Osteoporosis Understanding and Treatment

dr Putra Hendra SpPD UNIBA

Definition of Osteoporosis

Osteoporosis is a skeletal disease characterized by 1. low bone mineral density (BMD) 2. decreased bone strength 3. deterioration of bone microarchitecture 4.increase in bone fragility 5. increased risk of fracture

Life of Bones

Living, active tissue Bone remodeling

Osteoclasts

Bone consists of three major cell types: osteoblasts, osteocytes and osteoclasts.

Dissolve or break down bone tissue Stimulated by low calcium intake Rebuild bone tissue Stimulated by exercise

Osteoblasts

To maintain bone mass, osteoclastic and osteoblastic processes must be in equilibrium. With menopause and advancing age, there is an increased rate of bone remodeling. Bone reabsorption exceeds deposition and Osteoclasts mobilize Ca++ to plasma The reduction in both trabecular and cortical bone mass leads to disordered skeletal architecture and increased risk for fractures.

Osteoporosis: Disease of Bone Growth & Calcium Metabolism

Osteoporotic bone showing loss of bone with larger spaces decreasing its strength .2

Normal Bone

Female, age 30 years

Moderate Osteoporosis

Female, age 88 years

Etiology

Systemic hormones involved:

Parathyroid hormone :

is the most important regulator of calcium homeostasis. It maintains serum calcium concentrations by:

Stimulating bone resorption Increasing renal tubular calcium reabsorption Increasing renal calcitriol production.

PTH stimulates bone formation when given intermittently, but inhibits collagen synthesis at high concentrations . It stimulates osteoclast mediated bone resorption when given (or secreted) continuously. It also stimulates gene expression and increases the production of several local factors, including IL-6, IGF-1 and an IGF-binding protein, IGF-BP-5, and prostaglandin

Local cytokines and prostaglandins

Cytokine Interleukin-1 TNF-alpha Interleukin-4 Bone resorption + + Bone formation Prostaglandins + + -

Interleukin-6
Interleukin-7 Interleukin-11 Interleukin-13 Interleukin-18 Leukemia Inhibitory factor Interferon-gamma

+
+ + -

+
? + ? ? +

+
? ? ? +

Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings

 Calcitriol

: increases intestinal calcium and phosphorus absorption, thereby promoting bone mineralization. At high concentrations, under conditions of calcium and phosphate deficiency, it also stimulates bone resorption, thereby helping to maintain the supply of these ions to other tissues.

Calcitonin : inhibits osteoclasts and therefore bone resorption

in pharmacologic doses. However, its physiologic role is minimal in the adult skeleton. Its effects are transient, probably because of receptor downregulation.

Growth

and IGF-2 are important for skeletal growth, especially growth at the cartilaginous end plates and endochondral bone formation.

hormone and IGFs : The GH/IGF-1 system

 Glucocorticoids :

Have both stimulatory and inhibitory effects on bone cells. Essential for differentiation of osteoblasts and sensitize bone

to regulators of bone remodeling. Inhibition of bone formation is the major cause of glucocorticoidinduced osteoporosis and may be due to accelerated apoptosis of osteoblasts and osteocytes 38

cells

Thyroid

resorption and formation. Thus, bone turnover is increased in hyperthyroidism, and bone loss can occur. 39

hormones: stimulate both bone

Estrogen

loss by many local effects like: Reducing the number and depth of resorption cavities. Promoting osteoclast apoptosis.4 Increasing TGF-beta release from osteoblasts Inhibiting release of TNF-alpha

and Androgen: reduces rate of bone

Signs and Symptoms of Osteoporosis

Loss of Height Change in Body Shape and Size Pain Due to Fractures Difficulty in Breathing Abdominal Discomfort Difficulty in Buying Clothes

Diagnosis of Osteoporosis

Gold Standard is Dual Energy Xray Absorptiometry (DEXA)