  Special instructions:  Avoid food 2 hrs before and after taking in particular calcium- containing products  Side effects: severe allergic reactions such as drug rash with eosinophilia and systemic symptoms (DRESS). Signs: rash/fever/swollen glands/ ↑ WCC  Dose: 2 g OD.

 MOA: SERM, beneficial effects on bone, but no effect on breast or endometrium.  CI: past VTE, endometrial carcinoma  Dose: 60 mg OD

 MOA: recombinant fragment of parathyroid hormone. Increasing availability of Calcium.  Special instructions- only initiated by specialists experienced in the treatment of osteoporosis.  Dose: 20 mcg OD s/c

 Tx option for the 1 0 prevention of osteoporotic # if the following apply: 1. Postmenopausal women at ↑ ed risk of # 2. Unable to comply with special instructions for administering alendronate/risedronate/etidronate 3. Intolerances or CI to the above 4. Can be used in pts who have a combination of T-score + age and no. of independent clinical risk factors for # (see nxt box)

No of Factors Independent For # Clinical Risk Age (years) Not indicated or older Independent risk factors: 1. Parental history of hip # 2. Alcohol intake ≥ 4 units per day 3. RA

 Which of the following is considered a second line option for the primary prevention of # in postmenopausal women? Select ONE option only. A. Raloxifene B. Adcal D3 + Risedronate C. Teriparatide D. Alendronic acid

 B is the correct answer.  A+C are used in secondary prevention  D is first line for primary prevention

1. Osteoporosis. An Information booklet. Updated May Royal College of Physicians. Clinical Guidelines for the prevention and treatment of osteoporosis NICE guidance Oct /42486.pdf 486/42486.pdf 4. Oxford Handbook of General Practice. P

5. SIGN (Scottish intercollegiate guidelines network) guidelines for osteoporosis. updated BNF Chapter p463. Bisphospahtes and other drugs affecting bone metabolism. 7. Denosumab for the prevention of osteoporotic fractures in fractures in postmenopausal women Nice Guidance, Oct /51329.pdf