Treatment of Osteoporosis

Osteoporosis- is a disease of bones that leads to an increased risk of fracture.(break down of continuity in bone-indicate fxr fx) 

Types

• Primary-mostly seen in postmenopause womens

• Secondary-it occurs in old age above than 70 years of age.

• Its ratio 2:1 in male and female, fractures in hip,wrist,hand,foot,column,ribs

Causes

• As an adverse effect of long term administration of glucocorticoids. glucocorticoids( may increase bone resorption, inhibit bone formation, have indirect actions on bone by decreasing intestinal calcium absorption and induce hypercalciuria)

• Bone resorption is the process by which osteoclasts break down bone and release theminerals, resulting in a transfer of calcium from bone fluid to the blood

• As a manifestation of endocrine disease such as thyrotoxicosis or hyperparathyroidism. Hyperthyroidism is associated with an increased excretion of calcium and phosphorous in the urine and stool, which results in a loss of bone mineral.

• The parathyroid hormone regulates the amounts of calcium in our body. It is responsible for absorption of calcium from the bones and distribution of it among the body through the blood vessels.

• This means excessive amounts of PTH absorbs more calcium from the bones and since even the body cannot tolerate calcium more than its requirements, the extra calcium is excreted through urine. Hypercalcaemia for the body becomes hypocalcaemia for the bones. Thus, bones become deficit of calcium

• As a feature of malabsorption syndrome• As a consequence of alcohol abuse and cigarette

smoking.(in many cases smokers are thinner than nonsmokers, tend to drink more alcohol, may be less physically active, and have poor diets. Women who smoke also tend to have an earlier menopause than nonsmokers. These factors place many smokers at an increased risk for osteoporosis apart from their tobacco use)

• Without obvious cause

Drugs used in Osteoporosis

• 1.Teriparatide• 2.Raloxifene• 3.Calcitonin• 4.Biphosphonates

TERIPARATIDE

• It is a recombinant segment of human parathyroid hormone. Endogenous 84-amino acid parathyroid hormone (PTH) is the primary regulator of calcium and phosphate metabolism in bone and kidney. Physiological actions of PTH include regulation of bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption.

• It stimulates new bone formation.• It increases spinal bone density, and decreases the risk of

vertebral fractures.• It is given 20 mg S/C daily, rapidly degraded mostly in liver

and kidneys.• It is approved for use for two years only.

• Once-daily administration of teriparatide stimulates new bone formation on trabecular and cortical (periosteal and/or endosteal) bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity

Pharmacokinetics

• Teriparatide is absorbed after subcutaneous  injection; the absolute bioavailability is

approximately 95%,half life approximately 1 hour when administered by subcutaneous injection

Raloxifene

• It is an SERMselective estrogen receptor modulator ie non-hormonal agent that exhibit estrogen agonist action on estrogen receptors in bones. It has antagonist activity on estrogen receptors in mammary tissues and the uterus.

• MOA• It produces a dose-dependent increase in osteoblast

activity and reduction in osteoclast activity. •  Raloxifene appears to act as an estrogen agonist in bone. It

decreases bone resorption and bone turnover, increases bone mineral density (BMD) and decreases fracture incidence

PHARMACOKINETICS:

• It is well absorbed in GIT and undergoes extensive first pass hepatic metabolism. Thus bioavailibilty is only 2%. It is widely distributed in the tissues and is converted to an active metabolite in liver, lungs, bone, spleen, uterus and kidneys.It has avery long ½ life > 24 hours. It is mainly excreted in the feces.

Adverse effects

• Common: hot flushes and leg cramps.• Serious side effect: venous thromboembolism.• Drug interaction• When Warfarin is given with Raloxifene there is a

10% decrease in prothrombin time.• Colestyramine reduces the enterohepatic recycling of

Raloxifene by 60%. • Therapeutic use• It is approved for the prevention and treatment of

osteoporosis

CALCITONIN

• It is secreted by the parafollicular cells of mammalian thyroid as a single chain peptide hormone with 32 amino acids and a molecular weight of 3600.

• MOA • It inhibits osteoclastic bone resorption .But

with time both formation and resorption of bone are reduced.

• PHARMAKOKINETICS• Synthetic human calcitonin is now

available.It is given by S/C or I/M route, can also be given intranasally.It has a ½ life of about 10 minutes with a metabolic clearance of 8-9 ml/kg/min. Much of clearance occurs in kidneys although little intact calcitonin appears in the urine.

• Therapeutic uses • Osteoporosis• Pagets disease is a chronic disorder that can

result in enlarged and misshapen bones. The excessive breakdown and formation of bone tissue causes affected bone to weaken, resulting in pain, misshapen bones, fractures, and arthritis in the joints near the affected bones

• Hypercalcemia

BIPHOSPHONATES

• Alendronate• Risedronate• Ibandronate • Pamidronate• Zoledronate

• MODE OF ACTION• They retard formation and dissolution of

hydroxyapatite crystals within and outside the skeletal system. They localize to regions of bone resorption and so exert their greatest effects on osteoclasts. The exact mechanism by which they selectively inhibit bone resorption is not clear

• PHARMAKOKINETICS• About less than 10% of an oral dose of these

drugs is absorbed. Food reduces absorption even further. All currently available biphosphonates except Etindronate cause gastric irritation but only pamidronate is not available as an oral preparation.

• Nearly ½ of absorbed drug accumulates in bones the remainder is excreted unchanged in the urine.

• Adverse effects • 1.Gastric and esophageal irritation

particularly by Pamidronate and high doses of Alendronate. Esophageal irritation can be minimized by taking the drug with a full glass of water and remaining upright for 30 minutes.

• 2.Induction of mineralization defect by higher than approved doses of Etidronate .

• 3.Ostenecrosis of jaw (ONJ) rare in patients receiving the usual doses of Biphosphonates.

•  • Containdication

• Severe renal disease.

• Vitamin D and Calcium • To counter the reduced calcium transport

associated with osteoporosis, vitamin D therapy is often used in addition to dietary calcium supplementation.