Presented by:Siti Noraisah Bt Kifli

OUTLINES

• INTRODUCTION• STATISTICS IN MALAYSIA• PATHOPHYSIOLOGY • CLASSIFICATIONS• RISK FACTORS• SYMTOMPS• DIAGNOSIS• PREVENTION• MANAGEMENT

::introduction::::introduction::• Osteoporosis is a disease in which bones become fragile and

more likely to break. If not prevented or if left untreated, osteoporosis can progress painlessly until a bone breaks.

• These broken bones, also known as fractures, occur typically in the hip, spine, and wrist.

• Any bone can be affected, but of special concern are fractures of the hip and spine. A hip fracture almost always requires hospitalization and major surgery.

• It can impair a person's ability to walk unassisted

• may cause prolonged or permanent disability or even death.

• Spinal or vertebral fractures also have serious consequences, including loss of height, severe back pain, and deformity

• Osteoporosis makes your bones weak and more likely to break.

• Anyone can develop osteoporosis, but it is common in older women.

• As many as half of all women and a quarter of men older than 50

will break a bone due to osteoporosis

STATISTICS of STATISTICS of OSTEOPOROSIS IN OSTEOPOROSIS IN

MALAYSIAMALAYSIA

Osteoporosis-related fractures have been recognized as a major health problem, particularly in the elderly. In 1997, the

incidence of hip fracture in Malaysia among individuals above 50 years of age was 90 per 100 000. Hip fractures are associated

with a high morbidity and mortality rate of up to 20% in the first year.

 The majority who survive are disabled and only 25% will resume normal activities. The direct hospitalization cost for hip fracture in 1997 is estimated conservatively at RM 22

million.

PATHOPHYSIOLOGY OF OSTEOPOROSIS• As a result of physical stresses

experienced during activities of daily living micro fractures can occur. If left unattended, these micro fractures can become clinically evident as fractures.

•Thereafter, the osteoclasts abandon the pit while osteoblasts settle within it to deposit new bone. When resorption and deposition are coupled there is no net change in the amount of bone present. Following menopause and after some pathological processes the coupling is altered in favor of increased resorption and as a result there is a loss in bone mass.

•As a result of endocrine signals that are poorly understood and in the presence of a number of growth factors and cytokines the osteoclasts are recruited and create a "resorption pit" where bone is digested (see Figure 1).

•Osteoclasts and osteoblasts are in charge of repairing the micro fractures. These two cells originate in the bone marrow from a common precursor.

CLASSIFICATION OF OSTEOPOROSIS

PRIMARYSECONDARY

Postmenopausalosteoporosis

Age-related

idiopathic

Endocrine•Cushing’s syndrome•Hypogonadism•Thyrotoxicosis•hyperparathyroidism

Drugs•Glucocorticoids•Heparin•Anticonvulsants (phenytoin•Immunosuppressants

Chronic Dx•Renal impairment•Liver cirrhosis•Malabsorption•Chronic inflammatory polyarthropaties

Others•Nutritional•Multiple myeloma and maglinancy•Osteogenesis imperfects

::Who is at RisK ??::::Who is at RisK ??::

Risk factors you cannot change include:

• Gender. Women get osteoporosis more often than men.

• Age. The older you are, the greater your risk of osteoporosis.

• Body size. Small, thin women are at greater risk.

• Ethnicity. White and Asian women are at highest risk. Black and Hispanic women have a lower risk.

• Family history. Osteoporosis tends to run in families. If a family member has osteoporosis or breaks a bone, there is a greater chance that you will too.

Other risk factors are:• Sex hormones. Low estrogen levels due to missing menstrual periods

or to menopause can cause osteoporosis in women. Low testosterone levels can bring on osteoporosis in men. [During menopouse,bone loss can range from 4 to 8%]

• Calcium and vitamin D intake. A diet low in calcium and vitamin D makes you more prone to bone loss. [In Malaysia most people hate drinking milk and hence increase their probability towards osteoporosis]

• Medication use. Some medicines increase the risk of osteoporosis.

• Too Much acidity in Food. As the blood must be a neutral pH, your body pulls calcium from the bones to neutralize the acidity. This is often the major factor in the development of osteoporosis

• Activity level. Lack of exercise or long-term bed rest can cause weak bones.

• Smoking. Cigarettes are bad for bones, heart, and lungs.

• Drinking alcohol. Too much alcohol can cause bone loss and

broken bones. • Lack of magnesium may be the cause of osteoporosis.

Calcitonin relies on magnesium to function properly. When we lack magnesium, the balance between PTH and calcitonin tilts too far toward PTH. This results in excessive stimulation of osteoclasts, which causes net bone loss. Magnesium suppresses the hormone that tells your body to pull calcium from the bones, and stimulates the

hormone that tells the body to put calcium in your bones.

::SyMPTOmpS::::SyMPTOmpS::

Osteoporosis is called the

"silent disease“ because bone is lost with no signs. You may not know that you have osteoporosis until a strain, bump, or fall causes a bone

to break.

::DiagnosiS::::DiagnosiS::•Common clinical presentations

Increasing dorsal kyphosis (Dowager’s hump)

Low trauma fracture

Loss of height

Back pain

•Diagnosis

Primary osteoporosis is made after excluding secondary causes of bone loss

BMD measurement with dual energy x-ray absorptiometry (DEXA)

PREVENTIONPREVENTION

1. Enough calcium intake daily; 800-1000 mg, also other important nutrients; proteins, zinc, mg & vitamin D for healthy and strong bone

Vitamin D is important in absorption of Ca from food and incorporate it into bones

1 glass of high Ca milk = 500 mg Ca

2. Bone examination – free during World Osteoporosis Day – access risk of loss of mass of bone

3. Exercises but not excessive!!! (3-4 times a week) Exercise alters hormonal balances, favoring the

hormones that protects bone So, walk rather than ride, climb the stairs rather than using lift, stand rather than sit when appropriate :P

4. Importance of good posture Proper way to sit - Support your lower back

with a pillow or by a straight high-backed chair. When driving or reading, avoid bending the neck forward. When rising from a chair, do it slowly.

Proper way to walk and stand - Keep your head high, look forward with the chin in. Pull your shoulders back, pull your stomach in to maintain the natural

arch of the lower back, and tighten your buttocks. Wear low-heeled shoes with rubber soles

Proper way to lift - You must bend your knees when lifting heavy objects to avoid backstrain and

further compression fractures. Use your Leg muscles rather than your back!

5. Avoid taking too much coffee, tea or chocolate, because they help in loss of Ca.

6.High protein will reduce the ability of Ca resorption.

7.Alcohol destroys cells forming bone.

8.Smoking reduces estrogen• It is important to remember that we cannot

avoid hormonal and genetic factor thus, we control the environment and diet factor, so that we can overcome the osteoporosis problem.

•Proper nutrition•Calcium & Vit D supplementation if needed to achieve adequate intakes•Optimal physical activity•Healthy social habit•Fall & trauma prevention

Consider treating without measuring BMD•Men & women w/ increase risk + a fragility fracture•Men & women taking chronic systemic corticosteroids

Population appropriate for BMD testing•All women >65 yo•Women aged 60-64 y,w/ increased risk for osteoporotic fracture•Men at high risk

Hip osteoporosisT-score< -2.5 T-score< -2.0

Spine osteoporosis onlyT-score< -2.5 osteopenia

T-score of -1 to -2.5

Normal BMDT-score> -1

Treat w/ biophosphonate

Biophosphonate intolerant

Treatment option•Parenteral biophosphonate•Teriparatide•Raloxifene•Calcitonin

Workup for 2o osteoporosis•PTH•TSH•25-OH Vit D•CBC•Chemistry panel•Condition-specific tests

Treat underlying cause if present

Treatmet options•Biphosphonate•Raloxifene•calcitonin

Monitor DXA every 1-5 yrs

BONE HEALTH THERAPEUTIC ALGORITHMPHARMACOTHERAPY HANDBOOK

MANAGEMENT OF OSTEOPOROSIS

• Hormone replacement therapy

• Selective Estrogen Receptor Modulators (SERMs)

• Biphosphonates

• Calcitonin

• Calcium

• Vitamin D

Hormone replacement therapy (HRT)

• Beneficial in the prevention & tx of postmenopausal osteoporosis

• Estrogens ↓ osteclast recruitment & activity,inhibit PTH peripherally, ↑calcitriol concentrations & intestinal calcium absorption and decrease renal calcium excretion

• Max benefit to the bone when estrogen is started at menopause and continued for 10 yrs or more

• Other benefits; relief of vasomotor symptoms, psychological problems, vaginal dryness and reduction in risk of primary cardiovascular disease. Emerging potential benefits include a decreased incidence of colonic cancer, macular degeneration, prevention and delay in Alzheimer’s Disease and a positive effect on alveolar dentition

Effective Bone Protective Doses of Estrogen

Type of estrogen Dose

Conjugated Equine Estrogen 0.625mg

Estradiol Valerate 2.0 mg

Transdermal estradiol 50-100µg

Micronised Estradiol 1mg

Tibolone 2.5mg

• HRT do not prevent primary or secondary CVS disease and may even increase events within the 1st years of use.• C/I: undiagnosed vaginal bleeding, severe liver dx & a hx of VTE within • the past 12 months

Selcetive Estrogen Receptor Modulators (SERMs)

Raloxifene • MOA: affects some of the same receptors that estrogen

does, but not all, and in some instances, it antagonizes or blocks estrogen

• acts like estrogen to prevent bone loss and has the potential to block some estrogen effects in the breast and uterine tissues.

• decreases bone resorption, increasing bone mineral density and decreasing fracture incidence. decreases bone resorption, increasing bone mineral density and decreasing fracture incidence.

• Common s/e: hot flashes and cramps

• Associated w/ a threefold increased risk of VTE, similar to the risk with estrogen

• should be discontinued at least 72 hours prior to and during prolonged immobilization (e.g., post- surgical recovery, prolonged bed rest), and patients should be advised to avoid prolonged restrictions of movement during travel because of the increased risk of venous thromboembolic events

Biphosphonates

Dosage: 5 mg daily (prevetion); 10 mg daily,70mg weekly(treatment)

Alendronate Etidronate

Risedronate

Bind to hydroxyapatite in bone and decrease resorption by inhibiting osteclast adherence to bone surfaces

common side effects are nausea, GI irritation,perforation,ulceration and/ or bleeding

Dosage: 400mg/day for 2 weeks, followed by 13-week period with no etidronate,then repeat cycle

Postmenopasal: 5mg OD or 35 mg once weekly or one 75 mg tablet taken on 2 consecutive days once a month

Male: 35 mg once weekly

Glucocorticoid-induced: 5 mg OD

Calcitonin

• a polypeptide hormone secreted by the parafollicular cells of the thyroid gland in mammals and by the ultimobranchial gland of birds and fish.

• MOA: antagonizes the effects of parathyroid hormone. Directly inhibits osteoclastic bone resorption; promotes the renal excretion of calcium, phosphate, sodium, magnesium, and potassium by decreasing tubular reabsorption; increases the jejunal secretion of water, sodium, potassium, and chloride

• As a second line tx (reduces fracture risk to a lesser extent than other osteporosis medications)

• Dosage: injection solution (I.M., S/C): 100 units/every other day;Intranasal: 200 units (1 spray) in one nostril daily

Calcium

• Should be ingested in edequate amounts to prevent hyperparathyroidism and bone destruction

• Combination of calcium & Vit D decreases nonvertebral, vertebral & hip fractures

• According to NOF; -Adults under age 50 need 1,000 mg of calcium and 400-800 IU of vitamin

D daily. -Adults 50 and over need 1,200 mg of calcium and 800-1,000 IU of vitamin D daily.

• best absorbed when taken in amounts of 500 – 600 mg or less

Vitamin D

Activated Vitamin D calcitriol

alfacalcidol

•promoting absorption and utilization of calcium and phosphate and for normal calcification of bone.

•Along with parathyroid hormone and calcitonin, it regulates serum calcium concentrations by increasing serum calcium and phosphate concentrations as needed.

•stimulates calcium and phosphate absorption from the small intestine and mobilizes calcium from bone.

• Calcitriol:

-act by binding to a specific receptor in the cytoplasm of the intestinal mucosa and subsequently being incorporated into the nucleus, probably leading to formation of the calcium-binding protein that results in increased absorption of calcium from the intestine

-decreases excessive serum phosphatase levels, parathyroid hormone levels, and decreases bone resorption

-increases renal tubule phosphate resorption

dosage: Initial: 0.25 mcg/day, range: 0.5-2 mcg once daily

• Alfacalcidol:

-rapidly converted to 1,25-dihydroxycholecalciferol in the liver→most active form

dosage: Initial: 1 mcg/day. Maintenance: 0.25-1 mcg/day.

REFERENCES

• Clinical Practice Guidelines on the Maganement of Osteoporosis 2002

• Drug Information handbook,17th Edition 2008-2009• Well, G. B., DiPiro, J., T., Schwinghammer, T., L. &

Hamilton, C. W. 2006.Pharmacotherapy Handbook,6th Editon

• National Osteoporosis Foundation• Johann D. Ringe.Alfacalcidol in Prevention and

Treatment of All Major Forms of Osteoporosis and Renal Osteopathy

• www.drugs.com