Osteoporosis is defined as low bone mass and
microarchitectral deterioration of bone tissue, leading to
enhanced bone fragility and a consequent increase in fracture
World Health organization (WHO) defines Osteoporosis as a
bone density that falls 2.5 standard deviations (SD) below the
mean for young healthy adults of the same race and gender—
also referred to as a T-score of –2.5.
In US 8 million women and 2 million men have osteoporosis.
It occurs more frequently with increasing age as bone tissue is
One in three women and one in 12 men over the age of 50
worldwide are estimated to have osteoporosis.
7% of postmenopausal women had osteoporosis.
The prevalence of osteoporosis among American subgroup are
Non Hispanic white women: 20%
Mexican American women: 10%
Non Hispanic black women: 5%
Men of all ages: 6%
Epidemiology of fractures: At least
1.5 million fractures occurs in each
year in the US as a consequence of
In US and Europe, osteoporosis
related fractures are more among
women than men.
3 lakh hip fracture,7 lakh vertebral
fracture and 250,000 wrist fracture
occur each year in the US.
Multiple fractures lead to height loss,
kyphosis, secondary pain
Etiology and risk factors
The magnitude and significance of the risk factors varies by
gender, ethnicity, age, and the duration of risk factor presence.
4 major risk factors age, low BMD, gender, Family history.
The other factors that can contribute to osteoporosis are
Sedentary life style
Low body weight
Cigarette and excessive alcohol use
Low calcium intake & malnutrition
Low sun exposure
Medical problems like Rheumatoid
syndrome3, dementia, parkinsonism
Medications like immunosuppressant,
diuretics, cancer chemotherapy,
aluminums, glucocorticoids etc.
Bone loss due to normal age related changes in
bone remodelling as well as extrinsic and
intrinsic factors that exaggerate this process.
Bone remodelling has two primary functions:
To repair micro damage within the skeleton to
maintain skeletal strength.
To supply calcium supply from the skeleton to
maintain serum calcium.
After age 30 to 45,the resorption and formation
processes become imbalanced, and resorption
Excessive bone loss can be loss due to an
increase in osteoclastic activity and/or
osteoblastic activity. 10
Other reasons include
Peak bone mass may be
impaired by inadequate calcium
intake, leading to increased risk
It induce secondary
hyperparathyroidism and an
increase in the rate of
remodelling to maintain normal
serum calcium levels.
cause bone lose by
a) Activation of new bone
b) Exaggeration of the
imbalance b/w bone
formation and resorption
Glucocortcoid are the most
common cause of medication
Other medication include
Vit D deficiency: Vit D deficiency leads to
hyperparathyroidism and is an important risk
factor for osteoporosis and fractures.
Physical inactivity: Prolonged bed rest and
paralysis, results in significant bone loss.
Chronic disease : Disease associated with
an increased risk of osteoporosis in adult are
turner syndrome, Cushing's syndrome, DM
1,thyrotoxicosis, malnutrition, pernicious
anaemia, pregnancy and lactation.
Cigarettes consumption : over a long
period has detrimental effect on bone mass.
These effects may be mediated directly, by
toxic effects on osteoblasts, or indirectly by
modifying estrogen metabolism.
General : fractures occur after bending,
lifting, or falling.
Symptoms : pain, immobility, bruising,
depression and lower self esteem.
Signs : Shortened stature, Kyphosis, or
Lordosis, Bone pain or fracture(commonly of
vertebra ,hip or forearm).
Non pharmacologic treatment
Diet changes : For all individuals, a
well-balanced diet with adequate
calcium and vitamin D is essential for
Calcium contributors - Dairy
products like milk, yogurt, cheese,
ice cream, cottage cheese, and
fortified orange juice or soy products.
Most vitamin D comes from sun-induced
Vitamin D contributors - fatty fish,
few unfortified foods
Fruits and vegetable containg Mg is
essential for healthy bone.
Patients should be educated to avoid
consuming excessive amounts of Vit A.it
have increased risk of fracture in both
men and women.
Vitamin C influences collagen production,
and increases osteoblast formation and
Moderate protein intake is recommended.
Caffeine and Hypophosphatemia
decreases the BMD.
Social habit changes:
Smoking causes bone loss and
increases hip fracture risk by
several mechanisms such as
decreased body weight
enhanced estrogen metabolism
increased PTH concentrations
Excessive alcohol use has been associated
with low BMD and subsequent fracture in
some, but not all, studies.
Malnutrition associated with alcoholism
could also play a role. Alcohol use also
may increase the risk of falls.
Exercise : Long-term exercise during
youth increases peak BMD.
Physical activity, especially aerobics,
weight bearing, and resistance exercise
and walking preserves BMD .
Exercise also enhances calcium and estrogen therapy.
Excessive exercise in a premenstrual woman, however, can
lead to amenorrhea and estrogen deficiency with consequent
bone loss and increased fracture risk.
Prevention of fall : Ambulation-assistive devices (canes and
walkers) and Assistance.
The living environment should be evaluated and modified.
the use of hip protectant.
Medications should be reviewed .
Vision should be assessed.
Two FDA-approved indication for
osteoporosis medication- prevention and
There are two main classes of drugs.
Anti- resorptive therapy - Prevents
Bone formation Therapy - Improves bone
Newer procedures – Vertebroplasty &
Vitamin D & its metabolites
Selective estrogen modulators
Estrogen & hormonal therapy
Testosterone and Anabolic Steroids
BONE FORMATION THERAPY
Teriparatide (Parathyroid Hormone)
HMG - CoA Reductase Inhibitors
Growth Hormones and Factors
Calcium : adequate calcium intake is considered
standard for osteoporosis prevention and treatment
for all people.
Dose 200 – 1500 mg / day.
Adr include gas, upset stomach, rare kidney stones.
Drug interaction: absorption decreased with PPI,
decrease absorption of alendronate, etidronate,
fluoride, tetracycline and phenytoin, induce
hypercalcemia with diuretics.
Vitamin D and Its Metabolites
Vitamin D 400 units with calcium 500 mg
twice daily increased spine and hip BMD in
seniors with vitamin D deficiency.
Vitamin D maintain muscle function &
Orally administered vitamin D3, in a dosage of
100,000 units once every 4 months for 5 years,
reduced the risk of fracture by 22% to 33% in a
population of men and women.
Doxercalciferol (1α-hydroxyvitamin D2) is
under investigation for osteoporosis treatment.
MOA: It binds to the hydroxyapatite in bone,
they decrease resorption by inhibiting osteoclast
adherence to bone surfaces.
Etidronate - inhibit bone mineralization that
could lead to osteomalacia.
Alendronate(5mg daily) postmenopausal
Risedronate(5mg daily) osteoporosis
Alendronate - glucocorticoid-induced &
osteoporosis in men
Selective Estrogen Receptor Modulators
Raloxifene - the first SERM approved for
prevention and treatment of postmenopausal
osteoporosis, is an estrogen agonist in bone tissue
but an antagonist in the breast and uterus.
Tamoxifen approved for breast cancer
prevention, also inhibits bone loss.
Investigational SERM - Arzoxifene,
bazedoxifene, lasofoxifene, and ospemifene
Calcitonin is released from the thyroid gland
when serum calcium is elevated.
Salmon calcitonin is used clinically because it is
more potent and longer lasting than the
Calcitonin (200 units daily, intranasally every
other day) is indicated for osteoporosis treatment
for women at least 5 years past menopause.
Calcitonin may provide pain relief to some
patients with acute vertebral fractures, but this
effect is minimal.
Estrogen and Hormonal Therapy
decrease osteoclast recruitment and activity.
inhibit PTH peripherally.
increase calcitriol conc. and intestinal Ca absorption.
decrease renal calcium excretion.
decrease cytokine concentrations .
decrease the activity of the OPG/RANK/RANKL
pathway, inhibiting bone resorption.
Response to estrogen deficiency and replacement
may be related to estrogen receptors and
Hormonal therapy (HT) was shown to decrease
vertebral, hip, and all fractures by 34%, 34%, and
Tibolone, a synthetic steroid, and its metabolites
are weak estrogen-, progesterone-, and androgen-receptor
They relieve hot flushes and increase BMD, but
have no effect on the endometrium.
The isoflavonoids (soy proteins) and lignans (flaxseed) are the
most common forms of phytoestrogens.
Bone effects may be related to bone estrogen receptor agonist
activity or potentially direct or indirect effects on osteoblasts
Testosterone and Anabolic Steroids
In a few studies, women receiving methyl testosterone 1.25 or
2.5 mg oral daily or testosterone implants 50 mg every 3
months had increased BMD.
Testosterone, in various salt forms, was associated with
increased BMD in some studies when given to hypogonadal
men and senior men with normal hormone levels or mild
Transdermal gel, oral, intramuscular, and pellet testosterone
products are available.
Teriparatide (Parathyroid Hormone)
Therapeutic doses improve BMD and reduce fracture
Parathyroid hormone is currently the only approved
osteoporosis medication that works by stimulating
Teriparatide works equally well in women and men
Teriparatide : decrease the risk of new vertebral
fractures by 65% with osteoporosis and pre-existing
fractures & non vertebral fracture risk by 53%
with the 20-mcg/day in dosage
Teriparatide is commercially available as a prefilled 3-mL pen
type delivery device that administers subcutaneous injections
in the thigh or abdominal area.
Strontium stimulates bone formation and decreases bone
strontium ranelate 1 g twice daily or 2 g once daily reduced
new vertebral fractures by 41%, and increased lumbar spine
BMD by 14% and femoral neck BMD by 8% compared with
HMG-CoA Reductase Inhibitors (Statins)
These were discovered to increase bone density in
Although observational studies have linked statin
use with decreased fracture risk, a large case-control
study did not demonstrate reduction in
fracture risk for statin-treated patients
Although fluoride increases osteoblastic activity
and bone formation through intracellular signaling
pathways involving tyrosine phosphatases and
mitogen-activated protein kinases, it remains an
unapproved therapy despite 30 years of clinical
Growth Hormones and Factors
Growth hormone (GH) and IGF-1
play important roles in bone turnover
and remodeling, with multiple effects
on other tissues.
The longer-term studies showed a
positive effect that continued to
increase for 1 to 2 years after
discontinuation of GH therapy.
Recombinant IGF-1 injections, with
or without IGF-3 binding protein,
increased both bone formation and
Osteoprotegerin (OPG), a competitive
inhibitor of RANKL, blocks osteoclastic
differentiation and has decreased bone
resorption biomarkers (phase I and II).
Agents to block osteoclast attachment,
inhibit bone matrix degradation , or
change osteoclast cell structure have
been initially effective.
Vertebroplasty and kyphoplasty
The percutaneous injection of
polymethylmethacrylate (PMMA) bone cement
into a compressed vertebral fracture confers
significant pain relief for many patients.
Under local anesthetic, with computed tomography
scanning or fluoroscopic guidance, PMMA is
injected under slight pressure during vertebroplasty.
The procedure stabilizes the damaged vertebrae and
reduces pain in 70% to 92% of patients. Pain scores
usually improve by approximately 50% at 1 month
following the treatment.
Kyphoplasty is a
newer procedure that
requires drilling into
the vertebral body
and inflating a
balloon to re-expand
the fracture. The
process is followed
by the injection of
about 7 mL of the
Women with amenorrhea
For those with amenorrhea or anorexia, higher calcium
intakes of 1200 to 1500 mg and adequate vitamin D are
In anorexia, the primary therapy is normal diet, weight gain,
and return of normal menses.
The American Academy of Pediatrics recommends low-dose
estrogen supplementation for amenorrhea if age is greater than
16 until normal menses returns
Neither estrogens nor SERMs are used.
Bisphosphonates are the drugs of first choice.
Although alendronate is FDA-approved for men and reduces
the risk of vertebral fractures, other available bisphosphonates
are also clinically used.
Osteoporosis due to secondary causes should include treatment
of the underlying cause plus a bisphosphonate.
Adequate calcium and vitamin D intake should be
For most seniors, bisphosphonates are the preferred
Raloxifene, nasal calcitonin, or parenteral teriparatide
are treatment options for seniors who will not or
cannot take an oral bisphosphonate.
Patients taking glucocorticoids should be managed
with calcium and vitamin D supplementation plus a
Otherwise, standard osteoporosis prevention and
Before transplant, BMD should be measured and
vitamin D and gonadal status assessed.
Bone-healthy lifestyle changes and therapy should be
instituted as needed and hypogonadism corrected
before and after transplant.
Intermittent Pamidronate has decreased bone loss in
most transplant recipients.
Testosterone may cause hypoglycemia.
Although one study with alendronate documented
decreased insulin requirements, further data are
Current data suggest that both the virus and its medical
treatments can decrease BMD.
Standard treatment, usually consisting of a bisphosphonate
plus calcium and vitamin D supplementation, should be used
once osteoporosis is diagnosed, although no specific
population data yet exist.
Prevention and treatment efforts usually include adequate
Calcium and vitamin D intake.
Correction of hypogonadism.
Reductions in glucocorticoid use.
Women and men over age 50 should be assessed
for risk factors.
Patients with premature or severe osteoporosis
should be evaluated for secondary causes of bone
Male osteoporosis is often secondary to specific
diseases and drugs. Bisphosphonates are the
cornerstone for osteoporosis treatment.
Raloxifene is an alternative treatment option to
prevent vertebral fractures.
All people, regardless of age, should incorporate a
healthy lifestyle beginning at birth that emphasizes
regular exercise, nutritious diet, and tobacco
avoidance to prevent and treat osteoporosis 49
Harrison’s Principle of Internal Medicine ,Vol
1 by Longo, Fauci Kasper, Hasper, Jamesoli
Page No: 2268 – 2277,18 th edition
Pharmacotherapy- A path physiological
approach, by Joseph. T. Dipiro, Robert. L.
Talbert, Gary. C. Yee, Gary. R. Matzke ,
Barbara. G. Wells, L. Michael Posey; Page
No: 1645 – 1664 ,6 th edition.
All information were collected
from various sources, only for