Osteoporiasis

Osteoporosis
Dr. Prasad B. Chinchole
Pharm D
SCOP, Almala
@ Dr. Prasad B. Chinchole

Index
1. Introduction
2. Epidemiology
3. Bone physiology
4. Vitamin d, parathyroid hormone, and calcium
5. Etiology
1. Low bone density
2. Impaired bone quality
3. Falls

6. Pathophysiology
1. Postmenopausal osteoporosis
2. Male osteoporosis
3. Age-related osteoporosis
4. Secondary causes of osteoporosis
7. Clinical presentation
8. Diagnosis of osteoporosis
1. Screening using peripheral bone mineral density devices
2. Central dual-energy x-ray absorptiometry
3. Laboratory tests
4. Bone turnover markers
9. Prevention and treatment

Introduction
 Osteoporosis is defined as a “skeletal disorder characterized by compromised
bone strength predisposing a person to an increased risk of fracture.”
 The development of osteoporosis and osteoporotic fractures is multifactorial,
beginning with genetics and unhealthy bone lifestyles, along with other skeletal
factors, which lead to compromised bone strength, and nonskeletal factors that
lead to falls
 Postmenopausal women, men older than age 65 years, and those with potential
disease- or drug-induced bone loss.

Epidemiology
• Osteopenia (low bone mass), osteoporosis, and osteoporotic fractures are very
common and affect all ethnic groups.
• 50% of Asian, 47% of Hispanic, 45% of Native American,40% of white, and 28%
of black women.
• Osteoporosis affects 12% of Native American, 10% of Asian, 10% of Hispanic,
7% of white, and 4% of black women.
• Disease prevalence greatly increases with age; from 4% in women 50 to 59 years
of age to 44% to 52% in women 80 years of age and older.
• Fragility or low trauma wrist and vertebral fractures are common throughout
adulthood, whereas hip fractures are more common in seniors.

Bone Physiology
 Bone is made of collagen and mineral components. The collagen component
gives bone its flexibility and energy-absorbing capability.
 The mineral component gives bone its stiffness and strength. The correct
balance of these substances is needed for bone to adequately accommodate to
stress and strain and resist fractures. Imbalances can impair bone quality and
lead to reduced bone strength.
 Ninety percent of peak bone mass is attained by age 18 to 20 years, with small
gains until approximately age 30 years. Peak bone mass is highly dependent on
genetic factors that account for approximately 60% to 80% of the variability.
 The remaining 20% to 40% is influenced by modifiable factors such as
nutritional intake (e.g., calcium, vitamin D, and protein), exercise, adverse
lifestyle practices (e.g., smoking), hormonal status, and certain diseases and
medications.

Vitamin D, Parathyroid Hormone and Calcium
Vitamin D and parathyroid hormone (PTH) maintain calcium homeostasis.
The most abundant source of vitamin D is the endogenous production from
exposure to ultraviolet B light.
The sun’s ultraviolet B light converts 7-dehydrocholesterol in the skin to
cholecalciferol.
Maximal skin production occurs within 20 minutes for whites and 60 to 120
minutes for blacks or darker-skin individuals
Dietary vitamin D sources include cholecalciferol and ergocalciferol.
Subsequent conversion of cholecalciferol and ergocalciferol to 25-
hydroxyvitamin D [25(OH) D] (calcidiol) occurs in the liver and then PTH
stimulates conversion of 25(OH) D via 25(OH) D-1α-hydroxylase to its final
active form, 1α,25-dihydroxyvitamin D (calcitriol), in the kidney.

• Calcitriol binds to the intestinal vitamin D receptor and then increases calcium
binding protein.
• As a result, calcium and phosphorous intestinal absorption is increased. Vitamin D
receptors are also found in many tissues, such as bone, intestine, brain, heart,
stomach, pancreas, lymphocytes, skin, and gonads.
• Calcium absorption under normal conditions is approximately 30% to 40%,
decreasing to 10% to 15% with low vitamin D concentrations.

Etiology
1. LOW BONE DENSITY
1. BMD is a major predictor of
fracture risk.
2. Hormonal Status, Exercise,
Aging, Nutrition, Lifestyle,
Disease States, Medications, And
Some Genetic Influences.
2. Impaired bone quality
3. Falls

FALLS
• Risk of falling increases with advanced age predominantly as a result
of balance, gait, and mobility problems, poor vision, reduced muscle
strength, impaired cognition, multiple medical conditions (e.g., stroke,
Alzheimer’s dementia, Parkinson’s disease), and polypharmacy.
• Psychoactive medications such as benzodiazepines, antidepressants,
antipsychotics, sedative hypnotics, and narcotics have been strongly
associated with falls. The ability to adapt to falls also decreases with
aging. Seniors are more likely to sustain a hip or pelvic fracture
because they tend to fall backwards or sideways instead of forward.

Pathophysiology
• Osteoporosis pathophysiology depends on gender, age, and presence
of secondary causes.
1. Postmenopausal osteoporosis
2. Male osteoporosis
3. Age-related osteoporosis
4. Secondary causes of osteoporosis

Postmenopausal osteoporosis
• Result of the loss in ovarian hormone production, specifically
estrogen.
• Estrogen deficiency increases proliferation, differentiation, and
activation of new osteoclasts and prolongs survival of mature
osteoclasts.
• Significant bone density is lost and bone architecture is compromised.

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.
• The etiology of male osteoporosis tends to be multifactorial with
secondary causes and aging being the most common contributing
factors.
• Hypogonadism being the most common.
• Idiopathic osteoporosis

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 seniors as a consequence of the
cumulative loss of cortical and trabecular bone and an increased risk
for falls.

SECONDARY
CAUSES OF
OSTEOPOROSIS

Clinical Presentation
General
• Many patients are unaware they have osteoporosis and only present after fracture
• Fractures can occur after bending, lifting, or falling, or independent of any activity
Symptoms
• Pain
• Immobility
• Depression, fear, and low self-esteem from physical limitations and deformities
• Two-thirds of vertebral fractures are asymptomatic
Signs
• Shortened stature (>1.5'' loss), kyphosis, or lordosis
• Vertebral, hip, wrist, or forearm fracture
• Low bone density on radiography

Diagnosis of Osteoporosis
1. Screening using peripheral bone mineral density devices
2. Central dual-energy x-ray absorptiometry
3. Laboratory tests
4. Bone turnover markers

Screening using peripheral bone mineral
density devices
• Peripheral bone density devices that utilize x-ray absorptiometry or
quantitative ultrasonometry are helpful
• Peripheral DXA of the forearm, heel, and finger uses a low amount of
radiation.
• Controversial
• Predication lacking or not as robust in older

Laboratory tests
• Serum 25(OH) D is the best indicator of total body vitamin D status.
• Atleast 30 ng/mL.
• Vitamin D deficiency can be considered a 25(OH) D concentration of
≤10 ng/mL, insufficiency as a concentration between 11 and 29
ng/mL, and sufficiency as ≥30 ng/mL
• T Score

Bone turnover markers
• Urine and serum bone turnover markers are either enzymes or
proteins.
• alkaline phosphatase, osteocalcin and procollagen type 1
propeptides.

Prevention and treatment
Desired outcomes
General approach to prevention and treatment
Nonpharmacologic therapy
Pharmacologic therapy

Desired outcomes
• Primary goal of osteoporosis management should be prevention.
• Once osteopenia or osteoporosis develops, the objective is to stabilize
or improve bone mass and strength and prevent fractures.
• In patients who have already suffered osteoporotic fractures, reducing
future falls and fractures, improving functional capacity, reducing pain
and deformity, and improving quality of life are the main goals.

General approach to prevention and treatment
• Insuring adequate intakes of calcium and vitamin D along with other
bone healthy lifestyle practices.
• T-score less than –2.0 or less than –1.5 if they have one or more major
osteoporosis risk factors.
• Prescription medications, with bisphosphonates being the drug of
choice, are recommended for men and women with osteoporosis

Nonpharmacologic therapy
1. Diet
2. Calcium
3. Vitamin D
4. Other Nutrients and Minerals
5. Protein
6. Dietary Soy
7. Smoking Cessation
8. Exercise
9. Fall Prevention
10. Hip Protectors

Pharmacologic Therapy
1. Antiresorptive
1. Calcium supplementation
2. Vitamin D supplementation
3. Bisphosphonates
4. Mixed estrogen agonists/antagonists
5. Estrogen therapy
6. Calcitonin
7. Testosterone
8. Thiazide diuretics

2. Anabolic Therapies
1. Teriparatide
3. Combination Therapy
4. Investigational Therapies
1. Denosumab
5. Other Investigational Drug Classes
6. VERTEBROPLASTY AND KYPHOPLASTY

Drug Treatments of First Choice
• Bisphosphonates are the prescription drug of choice with teriparatide, raloxifene, and
calcitonin considered alternative agents.
• Duration of bisphosphonate therapy has not been defined, but safety data exist for
periods of 7–10 years.
• Short-term (18 to 24 months) teriparatide is used for severe osteoporosis and then
followed by bisphosphonate therapy.

Antiresorptive
Antiresorptive therapies include
• Calcium,
• Vitamin D,
• Bisphosphonates,
• Estrogen agonists/antagonists and
• Calcitonin.

Calcium Supplementation
• Calcium imbalance can result from inadequate dietary intake, decreased fractional
calcium absorption, or enhanced calcium excretion.
Efficacy.
• Although calcium increases BMD, fracture prevention is minimal.
• Nonbone benefits of calcium intake include decreased blood pressure,
cholesterol, and colorectal cancer risk, the last being controversial.
Adverse Events
• Constipation, Calcium carbonate can create gas and cause stomach upset, which
might resolve with calcium citrate
• rarely causes kidney stones

Vitamin D Supplementation
• Vitamin D intake is critical for the prevention and treatment of osteoporosis
because it maximizes intestinal calcium absorption. Given the safety, low cost, and
other benefits of vitamin D, no patient should have an inadequate intake.
Efficacy
• Higher doses of vitamin D (700 to 800 units/ day) demonstrated a significant
26% relative risk reduction in hip fractures, a 23% relative risk reduction in
any nonvertebral fracture, and a 22% relative risk reduction in falls
• Vitamin D has other potential nonskeletal benefits. Improvement in muscle
strength and cardiovascular function, decreased cancer risk (e.g., breast, colon,
and prostate cancers), and positive immunomodulatory effects (e.g., multiple
sclerosis, type 1 diabetes, rheumatoid arthritis) have been proposed.

Bisphosphonates
• Bisphosphonates mimic pyrophosphate, an endogenous bone resorption inhibitor.
• Bisphosphonate antiresorptive activity results from blocking prenylation and inhibiting
guanosine triphosphatase-signaling proteins, which lead to decreased osteoclast
maturation, number, recruitment, bone adhesion, and life span.
• All bisphosphonates become incorporated into bone, giving them long biologic half-lives
of up to 10 years.
Efficacy.
• Of the antiresorptive agents, bisphosphonates consistently provide the greatest fracture
risk reductions and BMD increases.
• BMD increases with bisphosphonates are dose dependent and greatest in the first 6 to 12
months of therapy.
• Small increases continue over time at the lumbar spine, but plateau after 2 to 5 years at
the hip.

Adverse Events
• less-serious GI effects (perforation, ulceration, GI bleeding)
• flu-like symptoms, and local injection-site reactions.
• Osteonecrosis of the jaw
Administration
• Because bioavailability is very poor for bisphosphonates (<1% to 5%)
and to minimize GI side effects, each oral dose should be taken with at
least 6 ounces of plain tap water (not coffee, juice, mineral water, or
milk) at least 30 (60 for ibandronate) minutes before consuming any
food, supplement (including calcium and vitamin D), or medication.

Mixed Estrogen Agonists/Antagonists
• Raloxifene, a secondgeneration mixed estrogen agonist/antagonist
(EAA) approved for prevention and treatment of postmenopausal
osteoporosis.
• Bazedoxifene, lasofoxifene
Efficacy.
• Raloxifene decreases vertebral fractures and increases spine and hip
BMD, but to a lesser extent than bisphosphonates.
• some positive lipid effects

Adverse events
• Hot flushes
• Endometrial bleeding
• Stroke or coronary events
• Might not be good candidates for this medication

Calcitonin
Calcitonin is released from the thyroid gland when serum calcium is
elevated
Salmon calcitonin is more potent and longer lasting than the
mammalian form.
Efficacy.
Only vertebral fractures
Calcitonin might provide pain relief to some patients with acute
vertebral fractures
Administration.
Subcutaneous administration with 100 units daily

Testosterone
Decreased testosterone concentrations are seen with certain gonadal
diseases, eating disorders, glucocorticoid therapy, oophorectomy,
menopause, and andropause.
Efficacy.
A few studies of testosterone replacement in women have demonstrated
increases in BMD.
Administration
Gel products can rub off and be absorbed by the patient’s partner.

Thiazide Diuretics
• Thiazide diuretics increase urinary calcium reabsorption.

Anabolic Therapies
Teriparatide
Recombinant product representing first 34 amino acids in human
PTH.
Teriparatide increases bone formation, the bone remodeling rate, and
osteoblast number and activity.
Efficacy.
Teriparatide reduces fracture risk in postmenopausal women.
Adverse Events
Hypercalcemia
Osteosarcoma

Investigational Therapies
Denosumab
Denosumab is a promising new antiresorptive agent with a unique
mechanism of action.
It is a fully human monoclonal antibody (immunoglobulin G2) that
binds to RANKL, blocking its ability to bind to its receptor activator
of nuclear factor kappa B on the surface of osteoclast precursor cells
and mature osteoclasts.
Thus denosumab inhibits osteoclastogenesis and increases osteoclast
apoptosis

SPECIAL POPULATIONS
• Children
• Premenopausal women
• The “older” senior
• Glucocorticoid-induced osteoporosis
• Transplantation osteoporosis
• Chronic kidney disease
• Gastrointestinal diseases

Osteoporiasis

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