Pharmacotherapy of Osteoporosis

Abera J. (BPharm., MSc in Clinical Pharmacy).

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 Learning objectives
Upon completion of the chapter, the student will be able to:
– Identify risk factors and list the criteria for diagnosis of
osteoporosis.
– Recommend appropriate lifestyle modifications to prevent
bone loss.
– Recommend an appropriate treatment regimen for a Pt.
with osteoporosis.

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 Introduction
• Osteoporosis is a common and often silent disorder,
• Cause significant morbidity and mortality and reduced
QoL.

• It is characterized by;
– low bone density and loss of strength in bone tissue
resulting in an increased risk and rate of bone fracture
• Common sites of fracture include;

• The spine, hip, and wrist, although almost all sites can
be affected.

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 Introduction….
• The fractures associated with osteoporosis have significant
impact on individual Pt.’s,
– Also associated with chronic pain, loss of mobility,
depression, and death.
– Pt.’s with vertebral fractures may also experience height
loss, kyphosis, and decreased mobility.
• Multiple vertebral fractures may lead to restrictive lung
disease and altered abdominal anatomy.

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 Epidemiology and Etiology

• Osteoporosis is the most common skeletal disorder, but only

a fraction of Pt.’s are evaluated and diagnosed.
• Osteoporosis can be classified as either;
– Primary………no known cause
• Most often found in postmenopausal women and
aging men
– Secondary……….caused by drugs or other diseases.

• The prevalence of osteoporosis varies by age, gender, and

race/ethnicity

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 Epidemiology and Etiology…
• Although both men and women lose bone as they age,
– Postmenopausal women have accelerated bone loss due to loss
of estrogen.
– Men have some protection from osteoporosis;

• Due to their larger initial bone mass and size and lack of
accelerated bone loss associated with menopause.

• Secondary causes of osteoporosis;

– Such as hypogonadism, are found more commonly in men with
fragility fractures

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Medical Conditions and Drugs Associated with
Osteoporosis

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Risk factors for Osteoporosis

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 Pathophysiology
• The human skeleton contains both cortical and trabecular
bone.
– Cortical bone;
• Comprises approximately 80% of the skeleton,
• Responsible for bone strength,
• It is found on the surfaces of long and flat bones.
– Trabecular bone;
• Has a sponge-like appearance
• Found along the inner surfaces of long bones
• This type of bone is more susceptible to osteoporotic
fractures.
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 Pathophysiology…
• Under normal circumstances,
– The skeleton undergoes a dynamic and constant process of bone
remodeling, and
– Respond to stress and injury through continuous replacement
and repair.
• This process is completed by the basic multicellular unit, including
both osteoblasts and osteoclasts.
– Osteoclasts………are involved with resorption or breakdown of
bone and continuously create microscopic cavities in bone tissue.
– Osteoblasts……are involved in bone formation and continuously
mineralize new bone in the cavities created by osteoclasts.

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 Pathophysiology…
• Until peak bone mass is achieved between the ages of 25 and
35, bone formation exceeds bone resorption for an overall
increase in bone mass.
• In osteoporosis, an imbalance in bone remodeling occurs.
– Most commonly, osteoclastic activity is enhanced,
resulting in overall bone loss,
– A reduction in osteoblastic activity and bone formation
also occurs in certain types of osteoporosis.

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 Pathophysiology…

Normal trabecular bone (left) compared with trabecular bone

from a Pt.’s with osteoporosis (right).
 The loss of mass in osteoporosis leaves bones more
susceptible to breakage.
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Clinical Presentation

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 Diagnostic Assessment
• The diagnostic assessment for osteoporosis may include;
– An assessment of BMD,
– Vertebral imaging,
– Laboratory workup, and
– Other factors for secondary causes of osteoporosis, and
biochemical markers of bone turnover

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 Diagnostic Assessment…
• Measurement of BMD
– Osteoporosis is characterized by weakened bone tissue,
and BMD is the best measure of bone strength
• Low BMD is associated with an increased risk of fractures.

– BMD can be measured at various sites throughout the

skeletal system and by various methods,
• Dual energy x-ray absorptiometry (DXA) can be used to
measure central and peripheral sites.
– Recommended by WHO for diagnosis of osteoporosis
– Standard approach of diagnosis of osteoporosis
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 Diagnostic Assessment…
• Other options to measure peripheral sites include;
– Quantitative US, peripheral quantitative computed
tomography, radiographic absorptiometry, and single-
energy x-ray absorptiometry.

• Less expensive than central DXA,

• Useful in identifying Pt.’s who are candidates for central DXA,

• But it should not be used for diagnosis.

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 Diagnostic Assessment…
• Once the BMD report is available,
– T-scores…..the number of standard deviations from the mean BMD in
healthy, young adult.
• Osteoporosis is defined as a T-score more than –2.5 SDs below the
mean BMD in young adults
– Z-score……the number of SDs from the mean BMD of age and sex
matched controls,
• Corrected for both age and sex of the Pt.’s
• More clinically relevant in evaluating BMD in premenopausal
women, men younger than the age of 50, and Pt.’s who may have
secondary causes for low BMD.

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 Diagnostic Assessment…
Screening and Risk Factor Assessment
• The NOF recommends BMD measurements in the following
groups:
– Women age 65 and older, men age 70 and older,
– Perimenopausal women and men age 50 to 69 with risk
factors,
– Anyone with a fracture after age 50, and adults with a
secondary cause for osteoporosis.

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 Diagnostic Assessment…
Vertebral Imaging
• Vertebral imaging is recommended in high-risk Pt.’s:
– Central T-score less than –1.0 in women age 70 and older
and men age 80 and older,
– Central T-score less than –1.5 in women age 65 to 69 or
men age 70 to 79,
– Postmenopausal women and men age 50 and older who
have had a fragility fracture in adulthood,
– Reported decrease in height of 4 or more centimeters,
– Documented reduction in height of 2 or more centimeters,
or
– Long-term glucocorticoid therapy.

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 Diagnostic Assessment…
Laboratory Evaluation
• Has little value in diagnosing osteoporosis
• But beneficial in identifying or excluding secondary causes
of bone loss, or for monitoring drug therapy.
• Screening laboratory tests for the most common causes of
secondary osteoporosis include;
– CBC, serum chemistries (electrolytes with calcium,
phosphorus, and liver enzymes), vitamin D, and urinalysis.

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WHO Definition of Osteoporosis

(T-Score)

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 Treatment
Desired Outcomes

• Treatment goals for osteoporosis include:

– Preventing fractures;

– Maintaining or increasing BMD;

– Preventing secondary causes of bone loss; and

– Reducing morbidity and mortality associated with osteoporosis.

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 Non-Pharmacologic Therapy
Modification of Risk Factors
• Modifiable risk factors should be modified;
– Smoking, low calcium intake, poor nutrition, inactivity, heavy
alcohol use, and vitamin D deficiency.

Nutrition
• Healthy diet as well as appropriate weight maintenance.
• Dietary calcium intake is important for achieving peak bone mass
and maintaining bone density.
– Vitamin D is essential for calcium absorption.

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 Non-Pharmacologic Therapy…
Exercise
• Exercise can help prevent fragility fractures.

– Weight-bearing exercise such as walking, jogging,

dancing, and climbing stairs can help build and maintain
bone strength.
– Muscle-strengthening can help improve and maintain
strength, and balance, which can reduce falls.

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 Non-Pharmacologic Therapy…
Falls Prevention
• Pt.s with poor vision, hearing loss, or those taking medications
affecting balance are at higher risk for falling and subsequent
fragility fractures.
• Medications associated with an increased risk of falling;
– Antipsychotics, BZPs, TCAs, anticholinergic, and corticosteroids.

– Some CV and antihypertensive

• Efforts to decrease the risk of falling include;
– Balance training, muscle strengthening, removal of hazards, and
– Discontinuation of predisposing medications

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 Pharmacologic Treatment

• Pharmacologic treatment is recommended in Pt.’s fulfilling

the following criteria:
– History of hip or vertebral fracture,
– T-score –2.5 or less at femoral neck or spine, or
– Osteopenia and at least a 3% 10-year probability of hip
fracture or
– At least a 20% 10-year probability of major osteoporosis-
related fracture

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 Calcium and Vitamin D
• The NOF recommends a daily calcium intake of;

– 1000mg……… for men between the ages of 51 to 70 and

– 1200mg……..for women older than 51 and men older than 71

• Intakes over 1200 to 1500mg/day may increase the risk of

developing kidney stones,
• Supplementation greater than 2500mg/day may lead to
hypercalciuria and hypercalcemia.
• Additionally, excessive calcium supplementation may be
associated with an increased risk of CV events

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 Calcium and Vitamin D…
• Calcium supplements are available in a variety of calcium
salts and dosage forms.
– Calcium carbonate should be taken with food to
maximize absorption.
– Calcium citrate does not require an acid environment
for its absorption
» Can be taken with or without food.

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 Calcium and Vitamin D…
• Common AEs include constipation, bloating, cramps, and
flatulence, especially with calcium carbonate.
• Changing to a different salt form may alleviate symptoms for
some Pt.’s.

• Calcium salts may reduce the absorption of iron and some

antibiotics, such as TTC and FQs.
– Calcium supplements should be administered 2 hours prior to or
four hours after antibiotic or iron therapy

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 Calcium and Vitamin D…

Vitamin D
• Needed for calcium absorption and may aid in balance and
reduce fall risk,
– Enhance bisphosphonate efficacy, improve BMD, and
reduce fracture risk.
• The NOF recommends a daily vitamin D intake of 800 to 1000
IU daily for all adults age 50 and older
• To avoid hypercalciuria and hypercalcemia,
• The maximum recommended dose for chronic use in
most Pt.’s is 4000 IU/day.
• High-dose vitamin D, 50,000 IU, is generally reserved
for Pt.’s with vitamin D deficiency.

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 Bisphosphonates
• Bisphosphonates are first-line therapy for osteoporosis
in both men and women
– They decrease bone resorption by rapidly binding to the
bone matrix and inhibiting osteoclast activity.
– Alendronate, risedronate, and zoledronic acid are
approved for use in men and women,
• Whereas ibandronate is only approved for postmenopausal
osteoporosis and considered as second line

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 Bisphosphonates…
Side effects
• Pt.'s may experience bone, muscle, or joint pain that resolves
upon bisphosphonate discontinuation.
• Upper GI AEs……..occur in up to 20% of Pt.'s receiving PO
bisphosphonates
• Range from relatively mild N/V to more severe esophageal
irritation and esophagitis.
• Risk of GI AEs increases with advanced age, previous upper
GIT disease, and use of NSAIDs
– Once-weekly administration of PO bisphosphonates may
decrease the risk.

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 Bisphosphonates…
• IV zoledronic acid is associated with acute-phase reactions
(flulike symptoms) that can last for days,
• Such as headache, arthralgia, myalgia, and fever.
• Pretreatment with acetaminophen may prevent these
symptoms.

• Pt.’s with moderate to severe renal impairment, severe

dehydration, or taking concomitant nephrotoxic drugs may
be at higher risk of developing ARF
– Laboratory monitoring, including SCr, phosphate, Mg, and Ca, is
recommended prior to administration of each zoledronic acid dose.
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 Bisphosphonates…
• Administration of bisphosphonates with food or calcium
supplementation reduces its absorption.
• CIs to bisphosphonates include hypersensitivity,
hypocalcemia, pregnancy and renal impairment (CrCl< 30 to
35 mL/min
• Pt.’s with esophageal abnormalities, GI malabsorption or
who cannot remain upright for 30 minutes should avoid PO
bisphosphonates;
– Consider IV bisphosphonates for these Pt.’s.

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 Denosumab
• Denosumab is the first human monoclonal antibody FDA
approved for treatment of postmenopausal osteoporosis.
• It is first-line therapy for women and men,
• Also be considered;
– In Pt.’s unable to tolerate bisphosphonates due to GI
contraindications or SEs
– For Pt.’s with malabsorption or adherence issues

• Administered as a SC injection once every 6 months.

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 Denosumab…

• Common AEs include;

– Back pain, arthralgias, fatigue, headache, dermatologic

reactions, diarrhea, and nausea.
• Serious ARs, include;
– Hypophosphatemia, hypocalcemia, dyspnea, and skin and
other infections.
• Denosumab can worsen hypocalcemia in predisposed Pt.’s,

– Those with severe kidney disease, and preexisting

hypocalcemia should be corrected before initiating therapy

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 Osteoanabolic Therapy
• Abaloparatide and teriparatide are osteoanabolic therapies
• Exert their effects on bone through stimulation of the
parathyroid hormone (PTH) type 1 receptor.
– Promotes osteoblastic activity and bone formation, but
may also enhance bone resorption.
– The overall net effect is an increase in BMD.

• Teriparatide, recombinant human PTH is FDA approved for

treatment of postmenopausal and male osteoporosis.
• Abaloparatide, a synthetic analog of PTH-related protein
was approved for treatment of postmenopausal women
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 Osteoanabolic Therapy…
• Common AEs of both drugs include;

– Nausea, headache, leg cramps, dizziness, orthostatic

hypotension, injection site discomfort, hypercalciuria, and

hypercalcemia.

– Abaloparatide may also be associated with palpitations.

– Neither drug should be used in Pt.’s with preexisting

hypercalcemia

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 Estrogen Agonists/Antagonists
Raloxifene
– Has estrogen-like activity on bones and estrogen antagonist
activity in breast and endometrium.
• Recommended as alternative therapy after
bisphosphonates, denosumab, or osteoanabolic therapies

• AEs of raloxifene include hot flushes, leg cramps, and increased

risk of VTE.
– Contraindicated in Pt.’s with previous history of VTE
– Hot flushes are very common and may be intolerable in
postmenopausal women

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 Calcitonin
– Calcitonin is a naturally occurring mammalian hormone
that plays a major role in regulating calcium levels.
– It inhibits bone resorption by binding to osteoclast
receptors.
– Calcitonin is considered a last-line agent for the treatment
of osteoporosis;
• Due to limited fracture prevention data.
• Generally, reserved for Pt.’s unable to tolerate or take
other agents.

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 Hormone Therapy
• Estrogen, either alone or in combination with a progestin as

HRT, used as an effective treatment of osteoporosis.

– a 34% reduction in both vertebral and hip fractures,

• But, significant risks associated with long-term HRT, including

breast CA and VTE,

– have limited its use in osteoporosis.

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 Treatment of Special Populations
Glucocorticoid-Induced Osteoporosis
• Glucocorticoids (prednisone, hydrocortisone, methylprednisolone,
and dexamethasone)
– Play a significant role in bone remodeling, including increasing
bone resorption, inhibiting bone formation, and changing bone
quality.
– They promote bone resorption through calcium absorption
from the GI tract and renal calcium excretion.
– Bone formation is reduced through inhibition of osteoblasts and
decreased estrogen and testosterone production.

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 Treatment of Special Populations…
• The ACR recommends PO bisphosphonate therapy;
– for all Pt.’s age 40 and over at moderate to high risk of
fracture receiving glucocorticoids (prednisone > 2.5 mg per
daily or equivalent) for 3 months or longer.
• For Pt.’s unable to take PO bisphosphonates,
– IV bisphosphonates, teriparatide, denosumab, and raloxifene
• Frequent clinical fracture risk assessment with BMD testing
every 1 to 3 years is recommended while receiving
glucocorticoids.

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 Outcome Evaluation
– Evaluate Pt.’s for progression of osteoporosis

– Assess Pt.’s on an annual basis or more often if new

symptoms present

– The NOF recommends a follow-up DXA scan every 2 years

to monitor the effects of therapy

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 Outcome Evaluation…
• Assess Pt.’ for AEs of therapy:
– Oral bisphosphonates: Dyspepsia, esophageal reflux,
esophageal pain, or burning,
– Injectable zoledronic acid: Influenza-type symptoms related to
infusion,
– Denosumab: Arthralgias, dermatologic reactions, and hypocalcemia,
– Abaloparatide and teriparatide: Nausea, headache, leg cramps,
hypercalcemia, and orthostatic hypotension,
– Raloxifene: Hot flushes, signs, or symptoms of
VTE (eg, pain, redness, or swelling in one extremity, chest pain, and
SOB).

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THANK YOU.

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