Drugs for Bone

Disorders
 BONE REMODELING

• 10% of the adult skeleton replaced each year.

 purpose of bone remodeling :
 Remove and replace damaged bone cells
 maintain calcium homeostasis.

Process of Bone Remodeling 3:

• 1. Bone resorption:
• 2.Bone formation
• 3.Bone mineralisation
 Bone disorders
Osteoporosis Paget disease Osteomalacia
• progressive loss of bone • Disorder of bone remodeling • softening of the bones
mass and skeletal that results in disorganized
fragility bone formation and enlarged Vita.. D deficiency.
or misshapen bones.
 Patient may express
• bone pain
• bone deformities
• fractures.

• Osteomalacia in
children is referred to
as rickets
As osteoporosis is more common, drug therapy
for osteoporosis is the focus of OUR
PRESENTATION
 TREATMENT OF OSTEOPOROSIS
Non Pharmacologic therapy
• adequate dietary intake of
calcium and vitamin D
• weight-bearing exercise
• smoking cessation.
• Avoid drugs that increase bone loss
such as glucocorticoids.
[Note: Use of glucocorticoids
(for example, prednisone 5 mg/day
or equivalent) for 3 months or more
is a significant risk factor for
osteoporosis.]
Pharmacologic therapy
• warranted in
postmenopausal women
and men aged 50 years
• who have a previous
osteoporotic fracture
• a bone mineral density
that is 2.5 standard
deviations or more below
that of a young adult, or a
low bone mass with a high
probability of future
fractures.
 Bisphosphonates
1. Alendronate • ALL Bisphosphonates are used for
Treatment of :
2. ibandronate
• Osteoporosis
3. risedronate • Paget disease
4. zoledronic acid • bone metastases
5. Etidronate • hypercalcemia of malignancy.
6. pamidronate
 Alendronate,ibandronate ,risedronate ,z
7. Tiludronate oledronic acid
• are preferred agents for prevention and
treatment of postmenopausal
osteoporosis

The beneficial effects of alendronate persist over several years of therapy but discontinuation
results in a gradual loss of effects.
 Mechanism of action
Bisphosphonates osteoclastic bone resorption mainly through osteoclastic apoptosis and
inhibition of the cholesterol biosynthetic pathway important for osteoclast function.
The decrease in osteoclastic bone resorption results bone mass and risk of
fractures in patients with osteoporosis.
 Pharmacokinetic
• The oral bisphosphonates alendronate, risedronate, and ibandronate are
dosed on a daily, weekly, or monthly basis depending on the drug.
• Absorption after oral administration is poor, with less than 1% of the dose
absorbed.
 Food and other medications significantly interfere with absorption of oral
bisphosphonates,the Following guidelines for administration should be
followed to maximize absorption

• Bisphosphonates are rapidly cleared from the plasma, primarily because they avidly bind to
hydroxyapatite in the bone. Once bound to bone, they are cleared over a period of hours to
years.
• Elimination is primarily via the kidney.
• Contraindications. Patients of Renal failure .
• patients unable to tolerate oral bisphosphonates, intravenous ibandronate and zoledronic acid
are alternatives.
 Adverse effects:

• Alendronate, risedronate, and ibandronate are associated with esophagitis and esophageal
ulcers.
• To minimize esophageal irritation, patients should remain upright after taking oral
bisphosphonates.
 Adverse effects:
The risk of atypical fractures may increase
with long-term use of bisphosphonate therapy.

Etidronate is the only bisphosphonate that causes osteomalacia following long-term

 Selective estrogen receptor modulators

 Lower estrogen levels after menopause promote proliferation

and activation of osteoclasts•••• bone mass
 Estrogen replacement is effective for the prevention of
postmenopausal bone loss.
 since estrogen may increase the risk of endometrial cancer (when used
without a progestin in women with an intact uterus)breast cancer, stroke,
venous thromboembolism, and coronary events
• Raloxifene
• 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
• Advers effects Include :

Hot flashes Leg cramps Venous thromboembolism

 Calcitonin

• ⬇ Bone Resorption & ⬆ Bone thicknes or density

• Less effective than Biphosphonates
• Salmon calcitonin is indicated for the treatment of
osteoporosis in women who are at least 5 years
postmenopausal
• A unique property of calcitoninis the relief of pain
associated with osteoporotic fracture.Therefore,
calcitonin may be benefcial inpatientswith arecent
vertebralfracture.
• Common adverse effects of intranasal administra-
tion include rhinitis and other nasal symptoms
 Denosumab
• Denosumab is a monoclonal antibody that targets receptor
activator of nuclear factor kappa-B ligand and inhibits
osteoclast formation and function.
• Denosumab is approved for the treatment of
postmenopausal osteoporosis in women at high risk of
fracture.
• It is administered via subcutaneous injection every 6 months.
• Denosumab has been associated with an increased risk of
infections, dermatological reactions, hypocalcemia,
osteonecrosis of the jaw, and atypical fractures.
• It be reserved for women at high risk of fracture and those
who are intolerant of or unresponsive to otheunresponsive
to other osteoporosis therapies.
 Teriparatide
• Teriparatide is a recombinant form of parathyroid
hormone that is administered subcutaneously daily
for the treatment of osteoporosis.
• Teriparatide promotes bone formation by
stimulating osteoblastic activity.
• Teriparatide causes osteosarcoma in rats.
• Teriparatide should be reserved for patients at high
risk of fractures and those who have failed or
cannot tolerate other osteoporosis therapies.
THANKS