631 Osteoporosis Review

T-score range for osteopenia?

-1 to -2.5

Steps of Vitamin D synthesis

1) 7-dehydrocholesterol is converted to vitamin D3 in sunlight in the skin 2) the liver converts D3 to 25-hydroxyvitamin D 3) the kidneys convert that to 1,25-dihydroxyvitamin D

The %DV on the nutrition facts label assumes what daily consumption of calcium?

1000 mg

What is an optimal 25-OH Vitamin D level?

30-150 ng/mL

Only ____ mg of calcium can be absorbed at a time

500 mg

Romosozumab contraindications?

Hx MI or stroke in past year, hypocalcemia

Is GERD a contraindication to PO bisphosphonates?

No, as long as the pt has not developed complications (e.g. Barrett's) from GERD

Can drug holidays be done for denosumab? Why/why not?

No, shorter half-life than bisphosphonates

If a patient has been taking alendronate for 2 yrs and has dental work scheduled soon, do you stop the bisphosphonate?

No- half-life is so long that holding it for days-weeks won't have much impact

Contraindications to PTH analogs?

Paget's disease, unexplained increased alkaline phosphatase, Hx of radiation

Denosumab decreases the risk of both hip and vertebral factures (T/F)

T

Which medications for osteoporosis can only be used in women?

calcitonin, estrogen, SERM's

How are PTH analogs cleared?

hepatic proteolysis

For which patient population with osteoporosis would a SERM be ideal?

patients with Hx of or high risk for breast cancer

Alendronate absorption?

poor (bioavailability ~0.6%)

denosumab ADR's?

rash, infection, ONJ, AFF, rebound fractures upon d/c

What are the two PTH analogs? How are they administered?

teriparatide, abaloparatide; SC daily for 18-24 months

ADR's of PTH analogs?

transient orthostasis, arthralgias, injection site reactions, hypercalcemia

At what fracture risk would anabolic treatment be indicated?

very high risk (multiple fractures AND T score < -2.5)

pharmacodynamic half-life of bisphosphonates (roughly)

years

How long does it take for bone turnover to return to baseline after discontinuing denosumab?

12 months

The Endocrine Society recommends that women over 50 with osteoporosis receive how much calcium each day through diet and/or supplements?

1200 mg

ibandronate PO vs IV dose?

150 mg PO vs 3 mg IV

Romosozumab dosing

210 mg SUBQ monthly x 12 months

denosumab half-life? onset of action

25-28 days, starts working in a few days with maximal activity at ~1 month

How much calcium do Americans get from nondairy sources?

250 mg/day

When to consider bisphosphonate holiday? How often to check BMD during holiday?

3 yrs for zoledronic acid and 5 yrs for alendronate; q2 yrs

denosumab dosing

60 mg SUBQ every 6 months

What 25-OH vitamin D level would be considered a deficiency?

<20 ng/mL

What Timed Up and Go Test result is suggestive of increased risk for falls?

>12 sec

At what age is screening for osteoporosis recommended?

>65 YO for women, >70 for men

Contraindications to denosumab?

CrCl < 15 mL/min, hypocalcemia

PTH analogs decrease risk of vertebral and hip fractures (T/F)

F (do not have data on hip fractures yet)

For which patients is a bisphosphonate holiday most appropriate?

Patients w/o high risk of fracture, not taking high dose steroids, and have not yet had a vertebral fracture

Denosumab MOA

RANKL inhibitor (which inhibits bone resorption)

How is Romosozumab administered?

SC monthly x 1 year

What are two ways to screen for fall risk?

STEADI guideline questionnaire; Timed Up and Go Test

How is denosumab administered?

SUBQ every 6 months

Romosozumab decreases vertebral, nonvertebral, and hip fractures (T/F)

T

Difference between T score and Z score on DXA report?

T-score = used for diagnosis; how many stdev's pt is away from average peak bone mass Z-score = used to determine if 2ndary workup needed; how many stdev's pt is away from average bone mass for their age/sex

Maintenance dosing of vit D for pt's w/ vit D deficiency?

Vit D3 1000-2000 IU daily

A 58 year old man with osteopenia has the following FRAX score: 10 year risk of major osteoporotic fracture 22%, 10 year risk of hip fracture 2%. How do you interpret these findings? a) The patient is eligible for pharmacologic treatment b) The patient should be treated with calcium and vitamin D c) His risk for fracture places him in the very high-risk category d) It was not necessary to calculate FRAX in this patient

a)

The following medication increases the risk of osteoporosis due to negative effects on bone quality: a) Prednisone b) Ibuprofen c) Baclofen d) Cyclobenzaprine

a)

The following signs/symptoms are associated with vertebral fracture due to osteoporosis: a) Kyphosis b) Enlarged thyroid gland c) Thigh pain d) Hypotension

a)

risk factors for ONJ

age > 65 YO, periodontitis, dental surgery, high dose antiresorptives, Tx > 2 yrs, smoking, cancer/chemo, steroids, DM

Bisphosphonates dosing

alendronate 70 mg weekly ibandronate 150 mg monthly risendronate 35 mg weekly or 150 mg monthly ibandronate IV 3 mg q3m zoledronic acid IV 5 mg annually

Which bisphosphonates decrease risk of hip and vertebral fractures?

all except ibandronate

Romosozumab ADR's

angioedema, rash, urticaria, arthralgia

calcitonin MOA

antagonizes effects of PTH, inhibits osteoclast function which inhibits bone resorption, lowers serum calcium

MOA of bisphosphonates

attach to hydroxyapatite on bone and prevent osteoclasts from completing resorption

Postmenopausal women experience accelerated bone loss because of increased _________ activity: a) Osteoblast b) Osteoclast c) Sclerostin d) Parathyroid hormone

b)

Does romosozumab affect osteoclast or osteoblast activity?

both

Guidelines recommend that treatment with teriparatide be followed sequentially with the following agent to prevent bone density decline and loss of fracture efficacy: a) Estrogen b) Raloxifene c) Alendronate d) Romosozumab

c)

The following type of fracture is considered an osteoporotic fragility fracture in a 70 year old female: a) Shoulder fracture after standing on a ladder to change a light bulb b) Broken leg after experiencing a motor vehicle accident c) Hip fracture after slipping on a kitchen throw rug d) Broken wrist after falling down icy steps

c)

The primary method to diagnose routine GERD is? a) Esophagogastroduodenoscopy b) 24-hour ambulatory pH monitoring c) Patient history (signs/symptoms) d) Esophageal biopsy

c)

Why shouldn't denosumab be stopped abruptly?

can lead to rebound fractures

Difference between a clinical and radiographic fracture?

clinical = pt has Sx from fracture radiographic = pt has no Sx, but fracture shows up on X-ray

What strategies can be used to reduce risk of bisphosphonate-associated ONJ?

complete any dental work before initiating bisphosphonate; use chlorhexidine rinse for dental surgeries completed while taking bisphosphonate

What drug class is most likely to increase risk of osteoporosis-related fracture?

corticosteroids

What medications can increase risk for osteoporosis-related fracture?

corticosteroids, aromatase inhibitors, PPI's, TZD's, antiepileptics, DMPA, heparin, lithium, SSRI's

Which of the following foods may exacerbate GERD symptoms? a) Alcohol b) Fatty foods c) Caffeinated beverages d) All of the above

d)

Unique advantage for zoledronic acid?

decreases mortality when administered <6 months after hip fracture

If someone would be a candidate for a bisphosphonate but their CrCl is too low, what are other options?

denosumab, teriparatide

Risk factors for bisphosphonate related ONJ?

dental work, length of therapy (>3-5 years)

ADR's associated with bisphosphonates?

esophagitis, acute phase rxn, muscle/bone/joint pain, hypocalcemia, afib, ONJ, AFF

contraindications to PO bisphosphonates? (6 of them)

esophagitis, esophageal strictures, Barrett's esophagus, swallowing disorders, inability to sit/stand upright for 30 min, CrCl < 35 mL/min

What other location may be used if a hip BMD cannot be obtained for DXA?

forearm

At what fracture risk should a patient be treated?

high risk (prior fracture or T score < -2.5)

What FRAX score indicates high risk?

hip fracture risk of >3% or major fracture risk of >20%

What FRAX score indicates very high risk?

hip fracture risk of >4.5% or major fracture risk of >30%

What 3 drug-related ADR's can increase risk for fall (and therefore fracture)?

hypotension, sedation, hypoglycemia

When to r/s osteoporosis Tx after a holiday?

if pt fractures or has decline in BMD

key disadvantage of romosozumab compared to PTH analogs?

increased CV risk

Risk factors for osteoporosis

postmenopausal, <127 lbs, family Hx, Ca/Vit D deficiency, not enough fruits/veggies, too much protein, sodium, or caffeine, inactivity, smoking, alcohol (>2 drinks/day for women)

A 65 year old woman undergoes screening for osteoporosis. The T-score of her femoral neck is - 2.1. How should you interpret this finding?

pt has osteopenia

According to the Endocrine guidelines, a repeat DXA to monitor response to therapy in a patient with osteoporosis is typically monitored how often?

q 2 years

If a patient has a low-moderate risk for fracture based on PMHx and T-score, what is the next step?

reassess in 2-4 years

How is alendronate cleared?

renal and biliary; avoid with CrCl < 30-35 mL/min

Which medication for osteoporosis has the greatest "bone building" capacity?

romosozumab

Romosozumab MOA

sclerostin inhibitor

What endocrine etiology should be part of the workup for osteoporosis?

secondary hyperthyroidism

Role of RANKL

secreted by osteoblasts to signal to osteoclasts to complete resorption

MOA of PTH analogs?

stimulates osteoblasts, increases GI absorption of calcium, increases renal tubular reabsorption of calcium

What is an atypical femoral fracture? What can increase the risk of it?

subtrochanteric or diaphyseal fracture; increased risk with bisphosphonates

What should happen next after a patient completes their regimen of a PTH analog?

switch to a bisphosphonate or denosumab to maintain bone built with PTH analog

Differences b/w teriparatide & abaloparatide?

teriparatide has lower Vd; abaloparatide is less expensive and has shorter length of therapy

PTH analogs dosing

teriparatide: 20 mcg SUBQ daily x 24 mo abaloparatide: 80 mcg SIBQ daily x 18 mo

Typical "loading dose" of vitamin D for patients with a deficiency?

vit D3 (cholecalciferol) 6000 IU daily x 8 weeks OR vit D2 (ergocalciferol) 50000 IU weekly x 8 weeks

Recommended calcium intake/day for older adults?

women > 50: 1200 mg daily men 50-70: 1000 mg daily men > 70: 1200 mg daily

Which medication for osteoporosis can cause an infusion reaction and typically requires premedication with APAP and/or NSAIDs?

zoledronic acid