Pathophysiology (13PH0304)

Unit: 4

Topic: Osteoporosis

Dr. S. BHARAT KUMAR REDDY

ASSISTANT PROFESSOR

FACULTY OF PHARMACY, Marwadi University

Rajkot, Gujarat, 360003, India

INTRODUCTION

Osteoporosis is a skeletal metabolic disease

characterized by low bone density and micro

architectural deterioration of bone tissue,

resulting in increased bone fragility and

susceptibility to fracture.

The most common site of fractures are wrist,

hip and vertebrae.

1. SEX (Females are more prone to male)

2. Advanced age (> 50 years)

3. Genetic factors such as family history

4. Lack of physical activity

5. Inadequate intake of calcium and vitamin D

6. Smoking and alcohol consumption

7. Amenorrhea

8. Late menarche

9. Low weight and body mass index

10.Drugs (Systemic steroids, chemotherapeutic agents, thyroid supplements)

RISK FACTORS

a. Idiopathic age related osteoporosis (Most common)

1. Young adults

2. Postmenopausal

3. Senile

b. Osteoporosis secondary to disease state

1. Metabolic conditions

Eg: Calcium deficiency, Vitamin D deficiency, Malnutrition, Scurvy

2. Endocrine conditions

Eg: Hyperparathyroidism

3. Renal disease

4. Bone marrow infiltration

CAUSES OF OSTEOPOROSIS

KyphosisScoliosis

PATHOPHYSIOLOGY

CALCIUM DEFICIENCY

Calcium, vitamin D, and PTH help maintain bone homeostasis. Insufficient

dietary calcium or impaired intestinal absorption of calcium due to aging or

disease can lead to secondary hyperparathyroidism. PTH is secreted in

response to low serum calcium levels. It increases calcium resorption from

bone, decreases renal calcium excretion, and increases renal production of

1,25-dihydroxyvitamin D (1,25[OH]2 D)-an active hormonal form of

vitamin D that optimizes calcium and phosphorus absorption, inhibits PTH

synthesis, and plays a minor role in bone resorption.

CAUSES OF OSTEOPOROSIS

ESTROGEN DEFICIENCY

Estrogen deficiency not only accelerates bone loss in postmenopausal

women but also plays a role in bone loss in men. Estrogen deficiency can

lead to excessive bone resorption accompanied by inadequate bone

formation. In the absence of estrogen, T cells promote osteoclast

recruitment, differentiation, and prolonged survival. T cells also inhibit

osteoblast differentiation and activity and cause premature apoptosis of

osteoblasts. Finally, estrogen deficiency sensitizes bone to the effects of

parathyroid hormone (PTH).

AGING

In contrast to postmenopausal bone loss, which is associated with

excessive osteoclast activity, the bone loss that accompanies aging is

associated with a progressive decline in the supply of osteoblasts in

proportion to the demand.

ADDITIONAL FACTORS AND CONDITIONS

Endocrinologic conditions or medications that lead to bone loss (e.g.,

glucocorticoids) can cause osteoporosis. Corticosteroids inhibit osteoblast

function and enhance osteoblast apoptosis. Other factors implicated in the

pathogenesis of osteoporosis include polymorphisms in the vitamin D

receptor; alterations in insulin-like growth factor 1, bone morphogenic

protein, prostaglandin E₂, nitrous oxide, and leukotrienes; collagen

abnormalities.

SYMPTOMS

Most often there are no symptoms for early detection.

In later stages

• Bone pain and low back pain

• Fractures without injury

• Slouched posture

• Osteoporosis generally does not become clinically apparent until a

fracture occurs

• Two thirds of vertebral fractures are painless.

• Typical findings in patients with painful vertebral fractures may include

• the following:- The episode of acute pain may follow a fall or minor trauma -

Pain is localized to a specific, identifiable, vertebral level in the mid thoracic to

lower thoracic or upper lumbar spine.

• The pain is described variably as sharp, nagging, or dull; movement may

exacerbate pain; in some cases, pain radiates to the abdomen

• Pain is often accompanied by paravertebral muscle spasms exacerbated by

activity and decreased by lying supine- Patients often remain motionless in bed

because of fear of causing an exacerbation of pain- Acute pain usually resolves

after 4-6 weeks; in the setting of multiple fractures with severe kyphosis, the

pain may become chronic

SYMPTOMS & COMPLICATIONS