Osteoporosis

Osteoporosis definition

Classified as weak bones, low bone mineral density, and increased fractured risk

Osteblast function

build bone

Osteoclast function

resorb bone (break down tissue in the bone)

Medications that increase osteoporosis risk

antiepileptics (divalproex, valproic acid, carbamazepine, phenytoin, phenobarbital), cyclosporin, lithium, PPIs, corticosteroids (ie 5 g prednisone or more x3 months or longer), medroxyprogesterone, SSRIs, levothyroxine, TCAs, TZDs, loop diuretics, GnRH agonists, anticoagulants, aromatase inhibitors, tenofovir disoproxil fumarate

Who should be tested for osteoporosis

All men 70 years or older and all women 65 years or older

How is osteoporosis diagnosed

1. FRAX: estimates 10-year fracture risk (in treatment naïve)

2. DEXA/DXA scan: bone mineral density scan of lumbar spine, femoral neck, and hip

• T-score: comparison to young adult

• Z-score: comparison to same population (age, sex, ethnicity)

Osteopenia vs osteoporosis T score and FRAX

Osteopenia:

• T score: -1 to -2.5 OR

• Frax 10 year major fracture risk is ≥ 20% OR

• FRAX 10 year hip fracture risk is ≥ 3%

Osteoporosis:

• T score ≤ -2.5 OR

• Fragility fracture

Goals of osteoporosis treatment

prevent fractures (can occur without a fall) and bone loss

Nonpharmacologic treatment of osteoporosis

weight bearing exercise, smoking cessation, limit alcohol, MUST SUPPLEMENT vitamin D and Calcium supplementation

When do you treat osteopenia?

Treat if T score: -1 to -2.5 AND

• Frax 10 year major fracture risk is ≥ 20% OR

• Frax 10 year hip fracture risk is ≥ 3%

When do you treat osteoporosis?

Always

First line treatment for osteopenia

bisphosphonates

First line treatment for osteoporosis

bisphosphonates - specifically: alendronate, risedronate, or zoledronic acid

• If bisphosphonate is contraindicated - use denosumab

First line treatment for women with very high fracture risk

Romosozumab followed by bisphosphonate OR Teriparatide followed by bisphosphonate

Bisphosphonates examples

Alendronate (Fosamax), Ibandronate (Boniva), Risedronate (Actonel), Zoledronic acid (Reclast)

Bisphosphonates MOA

Inhibit osteoclasts which inhibits bone resorption (maintains or increases bone mineral density)

Alendronate dosing for prevention and treatment

Prevention: 5mg daily or 35 mg weekly

Treatment: 10 mg daily or 70 mg weekly

Ibandronate dosing for prevention and treatment

Prevention: 150 mg monthly

Treatment: 150 mg monthly or IV q3 months

Risedronate dosing for prevention and treatment

Prevention and Treatment: 5mg daily, 35 mg weekly, or 150 mg monthly

Zoledronic Acid dosing for prevention and treatment

Prevention: 5 mg IV q2 years

Treatment: 5mg IV q1 year

What class of medication is zoledronic acid

bisphosphonates

Bisphosphonate ADE

GI, dyspepsia, muscle pain, osteonecrosis of jaw, atypical fractures, hypocalcemia

Bisphosphonate CI

Hypocalcemia

Bisphosphonate Fraction Prevention Benefit

Vertebral

Non-vertebral

Hip

(Ibandronate: vertebral only)

Zoledronic Acid specific patient counseling

Stay hydrated to prevent dehydration and kidney problems

Can you give bisphosphonates in liver failure?

What class of medication is zolendronic acid

bisphosphonates

Can you give bisphosphonates in renal impairment?

use caution

Counseling points for bisphosphonates

Take in the morning with 4-8 oz of water 30-60 minutes before other meds or food and patient must stay upright

T/F: Should all patients take bisphosphonates indefinitely?

False- Consider drug holiday after 5 years (PO) or 3 years (IV) in patients

RANKL Antagonist for treatment of osteoporosis

Denosumab (Prolia)

Denosumab MOA

RANKL activates RANK receptor on osteoclasts to increase bone resorption which is blocked by denosumab to decrease osteoclast activity (Maintains or increases bone mineral density)

Denosumab dosing for osteoporosis

60mg SubQ every 6 months- administered by healthcare professional

Denosumab ADE

Cellulitis, rash, GI, hypocalcemia, osteonecrosis of the jaw, infection, atypical fractures, muscle pain, injection site reaction

Can denosumab be used to treat hypercalcemia in cancer?

yes

Can you take denosumab while pregnant?

no

Denosumab Fraction Prevention Benefits

Vertebral, Non-vertebral, Hip

Sclerostin Inhibitor used for treatment of osteoporosis

Romosozumab (Evenity)

Romosozumab MOA

Inhibits sclerostin, which normally blocks bone formation - Anabolic effect

Romosozumab dosing for osteoporosis

Monthly SubQ injection- administered by healthcare professional

Romosozumab ADE

Hypocalcemia, osteonecrosis of the jaw, muscle/joint pain, headache, injection site reaction

Romosozumab BW

may increase MI, stroke, CV death risk

Can you take romosozumab indefinitely?

No- max 1 year then switch to bisphosponate or denosumab

Romosozumab Fraction Prevention Benefit

Vertebral, Non-vertebral

Parathyroid hormones used to treat osteoporosis

Teriparatide (Forteo) and Abaloparatide (Tymlos)

When are parathyroid hormones used to treat osteoporosis?

High risk osteoporosis treatment only

Parathyroid hormone MOA

Stimulate osteoblasts

Parathyroid hormone ADE

Hypercalciuria, increased uric acid, GI, hypotension, flu-like, injection site reactions, dizziness, orthostasis

Abaloparatide fraction prevention benefit

Vertebral, Non-vertebral

Teriparatide fraction prevention benefit

Vertebral, Non-vertebral

Teriparatide dosing for osteoporosis

20 mcg SC daily

Abaloparatide dosing for osteoporosis

80 mcg SC daily

Teriparatide BW

Osteosarcoma

How long can you take parathyroid hormones for treatment of high risk osteoporosis?

Max two years, then switch to bisphosphonate or denosumab

Estrogen options for osteoporosis

Raloxifene and estrogen replacement

Raloxifene MOA

Estrogen receptor agonist/antagonist

Estrogen replacement MOA

Inhibits osteoclasts

Raloxifene ADE

Stroke, VTE, muscle pain, hot flash, edema

Estrogen replacement ADE

CVD, stroke, breast cancer, VTE, GI, headache

Raloxifene BW

VTE, stroke

T/F: Often estrogen replacement has more risks than benefits

True

Raloxifene fracture prevention benefit

Vertebral

Estrogen fracture prevention benefit

Vertebral, Non-vertebral

Calcitonin MOA

Inhibits osteoclasts

Calcitonin ROA

Injection and nasal spray

Calcitonin ADE

Injection: GI, flushing, anaphylaxis; Nasal: congestion, rhinitis, irritation

Calcitonin is made from?

Salmon

Calcitonin fracture prevention benefit

Non-recurrent vertebral