Osteoporosis PHCL 442 Hadeel Al-Kofide MS.c. Topics to be covered Definition & epidemiology Pathophysiology Classification Risk factors Diagnosis Management:

Osteoporosis

PHCL 442

Osteoporosis

PHCL 442

Hadeel Al-Kofide MS.c

Topics to be coveredTopics to be covered

• Definition & epidemiology

• Pathophysiology

• Classification

• Risk factors

• Diagnosis

• Management:

• Non-Pharmacological & Pharmacological

DefinitionDefinition

• Osteoporosis is a systemic skeletal disorder characterized by:

low BMD & microarchitectural deterioration of bone tissue,

leading to enhanced bone fragility & a consequent increase in

fracture risk

• The condition is usually painless until a fracture occurs

• It affects 1:2 women & 1:8 men

PathophysiologyPathophysiology

• Normally there is a balance between osteoblast & osteoclast

activity

• In osteoporosis either one of 2 or both will happen:

Space where some bone has been resorbed (due to osteoclast)

but not yet replaced during the remodeling process (with

osteoblas), this happens by advanced age

Remodeling space is increased (due to osteoclast) in

postmenopausal osteoporosis

ClassificationClassification

• Primary:

Type I: Postmenopausal osteoporosis, it occurs in women 3-6 years after menopause (due to increase osteoclast resorption activity)

Type II: In both men & women after age 75, female to male ratio 2:1

• Secondary:

Due to drugs, medical problems & other causes it is equal in men & women

Risk Factors for OsteoporosisRisk Factors for Osteoporosis

• Age – especially after 60 yr

• Female gender

• Small stature

• Caucasian, Asian, Latin American

• Slight body build

• Estrogen depletion (menopause or amenorrhea)

• Family history of osteoporosis

• Lack of exercise


• Cigarette smoking

• Underweight

• Excessive use of alcohol

• Excessive fiber consumption

• Excessive caffeine consumption

• Inadequate lifetime calcium intake

• Poor vitamin D status


Use of certain medications

• Phenytoin, Phenobarbital

• Thyroid hormone

• Corticosteroids

• Methotrexate

• Aluminum-containing antacids

• Heparin


Certain diseases or conditions

• Hyperthyroidism

• Diabetes

• Chronic renal failure

• Chronic diarrhea/malabsorption

• Hyperparathyroidism

• Chronic obstructive lung disease

DiagnosisDiagnosis

• Radiographic measurement of bone density

• Laboratory biochemical markers

Bone resorption markers (eg., collagen cross-linked N-

telopeptides)

Bone formation markers (eg., bone-specific alkaline

phosphatase)

• Bone biopsy with pathologic assessment: only used under

research setting or with difficult to diagnosis cases

Bone Mineral DensityBone Mineral Density

Indications:

• In women with strong risk factors

• In those with osteoporosis-related fractures (wrist, spine,

proximal femur, or humerus after mild or moderate trauma)

• For monitoring treatment


Techniques:


WHO Diagnostic Categories for BMD

Normal BMD not more than 1 SD below the peak bone mass or young adult mean (T-score above -1)

Osteopenia BMD between 1 & 2.5 SD below the young adult mean (T-score between -1 and -2.5)

Osteoporosis BMD 2.5 SD or more below the young adult mean (T-score at or below -2.5)

Severe osteoporosis (established osteoporosis)

BMD 2.5 SD or more below the young adult mean (T-score at or below -2.5) & the presence of one or more fragility fractures

ManagementManagement

Management & PreventionManagement & Prevention

• Keep in mind you have two prevent osteoporosis in 2 settings:

Premenopausal women

Postmenopausal women

Non-PharmacologicalNon-Pharmacological

• Appropriate levels of exercise should be recommended

• Smoking & alcohol abuse should be discouraged

• Physiotherapy & pain relief are important in managing

fractures

PharmacologicalPharmacological

• Calcium & vitamin D

• Hormone replacement therapy

• Raloxifene

• Bisphosphonates

• Calcitonin

• Parathyroid hormone peptides

• Strontium ranelate

Calcium & Vitamin DCalcium & Vitamin D

• All patients at risk for osteoporosis (for prevention) & patients

with osteoporosis (for treatment) should be on adequate Ca &

vitamin D supplements

• Calcium dose: 1200 mg elemental Ca

• Vitamin D dose: 400 IU/day if age more than 70 years 600

IU/day

Calcium & Vitamin DCalcium & Vitamin D

• Calcium carbonate: highest amount of calcium per tablet, but

may cause intestinal gas &/or constipation

• Calcium citrate: less calcium per tablet, but better absorbed

than carbonate; no known side effects

• Calcium phosphate: most diets already high in phosphorous;

better to avoid this form

• Calcium gluconate: requires many tablets to obtain sufficient

calcium

Vitamin D inadequacy worldwide

Vitamin D inadequacy defined as serum 25(OH)D <30 ng/ml

1285 community-dwelling women with osteoporosis from 18 countries to evaluate serum 25(OH)D distribution.

Lim S-K et al, 2005

Pre

vale

nce

(%

)

0

10

30

40

60

80

90

LatinAmerica

51%

63%

AsiaAll

59%

Australia

59%

Europe

52%

Regions

N=1285 81%

MiddleEast

50

70

20

Hormone Replacement TherapyHormone Replacement Therapy

• In the past was considered as 1st line treatment

• It is an appropriate option in younger postmenopausal women

at high risk of fracture, particularly those with vasomotor

symptoms

• Generally a second line treatment option because risk-benefit

balance is unfavorable in older women

RaloxifeneRaloxifene

Mechanism of action:

• Selective estrogen receptor modulator (SERM)

• Mixed estrogen receptor agonist/antagonist

• Acts as an agonist in the bone, reducing turnover by inhibiting

osteoclast recruitment & activity

• Acts as an antagonist in the breast & uterus


Role in Therapy:

• Second line agent for the treatment of postmenopausal

osteoporosis

Advantage:

• Favorable changes in lipid profile

• Decreases the risk for CV events and breast cancer


Dose:

• 60 mg/day

Adverse effects:

• Hot flushes, & leg cramps

• Increase in the relative risk of venous thromboembolism

BisphosphonatesBisphosphonates


• Deposited in bone at the site of mineralization; apparently

causing the death of osteoclasts which results in decreased

bone resorption

They have very long half life 1-2 years

Less than 10% absorbed


• Alendronate & risedronate have been shown to reduce

vertebral & non-vertebral fractures, including hip fractures

• They are considered first line options for treating

postmenopausal osteoporosis


Dose:

Alendronate Oral 70 mg 1/w, or

5 mg or 10 mg OD

Etidronate Oral 400 mg OD for 2 w every 3 mo

Ibandronate Oral

IV

150 mg 1/mo

3 mg 1/3 mo

Risedronate Oral 35 mg 1/w, or

5 mg OD

Most common regimen used

The only one with IV form


Adverse effects:

• Acid regurgitation, dyspepsia, abdominal distention, gastritis,

nausea & dysphagia

• Esophageal ulceration & strictures

• Musculoskeletal pain, headache & rash


Contraindications:

• Not given if CrCl less than 35 ml/min

• If hypocalcaemia exists it should be corrected before starting

therapy

• Caution in patients with upper GI problem (esophagus)


Precautions:

• Oral bisphosphonates must be taken fasting, with a full glass

of water

• The individual must be upright & stay sitting or standing

without taking food or drink for the next 30-60 minutes

• This is done to prevent esophageal ulceration

CalcitoninCalcitonin


• Inhibits osteoclast formation & attachment

• Analgesic effect?

Dose:

• 200 IU/day by nasal spray

• 100 IU/day IM


Adverse effects:

• Rhinitis & epistaxis (from nasal form)

• Arthralgia, headache & back pain

• Flushing, nausea, vomiting & local irritation (IM)


Precautions:

• Nasal form should be refrigerated until it is open for use

• After opening it is only stable for 30 days at room temperature

Role in Therapy:

• Not used as first line treatment

• Mainly used in patients with back pain & acute vertebral fracture

Parathyroid HormoneParathyroid Hormone


• Produced normally by PT gland, helps control calcium

exchange between the bones & the blood stream

• Low dose synthetic human PTH causes anabolic response,

increasing the number and action of osteoblasts


Side effects:

• Asymptomatic mild hypercalcemia

• Increase risk of osteosarcoma

Dose:

• Teriparatide (rPTH): 20 mcg/d SC for upto 24 months


Contraindications:

• Children, adolescents & patients with paget’s disease because of

increased risk of osteosarcoma

• Hypercalcemia

Role in Therapy:

• Postmenopausal women & men with osteoporosis who are at

high risk for fracture, such as individuals with prior osteoporotic

fractures (mainly as second line agent)

Strontium RanelateStrontium Ranelate


• It has a dual mode of action, both increasing bone formation &

decreasing bone resorption

• It has been shown to enhance osteoblastic cell replication &

increase collagen synthesis while it decreases bone-resorbing

activity of mature osteoclasts


Adverse effects:

• Diarrhoea, nausea, headache, dermatitis & eczema

• Rare: DVT

Contraindications:

• Not recommended in patients with a CrCl below 30 ml/min

Dose:

• 2 g sachet once daily 2 hours after food, must taken as

suspension in water & drink immediately


Role in Therapy:

• Postmenopausal women & men with osteoporosis who are at

high risk for fracture, such as individuals with prior

osteoporotic fractures (mainly as second line agent)

Which Dug for Which Patient??Which Dug for Which Patient??

Which drug for which patient?

Agent Rx PM OP to reduce risk of

Steroid induced

OP

OP in men

Vertebral fractures

Hip fractures

Alendronate Risedronate

Etidronate

Raloxifene

Strontium ranelate

Teriparatide

LOOK AT THE ATTACHED GUIDELINE

Thank youThank you

Osteoporosis PHCL 442 Hadeel Al-Kofide MS.c. Topics to be covered Definition & epidemiology Pathophysiology Classification Risk factors Diagnosis Management:

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