Osteoporosis

Question 1

Bone Remodeling

Answer 1

• Osteoblasts—bone forming cells
• Osteoclasts—bone resorbing cells
• Osteocytes—bone communication cells
Bone remodeling regulated by estrogens,
androgens, vitamin D, parathyroid hormone (PTH), and others, including the cytokine RANK-ligand (RANKL)
• Secondary hyperparathyroidism may also
cause bone remodeling

Question 2

Regulation of Remodeling

Answer 2

Bone Remodeling mediated by:

1. Serum Ca
2. Vitamin D

Question 3

Life Style Risk Factors

Answer 3

• Low calcium/vitamin D intake
• Smoking
• Prior fractures
• Immobilization/low physical activity
• History of falls
• Low body weight
• Excess alcohol (≥ 2-3 per day)

Question 4

Risk factors

Answer 4

Female, age, race
•35% women ≥ 80 years of age
• White/Hispanic > Native American > African
American > Asian
• 11% men ≥ 80 years of age

Question 5

Conditions Risk factors

Answer 5

• Menopause (premature)
• Malabsorption
• RA and Lupus
• Fall risk conditions
• Vit D deficiency
• Cognitive impairment
• Height loss
• Family history

Question 6

Medication Risk Factors

Answer 6

• Glucocorticoids - 5mg+ prednisone equivalent for 3+ months
• Anti-androgens
• Thyroid supplementation
• Antiepileptic drugs
• Aluminum
• PPIs
• Thiazolidinediones

Question 7

Who to screen?

Answer 7

• All women by age 65
• All men over age 70
• All post-menopausal (PM) women ≥ 50 years
• Men age ≥ 50 years with risk factors

Question 8

gold standard

Answer 8

• Central DXA X-ray gold standard
• Peripheral devices used for screening only
• Lumbar spine and hip (femoral neck, total hip)
• Reported as standard deviations (SD) from either:
• Matched population: Z-score
• “Normal”, young population: T-score
• Each SD = 10% ↓ bone mass, 1.5-2.5 x ↑ fracture risk

Question 9

Risk Prediction: FRAX®

Answer 9

Used to predict fracture risk:

1. Limited DXA access
2. Determine DXA need
3. NOT already treated

Question 10

Diagnostic Criteria Osteopenia

Answer 10

Osteopenia (low bone mass)

T-score: -1 to -2.5

Question 11

Diagnostic Criteria Osteoporosis

Answer 11

• T-score: -2.5 or less
• Fragility fracture
• Spine, hip, humerus, pelvis, or wrist
• Independent of T-score
• Osteopenia + elevated FRAX OR fragility
fracture
• 10-year probability ≥ 3 % for hip fracture
• ≥ 20 % for major osteoporotic fracture

Question 12

Normal bone density

Answer 12

T score +1 to -1

Question 13

Osteoporosis Prevention and Treatment

Answer 13

• Calcium and Vit D
• Exercise, Smoking Cessation, Low Alcohol Intake, Fall Prevention,
Hip Protectors, Physical Therapy

Question 14

Dosing & Formulations

Answer 14

• 1,000-1,200 mg/day (no more than 1,500 mg/day)
• < 600 elemental per dose (500 – 600 mg twice daily)
• Citrate in low acid
• No oyster shell!

Question 15

% of Elemental Calcium in Supplements

Answer 15

Carbonate (40% elemental)
Citrate (21% elemental)
Gluconate (9% elemental)

Question 16

Considerations

Answer 16

• ↑ Constipation = ↑ elemental Ca
• Kidney stones
• Dietary sources preferred
• QS dietary intake (average 600 mg/day)
• OP patients are high bone risk—Ca benefit outweighs any CV risk

Question 17

Osteoclasts

Answer 17

Move from immature to mature cells
when their RANK receptor is
stimulated by the RANK-Ligand

Question 18

RANKL inhibitors

Answer 18

Block maturation, activation, shorten lifespan of clasts, increase apoptosis

Question 19

Calcitonin

Answer 19

Prevents clasts from adhering to bone

Question 20

Bisphosphonates

Answer 20

Incorporate into bone to impair clast function and cause apoptosis

Question 21

Estrogen and SERMs

Answer 21

Increase clast apoptosis, decrease RANK-Ligand

Question 22

Osteoblasts function

Answer 22

Bone forming cells

Question 23

PTH analogs affect on Osteoblasts

Answer 23

activate blasts

Question 24

Estrogen and SERMs affect on Osteoblasts

Answer 24

decrease blast apoptosis

Question 25

Sclerostin inhibitor

Answer 25

increases osteoblast activity

Question 26

Denosumab is drug of choice for?

Answer 26

Denosumab—drug of choice for osteoporosis with renal insufficiency

Question 27

Osteoporosis Treatment Algorithm First Line for Most

Answer 27

alendronate, risedronate, zoledronic acid, denosumab

Question 28

Osteoporosis Treatment for Low Risk (younger, no fractures, low mod T-score)

Answer 28

Oral Agents ibandronate alendronate, risedronate

Question 29

Treatment for Highest Fracture Risk (FRAX hip >4.5% or major OP >30%, multiple fractures, T-score ≤ -3.0)

Answer 29

``` abaloparatide, denosumab, romosozumab, teriparatide, zoledronic acid ```

Question 30

Treatment for High Risk Spine Fracture, low risk Hip or nonvertebral fractures

Answer 30

ibandronate or raloxifene

Question 31

Does 1 fracture = therapy failure

Answer 31

1 fracture DOES NOT = therapy failure • Suggest fracture risk is high • May change treatment selection and/or duration

Question 32

What is stable bone mineral density (BMD)

Answer 32

• Stable BMD = not worsened by more than ~4% in spine or ~6% in hip

Question 33

Recheck BMD?

Answer 33

every 1-2 years after starting therapy and then every 2 years

Question 34

Bisphosphonates for Postmenopausal Osteoporosis

Answer 34

* Alendronate Fosamax®, * Ibandronate Boniva®, * Risedronate Actonel®,Atelvia® * Zoledronic acid (Reclast®) 5 mg IV every 2nd year 5 mg IV once yearly

Question 35

Bisphosphonates Caution in renal impairment

Answer 35

at risk of dehydration, on diuretics or nephrotoxic drugs NR if CrCl < 35 mL/min

Question 36

Duration of Bisphosphonate Use

Answer 36

• Risedronate VERT-MN trial (VERT-NA extension) DC at 3, 5 or 7 years BMD ↓ after DC BUT higher than baseline •Alendronate FLEX trial (FIT-extension) DC at 5 years vs. continuation to 10 years BMD ↓ after DC BUT remained higher than baseline. No fracture differences......unless T-score at 5 years < -2.5 (2x higher!) •Zoledronic Acid Horizon-PVT trial DC at 3 or 6 years vs. continuation to 9 years. BMD ↓ after DC BUT remained higher than baseline No notable differences in fracture

Question 37

Bottom Line on “Holidays”

Answer 37

* Lower Risk: Stop after 3 years (ZA) or 5 years (oral agents) * Higher Risk: Continue for 6 years (ZA) or 10 years (oral agents) * End holiday if fracture, significant BMD loss

Question 38

Continuum of Bisphosphonates

Answer 38

3-5 Year Evaluation

Question 39

RANK-L inhibitor: Denosumab

Answer 39

* 60 mg SQ in upper arm, thigh, abdomen every 6 months by a healthcare provider * No drug holiday recommended * Must correct Ca and Vit D before initiation 25-day half-life * Drug of choice in renal impairment

Question 40

PTH Analogs: Abaloparatide, Teriparatide

Answer 40

* Anabolic agents * Use should be immediately followed by anti-resorptive therapy (bisphosphonate, denosumab) * Use should not follow anti-resorptive therapy—lower BMD increases * Must correct Ca and Vit D before initiation * Nausea, orthostatic hypotension, leg cramps * 2-year duration only

Question 41

Sclerostin Inhibitor: Romosozumab

Answer 41

•210 mg once monthly (two consecutive 105 mg injections) in the upper arm, thigh, or abdomen by a healthcare professional 12 month duration •Must correct hypocalcemia prior to use, supplement Ca and Vit D •Boxed Warning—increased risk of MI, stroke, and CV death

Question 42

Why Estrogens aren't used

Answer 42

↑ fatal and nonfatal MI , stroke, VTE, breast cancer

Question 43

Why Selective Estrogen Receptor Modulators aren't used for Osteoporosis

Answer 43

↑ VTE Stroke risk in women 70+: not recommended Concomitant therapy is not recommended (exception: raloxifene and breast cancer reduction)

Question 44

When to Stop Treating?

Answer 44

``` When to consider: • Prognosis & limited life expectancy • Goals of care • Immobility/low fall or fracture risk • Administration concerns • All can be stopped without taper ```

Question 45

Osteoporosis: Clinical Pearls

Answer 45

•Upon dc of an anabolic agent, therapy with an antiresorptive agent is recommended • Switching from bisphosphonate to an anabolic agent can be done • Switching from denosumab to an anabolic agent is NOT recommended • Dietary calcium > supplement