Osteoporosis

Front 1

Describe effects of glucocorticoids on bone density

Back 1

They inhibit OB function, decreasing bone density.

Front 2

Describe effects of progesterone on bone density

Back 2

It inhibits LH/FSH, therefore inhibiting E2, which decreases bone density.

Front 3

Describe effects of Aromatase inhibitors on bone density

Back 3

They decrease E2, decreasing bone density.

Front 4

What Causes Osteoporosis ?

Back 4

*Result of a "mismatch" between bone formation and resorption

*Bone becomes abnormally thin and porous i.e. Osteopenia/Osteoporosis

*Increasing fragility and risk of fracture

Front 5

Back 5

Front 6

Back 6

Front 7

Factors that impact bone homeostasis:

Back 7

Estrogen
Androgens
PTH
Vitamin D 1,25
Glucocorticoids
Thyroid hormone
Insulin
Growth Hormone
Immobilization
Cytokines

Front 8

Symptoms of Osteoporosis:

Back 8

*Asymptomatic

*Fracture
-Vertebral Fracture
2/3 asymptomatic
Height loss --> Kyphosis

-Hip Fracture
Increase in mortality
Disability --> Nursing home

-Wrist Fracture
Hands out stretched to stop a fall

Front 9

WHO: DEFINITONS of osteoporosis, etc:

Back 9

*Normal bone density (T-score >-1)
Within 1 SD of the mean in young adults of the same sex and race

*Osteopenia (T-score –1 to-2.5)
More than 1 and less than or equal to 2.5 standard deviations below the mean in young adults of the same sex and race

*Osteoporosis (T-score < -2.5)
More than 2.5 standard deviations below the mean in young adults of the same sex and race
Associated with skeletal fragility

Front 10

Back 10

Front 11

Back 11

Front 12

Back 12

Most people need 1000-1200 mg daily.

Front 13

Back 13

Front 14

Back 14

elemental Ca is what you need

Front 15

What effect does Ca intake have on bone density?

Back 15

It prevents bone density loss.
Ca + Vit D is even better.

Front 16

Adverse Reactions of Calcium:

Back 16

*Safe upper limit for calcium of 2000mg/day

*Related to a high calcium intake
-GI symptoms (dyspepsia/constipation)
-Hypercalciuria --> kidney stones
-Vascular calcifications --> MI or stroke
-Other symptoms associated with hypercalcemia

*Drug Interaction
-Antagonize effects of calcium channel blockers
-Decreases the GI absorption of various drugs (e.g. Iron, bisphosphonates)

Front 17

Back 17

Front 18

Vitamin D Deficiency:

Back 18

Prevalence:

*Overt RARE
hypocalcemia
hypophosphatemia
rickets or osteomalacia

*Subclinical COMMON
osteoporosis

*Contributing factors include reduced cutaneous production and Vitamin D intake

Front 19

Back 19

-Study showed 50% of women had subclinical Vit D deficiency.

Front 20

Back 20

Vit D levels are inversely proportional to PTH levels.

Front 21

Diagnosis and Treatment of Vit D deficiency:

Back 21

*Diagnosis
25-OH D: < 20-30 ng/mL

*Treatment
1) Ergocalciferol (D2) 50,000 IU q wk 12 wks decreases PTH and improves BMD
2) Calcium intake of 1000-1200 mg a day

**Don't need to memorize these numbers**

Front 22

Back 22

Front 23

Back 23

Fracture Risk Reduction:

**Calcium 1200mg and Vitamin D 800IU /day**
- BMD: 2.7% increase with treatment versus 4.6% decrease in the placebo group
- Fracture: 43% reduction in hip fracture and 34% reduction in non vertebral fracture

Front 24

Back 24

Front 25

Dermal Synthesis of Vitamin D:

Back 25

*Major source of the Vitamin D
10-15 minutes of sun exposure at least two times per week to the face, arms, hands, or back without sunscreen is equivalent to ingestion of 200 IU/day

*Limitations
Winter season
Northern latitude
Cloud cover/ smog
Sunscreen (SPF>8)
Greater melanin content

Front 26

Discuss Vitamin D Supplements:

Back 26

*Maintenance
Cholecalciferol (Vitamin D3)

*Vitamin D deficiency or insufficiency
Ergocalciferol (Vitamin D2)

*Renal failure or hypoparathyroidism
Dihydrotachysterol (1-hydroxyvitamin D)
Calcitriol (1,25-OHD)

*Liver disease
Calcidiol (25-hydroxyvitamin D)
Calcitriol (1,25-OHD)

Front 27

Adverse Reactions of Vitamin D:

Back 27

*Toxicity
-Not associated with sun exposure
-Associated with very high oral intake i.e. intake of 25,000-60,000 IU daily for 1-4 months

*Toxicity symptoms
-Monitor symptoms of hypercalcemia

Front 28

Back 28

Front 29

Osteoporosis Risk Assessment:

Back 29

Front 30

Risk factors for osteoporosis: 12

Back 30

Personal history of fracture
Fracture in first degree relative
Current cigarette smoking
Low body weight (127lbs)
Oral corticosteroid therapy > 3mo
Early estrogen deficiency (< 45) Lifelong low calcium intake
Alcoholism (>2 drinks/day)
Inadequate physical activity
Recurrent falls
Dementia
Impaired eye sight
Poor health/ frailty

Front 31

Meds that put you at risk for osteoporosis: 6

Back 31

Glucocorticoids
Progesterone (depo)
Aromatase Inhibitors
GNRH agonists
Anticonvulsants
Immunosuppressants

Front 32

Describe effects of GnRH agonists on bone density

Back 32

Continuous use decreases LH/FSH, leading to decreased E2 and decreased bone density.

Front 33

Describe effects of anticonvulsants on bone density

Back 33

Blocks activation of Vit D to 1,25OH active form

Front 34

Describe effects of immunosuppressants on bone density

Back 34

Cause direct bone breakdown

Front 35

Medical conditions that put you at risk for osteoporosis:

Back 35

Hypogonadism [decreased testosterone]
Anorexia [decreased LH/FSH, E2]
Hyperparathyroidism [increased bone resorption]
CRF [no Vit D]
Thyrotoxicosis [direct effect on bone]
IBS/Malabsorption/Sprue [decreased Vit D]
Immobilization
Multiple Myeloma
HIV/DM/RA

Front 36

Who should undergo testing for osteoporosis?

Back 36

Front 37

Who should be treated for osteoporosis?

Back 37

*know these 3 treatment recommendations*
1000-1200mg Ca
800-1000 IU Vit D

Front 38

What hx = automatic osteoporosis diagnosis?

Back 38

Hx of a fragility fx

Front 39

Back 39

Front 40

Back 40

Front 41

Effects of estrogen on bone density:

Back 41

*estrogen maintains bone density; prevents bone loss.

Front 42

Risks of HRT?

Back 42

CHD
Stroke
Pulmonary embolism
Breast Cancer, Colon cancer

Front 43

Back 43

Front 44

Selective Estrogen Receptor Modulators (SERMS):

Back 44

*SERMS:
-Triphenylethylenes: Clomiphene / Tamoxifen
-Benzothiophenes: Raloxifene

*Mixed agonist and antagonist activity

*Raloxifene
Estrogen action inhibited --> Breast / Uterus*
Estrogen action retained --> Skeleton / Lipids*
Indications: prevention and treatment of osteoporosis
Dose: 60mg oral every day
Side Effect – hot flashes, leg cramps, thrombosis

[* decreased Ca risk compared to HRT]

Front 45

Pharma effects of estrogen vs. Raloxifene vs. Tamoxifen:

Back 45

Front 46

Efficacy limitations of SERMS?

Back 46

-They've been shown to reduce vertebral fxs; but NOT hip fxs.

Front 47

Calcitonin:

Back 47

*Produced by parafollicular cells of the thyroid

*Physiologic antagonist to PTH

*Stimulated by high calcium levels
-Inhibits osteoclast formation and function
-Increases renal calcium excretion by decreasing tubular reabsorption.

Front 48

Describe calcitonin's role in osteoporosis prevention and treatment:

Back 48

*Osteoporosis: prevention and treatment
-Intranasal 200 units (1 spray)/day
-IM/SQ 100 units/every other day
-Effect: Increase BMD and decrease spine fracture (NOT HIP)

*Side effects:
-Intranasal: rhinitis, epistaxis
-SQ/IM: nausea, vomiting, facial flushing, allergic reaction, develop anti-calcitonin antibodies and become resistant to therapy

Front 49

HOW DO bisphosphanates work?

Back 49

-Inhibit OC function
-INCREASE BONE DENSITY
-DECREASE ALL INCIDENCES OF FX IN HIP, SPINE, WRIST.

Front 50

4 BISPHOSPHANATE AGENTS:

Back 50

Alendronate - Oral
Residronate - Oral
Ibandronate - Oral or IV
Zolendronate - IV

Front 51

SEs of bisphosphanates:

Back 51

*GI Symptoms
-Esophagitis
-Ulcers
[pill lodges in esophagus; pts must drink with full glass of H2O and not lie down after taking pill]

*Transient acute phase reaction with IV
-Myalgias
-Arthralgia
-Fever

*Hypocalcemia

*Atrial Fibrillation

*Osteonecrosis of jaw

*Atypical fractures (?)

Front 52

Denosumab:

Back 52

Osteoclasts express RANK
Osteoblasts express RANKL
RANKL/RANK stimulates osteoclastogenesis

*Denosumab
Humanized monoclonal antibody
Anti-RANKL
Inhibit RANKL/RANK signaling
Decrease bone resorption.
*Blocks RANKL --> No OC activation*

Front 53

Results of the FREEDOM trial:

Back 53

-good fx reduction
-infections are a problem
-possible neoplasms

Front 54

Counterintuitive usage of PTH to increase bone formation:

Back 54

*daily injections increase bone formation*

Front 55

Recombinant Human Parathyroid Hormone:

Back 55

*osteosarcoma is the big one*

Front 56

Indications and CIS for using rPTH in osteoporosis therapy:

Back 56

*Failed/intolerant of therapies
*Limited to 2 years

Front 57

Therapies and their fx reduction abilities:

Back 57

Front 58

Overall chart summarizing BMD effects, fx effects, and SEs of all osteoporosis treatments.

Back 58

Front 59

First line bisphosphanate:

Back 59

Alendronate b/c it's oral.

Front 60

If you see low BMD in forearm as compared to spine and hip, think:

Back 60

hyperparathyroidism

Front 61

You pick osteoporosis drugs based on:

Back 61

the SE profiles of the drugs.