FACILITATED BY:DR.RAJU KONERI SIR

HOD of Pharmacology

department

SUBMITTED BY:Dipankar acharjee

M.Pharmacy 1st year

Department

pharmacology

Osteoporosis is defined as a “skeletal

disorder characterized by compromised bone

strength predisposing a person to an increased risk

of fracture’’

The development of osteoporosis is multifactorial,

beginning with genetics and unhealthy bone

lifestyles, along with other skeletal factors, which

lead to compromised bone strength, and nonskeletal

factors

PATHOPHISIOLOGYBone is comprised of three types of cell.

Osteoblasts.

Osteocytes.

osteoclasts.

Osteoblast:-These are mononucleate bone-forming cells.

Osteoblasts also manufacture hormones.

Osteocytes:- These are mostly inactive osteoblasts.

Osteoclast:-These are the cells responsible for bone

resorption, thus they break down bone. New bone is then

formed by the osteoblasts. Bone is constantly remodelled by

the resorption of osteoclasts and created by osteoblasts.

Bone remodelling

o Bone remodelling is a dynamic process that occurs

continuously throughout life.

o The purpose of remodelling is to regulate calcium

homeostasis, repair micro-damaged bones from

everyday stress.

o The action of osteoblasts and osteoclasts are

controlled by a number of chemical enzymes that

either promote or inhibit the activity of the bone

remodeling cells, controlling the rate at which

bone is made, destroyed, or changed in shape.

In osteoporosis,, bone mass (the amount of bone

tissue) is reduced because its deposition does not keep

pace with resorption. Peak bone mass occurs around 35

years and then gradually declines in both sexes. Lowered

oestrogen levels after the menopause are associated with

a period of accelerated bone loss in women. Thereafter

bone density in women is less than in men for any given

age. Bone is progressively weakened with cancellous bone

affected first by thinning and loss of trabeculae. In the

postmenopausal period an imbalance of hormones probably

causes bone weakening.

The accelerated bone loss during perimenopauseand postmenopause results from enhanced resorption mainly as a result of the loss in ovarian hormone production, specifically estrogen.

Estrogen deficiency increases proliferation, differentiation, and activation of new osteoclasts and prolongs survival of mature osteoclasts.

The number of remodeling sites increases and resorption pits are deeper and inadequately filled by normal osteoblastic function.

Men are at a lower risk for developing osteoporosis and osteoporotic fractures because of larger bone size, greater peak bone mass, and fewer falls

The etiology of male osteoporosis tends to be multifactorial with secondary causes and aging being the most common contributing factors

SECONDARY CAUSES OF

OSTEOPOROSIS

CAUSES

CausesThe major factors influencing bone losses are hormonal status,

exercise, aging, nutrition, lifestyle, disease states, medications,

and some genetic influences. Non hormonal risk factors are

similar between women and men.

LOW BONE DENSITY: Bone loss occurs when bone

resorption exceeds bone formation. Bone resorption sites

greatly exceed the rate and ability of osteoblasts to form new

bone. During peri-menopause and for up to 5 to 7 years after

menopause, women can experience an accelerated rate of

bone loss because of the drop in circulating estrogen and an

increase in bone resorption

IMPAIRED BONE QUALITY

The strength of bone is highly impacted by the quality

of the bone’s material properties and its structure. . Bone quality assessment is important because changes

in bone quality effect bone strength much more than

bone mass changes

FALLS

Risk of falling increases with advanced age

predominantly as a result of balance, gait, and mobility

problems, poor vision, reduced muscle strength,

impaired cognition, multiple medical conditions

PREVENTION AND TREATMENTOsteoporosis prevention and treatment begins with a

bone-healthy lifestyle and uses non prescription and

prescription medications as needed.

The primary goal of osteoporosis management

should be prevention.

Once osteopenia or osteoporosis develops, the

objective is to stabilize or improve bone mass and

strength and prevent fractures.

NONPHARMACOLOGIC THERAPY

Diet:- Overall, a diet well balanced in nutrients and

minerals is important for bone health. In addition, limiting

intakes of caffeine, alcohol, sodium, cola, and other

carbonated beverages.

Excessive caffeine consumption is associated with

increased calcium excretion, increased rates of bone loss,

and a modest increased risk for fracture.

Calcium:- Data clearly indicate that adequate calcium

intake is necessary for the development of bone mass

during growth and for its maintenance throughout life.

Vitamin D:- The three main sources of vitamin D

are sunlight, diet, and supplements. Because few

foods are naturally high or fortified with vitamin D .

(at least 800 to 2,000 units of vitamin D daily are needed)

Other Nutrients and Minerals:-

Protein :-

Dietary protein represents a key nutrient for bone

health , evidence suggests that low protein intakes

increase osteoporosis risk and that higher protein

intakes are protective against bone.

Dietary Soy

Isoflavone phytoestrogens are plant-derived

compounds that possess weak estrogenic agonist and

antagonist effects. The most common source for

isoflavone is dietary soy products. Genistein is the

most abundant and biologically active isoflavone in

soybeans.

Smoking

Smoking cessation can help to optimize peak bone

mass, minimize bone loss, and ultimately reduce

fracture risk

Exercise

Physical activity or exercise is an important

nonpharmacologic approach to preventing

osteoporotic fractures. Exercise can decrease the risk

of falls and fractures by improving muscle strength,

coordination, balance, and mobility.

Fall Prevention

Because of the link between falls and fractures,

homes should be made safe and potentially harmful

medications eliminated.

PHARMACOLOGIC THERAPY

Non-pharmacologic interventions alone frequently are

insufficient to prevent or treat osteoporosis, drug

therapy is often necessary.

Antiresorptive

Antiresorptive therapies include calcium, vitamin D,

bisphosphonates, estrogen agonists/antagonists and

calcitonin.

Calcium Supplementation

Calcium imbalance can result from inadequate dietary

intake, decreased fractional calcium absorption, or

enhanced calcium excretion. Adequate calcium intake

is considered the minimal standard for osteoporosis

prevention and treatment and should be combined

with vitamin D and osteoporosis medications when

needed.

Adverse Events/Precautions:- Calcium’s most

common adverse reaction constipation.

Vitamin D Supplementation

Vitamin D intake is critical for the prevention and

treatment of osteoporosis because it maximizes

intestinal calcium absorption.

Seniors and patients being treated for osteoporosis

should take at minimum 800 units of vitamin D

through food and supplementation.

Bisphosphonate

Bisphosphonates mimic pyrophosphate, an endogenous

bone reabsorption inhibitor. Bisphosphonates

consistently provide the greatest fracture risk reductions

and BMD increases

Adverse Events/Precautions;-Bisphosphonate GI adverse

effects are minimal if the medication is taken correctly.

Intravenous bisphosphonates include fever, flu-like

symptoms.

Each oral dose should be taken with at least 6 ounces

of plain tap water at least 30 minutes before

consuming any food.

Mixed Estrogen Agonists/Antagonists

Raloxifene, a second generation mixed estrogen

agonist/antagonist (EAA) approved for prevention and

treatment of postmenopausal osteoporosis, is an

estrogen agonist on bone. Raloxifene decreases

vertebral fractures and increases spine and hip BMD

Calcitonin

Calcitonin is FDA indicated for osteoporosis treatment

for women who are at least 5 years past menopause.

Estrogen Therapy

Although estrogens are FDA indicated for prevention

of osteoporosis, they should only be used short-term in

women who need estrogen therapy for the management

of menopausal symptoms such as hot flushes.

Thiazide Diuretics

It increase urinary calcium reabsorption.

Observational studies suggest that patients who receive

thiazide diuretics have a greater bone mass, lower rates

of bone loss, and fewer fractures

REFERENCES

Dipiro J.T. et al., Pharmacotherapy. A

Pathophysiologic Approach. 7th ed.

Pg. no. 1483-1504

Waugh A, Grant A., Ross and Wilson

Anatomy and Physiology in Health

and Illness. 9th ed. Pg. no. 494