l36 - back pain in an elderly woman_2012

7/27/2019 L36 - Back Pain in an Elderly Woman_2012

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Back pain in an elderly woman:

Osteoporosis and related fractures

Prof Annie Kung

Department of Medicine

University of Hong Kong


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Pathogenesis of osteoporosis

Resorbed cavity

too large

Newly formed packet

of bone too small

Formation does not

match resorption

Increased numbers of

remodeling units

INCREASED BONE LOSS


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Bone turnover

Trabecular bone20% of the skeletal mass

80% of bone turnover

Cortical bone80% of the skeletal mass

20% of bone turnover


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Bone remodeling

Bone marrow precursorsHematopoietic cellsMesenchymal cells

OsteoblastOsteoclast

Lining cells


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Regulation of osteoclastogenesis by

factors from osteoblast/stromal cells

Hofbauer LC & Heufelder AE, JMol Med, 2001;79:243-253

Osteoclast precursor

Differentiation

Inhibition

OPG"decoy receptor"

Osteoblast / stromal cell

M - CSF RANK

RANKL

RANKL

Mature osteoclast


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Estrogens:

mechanism of action in bone

Estrogens

Cytokines

RANK-L

Cytokines

IL-1, TNF-a

IL-6, TGF-b,....

apoptosis

TGF- +

apoptosis

TNF-

Precursor

(Osteoblast)

Precursor

(Osteoclast)

osteoblast osteoclast


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Regulation of RANKL and OPG

by systemic hormones

Aubin JE & Bonnelye E, Osteoporos Int, 2000;11:905-913

Stimulation

Inhibition

RANKL OPG

17-EstradiolDexametasone1,25-(OH2)D3PTH

PGE2

Hydrocortisone17-Estradiol1,25-(OH2)D3PTH

PGE2


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BONE LOSS

Calcium absorption Estrogen deficiency

Vitamin D intake and synthesisDietary calcium intake

Plasma calcium PTH secretion

Bone turnover and resorption

Age-related bone loss


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Secondary osteoporosis

Endocrine Nutritional Drug-induced Immobilization Others

HyperthyroidismHypogonadism

Cushing Syndrome

GlucocorticoidsImmunosuppressly

Anticonvulsants

Rheumatoid A.Diabetes Tumors

(Myeloma, etc.)


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Osteomalacia

Equivalent to Rickets in childrenAbnormal histology: unmineralized osteoid

Cause: vitamin D deficiency,

very low level of serum 25(OH)D New conception: osteoporosis and

osteomalacia a continuum


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Clinical Diagnosis of

Osteoporosis

Spinal fracture Hip fractureWrist fracture


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Clinical Diagnosis of Osteoporosis

Previous fragility fracture

Back pain

Height loss (>2cm since age 25)

KyphosisOcciput to wall distance

Gap between costal margin

and iliac crest


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WHO Definition of Osteoporosis

A condition characterised by low

bone mass and microarchitectural

deterioration of bone tissue, with a

consequent increase in bone

fragility and increase susceptibility

to fracture.

1994, WHO Working Grou

Di i B d BMD


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Kanis JA e

Osteoporos Int. 1994; 4

Diagnosis Based on BMD


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Prevalence estimate of osteoporosis in apopulation

Results expressed as SD from mean ofyoung adult Caucasian women (T score)

Evaluated in postmenopausal Caucasianwomen

1 SD reduction in BMD (using DXA ofspine, hip or forearm) corresponds to a 2-fold increased risk in hip fracture


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Normal T score -1

Ostopenia T score < -1 and > -2.5

Osteoporosis T score -2.5

Establishedosteoporosis

T score -2.5 with fracture

T scores allow comparison using the same diagnostic criteria

for different machines.


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Young normal adult reference of same ethnicity

Patients BMD Young Adult Mean BMD

1 SD of Young Adult BMD

(a large population SD can affect the T score value)

T-score


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Why Cut-off at T score -2.5

This cutoff value identifies approximately

30% of postmenopausal women as having

osteoporosis using measurements madeat the spine, hip or forearm. This is

approximately equivalent to the lifetime

risk of fracture at these sites.

Kanis JA et al. JBMR 1994;9:1137


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Prevalence of Osteoporosis and Lifetime

Fracture Risk in White Women

Melton L J I I I , et al. J Bone Miner Res. 1995;10:175Melton L J I I I , et al. J Bone Miner Res. 1992;7:1005

** Clinical vertebral

fractures

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%

35.0%

40.0%

lumbar spine femoral neck forearm any of three

T-score equal to orlower than -2.5

Lifetime fracturerisk


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WHO Diagnostic Criteria,

and BMD Profile in a Population

Age (years)

30 40 50 60 70 80 90

TotalHipBMD

(g/cm2)

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

+1 SD

+2 SD

Mean

-1 SD

-2 SD

OSTEOPOROSIS

LOW

BONE

MASS

NORMAL

-2.5 SD

T-Score


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Normal bone Osteoporotic Bone

Osteoporosis is a skeletal disorder characterised by compromised

bone strength predisposing a person to an increased risk of

fracture. Bone strength reflects the integration ofbone densityand bone quality.

NIH Consensus Conference 2001

New Definition of Osteoporosis

NIH Consensus Development Panel on Osteoporosis. JAMA 285 (2001): 785-9


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Determinants of bone strength

Bone Remodeling

Bone Strength

Tissue Properties

Mineralization

Collagen(structure, cross-links)

Micro damage

Micro-architecture

Mass(Size, Geometry)


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Osteoporosis is a disease characterisedby low bone mass and increased fracturerisk

1 SD reduction in BMD corresponds to a2-fold increased risk in hip fracture

BMD measurement can diagnose

osteoporosis before fracture occurs

BMD and Risk of Fracture


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Prevalence of Osteoporotic

Fractures in Hong Kong Women

60 - 69 years 1 : 6

70 - 79 years 1 : 5

80 and above 1 : 4


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Osteoporosis Risk Factors

Nonmodifiable Modifiable

gender low estrogen level

race low dietary calcium or vitamin D

heredity, body frame sedentary

age smoking

alcoholismmedications (glucocorticoids, etc)


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Recommended Intakes (USA)

Age range Ca (mg) Vit D (IU/d)

19 - 50 1,000 200 (5 mcg)51 - 70 1,200 400

> 70 1,200 600

Upper limit 2,500 2,000

Osteoporosis 2,500 800


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Clinical Evaluation of Patient with

Established Osteoporosis (2)

B. Physical Examination

Height and weight

Dental exam (loss of teeth, dentures)

Evidence of hyperthyroidism, Cushings diseaseEstimate degree of kyphosis, observe posture,sites of tenderness

Factors that influence propensity to fall

(agility, hearing, eyesight, postural sway)

Gait, mobility muscle strength


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C. Laboratory Tests

Serum calcium, phosphate

24 hour urine calcium25 OH vitamin D

PTH , TSH

Biochemical Markers of Bone Turnover


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D. Radiologic Evaluations/Non-invasive

Bone Mass Quantitations

X-ray thoracolumbar spine

Dual-energy X-ray absorptiometry

Computed tomography


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Treatment Options

1. Lifestyle modification

2. Therapeutic Agents


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Life Style Modification

1. Adequate Dietary Calcium Intake

2. Weight bearing exercise

3. Avoid vitamin D deficiency


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Therapeutic Agents

Resorption InhibitorsEstrogenSERMBisphosphonatesCalcitonin

RANKL Ab

Alter Bone Turnover

Strontium Ranelate

Formation StimulatorsPTH


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HRT Inhibits bone resorption

calcium excretion in urine cytokines production by stromal cells

Additional advantage

CVD risk factors e.g. cholesterol, but outcome

events (i.e. MI, stroke) not reduced menopausal symptoms

Disadvantage

Endometrial cancer (additional progestogens ifuterus intact)

Slight risk of breast cancer

Venothrombolic disease


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Selective Estrogen Receptor

Modulators (SERMS)

Selective stimulatory action on bone

Decreases LDL

Little effect on breast and uterus Raloxifene

vertebral fracture risk by 50% but not

non-vertebral fracture

Bi h h


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Bisphosphonates

Derivatives of pyrophosphates

Inhibit osteoclast activity, specific inhibitionof bone resorption

Bound onto surface of osteoclast, inhibit

farnesyl pyrophosphate synthase (FPPS),the key enzyme in the mevalonate pathwayand induce apotosis of osteoclast

e.g. etidronate, alendronate, risedronate,

ibandronate, zolendronate fracture risk (both vertebral and non-

vertebral, including hip) by about 50%

Bi h h t


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Bisphosphonates Oral/IV preparation

Poor intestinal absorption

Selective uptake at active bone sites

Short plasma half-life

No active metabolites

Renal excertion

Side-effects: oesophagitis, first phase reaction

(fever, muscle/bone pain)

Action persist, may cause adverse effect of

oversuppression of bone turnover and atypicalfractures (5 in 10,000) and osteonecrosis of

jaw (1 in 10,000)


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Calcitonin

Inhibits osteoclast activity

Intramuscular or Intranasal

BMD 2 - 3 %

vertebral fracture risk by 30% but notnon-vertebral fracture

Additional benefit on pain relief


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RANKL Ab

Human monoclonal Ab to RANKL

Interfere with RANKL and decrease

osteoclast differentiation and activation

Given as SC injection q 6 months

Decrease vertebral fracture by 50%,

non-vertebral fracture 30%


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PTH

High level, continuous: bone

resorption cortical > trabecular bone

Low dose, intermittent: anabolic actione.g. daily IMI can BMD and

vertebral fracture risk by 70%


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Strontium Ranelate

Strontium belongs to Group 2

compounds in chemistry periodic table,

same as calcium

Act through Ca-sensing receptor

Alter bone turnover, increases bone

formation and decreases bone

resorption


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Biochemical Bone Markers

Bone Formation Bone Resorption

Osteocalcin Hydroxyproline

Alkaline phosphatase Deoxypyridinoline

PINP (Type I Pro- Pyridinoline II (PYD)

Collagen Peptide) C-telopeptides (CTx)

urine N-Telopeptide

(NTx)


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Usefulness of Biochemical Markers

Study of normal bone metabolism

Diagnosis and monitoring of bone disease

Evaluate effectiveness of therapeuticagent, monitor treatment progress

Not useful as a screening agent

M j S d C f


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Major Secondary Causes of

Osteoporosis

Disease Ix

Myeloma SIEP

Hyperparathyroidism Ca2+

, PTHHyperthyroidism TSH

Cushings Syndrome Cortisol, ACTH

Hypogonadism E2, testosterone

M h i f St id


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Mechanisms for Steroid

Induced Osteoporosis

1. Decreases osteoblast function,decreases bone formation

2. Increases osteoclast resorption3. Causes negative calcium balance

( GI absorption, renal excretion)

4. Induces hypogonadism

Gl ti id I d d


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Glucocorticoid-Induced

Osteoporosis

Progressive demineralization

Trabecular >> cortical bone

Bone loss greatest within first year (can

loss up to 20% of trabecular bone)

Rate of loss greatest in those subjects

with high bone remodeling rates

l36 - back pain in an elderly woman_2012

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