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Current Trend in Osteoporosis Management for Elderly in HK-

Medical Perspective

Dr Dicky T.K. ChoyPhysician

Jockey Club Centre for Osteoporosis Care and Control, CUHK

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Osteoporosis

• Global public health problem• It is an intermediate outcome for fractures

and is a risk factor for fracture just as HT is for stroke

• ** The majority of fractures, however, occur in patients with low bone mass rather than osteoporosis

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A systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture.

Old Definition of Osteoporosis

Conference Report from the Consensus Development Conference:Am J Med 94: 646-650, 1993 4

Normal bone Osteoporosis

Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Bone strength primarily reflects the integration of bone density and bone quality.

Current Definition of Osteoporosis

NIH Consensus Development Panel on Osteoporosis JAMA 285:785-95; 2001

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Pathophysiology

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A diagram of a cutting cone with osteoclasts resorbingbone followed by osteoblasts depositing new osteoid,

which subsequently becomes calcified

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Bone remodeling

• Bone loss occurs when this balance is altered, resulting in greater bone removal than replacement

• This imbalance occurs with menopause and advancing age.

Vertebral FractureVertebral FractureVertebral Fracture

Hip FractureHip FractureHip Fracture

Colles FractureCollesColles FractureFracture

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Epidemiology

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3%3%5%5%6%6%13%13%MenMen

16%16%16%16%18%18%40%40%WomenWomen

forearmforearmSpine Spine HipHipAllAll

((Melton, 1992)Melton, 1992)

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Men(1.8 million)

Asia Asia 51%51%

Hip fracture for men and Hip fracture for men and women in 2050women in 2050

Asia Asia 54%54%

EuropeEurope11%11%Others Others

8%8% Latin Latin AmericaAmerica

6%6%

North North AmericaAmerica

13%13%

Women(4.5 million)

Middle Middle EastEast8%8%

EuropeEurope12%12%Others Others

6%6% Latin Latin AmericaAmerica

12%12%

North North AmericaAmerica

12%12%

Middle Middle EastEast6%6% 12

0

100

200

300

400

500

600

Adj

uste

d R

ates

(100

,000

)

US (White) Hong Kong Singapore Thailand Malaysia

535459 442

269218

Age-adjusted incidence rates in women

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0

50

100

150

200

Adj

uste

d R

ates

(100

,000

)

US (White) Hong Kong Singapore Thailand Malaysia

187 180164

11488

Age-adjusted incidence rates in men

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Age specific incidence rates for hip, vertebral, and Age specific incidence rates for hip, vertebral, and distal forearm fractures in men and womendistal forearm fractures in men and women

0

1000

2000

3000

4000Men Women

Inci

denc

e/10

0,00

0 pe

rson

-yr

35-39 ≥85 ≥85

Age group, yr

Hip

Vertebral

Colles’

Hip

Vertebral

Colles’

15

0

500

1000

1500

2000

2500

Per 1

00,0

00

50-59 60-69 70-79 80+Age

1966

1985

1995

Incidence of hip fracture in Hong Kong women

16

0

400

800

1200

Per 1

00,0

00

50-59 60-69 70-79 80+Age

1966

1985

1995

Incidence of hip fracture in Hong Kong men

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Direct cost for osteoporotic fractures

1.1 billion

2.7 billion

Men

2.9 billionHong Kong (hip fracture)

11.1 billionUSA

Women

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Mortality and morbidity due to hip fracture is high

• 10-20% excess mortality within 1 year

• Up to 25% remain in long term nursing home care

• Only 40% fully regain their pre fracture level of independence

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Mortality and morbidity due to vertebral fracture is also high

• Significant complications including back pain, height loss and kyphosis

• Limited activity including bending and reaching

• May result in restrictive lung disease if multiple thoracic fractures

• Lumbar fracture may alter abdominal anatomy

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Approach to the Diagnosis and Management

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Comprehensive approach

• Detailed history (clinical risk factors assessment including fall risk assessment )

• Bone mineral density (BMD) assessment• Establish fracture risk using WHO 10-year

estimated fracture probability

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Risk factors included in the WHO 10-year Fracture Risk Assessment Model

• Age• Gender• Personal history of fracture• Parental history of hip fracture• Low body mass index (BMI)• Use of oral glucocorticoid• Secondary osteoporosis (e.g RA )• Current smoking• Alcohol intake 3 or more drinks/day• Femoral neck BMD

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Risk Factors for Falls

1. Environmental2. Medical3. Neuromuscular4. Fear of falling

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Environmental

• Low level lighting• Obstacles in the walking path• Lack of assist devices in bathrooms• Slippery outdoor conditions

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Medical• Age• Arrthymias• Poor vision• Urgent urinary incontinence• Previous fall• Orthostatic hypotension• Medications ( narcotic analgesics, anticonvulsants,

psychotropics )• Depression• Anxiety and agitation• Vit D def• Malnutrition

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Neuromuscular

• Poor balance• Weak muscles• Kyphosis• Reduced proprioception

WHO definition of osteoporosisWHO definition of osteoporosis

NormalBelow the mean peak adult

<1SDAt -1.0 and above

BMDT score

OsteopeniaBelow the mean peak adult

1-2.5SDBetween -1 and -2.5

BMDT score

OsteoporosisBelow the mean peak adult

>2.5SDat or below -2.5

BMDT score

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WHO Definition

• Although these definition are necessary to establish the presence of osteoporosis, they should not be used as sole determinant of treatment decisions

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Bone Densitometry

• Dual x-ray absorptiometry (DXA)

• Quantitative computed tomography (QCT) –

mainly use in research field

• Quantitative ultrasound

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Dual x-ray absorptiometry(DXA)

• Measure the BMD of lumbar spine ( L1-L4)

and the hip ( femoral neck and total hip )

• Diagnosis based on T-score ( WHO

definition of osteoporosis )

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Quantitative Ultrasound (QUS )

Quantitative Ultrasound (QUS )

• Can only used on peripheral bones e.g heel

• Advantages of small size, relatively quick

and simple measurements, and no radiation

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Indications for BMD testing( NOF recommendation )

• Women > 65 and men > 70, regardless of clinical risk factors

• Younger postmenopausal women and men age 50-70 about whom you have concern based on their clinical risk factor profile

• Women in the menopausal transition if there is a specific risk factor associated with increased fracture risk such as low body weight, prior low trauma fracture, or high risk medication

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Indications for BMD testing( NOF recommendation )

• Adults with a condition (e.g RA ) or taking a medication (e.g, steroid >5mg/day for > 3months) associated with low bone mass or bone loss

• Anyone being considered for pharmacologic therapy for osteoporosis

• Anyone being treated for osteoporosis, to monitor treatment effect

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Management

***Multidisciplinary approach

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Universial Recommendations

1. Adequate intake of calcium and Vit D2. Regular weight bearing exercise3. Fall prevention4. Avoidance of tobacco use and excessive

alcohol intake

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Adequate intake of calcium and vitamin D

• Lifelong adequate calcium intake is necessary for the acquisition of peak bone mass and subsequent maintenance of bone health

• NOF recommend 1200mg for women age over 50

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Adequate intake of calcium and vitamin D

• Vitamin D plays a major role in calcium absorption, bone health, muscle performance, balance, and risk of falling

• NOF recommends an intake of 800 to 1000 IU of vitamin D3 ( cholecalciferol ) per day for adults over age 50

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Drug Treatment

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Who Should Be Treated???

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NOF Guideline

Postmenopausal women and men age 50 and older presenting with the following should be treated :

• A hip or vertebral fracture• Other prior fracture and low bone mass• T score <2.5 at the femoral neck, total hip

or lumbar spine after appropriate evaluation to exclude secondary causes

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NOF Guideline

• Low bone mass with secondary causes associated with high risk of fracture ( such as steroid use or total immobilization )

• Low bone mass and 10-yr probability of hip fracture >3% or a 10-yr probability of any major osteoporosis related fracture >20% based on the WHO model

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Antiresorptive agents

Bisphosphonates- Alendronate- Risedronate- Ibandronate ( oral and IV )- Zoledronate (IV)Selective Estrogen Receptor Modulators (SERM)

- RaloxifeneStrontium * ( dual action )CalcitoninHRT

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Anabolic agent

• PTH 1-34 ( Parathyroid hormone )

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Bisphosphonate

• Inhibitors of osteoclast activity• Strong affinity for calcium ions and are

rapidly taken up by bone• Long skeletal half life• ??? Long term side effects – over

suppressed bone turnover

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Alendronate ( Fosamax )

• 70mg oral weekly• New formulation ( fosamax plus ) had

vitamin D3 2800/5600IU• Reduce vertebral fracture by 48% over 3

years in patient w/o prior vertebral fracture• Reduce the incidence of vertebral and non-

vertebral fracture by around 50% in patient with prior vertebral fracture

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Ibandronate ( Bonviva )

• 150mg oral once a month• 3mg every 3 months by IV injection• Reduces the incidence of vertebral fracture

by about 50% over 3 years

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Risedronate ( Actonel )

• 35 mg oral weekly• Reduces the incidence of vertebral fracture

by 41-49% and non-vertebral fracture by 36% over 3 years

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Zoledronate ( Aclasta )

• 5mg by IV infusion over at least 15 minsonce yearly

• Reduces the incidence of vertebral fracture by 70%, hip fracture 41% and non-vertebral fracture by 25% over 3 years

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Side effects of Bisphosphonates

• Similar for all oral bisphosphonates which include GI problems such as dyspepsia, nausea, pain in the bones, muscles and joints. ( need to be taken on an empty stomach, 1st thing in the morning with plenty of plain water, at least 30-60 minsbefore eating or drinking, remain upright during this interval as well )

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Side effects of Bisphosphonates

• Osteonecrosis of the jaw have been reported (very rare in osteoporosis cases)- usually seen in oncology cases with high dose IV bisphosphonate

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Drug Interactions with bisphosphonate

• No clinical significant interactions with most common medications

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SERM(Selective Estrogen Receptor Modulator)

• Raloxifene ( Evista )• 60mg oral daily• Reduces the risk of vertebral fracture by 55% in

patients with prior fracture, 30% in patients w/o prior fracture over 3 years

• Reduces the risk of breast cancer• Increase risk of DVT• Increase hot flashes

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Effect of Raloxifene on All Breast Cancer IncidenceMORE Trial - 4 Years

Years since Randomization

Total Cases = 77Arrow denotes annual mammogram (*optional)

Adapted from Cauley J et al. Breast Cancer Res Treatment 65:125-34, 2001

0.0

2.0

1.0

1.5

0.5

% o

f Ran

dom

ized

Pat

ient

s

0 1 2 3 4

RR = 0.38 (95% CI = 0.24-0.58)NNT = 94

62%

*

RLX (pooled)

Placebo

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Strontium Ranelate ( Protos )

• Both anti-resorptive and anabolic effects• 1 sachet ( 2 g ) daily to be taken at bedtime• Reduces vertebral fracture risk by 41% in 3

years, non-vertebral fracture risk by 16%• Side effects of nausea, diarrhea, headache, skin

irritation• Risk of DVT may be increased

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Calcitonin

• Salmon calcitonin• Single daily intranasal spray / s.c inj• No big RCT data to look at fracture risk

reduction• May reduce back pain caused by acute

vertebral fracture• S/E of nausea, vomiting, dizziness and

flushing may occur60

HRT ( Hormone Replacement Therapy )

• Reduces the risk of clinical vertebral fracture and hip fracture by 34% and other osteoporotic fracture by 23% over 5 years

• Increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli and DVT during the 5 years of treatment

• No longer used as 1st line agent to treat osteoporosis

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Anabolic agent

• PTH 1-34 ( Forteo )• Daily s.c injection• Reduces the risk of vertebral fracture by 65%

and non-vertebral fracture by 53% in patients with osteoporosis, after an average use of 18 months

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PTH 1-34 (Forteo)

• Side effects of leg cramps and dizziness• Relatively expensive• Safety and efficacy has not been

demonstrated beyond 2 years of treatment• Common practice to follow PTH treatment

with an anti-resorptive agent

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Combination therapy??

Not recommended – no good research evidence to show better fracture outcome

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Remaining issues……

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• How can we better assess bone strength using non-invasive technologies and thus improve identification of patients at high risk of fracture?

• How effective are different drug treatments in preventing fractures in patients with moderately low bone mass?

• How long should anti-resorptive therapies be continued, and are there long term side effects as yet unknown?

• Are combination therapies useful, and if so, which are the useful drug combinations and when should they be used?

• Can we identify agents that will significantly increase bone mass and return bone structure to normal

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Summary

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Osteoporosis

• Global public health problem• Very common condition among elderly

( 1 in 2 for women and 1 in 5 in men )• Fracture can KILL• Can be easily diagnosed and have very

effective drug treatment• Multidisciplinary approach

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