OSTEOPOROSIS OSTEOPOROSIS

DefinitionsDefinitions CausesCauses InvestigationsInvestigations TreatmentsTreatments Case studiesCase studies

DefinitionsDefinitions

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

Osteopaenia: reduction by 1-2.5 SD.Osteopaenia: reduction by 1-2.5 SD.

T scores in DEXA ScanningT scores in DEXA Scanning

OsteoporosisOsteoporosis

Group work: produce a list of causes for Group work: produce a list of causes for osteoporosisosteoporosis

Causes of osteoporosisCauses of osteoporosis

Age relatedAge related ImmobilityImmobility RARA EndocrineEndocrine NutritionalNutritional GeneticGenetic LifestyleLifestyle IdiopathicIdiopathic IatrogenicIatrogenic

NICE guidelines (2005)NICE guidelines (2005)

Secondary prevention of osteoporotic fragility Secondary prevention of osteoporotic fragility fractures in postmenopausal women who have fractures in postmenopausal women who have sustained a clinically apparent osteoporotic sustained a clinically apparent osteoporotic fracturefracture

Due for review October 2007Due for review October 2007

Bisphosphonates recommendedBisphosphonates recommended Women aged 75 and older without need for DEXA Women aged 75 and older without need for DEXA

scan.scan.

Women aged 65-74 when osteoporosis confirmed by Women aged 65-74 when osteoporosis confirmed by DEXA scan.DEXA scan.

Women under 65 if:Women under 65 if:

have very low BMD (T-score =/< -3SD)have very low BMD (T-score =/< -3SD)oror Confirmed osteoporosis plus one or more risk factors:Confirmed osteoporosis plus one or more risk factors:

Risk factors in women under 65Risk factors in women under 65

BMI<19kg/m2BMI<19kg/m2 family history of hip fracture <75yrfamily history of hip fracture <75yr premature menopausepremature menopause disorders associated with bone lossdisorders associated with bone loss conditions associated with prolonged immobilityconditions associated with prolonged immobility

Available drugsAvailable drugs

Calcium and Vitamin DCalcium and Vitamin D AlendronateAlendronate EtidronateEtidronate RisedronateRisedronate TibiloneTibilone RaloxifeneRaloxifene HRTHRT Strontium ranelateStrontium ranelate CalcitoninCalcitonin Teriparatide (parathyroid hormone)Teriparatide (parathyroid hormone)

HRT and osteoporosisHRT and osteoporosis

33% reduction in vertebral fractures (review 33% reduction in vertebral fractures (review 13 RCTs), and 30% reduction in non vertebral 13 RCTs), and 30% reduction in non vertebral fractures 2001fractures 2001

But beware in >50yrs.But beware in >50yrs. Several non hormonal alternativesSeveral non hormonal alternatives

Vitamin D has a small effect on Vitamin D has a small effect on preventing fallspreventing falls

(HA Bischoff-Ferrari et al. Effect of vitamin D on falls: (HA Bischoff-Ferrari et al. Effect of vitamin D on falls:

a meta-analysis. JAMA 2004 291: 1999-2006).a meta-analysis. JAMA 2004 291: 1999-2006).

37% of people had a fall 37% of people had a fall with control, compared with control, compared with 30% with vitamin with 30% with vitamin D. D.

NNT =14 to prevent one NNT =14 to prevent one fall fall

Numbers needed to treatNumbers needed to treat Alendronate for 3 years in patients with a confirmed vertebral Alendronate for 3 years in patients with a confirmed vertebral

fracture to prevent one hip fracturefracture to prevent one hip fracture NNT = 91NNT = 91 (cost (cost £100,000)£100,000) Prevention of vertebral fracture Prevention of vertebral fracture NNT = 14 NNT = 14 (£18,000)(£18,000)

Risedronate in elderly people with osteoporosis to reduce a hip Risedronate in elderly people with osteoporosis to reduce a hip fracture fracture NNT = 77NNT = 77

Calcium and vitamin D (800iu) for 3 years to prevent one hip Calcium and vitamin D (800iu) for 3 years to prevent one hip fracture in old people in care homes fracture in old people in care homes NNT=20NNT=20 (cost £3,900) (cost £3,900)

How does this compare?How does this compare?

Statin for 5 years in secondary prevention of Statin for 5 years in secondary prevention of MI to prevent further MI or CVA MI to prevent further MI or CVA NNT= 16NNT= 16 (cost £21,000 with atorvastatin)(cost £21,000 with atorvastatin)

Beta blocker and thiazide for 6 years to Beta blocker and thiazide for 6 years to prevent a stroke in people aged 65 to 74 prevent a stroke in people aged 65 to 74 NNT NNT = 45 = 45 (cost £16,000)(cost £16,000)

Drug treatment for hypertension for 5 years in Drug treatment for hypertension for 5 years in the elderly to prevent any cardiovascular event the elderly to prevent any cardiovascular event NNT=18NNT=18

AlendronateAlendronate

Fracture Intervention Trial (FIT)Fracture Intervention Trial (FIT) Postmenopausal womenPostmenopausal women All given calcium and Vitamin DAll given calcium and Vitamin D

Provided protection against vertebral fracture in Provided protection against vertebral fracture in women with osteoporosis but not osteopenia.women with osteoporosis but not osteopenia.

Some benefit for hip and wrist fractures for Some benefit for hip and wrist fractures for women with osteoporosis.women with osteoporosis.

What does this mean?What does this mean?

Significant effects of alendronate were found Significant effects of alendronate were found in women whose bone mineral density was in women whose bone mineral density was more than 2.5 standard deviations below that more than 2.5 standard deviations below that of young white women.of young white women.

i.e. More effective in postmenopausal women i.e. More effective in postmenopausal women with osteoporosis.with osteoporosis.

RisedronateRisedronate

Effective in preventing vertebral, non vertebral Effective in preventing vertebral, non vertebral and hip fractures in women with and hip fractures in women with severesevere osteoporosis.osteoporosis.

Less effective in women with osteoporosis.Less effective in women with osteoporosis. Probably ineffective in women aged 80 and Probably ineffective in women aged 80 and

over.over. No evidence for benefit in postmenopausal No evidence for benefit in postmenopausal

women with normal BMD.women with normal BMD.

Etidronate Etidronate

Studies show mixed effect on preventing Studies show mixed effect on preventing vertebral fractures.vertebral fractures.

Effect seen only in women with severe Effect seen only in women with severe osteoporosis. osteoporosis.

No convincing evidence for use of etidronate No convincing evidence for use of etidronate for prevention of hip fractures.for prevention of hip fractures.

Difficult dosage regimenDifficult dosage regimen

Bisphosphonate administrationBisphosphonate administration

5% absorption if taken perfectly5% absorption if taken perfectly Take with glass of waterTake with glass of water Patient must not drink before or after taking tabletPatient must not drink before or after taking tablet Remain upright for a period after takingRemain upright for a period after taking

50% of people do not comply with instructions50% 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.

RaloxifeneRaloxifene

A selective oestrogen receptor modulator A selective oestrogen receptor modulator (SERM) which inhibits bone resorption.(SERM) which inhibits bone resorption.

Effective in preventing vertebral fractures in Effective in preventing vertebral fractures in women with existing vertebral fracture or women with existing vertebral fracture or severe osteoporosissevere osteoporosis

Not effective in preventing wrist and hip Not effective in preventing wrist and hip fractures.fractures.

Increased risk of thromboembolismIncreased risk of thromboembolism

TibiloneTibilone

Oestrogenic, progestogenic and weak Oestrogenic, progestogenic and weak androgenic effects.androgenic effects.

Increases BMD but effects on fractures is Increases BMD but effects on fractures is unknownunknown

CalcitoninCalcitonin

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.

Teriparatide (Parathyroid hormone)Teriparatide (Parathyroid hormone)

Specialist useSpecialist use Women 65 + with satisfactory response to a Women 65 + with satisfactory response to a

bisphosphonate (or intolerant).bisphosphonate (or intolerant). T score </= -4SDT score </= -4SD Or T score < -3SD plus other risk Or T score < -3SD plus other risk

fracture/fractures (see NICE guide)fracture/fractures (see NICE guide)

Strontium ranelateStrontium ranelate

Strontium incorporates into boneStrontium incorporates into bone Increases bone mineral density by about 8% in spine Increases bone mineral density by about 8% in spine

? 5% hip? 5% hip Evidence for reduction in vertebral and non vertebral Evidence for reduction in vertebral and non vertebral

fractures in post-menopausal women with a vertebral fractures in post-menopausal women with a vertebral fracture.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 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;350:459-68in women with postmenopausal osteoporosis. N Engl J Med 2004;350:459-68

ConclusionConclusion

Calcium and Vitamin D for elderly care home Calcium and Vitamin D for elderly care home residents and people with poor diet/house residents and people with poor diet/house bound.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 treatBe selective about who to treat Ensure patient takes dose properlyEnsure patient takes dose properly HRT?HRT?