Osteoporosis - Therapeutics

OSTEOPOROSIS
Dr.Prabhakar B.Pharm, PharmD -
SRMC, Chennai 1

 INTRODUCTION
 DEFINITION
 EPIDEMIOLOGY
 CLASSIFICATION
 ETIOLOGY
 RISK FACTORS
 PATHOLOGY
 CLINICAL MANIFESTATION
 DIAGNOSIS
 PREVENTION
 TREATMENT
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INTRODUCTION
 OSTEOPOROSIS is a condition characterized
by a decrease in the density of bone, its strength,
structural deterioration of bone tissue and resulting
in fragile bones having increased risk to fractures.
 Osteoporosis leads to abnormal porous bone that is compressible,
like a sponge resulting in frequent fractures in the bones.
 Osteoporosis can cause fracture that can be either in the form of
a. Cracking (as in a hip fracture) or
b. Collapsing (as in a compression fracture of the vertebrae of the
spine).
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The Common areas of bone fractures from osteoporosis
 Spine, Hips, Ribs, and Wrists
 Although osteoporosis-related fractures can occur in almost any
skeletal bone.
HALLMARK OF OSTEOPOROSIS is the loss of bone mineral and
bone matrix.
Bone mineral density (T-score):
Normal <1 SD
Osteopenia 1-2.5 SD
Osteoporosis ≥ 2.5 SD
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EPIDEMIOLOGY
 Over 200 million people worldwide suffer from this
disease.
 Aging of populations worldwide is responsible for a
major increase of the incidence of osteoporosis in
postmenopausal women.
 After 50 years of age there is an exponential rise of
fractures, such that 40% of women and 13% of men
develop one or more osteoporotic fractures.
 Women loss appro 50% of trabecular and 30% of
cortical bone on over life.
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CLASSIFICATION
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Primary Type I or Postmenopausal osteoporosis (first 3 to 6 years
after menopause) associated with increased cortical and cancellous
bone loss resulting from increased bone resorption.
Manifested by vertebral fractures, distal radius fractures, hip
fractures, and even an increased tooth loss secondary to
osteoporosis of the mandible.
Primary Type II or senile osteoporosis, occurs in both women and
men 75 years of age and older with a female:male ratio of 2:1.
These persons are at greatest risk for hip, pelvic, and vertebral
fractures.
Secondary osteoporosis results from the use of various medications
or the presence of particular disease states . This type of osteoporosis
can occur at any age and is equally common in men and women.
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The skeleton undergoes constant remodeling throughout
life. Peak bone mass is achieved by age 20 to 30 years.
Involves teams of osteoclasts and osteoblasts, termed
basic multicellular units (BMUs),
Phases in remodeling are:
1. Resorption (3 to 4 weeks)
2. Reversal
3. Formation(3 to 4 months)
4. Quiescence
BONE REMODELLING
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Calcium AND Vitamin D - required for bone growth.
PTH, Glucocorticoid Hormones, Calcitonin, Estrogen, And Testosterone - involved
in bone remodeling.
PTH & Glucocorticoid - Bone resorption
Calcitonin, Estrogen & Testosterone - Bone formation.
Calcium is primarily regulated by the actions of PTH, vitamin D, and calcitonin.
The parathyroid gland releases PTH in response to low serum calcium levels,
which in turn facilitates the mobilization of calcium and phosphate from bone
and stimulates reabsorption of calcium through the tubular system in the kidneys.
Increase in Vitamin D levels decreases PTH levels increasing bone resorption to
prevent symptomatic hypocalcemia.
Calcitonin is released in response to high serum calcium levels and decreases
intestinal absorption of calcium and phosphorous, inhibits calcium excretion in
the kidneys, and prevents bone resorption.
CALCIUM HOMEOSTASIS
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• PRIMARY OSTEOPOROSIS: Multifactorial, resulting from a
combination of factors including nutrition, peak bone mass,
genetics, level of physical activity, age of menopause (spontaneous
vs. Surgical), and estrogen status.
• SECONDARY OSTEOPOROSIS: Associated decrease in bone mass
resulting from an identified cause, including endocrinopathies,
hypogonadism, hyperthyroidism, hyperparathyroidism, cushing’s
syndrome,hyperprolactinemia, acromegaly, diabetes mellitus,
gastrointestinal disease, malabsorption, primary biliary cirrhosis,
gastrectomy, malnutrition (including anorexia),and medications
(corticosteroids, PPIs, rosiglitazone, pioglitazone)
ETIOLOGY
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LOW BONE DENSITY:
 Bone mineral density (BMD) is a major predictor of fracture risk.
 Bone loss occurs when bone resorption exceeds bone formation,
usually from high bone turnover; when the number and/or depth
of bone resorption sites greatly exceed the rate and ability of
osteoblasts to form new bone.
 Women and men begin to lose a small amount of bone mass
starting in the third to fourth decade of life as a consequence of a
slight reduction in bone formation.
ETIOLOGY
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IMPAIRED BONE QUALITY:
 In addition to BMD, the strength of bone is highly impacted by
the quality of the bone’s material properties and its structure.
 For example, accelerated bone turnover can result in bone loss,
but also can impair bone quality and the structural integrity of
bone by increasing the quantity of immature bone that is not yet
adequately mineralized.
 Bone quality assessment is important because changes in bone
quality effect bone strength much more than bone mass changes.
ETIOLOGY
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PATHOPHYSIOLOGY
POSTMENOPAUSAL OSTEOPOROSIS:
The accelerated bone loss during pre-menopause and
postmenopause results from enhanced resorption mainly as a
result of the loss in ovarian hormone production, Estrogen.
Estrogen deficiency increases proliferation, differentiation, and
activation of new osteoclasts and prolongs survival of mature
osteoclasts.
 The number of remodeling sites increases and resorption pits
are deeper and inadequately filled by normal osteoblastic
function.
 Trabecular bone is most susceptible leading to vertebral and
wrist fractures.
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PATHOPHYSIOLOGY
MALE OSTEOPOROSIS:
 Men are at a lower risk for developing osteoporosis and
osteoporotic fractures because of larger bone size, greater peak
bone mass, and fewer falls.
 Men also do not undergo a period of accelerated bone
resorption similar to menopause. However, men have a higher
mortality rate after fractures.
 The etiology of male osteoporosis tends to be multifactorial with
secondary causes and aging being the most common contributing
factors.
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 In young and middle-age men, a secondary cause for bone loss is
usually identified, with hypogonadism being the most common.
Idiopathic osteoporosis (no known cause) can occur and is
probably a result of genetic factors that have yet to be determined
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AGE-RELATED OSTEOPOROSIS:
 Age-related osteoporosis occurs in seniors mainly as a result of
hormone, calcium, and vitamin D deficiencies leading to an
accelerated bone turnover rate in combination with reduced
osteoblast bone formation.
 Hip fracture risk rises dramatically in gedriatics as a consequence
of the cumulative loss of cortical and trabecular bone and an
increased risk for falls.
PATHOPHYSIOLOGY
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 Current cigarette smoking
 Low body weight or body mass index
 Advanced age
 Alcohol in amounts >2 drinks/day
 Systemic glucocorticoid therapy
 Female sex
 Osteoporotic fracture in a first-degree relative (especially hip
fracture)
 Secondary osteoporosis (especially rheumatoid arthritis )
 Low calcium intake & physical activity
 Poor health/frailty
 Minimal sun exposure
 Recent falls
 Estrogen deficiency before 45 years old
 Impaired vision Dr.Prabhakar B.Pharm, PharmD -
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CONDITION ASSOCIATED WITH OSTEOPOROSIS OR LOW BONE
MASS:
- Chronic renal disease
- Cushing’s syndrome - Cystic fibrosis
- Diabetes mellitus - Eating disorders
- Gastrointestinal disorders
(e.g., gastrectomy,
- Malabsorption syndromes)
(e.g., hemophilia)
- Hyperparathyroidism
- Hyperthyroidism
- Hypogonadal states
- Organ transplantation
- Skeletal cancer (e.g., myeloma)
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DRUGS ASSOCIATED WITH OSTEOPOROSIS OR LOW BONE MASS:
-Anticonvulsants (phenytoin, phenobarbital)
-Aromatase inhibitors (anastrazole, exemestane, letrozole)
-Cytotoxic drugs (e.g., methotrexate, cisplatin)
-Glucocorticoids, Thyroid supplements
-Gonadotropin-releasing hormone analogs (e.g.,
leuprolide acetate, nafarelin, gosarelin)
-Heparin, Immunosuppressants (e.g., tacrolimus)
-Lithium, Medroxyprogesterone acetate
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Clinical Manifestations
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CONSEQUENCE
Elderly patients can develop pneumonia and blood clots in the leg
veins that can travel to the lungs (pulmonary embolism) due to
prolonged bed rest after the hip fracture.
Osteoporosis has even been linked with an increased risk of
Hip fracture (more common)
Fractures
Vertebrae fracture
Wrist fracture
Death
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DIAGNOSIS
WORKUP
• History and physical examination (20% of women with type I
osteoporosis have associated secondary cause), with appropriate
evaluation for identified risk factors and secondary causes
• Diagnosis of osteoporosis made by bone mineral density (BMD)
determination (BMD should ideally evaluate the hip, spine, and
wrist):
1. DUAL-ENERGY X-RAY ABSORPTIOMETRY
2. Single-energy x-ray
3. Peripheral dual-energy x-ray
4. Single-photon absorptiometry
5. Dual-photon absorptiometry
6. Quantitative CT scan
7. Radiographic absorptiometry
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DUAL-ENERGY X-RAY ABSORPTIOMETRY SCAN (DXA)
 Reveals bones status, whether appears much thinner and lighter
than normal bones.
 The National Osteoporosis Foundation, the American Medical
Association, and other major medical organizations recommend a
dual-energy X-ray absorptiometry scan (DXA, formerly known as
DEXA) for diagnosing osteoporosis.
 DXA measures bone density in the hip and the spine. The test
takes only five to 15 minutes to perform, exposes patients to very
little radiation and is quite precise.
 The bone density of the patient is compared to the average peak
bone density of young adults of the same sex and race.
 This score is called the "T score," and it expresses the bone
density in terms of the number of standard deviations (SD) below
peak young adult bone mass.
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 Osteoporosis is defined as a bone density T score of -2.5 or
below.
 It is important to note that while osteopenia is considered a
lesser degree of bone loss than osteoporosis, it nevertheless can be
of concern when it is associated with other risk factors (such as
smoking, cortisone steroid usage, rheumatoid arthritis, family
history of osteoporosis, etc.) that can increase the chances for
developing vertebral, hip, and other fractures.
Bone Mineral Density (T-score):
Normal <1 SD
Osteopenia 1-2.5 SD
Osteoporosis ≥ 2.5 SD
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PREVENTION AND TREATMENT:
DESIRED OUTCOMES:
Pharmacologic and Non-pharmacologic therapies are aimed at the
following goals:
(1) Preventing Fractures And Their Complications,
(2) Maintaining Or Increasing Bone Mineral Density,
(3) Preventing Secondary Causes Of Bone Loss, And
(4)Reducing Morbidity And Mortality Associated With
Osteoporosis.
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TO PREVENT
FALL AND CONSEQUENT FRACTURES
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MODIFICATION OF RISK FACTORS:
Non-modifiable - Family history, age, ethnicity, sex, and
concomitant disease states.
Modifiable - bone loss may be minimized or prevented by early
intervention, including smoking, low calcium intake, poor
nutrition, inactivity, heavy alcohol use, and vitamin D deficiency.
In order to prevent certain risk factors and maximize peak bone
mass, efforts must be directed toward osteoporosis prevention at an
early age.
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NUTRITION:
Good nutrition is essential for intake of sufficient nutrients and
maintenance of appropriate weight.
Dietary calcium intake is important for achieving peak bone mass
and maintaining bone density.
Adequate dietary intake of vitamin D is essential for calcium
absorption.
Good dietary sources of calcium include dairy products.
The most common source of vitamin D comes from exposure to
sunlight. Ultraviolet rays from the sun promote the synthesis of
vitamin D3 (cholecalciferol) in the skin. This generally occurs
within 15 minutes of sunlight exposure. Vitamin D also may be
found in some dietary sources, including fortified milk, egg yolks,
saltwater fish, and liver.
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EXERCISE:
Exercise can be beneficial in preventing fragility fractures.
Weight-bearing exercise such as walking, jogging, and climbing
stairs can help to build and maintain bone strength.
Muscle-strengthening or resistance exercises can help to improve
and maintain strength, agility, and balance, which can reduce falls.
A Word Of Caution About Exercise: It is important to avoid over
exercises that can injure already weakened bones. In patients over
40 and those with heart disease, obesity, diabetes mellitus, and
high blood pressure, exercise should be prescribed and monitored
by physicians.
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PREVENTION OF HIP FRACTURES IN ELDERLY PEOPLE WITH
OSTEOPOROSIS:
The FDA has approved hip protector garments for the prevention
of hip fractures in elderly people with known osteoporosis.
Brand names available include Hipsaver and Safe-hip.
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Prevention Of Osteoporosis Due To Long-term Corticosteroids:
• The long-term use of corticosteroids (such as prednisone,
cortisone, and prednisolone) can lead to osteoporosis.
• Corticosteroids cause decreased calcium absorption from the
intestines, increased loss of calcium through the kidneys in urine,
and increased calcium loss from the bones.
• To prevent bone loss while on long-term corticosteroids, patients
should have an adequate calcium (1,000 mg daily if
premenopausal, 1,500 mg daily if postmenopausal) and vitamin D
intake; however, calcium alone or combined with vitamin D
cannot be relied upon to prevent bone loss from corticosteroids
unless other prescription medications are added.
• Having a DXA bone density scan prior to beginning therapy and
careful monitoring for osteoporosis during therapy.Dr.Prabhakar B.Pharm, PharmD -
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PHARMACOLOGICAL THERAPY
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ANTI-RESORPTIVE THERAPY:
CALCIUM AND VITAMIN D:
Calcium and vitamin D supplements to meet requirements should be added to
all drug therapy regimens for osteoporosis.
M.O.A: Physiology--Hypocalcemia can result from inadequate dietary intake,
decreased fractional calcium absorption (as seen with increasing age), or
enhanced calcium excretion. To restore calcium homeostasis after
hypocalcemia, PTH concentrations rise, and vitamin D metabolism increases to
enhance intestinal calcium absorption, renal calcium reabsorption, and bone
resorption.
SIDE EFFECTS:
Loss of appetite, nausea , headache , fever , vomit , stomach ache ,
constipation, irregular or rapid heart beat .
DOSE:
SHELCAL-500 - Calcium with Vitamin D Tablet (500 mg).
Daily calcium and vitamin D requirements are highest in postmenopausal
women and elderly men: 1500 mg elemental calcium and 400 to 800 IU
vitamin D. Dr.Prabhakar B.Pharm, PharmD -
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TOXICITY:
Calcium intake greater than 2500 mg/day should be avoided due to
increased risk of toxicity, including hypercalciuria and hypercalcemia.
SALT FORMS:
Calcium carbonate should be taken with food to maximize absorption.
Better absorption may occur in form of calcium citrate because an acid
environment is not needed for absorption; it may be taken with or without
food.
Common adverse effects of calcium salts include constipation, bloating,
cramps, and flatulence.
Changing to a different salt form may alleviate symptoms for some patients.
PARENTERAL – Calcium gluconate inj – hyperkalaemia
VITAMIN D is often combined in varying amounts with calcium salts.
Vitamin D is also available as a single entity. Doses above 2000 IU/day
should be avoided owing to the risk of hypercalciuria and hypercalcemia.
Ergocalciferol (vitamin D2) and Cholecalciferol (vitamin D3) are available in
higher doses and generally are reserved for patients with vitamin D
deficiency. Dr.Prabhakar B.Pharm, PharmD -
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INTERACTION:
Alendronate -interfere with the absorption of alendronate, should be
taken atleast 2 hours before or after alendronate.
Antacids that contain aluminum-particular problem for people with
kidney disease, for whom the aluminum levels may become toxic.
Cholesterol-lowering medications -cholestyramine, colestipol, may
interfere with normal calcium absorption and increase the loss of calcium
in the urine.
Digoxin - may increase the risk of a toxic reaction to digoxin.
Diuretics -
Thiazide diuretics can raise calcium levels in the blood.
Loop diuretics (such as furosemide and bumetanide) can decrease calcium
levels.
Estrogens - increase in calcium blood levels.
Gentamicin - increase the potential for toxic effects on the kidneys.
Antibiotics - Different types of antibiotics interact with calcium.
Quinolones: interfere with the body's ability to absorb quinolone
antibiotics. Tetracyclines: interfere with the body's ability to absorb
tetracycline antibiotics. Dr.Prabhakar B.Pharm, PharmD -
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HORMONE THERAPY
MENOPAUSAL HORMONE THERAPY:
Estrogen hormone therapy after menopause (previously referred to as hormone
replacement therapy or HRT) to prevent bone loss, increase bone density, and
prevent bone fractures.
Estrogen also is available in combination with progesterone as pills and patches.
Progesterone is routinely given along with estrogen to prevent uterine cancer that
might result from estrogen use alone.
Women who have had a hysterectomy (surgical removal of the uterus) may take
estrogen alone since they no longer have a uterus to become cancerous.
HRT does not provide contraception and a woman is considered potentially fertile
for 2 years after her last menstrual period if she is under 50 years, and for 1 year
if she is over 50 years. A woman who is under 50 years and free of all risk factors
for venous and arterial disease can use a low-oestrogen combined oral
contraceptive pill to provide both relief of menopausal symptoms and
contraception.
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ESTROGEN
SYNTHETIC
ESTROGEN
STERIODAL
Ethinylestradiol,
Tibolone
NON-STEROIDAL
Diethylstilbestrol—oral
Dienestrol—topical
NATURAL
ESTROGEN
ESTRODIOL
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KINETICS:
Well absorbed orally and transdermally.
Conjugates with glucuronic acid and sulfate to get excreted via urine.
Ethinylestradiol metabolises very slowly (t1/2-12-24hr) that more active and
potent.
SIDE-EFFECTS:
Abdominal cramps and bloating, weight changes,
Breast enlargement and tenderness,
Premenstrual-like syndrome,
Sodium and fluid retention, cholestatic jaundice,
Pancreatitis, changes in libido, depression,
Mood changes, headache, migraine, dizziness &, vaginal candidiasis
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Counselling on patches Patch should be removed after 3–4 days (or once a week
in case of 7-day patch) and replaced with fresh patch on slightly different site;
recommended sites: clean, dry, unbroken areas of skin on trunk below waistline.
CAUTION:
Increase risk of developing endometrial cancer ;
Migraine (or migraine-like headaches);
Diabetes (increased risk of heart disease);
History of breast nodules or fibrocystic disease.
Tumours (e.g. Breast cancer in first-degree relative);
Symptoms of Endometriosis may be exacerbated;
Thromboembolism
DOSE:
Progynon: im 10 mg/ml(Estradiol)
Dienestrol: 0.01% cream
Estraderm-MX: 25-50 µg per 24 hrs (Estradiol patch)
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CALCITONIN:
Calcitonin is a naturally occurring mammalian hormone that plays a major role in
regulation of calcium levels.
KINETICS: Calcitonin is available in injectable and intranasal formulations. It
cannot be administered orally owing to inactivation by gastric fluids.
M.O.A:
It inhibits bone resorption by binding to osteoclast receptors.
Direct action on osteoclast –decreasing their ruffled surface.
Inhibits proximal tubular calcium and resorption by direct action kidney.
R.O.A: The parenteral formulation must be administered either subcutaneously or
intramuscularly every other day.
ADVERSE EFFECTS: including flushing, urinary frequency, nausea, vomiting,
abdominal cramping, and irritation at the injection site.
DOSE: Postmenopausal osteoporosis Adult: 100 units daily or every other day by
SC/IM Inj together with calcium and vitamin D supplements.
Renal impairment: Dosage reduction may be required.
Nasal Postmenopausal osteoporosis 200 u/day, alternating nostrils everyday.
INTERACTION: Calcitonin reduces effect of lithium.Dr.Prabhakar B.Pharm, PharmD -
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BISPHOSPHONATES:
- Analogue of pyrophosphate.
-Both alendronate and risedronate are approved for the prevention and
treatment of postmenopausal osteoporosis and treatment of steroid-induced
osteoporosis.
-Alendronate is approved for treatment of osteoporosis in men.
-Risedronate is also approved for the prevention of steroid-induced
osteoporosis.
CLASSIFICATION:
1) First-generation drugs (e.g., medronate, clodronate, and etidronate)
2) Second-generation (e.g., pamidronate, alendronate, and ibandronate): 10–
100 times more potent than the first-generation drugs.
3) Third-generation drugs (e.g., risedronate and zoledronate): are up to 10,000
times more potent than first-generation drugs.
Dose:
DRONATE: 200 mg (ETIDRONATE)
AREDRONATE: 30 mg (PAMIDRONATE)
ALENDRONATE: 5, 10 mg
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M.O.A:
Bisphosphonates concentrate at sites of active
remodeling
Incorporates into the bone matrix
When the bone is remodeled, they are released in the acid
environment of the resorption Lacunae
INDUCES APOPTOSIS TO OSTEOCLAST
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ABSORPTION, FATE, AND EXCRETION:
All oral bisphosphonates have very limited bioavailability.
They should be administered with a full glass of water following an overnight
fast and at least 30 minutes before breakfast.
Patient should be advised not to lie down for 30 min after administering orally.
They are excreted primarily by the kidneys and are not recommended for
patients with a creatinine clearance of less than 30 mL/min.
INTERACTIONS:
Antacids: absorption of bisphosphonates reduced by antacids
Antibacterials: increased risk of hypocalcaemia when bisphosphonates given
with aminoglycosides
Calcium Salts: absorption of bisphosphonates reduced by calcium salts
Iron: absorption of bisphosphonates reduced by oral iron.
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TESTOSTERONE:
Decreased testosterone concentrations are seen with certain gonadal diseases,
eating disorders, glucocorticoid therapy, oophorectomy, and menopause, and in
aging men with hypogonadism.
DOSE:
Women receiving methyltestosterone 1.25 or 2.5 mg oral daily or testosterone
implants 50 mg every 3 months had increased BMD.
Transdermal gel, oral, intramuscular, and pellet testosterone products are
available.
Patients using these products should be evaluated within 1 to 2 months of onset
and then every 3 to 6 months thereafter.
M.O.A:
Acts on bone leading to increased BMD in hypogonadal men and senior men
with normal or mild hormonal deficiency.
Testosterone replacement should not be used solely for the prevention or
treatment of osteoporosis, but might be beneficial to reduce bone loss in
patients needing therapy for hypogonadal symptoms.
As antiresorptive agents to reduce bone turnover but may also
stimulate osteoblastic activity.Dr.Prabhakar B.Pharm, PharmD -
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TESTOSTERONE: acts on both osteoblasts and osteoclasts via both androgen
receptorsand, following aromatization, via estrogen receptors. Thus,the
conversion of testosterone to estrogens is of crucial importancefor maintaining
normal bone metabolism.
Androgen receptor- mediated
effects
Estrogen receptor- mediated
effects
Increased osteoblast lifespan (by
increasing proliferation and
decreasing apoptosis)
Decreased osteoclast lifespan (by
decreasing proliferation and
increasing apoptosis)
Decreased early bone turnover Decreased bone turnover
Increased bone formation Decreased bone resorption and
possible increased bone formation
Increased periosteal apposition of
bone
Decreased periosteal apposition of
bone
Increased long bone growth Promotion of epiphyseal closure
Increased bone size
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KINETICS:
Inactive orally due to 1st pass metabolism in liver.
In circulation 98% bound to a specific golbulin and to albumin.
T ½ is 10-20 mins.
SIDE EFFECTS:
Virilization
Acne
Oligozoospermia
Cholestatic jaundice
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PARATHYROID HORMONE:
Teriparatide, recombinant human parathyroid hormone, is the first anabolic
agent approved by the FDA for treatment of osteoporosis.
This agent differs from antiresorptive therapies in that it stimulates osteoblastic
activity to form new bone with once-daily administration.
Its action similar to endogenous parathyroid hormone, and continuous infusions
actually stimulate osteoclastic activity and increase bone resorption.
M.O.A: Teriparatide increases bone formation by increasing the number of bone-
building cells (osteoblasts). It also increases serum levels of calcium and calcitriol
(a metabolite of vitamin D that promotes absorption and use of calcium in bone-
building).
It is recommended for use in patients with severe osteoporosis or those who have
not responded adequately to other treatments.
DOSE AND ROA: The dose of teriparatide is 20 mcg given by subcutaneous
injection once daily. It is available in a prefilled multiple-dose pen delivery
system.
ADVERSE: Nausea, headache, leg cramps, dizziness, injection-site discomfort, and
hypercalcemia. It should not be used in patients with preexisting hypercalcemia
CONTRA-INDICATION: Pregnancy
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SELECTIVE ESTROGEN RECEPTOR MODULATOR:
The actions of SERMs on various tissues:
Bone turnover and postmenopausal osteoporosis respond favorably to most
SERMs,
Breast - all SERMs decrease breast cancer risk, and tamoxifen is mainly used
for its ability to inhibit growth in estrogen receptor-positive breast cancer.
Deep venous thrombosis - the risk may be elevated in at least some SERMs.
Hot flashes are increased by some SERMs.
Name Uses Effects/location
clomifene used in anovulation antagonist at hypothalamus
Femarelle
managing menopause symptoms,
osteoporosis
agonist at brain and bone
Ormeloxifene Contraception
agonist at bone; antagonist
at uterus and breast
Raloxifene osteoporosis, breast cancer
agonist at bone; antagonist
at uterus and breast
Tamoxifen breast cancer
agonist at bone and uterus,
antagonist at breast
Toremifene breast cancerDr.Prabhakar B.Pharm, PharmD -
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RALOXIFENE: is used to prevent and treat bone loss (osteoporosis) in women
after menopause. It’s an estrogen agonist in bone and reduces the number of
vertebral fractures by up to 50% in a dose-dependent manner.
M.O.A:
It works by acting like estrogen (as a selective estrogen receptor modulator or
SERM) in body.
Raloxifene helps to preserve bone mass, but it does not affect the breast and
uterus like estrogen or relieve symptoms of menopause such as hot flashes.
ADV:
The drug also acts as an estrogen agonist in reducing total cholesterol and
LDL but does not increase HDL or normalize plasminogen-activator inhibitor
in postmenopausal women.
Raloxifene does not cause proliferation of the endometrium. Raloxifene has
an antiproliferative effect on ER-positive breast tumors and on proliferation
of ER positive breast cancer cell lines and significantly reduces the risk of ER-
positive but not ER-negative breast cancer.
Raloxifene does not alleviate the vasomotor symptoms associated with
menopause.
ADR: Leg cramps and a threefold increase in deep vein thrombosis
and pulmonary embolism. Dr.Prabhakar B.Pharm, PharmD -
SRMC, Chennai 59

CONTRA: This medication is not recommended for use in women before
menopause. It should not be used in children.
R.O.A: orally once a day, with or without food.
SIDE EFFECTS: Hot flashes, sweating, or leg cramps may occur. If these
effects persist or worsen, unlikely but serious side effects occur: leg
swelling/pain, trouble breathing, chest pain, vision changes.
PRECAUTIONS: active or past history of blood clots (e.g., deep venous
thrombosis, pulmonary embolism, retinal vein thrombosis). Lack of
movement may increase the risk for blood clots.
DOSE:
Evista - (raloxifene hydrochloride, 60 mg) for the prevention of
osteoporosis in postmenopausal women. Evista, the first in a class of new
drugs called selective estrogen receptor modulators (SERMs) to be
approved by the FDA for marketing for the prevention of osteoporosis.
SRMC, Chennai 60

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DRUGS DOSE KINETICS SIDE EFFECTS MAJOR INTERACTION
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DRUGS DOSE KINETICS SIDE EFFECTS
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REFERENCE:
1. DIPIRO A PATHOPHYSIOLOGIC APPROACH 7THEDITION
2. HARRISONS PRINCIPLES OF INTERNAL MEDICINE 16TH EDITION
3. APPLIED THERAPEUTICS - KODA KIMBLE(9TH ED. 2009)
4. HERFINDAL
5. CLINICAL PRACTICE AND THERAPEUTICS BY ROGER WALKER
6. ESSENTIALS OF MEDICAL PHARMACOLOGY 7TH EDITION.
7. GOODMAN & GILMAN'S THE PHARMACOLOGICAL BASIS OF THERAPEUTICS
- 11TH ED. (2006)
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Osteoporosis - Therapeutics

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