DRUGS for OSTEOPOROSIS

BONES
is the substance that forms the skeleton of the body
It is composed chiefly of calcium phosphate and calcium carbonate
It also serves as a storage area for calcium, playing a large role in calcium balance in the blood.
They also support and protect internal organs
Bone marrow, the soft, spongy tissue in the center of many bones, makes and stores blood cells

FOUR TYPES OF BONE TISSUE

OSTEOCLASTS
breaks down old bone tissue by releasing chemicals
OSTEOBLASTS
bone building cells, create collagen to build the matrix
OSTEOCYTE
the main cell in bone tissue. Mature bone cell, maintains metabolism
Osteoprogenitor
bone stem cells creates new cells, under goes cell division
BONE REMODELLING
The purpose of bone remodeling is to remove and replace damaged bone and to maintain calcium
homeostasis.
BONE REMODELLING

BONE RESORPTION
Osteoclasts are cells that break down bone and release the minerals, resulting in a
transfer of calcium from bone fluid to the blood.
Reversal phase
Bone resorption transition to bone formation
they complete the resorption process and produce the signals that initiate
formation
BONE FORMATION
Osteoblasts or bone-building cells synthesize new bone
BONE MINERALIZATION
Osteocytes are mature bone cells that help in mineralization of bone
Crystals of calcium phosphate known as hydroxyapatite are deposited in the new
bone matrix
 is essential for bone strength
OSTEOPOROSIS
causes bones to become weak and brittle
is characterized by progressive loss of bone mass and skeletal fragility
occurs when the creation of new bone doesn't keep up with the removal of old bone
occurs in older men and women but is most pronounced in postmenopausal women
PATHOGENESIS OF DEVELOPING OSTEOPOROSIS
Inadequate Peak Bone Mass
amount of bone tissue in skeleton is known as bone mass(keeps growing till the age
of 30 years )
bone peak mass is when the bones reach their maximum strength and
density
Excessive Bone Resorption
Overproduction of osteoclast cells
Hormonal factors
Lack of calcitonin
estrogen (A hormone that is lost after menopause)
parathyroid hormone
Inadequate formation of new bone
Underproduction of osteoblast cells
Deficiency of calcium and vitamin-D also leads to impaired bone deposition
TREATMENT FOR OSTEOPOROSIS
Nondrug strategies to reduce bone loss in postmenopausal women include
adequate dietary intake of calcium and
vitamin D
weight-bearing exercise
smoking cessation
avoid drugs that increase bone loss such as glucocorticoids
EFFECTS OF GLUCORTICOIDS TO BONES

B ISPHOSPHONATES

ALENDRONATE
IBANDRONATE
R ISEDRONATE
ZOLEDRON IC ACID
 are preferred agents for prevention and treatment of postmenopausal osteoporosis
MECHANISM OF ACTION
Decrease osteoclastic bone resorption mainly through
an increase in osteoclastic apoptosis (programmed cell death)
inhibition of the cholesterol biosynthetic pathway important for osteoclast function
The decrease in osteoclastic bone resorption

small increase in bone mass
and a decreased risk of fractures in patients with osteoporosis.
BENEFICIAL EFFECTS of alenronate: several years of therapy DISCONTINUATION: gradual loss of
effects
PHARMACOKINETICS:
Food and other medications significantly interfere with absorption of oral Bisphosphonates
Once bound to bone, they are cleared over a period of hours to years
Elimination is primarily via the kidney, and bisphosphonates should be avoided in severe
renal impairment.
For patients unable to tolerate oral bisphosphonates, intravenous ibandronate and
zoledronic acid are alternatives.
Specific Guidelines to Maximize Absorption

ADVERSE EFFECTS
Diarrhea
abdominal pain
musculoskeletal pain
Osteonecrosis of the jaw
risk of atypical fractures may increase with long-term use
Etidronate: osteomalacia
Alendronate, risedronate, and ibandronate
Esophagitis
esophageal ulcers
To minimize esophageal irritation:should remain upright after taking oral bisphosphonates.
SELECTIVE ESTROGEN RECEPTOR MODULATORS
Lower estrogen levels after menopause promote proliferation and
activation of osteoclasts, and bone mass can decline rapidly.
 Estrogen replacement is effective for the prevention of postmenopausal bone loss.
RALOXIFENE
Is a selective estrogen receptor modulator approved for the prevention and
treatment of osteoporosis.
It has estrogen-like effects on bone and estrogen antagonist effects on breast and
endometrial tissue.
It is an alternative for postmenopausal osteoporosis in women who are intolerant
to bisphosphonates
It also increases bone density without increasing the risk of endometrial cancer
it decreases the risk of invasive breast cancer
also reduces levels of total and LDL cholesterol
ADVERSE EFFECTS
hot flashes
Leg cramps
risk of venous thromboembolism
CALCITONIN
SALMON CALCITONIN
is indicated for the treatment of osteoporosis in women who are at least 5 years
postmenopausal.
reduces bone resorption, but it is less effective than bisphosphonates.
unique property: relief of pain associated with osteoporotic fracture
beneficial in patients with a recent vertebral fracture
It is available in intranasal and parenteral formulations
ADVERSE EFFECTS
intranasal administration: rhinitis and other nasal symptoms
Potential increased risk of malignancy
should be reserved for patients intolerant of other drugs for osteoporosis.
DENOSUMAB
is a monoclonal antibody that targets receptor activator of nuclear factor kappa-B ligand
Inhibits osteoclast formation and function
for the treatment of postmenopausal osteoporosis in women at high risk of fracture
administered via subcutaneous injection every 6 months
ADR
increased risk of infections
dermatological reactions
Hypocalcemia
osteonecrosis of the jaw
atypical fractures
It should be reserved for women at high risk of fracture and those who are intolerant
of or unresponsive to other osteoporosis therapies
TERIPARATIDE

is a recombinant form of human parathyroid hormone

administered subcutaneously daily for the treatment of osteoporosis. the first approved
treatment for osteoporosis that stimulates bone formation
promotes bone formation by stimulating osteoblastic activity
increased risk of osteosarcoma in rats
The safety and efficacy of this agent have not been evaluated beyond 2 years
should be reserved for patients at high risk of fractures and those who have failed or
cannot tolerate other osteoporosis therapies