1. OSTEOPOROSIS Definitions Definitions Causes Causes Investigations Investigations Treatments Treatments Case studies Case studies

2. Definitions Osteoporosis: reduction in amount of bone per unit volume, without a change in its composition- reduction bone mass >2SD below the mean for young healthy adults Osteoporosis: reduction in amount of bone per unit volume, without a change in its composition- reduction bone mass >2SD below the mean for young healthy adults Osteopaenia: reduction by 1-2.5 SD. Osteopaenia: reduction by 1-2.5 SD.

3. T scores in DEXA Scanning

4. Osteoporosis Group work: produce a list of causes for osteoporosis Group work: produce a list of causes for osteoporosis

5. Causes of osteoporosis Age related Age related Immobility Immobility RA RA Endocrine Endocrine Nutritional Nutritional Genetic Genetic Lifestyle Lifestyle Idiopathic Idiopathic Iatrogenic Iatrogenic

6. NICE guidelines (2005) Secondary prevention of osteoporotic fragility fractures in postmenopausal women who have sustained a clinically apparent osteoporotic fracture Due for review October 2007

7. Bisphosphonates recommended Women aged 75 and older without need for DEXA scan. Women aged 75 and older without need for DEXA scan. Women aged 65-74 when osteoporosis confirmed by DEXA scan. Women aged 65-74 when osteoporosis confirmed by DEXA scan. Women under 65 if: Women under 65 if: have very low BMD (T-score =/< -3SD) have very low BMD (T-score =/< -3SD)or Confirmed osteoporosis plus one or more risk factors: Confirmed osteoporosis plus one or more risk factors:

8. Risk factors in women under 65 BMI<19kg/m2 BMI<19kg/m2 family history of hip fracture <75yr family history of hip fracture <75yr premature menopause premature menopause disorders associated with bone loss disorders associated with bone loss conditions associated with prolonged immobility conditions associated with prolonged immobility

9. Available drugs Calcium and Vitamin D Calcium and Vitamin D Alendronate Alendronate Etidronate Etidronate Risedronate Risedronate Tibilone Tibilone Raloxifene Raloxifene HRT HRT Strontium ranelate Strontium ranelate Calcitonin Calcitonin Teriparatide (parathyroid hormone) Teriparatide (parathyroid hormone)

10. HRT and osteoporosis 33% reduction in vertebral fractures (review 13 RCTs), and 30% reduction in non vertebral fractures 2001 33% reduction in vertebral fractures (review 13 RCTs), and 30% reduction in non vertebral fractures 2001 But beware in >50yrs. But beware in >50yrs. Several non hormonal alternatives Several non hormonal alternatives

11. Vitamin D has a small effect on preventing falls (HA Bischoff-Ferrari et al. Effect of vitamin D on falls: a meta-analysis. JAMA 2004 291: 1999-2006). 37% of people had a fall with control, compared with 30% with vitamin D. 37% of people had a fall with control, compared with 30% with vitamin D. NNT =14 to prevent one fall NNT =14 to prevent one fall

12. Numbers needed to treat Alendronate for 3 years in patients with a confirmed vertebral fracture to prevent one hip fractureNNT = 91 (cost £100,000) Alendronate for 3 years in patients with a confirmed vertebral fracture to prevent one hip fractureNNT = 91 (cost £100,000) Prevention of vertebral fracture NNT = 14 (£18,000) Prevention of vertebral fracture NNT = 14 (£18,000) Risedronate in elderly people with osteoporosis to reduce a hip fracture NNT = 77 Risedronate in elderly people with osteoporosis to reduce a hip fracture NNT = 77 Calcium and vitamin D (800iu) for 3 years to prevent one hip fracture in old people in care homes NNT=20 (cost £3,900) Calcium and vitamin D (800iu) for 3 years to prevent one hip fracture in old people in care homes NNT=20 (cost £3,900)

13. How does this compare? Statin for 5 years in secondary prevention of MI to prevent further MI or CVA NNT= 16 (cost £21,000 with atorvastatin) Statin for 5 years in secondary prevention of MI to prevent further MI or CVA NNT= 16 (cost £21,000 with atorvastatin) Beta blocker and thiazide for 6 years to prevent a stroke in people aged 65 to 74 NNT = 45 (cost £16,000) Beta blocker and thiazide for 6 years to prevent a stroke in people aged 65 to 74 NNT = 45 (cost £16,000) Drug treatment for hypertension for 5 years in the elderly to prevent any cardiovascular event NNT=18 Drug treatment for hypertension for 5 years in the elderly to prevent any cardiovascular event NNT=18

14. Alendronate Fracture Intervention Trial (FIT) Fracture Intervention Trial (FIT) Postmenopausal women Postmenopausal women All given calcium and Vitamin D All given calcium and Vitamin D Provided protection against vertebral fracture in women with osteoporosis but not osteopenia. Provided protection against vertebral fracture in women with osteoporosis but not osteopenia. Some benefit for hip and wrist fractures for women with osteoporosis. Some benefit for hip and wrist fractures for women with osteoporosis.

15. What does this mean? Significant effects of alendronate were found in women whose bone mineral density was more than 2.5 standard deviations below that of young white women. Significant effects of alendronate were found in women whose bone mineral density was more than 2.5 standard deviations below that of young white women. i.e. More effective in postmenopausal women with osteoporosis. i.e. More effective in postmenopausal women with osteoporosis.

16. Risedronate Effective in preventing vertebral, non vertebral and hip fractures in women with severe osteoporosis. Effective in preventing vertebral, non vertebral and hip fractures in women with severe osteoporosis. Less effective in women with osteoporosis. Less effective in women with osteoporosis. Probably ineffective in women aged 80 and over. Probably ineffective in women aged 80 and over. No evidence for benefit in postmenopausal women with normal BMD. No evidence for benefit in postmenopausal women with normal BMD.

17. Etidronate Studies show mixed effect on preventing vertebral fractures. Studies show mixed effect on preventing vertebral fractures. Effect seen only in women with severe osteoporosis. Effect seen only in women with severe osteoporosis. No convincing evidence for use of etidronate for prevention of hip fractures. No convincing evidence for use of etidronate for prevention of hip fractures. Difficult dosage regimen Difficult dosage regimen

18. Bisphosphonate administration 5% absorption if taken perfectly 5% absorption if taken perfectly Take with glass of water Take with glass of water Patient must not drink before or after taking tablet Patient must not drink before or after taking tablet Remain upright for a period after taking Remain upright for a period after taking 50% of people do not comply with instructions 50% of people do not comply with instructions ? Long term compliance over 5 years ? Long term compliance over 5 years Giving as once weekly dose may help. Giving as once weekly dose may help.

19. Raloxifene A selective oestrogen receptor modulator (SERM) which inhibits bone resorption. A selective oestrogen receptor modulator (SERM) which inhibits bone resorption. Effective in preventing vertebral fractures in women with existing vertebral fracture or severe osteoporosis Effective in preventing vertebral fractures in women with existing vertebral fracture or severe osteoporosis Not effective in preventing wrist and hip fractures. Not effective in preventing wrist and hip fractures. Increased risk of thromboembolism Increased risk of thromboembolism

20. Tibilone Oestrogenic, progestogenic and weak androgenic effects. Oestrogenic, progestogenic and weak androgenic effects. Increases BMD but effects on fractures is unknown Increases BMD but effects on fractures is unknown

21. Calcitonin Inhibits osteoclasts and decreases bone Inhibits osteoclasts and decreases bone Has analgesic properties. Has analgesic properties. Useful for pain from bone mets. Useful for pain from bone mets.

22. Teriparatide (Parathyroid hormone) Specialist use Specialist use Women 65 + with satisfactory response to a bisphosphonate (or intolerant). Women 65 + with satisfactory response to a bisphosphonate (or intolerant). T score </= -4SD T score </= -4SD Or T score < -3SD plus other risk fracture/fractures (see NICE guide) Or T score < -3SD plus other risk fracture/fractures (see NICE guide)

23. Strontium ranelate Strontium incorporates into bone Strontium incorporates into bone Increases bone mineral density by about 8% in spine ? 5% hip Increases bone mineral density by about 8% in spine ? 5% hip Evidence for reduction in vertebral and non vertebral fractures in post-menopausal women with a vertebral fracture. Evidence for reduction in vertebral and non vertebral fractures in post-menopausal women with a vertebral fracture. Low ADR profile, mostly nausea and diarrhoea. Low ADR profile, mostly nausea and diarrhoea. Seeman E, Ortolani S, Spector TD, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 2004;350:459-68

24. Conclusion Calcium and Vitamin D for elderly care home residents and people with poor diet/house bound. Calcium and Vitamin D for elderly care home residents and people with poor diet/house bound. Preferred choice of bisphosphonate weekly. Preferred choice of bisphosphonate weekly. Second line choice raloxifene(?) or strontium. Second line choice raloxifene(?) or strontium. Be selective about who to treat Be selective about who to treat Ensure patient takes dose properly Ensure patient takes dose properly HRT? HRT?