Osteoporosis

Introduction
Osteoporosis is a bone disorder
characterized by low bone density,
impaired bone architecture, and
compromised bone strength
predisposing to fracture

Pathophysiology
1-Bone loss occurs when resorption exceeds
formation (when the bone resorption
greatly exceeds the ability of osteoblasts to
form new bone).

2-Men and women begin to lose bone mass

starting in the third or fourth decade
because of reduced bone formation.
Estrogen deficiency during menopause
increases osteoclast activity, increasing
bone resorption more than formation.
3-Men are at a lower risk for developing
osteoporosis and osteoporotic fractures.
Male osteoporosis results from aging or
secondary causes.

4-Age-related osteoporosis results from

hormone, calcium, and vitamin D
deficiencies; less exercise; and other
factors.
5-Drug-induced osteoporosis may result from
systemic corticosteroids, excessive thyroid
hormone replacement, antiepileptic drugs
(eg, phenytoin, phenobarbital), depot
medroxyprogesterone acetate, and other
agents.

Clinical presentation
1-Many patients are unaware that they
have osteoporosis and only present
after fracture.

Fractures can occur after bending, lifting,

or falling or independent of any activity.
2-The most common fractures involve
vertebrae, proximal femur, and distal
radius

.
3-Multiple vertebral
fractures decrease
height and
sometimes curve the
spine (kyphosis or
lordosis).

5-Patients with a nonvertebral fracture

frequently present with severe pain,
swelling, and reduced function and
mobility at the fracture site.
Diagnosis
1-Physical examination findings may
include bone pain, postural changes (ie,
kyphosis), and loss of height (>1.5 in [3.8
cm]).

2-Bone mineral density (BMD) is

measured by dual-energy x-ray
absorptiometry (DXA) scan.
Treatment
Goals of Treatment:
1-The primary goal of osteoporosis care is
prevention.

2-After osteoporosis develops, the objective

is to prevent fractures.

3-Goals in patients with osteoporotic

fractures include reducing pain and
deformity, and improving quality of life.

Nonpharmacologic Therapy
1-All individuals should have a balanced
diet with adequate intake of calcium
and vitamin D. Protein is required for
bone formation.

2- Smoking cessation, and reduced

alcohol and caffeine consumption are
recommended.
3-Weight-bearing
aerobic and
strengthening exercises
can decrease risk of falls
and fractures by
improving muscle
strength.

4-Fall
prevention
programs can
decrease falls,
and fractures.
5-Vertebroplasty and kyphoplasty involve
injection of cement into fractured
vertebra(e) for patients with debilitating
pain from compression fractures. Research
demonstrated only short term benefit with
no major pain relief and the potential for
post-procedure complications.

Pharmacologic Therapy
General Approach
1-Alendronate, risedronate, zoledronic
acid, and denosumab reduce both hip and
vertebral fracture risks.

2-Abaloparatide, calcitonin, ibandronate,

raloxifene, romosozumab, and teriparatide
reduce vertebral but not hip fracture
risks.
3-Calcitonin is last-line therapy. Estrogen and
testosterone are not used for osteoporosis
treatment but can have a positive bone
effect when prescribed for other conditions.

Antiresorptive
Therapy
Calcium Supplementation
1-Because the fraction of
calcium absorbed
decreases with increasing
dose, maximum single
doses of 600 mg or less of
elemental calcium are
recommended.

2-Calcium carbonate is the salt of

choice because it contains the
highest concentration of elemental
calcium (40%) and is typically least
expensive. It should be ingested
with meals to enhance absorption
in an acidic environment.

3-Calcium citrate (21% calcium)

has acid-independent absorption
and need not be taken with
meals. It may have fewer GI side
effects than calcium carbonate.
4-Tricalcium phosphate contains 38%
calcium. It may be useful in patients with
hypophosphatemia that cannot be
resolved with increased dietary intake.

5-Constipation is the most common

calcium-related adverse reaction; treat
with increased water intake, dietary fiber
, and exercise.
6-Calcium carbonate can sometimes
cause flatulence or upset stomach.
Calcium causes kidney stones rarely.

7-Calcium can decrease the oral

absorption of some drugs including iron,
tetracyclines, quinolones,
bisphosphonates, and thyroid
supplements.

Vitamin D
Supplementation
1-Supplementation is
usually provided with
daily nonprescription
cholecalciferol (vitamin
D3) products. Higher-
dose prescription
ergocalciferol (vitamin
D2) regimens given
weekly, monthly, or
quarterly may be used
for replacement and
maintenance therapy.
2-Current guidelines recommend treating
patients with osteoporosis to a 25-
hydroxyvitamin D concentration of at
least 20 ng/mL or 30 50 ng/mL.

3-Because the half-life of vitamin D is

about 1 month, recheck the vitamin D
concentration after about 3 months of
therapy.

Bisphosphonates
1-Bisphosphonates mimic pyrophosphate,
an endogenous bone resorption inhibitor.
Therapy leads to decreased osteoclast
maturation, number, recruitment, and life
span.

.
2-Incorporation into bone gives
bisphosphonates long biologic half-lives
of up to 10 years.

3-Ibandronate is not a first-line therapy

because of the lack of hip fracture
reduction data.

4-BMD increases are dose dependent

and greatest in the first 12 months of
therapy.
After discontinuation, the increased BMD
is sustained for a prolonged period that
varies per bisphosphonate.
5-Oral bisphosphonates must be
administered correctly to optimize
clinical benefit and minimize adverse GI
effects.

A-Each oral tablet should be taken in the

morning with at least (180 mL) of plain
water (not coffee, juice, mineral water, or
milk) at least 30 minutes (60 minutes for
oral ibandronate) before consuming
any food, supplements, or medications.

B-An exception is delayed-release

risedronate, which is administered
immediately after breakfast with at least
(120 mL) of plain water.
C-The patient should remain upright (sitting
or standing) for at least 30 minutes after
alendronate and risedronate and 1 hour
after ibandronate to prevent esophageal
irritation and ulceration.

D-If a patient misses a weekly dose, it can

be taken the next day. If more than 1 day has
elapsed, that dose is skipped. If a patient
misses a monthly dose, it can be taken up to
7 days before the next scheduled dose.
6-The most common bisphosphonate
adverse effects include nausea,
abdominal pain, and dyspepsia.
Esophageal, gastric, or duodenal
irritation, perforation, ulceration, or
bleeding may occur.

7-The most common adverse effects of IV

bisphosphonates include fever, flu-like
symptoms, and local injection-site
reactions.

11-The optimal duration of

bisphosphonate therapy is unknown.
Denosumab
1-Denosumab is a RANK (Receptor
activator of nuclear factor kappa) ligand
inhibitor that inhibits osteoclast
formation and increases osteoclast
apoptosis.

It is indicated for treatment of

osteoporosis in women and men .
2-Denosumab is contraindicated in
patients with hypocalcemia until the
condition is corrected.
Mixed Estrogen Agonists/Antagonists and
Tissue-Selective Estrogen Complexes
1-Raloxifene is an estrogen agonist/antagonist
that is an estrogen agonist on bone receptors
but an antagonist at breast receptors, with
minimal effects on the uterus.

2-It is approved for prevention and

treatment of postmenopausal
osteoporosis.
3-Bazedoxifene is an estrogen
agonist/antagonist that is an agonist at bone
and antagonist at the uterus and breast;
however, reduction in breast cancer risk
has not yet been demonstrated.
The proprietary product Duavee is combined
with conjugated equine estrogens (CEE),
making it a tissue-selective estrogen
complex. It is approved for prevention of
postmenopausal osteoporosis and
vasomotor menstrual symptoms.
Calcitonin
Calcitonin is FDA
approved for
osteoporosis treatment
for women at least 5
years past menopause.
Calcitonin is considered
as a last line therapy
because there are more
effective treatment
options.

Hormone Therapies
1-Estrogen therapy is FDA approved for
prevention of postmenopausal
osteoporosis but not for treatment.
Estrogen therapy can be a good choice
for women going through early
menopause when protection against
bone loss is needed in addition to
reduction of vasomotor symptoms.
2-Testosterone is used to treat
hypogonadism in men, but an
osteoporosis medication should be
added when risk for osteoporotic
fracture is high.
 Formation
Medications

Parathyroid Hormone Analogs

1-Abaloparatide is an analog of parathyroid
hormone-related peptide (PTHrP), and
teriparatide is an analogs of parathyroid
hormone (PTH); these agents are indicated for
the treatment of postmenopausal women with
osteoporosis at high risk for fracture.
1-Transient hypercalcemia can occur.
PTH analogs should not be used in
patients with hypercalcemia.

Formation and
Antiresorptive Medication
Romosozumab
1-Romosozumab
prevent inhibition of
bone formation and
decrease bone
resorption, an activity
that differentiates
this medication from
other anabolic
therapies.

2-It indicated for

postmenopausal
women at high risk
for fracture.

Sequential and Combination Therapy

1-In sequential therapy, an anabolic agent
is given first to increase bone mass,
followed by an antiresorptive agent.

2-Combination therapy is rarely used

because of no documented fracture benefit,
increased cost, and potential for more
adverse effects.
Glucocorticoid-induced osteoporosis
1-Glucocorticoids decrease bone
formation through decreased
proliferation and differentiation as well
as enhanced apoptosis of osteoblasts.
They also increase the number of
osteoclasts, increase bone resorption,
decrease calcium absorption, and
increase renal calcium excretion.

2-All glucocorticoid doses and

formulations have been associated
with increased bone loss and
fractures; however, risk is much
greater with oral prednisone doses 5
mg daily (or equivalent) and oral
therapy compared to inhaler or
intranasal therapy.
3-All patients starting or receiving
systemic glucocorticoid therapy (any
dose or duration) should practice a bone-
healthy lifestyle and ingest 1000 1200
mg elemental calcium and 600 800 units
of vitamin D daily to achieve therapeutic
25-hydroxyvitamin D concentrations.

4-Use the lowest possible corticosteroid

dose and duration.

5- Alendronate, risedronate, zoledronic

acid, denosumab, and teriparatide are
FDA approved for glucocorticoid-induced
osteoporosis.
6-Oral bisphosphonates are
recommended first-line, although IV
bisphosphonates can be used in
nonadherent patients or those unable to
take the oral preparations.

7-Teriparatide is recommended for

patients who cannot use a
bisphosphonate, and denosumab is
recommended if neither a bisphosphonate
nor teriparatide can be used.

8-Denosumab is not recommended as

first-line therapy due to limited safety
data in this population.
Evaluation of therapeutic outcomes
1-Assess medication adherence and
tolerability at each visit.

2-Ask patients about possible fracture

symptoms (eg, bone pain, disability) at
each visit.

3-Obtain a central DXA BMD

measurement after 1 2 years or 3 5
years after initiating a medication therapy
to monitor response.

4-Repeat a central DXA every 2 years

until BMD is stable, at which time the
reassessment interval can be lengthened.
Thank You